Name: 18680-27-8|(1S,2S,3R,5S)-2,6,6-Trimethylbicyclo[3.1.1]heptane-2,3-diol|97%
Brand: Ambeed
SKU: A148975
Price: 9.0 USD
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1
[ 7785-70-8 ]
[ 18680-27-8 ]

Yield	Reaction Conditions	Operation in experiment
91%	With pyridine; osmium(VIII) oxide; trimethylamine-N-oxide; In tert-butyl alcohol; for 24h;Inert atmosphere; Reflux;	Under nitrogen protection conditions,To 100 mL of tert-butanol was added Me3NO 2H2O (11 g, 102 mmol)(+) - alpha-pinene (15 mL, 97 mmol) was added successively with stirring,Pyridine (7 mL) and osmium tetroxide (51 mg, 0.2 mmol)And then heated to reflux, 24 hours after the TLC test showed complete reaction,The reaction was reduced to room temperature and NaHSO3 (1.2 g, 12 mmol)The mixture was stirred for 1 hour, the reaction solution was transferred to a separatory funnel, the organic phase was separated,The aqueous phase was extracted with ether (3 x 20 mL), the organic phases were combined,Add anhydrous sodium sulfate drying, drying and filtering, Using a rotary evaporator in addition to solvent, column chromatography separation (petroleum ether:Ethyl acetate = 30: 1) to give 15 g of a white solid in 91% yield.
83%	With pyridine; osmium(VIII) oxide; trimethylamine-N-oxide; In water; tert-butyl alcohol; for 24h;Reflux;	This compound was synthesized according to previously reported method.1 To a mixture of (+)-alpha-pinene (15.4 mL, 96.9 mmol), trimethylamine oxide dihydrate (11.3 g, 102 mmol), pyridine (8.0 mL, 0.1 mmol), water (16 mL), and t-butyl alcohol (74 mL) was added osmium tetraoxide (100 mg, 0.39 mmol). The reaction was refluxed for 24 h. After cooling, sodium bisulfite (1.2 g, 11.5 mmol) was added and the resulting mixture was stirred for 10 min, and the aqueous phase was extracted with ether (3 × 20 mL). The combined organic phase was dried over anhydrous Na2SO4 and the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography to yield 13.7 g (83% yield) of (+)-pinanediol 13 as a white solid. 1H NMR (CDCl3, 400 MHz) delta 3.97 (m, 1H), 2.98 (s, 2H), 2.45 (m, 1H), 2.17 (m, 1H), 1.99 (t, 1H, J=5.8Hz), 1.90 (m, 1H), 1.62 (m, 1H), 1.35 (d, 1H, J=10.4Hz), 1.28 (s, 3H), 1.25 (s, 3H), 0.92 (s, 3H). MS (ESI) m/z 193.1 [M + Na]+ .

Reference： [1]Journal of the Indian Chemical Society,1982,vol. 59,p. 119 - 123
[2]Journal of Medicinal Chemistry,2009,vol. 52,p. 4192 - 4199
[3]Patent: CN107151255,2017,A .Location in patent: Paragraph 0164; 0165; 0166
[4]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 2148 - 2152
[5]Tetrahedron,2007,vol. 63,p. 6577 - 6586
[6]Journal of Organic Chemistry,1995,vol. 60,p. 3717 - 3722
[7]Australian Journal of Chemistry,1974,vol. 27,p. 2199 - 2204
[8]Roczniki Chemii,1973,vol. 47,p. 1555 - 1559
[9]Journal of Organic Chemistry,1971,vol. 36,p. 2319 - 2324
[10]Angewandte Chemie - International Edition,2015,vol. 54,p. 12952 - 12956
Angew. Chem.,2015,vol. 127,p. 13144 - 13148,5
[11]European Journal of Organic Chemistry,2016,vol. 2016,p. 958 - 964

2
[ 18680-27-8 ]
[ 1845-25-6 ]

Yield	Reaction Conditions	Operation in experiment
98 % Chromat.	With 3,3-dimethyldioxirane In dichloromethane; acetone at 0℃; for 4h;
19.2 g	With sulfur trioxide pyridine complex; dimethyl sulfoxide; triethylamine In dichloromethane at 10 - 20℃; for 2.5h;	1.2.2 Step 2.2: (1R,2R,5R)-(+)-2-Hydroxy-3-Pinanone Step 2.2: (1R,2R,5R)-(+)-2-Hydroxy-3-Pinanone Triethylamine (Et3N) (80.2 mL; 0.58 mol) was added to a solution of (1R,2R,3S, 5R)-(-)-Pinanediol (24.5 g; 143.9 mmol) in a dimethyl sulfoxide/methylene chloride solvent mixture (154 mL; 1/1) at 10° C. SO3.Pyridine (68.7 g; 0.43 mol) was then added portion-wise over 30 minutes while the temperature was maintained below 20° C. The reaction mixture was stirred for 2 hours at 10° C. then diluted with ethyl acetate (300 mL). The organic layer was washed with HCl 0.5 N (2*150 mL), brine (150 mL), then dried over MgSO4 and filtered. The solvents were removed under vacuum to give a brown oil. The crude product was purified by flash chromatography on silica gel (methylcyclohexane-ethyl acetate: 9/1) to give the title compound as a yellow oil (19.2 g; 63% over two steps). GC: tr=10.9 min; Distillation: B.p=100-104° C. (3-4 mmHg) 1H NMR (400 MHz, CDCl3): 0.90 (s, 3H); 1.30 (s, 3H); 1.40 (s, 3H); 1.70 (d, 1H, J=12.0 Hz); 2.10 (m, 2H); 2.30 (s, 1H); 2.50 (m, 1H); 2.60 (brs, 2H).

Reference： [1]Curci, Ruggero; D'Accolti, Lucia; Detomaso, Antonia; Fusco, Caterina; Takeuchi, Ken'ichi; Ohga, Yasushi; Eaton, Philip E.; Yip, Yu Chi [Tetrahedron Letters, 1993, vol. 34, # 28, p. 4559 - 4562]
[2]Current Patent Assignee: CERENIS THERAPEUTICS HOLDING - US2014/275590, 2014, A1 Location in patent: Paragraph 0256-0260

3
[ 6336-45-4 ]
[ 18680-27-8 ]
pinanediol vinylboronic ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	In diethyl ether; pentane at 20℃; for 6h;
98%	In diethyl ether; pentane equimolar amts., stirring in pentane/ether=10:1 at room temp. for 6 h; solvent removal (reduced pressure), distn. (61°C, 0.1 Torr);
92%	In diethyl ether (+)-α-pinanediol and CH2=CHB(OBu)2 were stirred in ether overnight under Ar; soln. was concd., residue distilled in the presence of galvinoxyl free radical; elem. anal.;

Reference： [1]Wallace, Richard H.; Zong [Journal of Organometallic Chemistry, 1999, vol. 581, # 1-2, p. 87 - 91]
[2]Wallace, Richard H.; Zong [Journal of Organometallic Chemistry, 1999, vol. 581, # 1-2, p. 87 - 91]
[3]Tsai, David J. S.; Matteson, Donald S. [Organometallics, 1983, vol. 2, # 2, p. 236 - 241]

4
[ 13061-96-6 ]
[ 18680-27-8 ]
[ 84110-38-3 ]

Yield	Reaction Conditions	Operation in experiment
95%	In tetrahydrofuran for 0.333333h; Inert atmosphere;	VII.B.2 (+)-Pinanediol methaneboronate (GBS27). A solution of (+)-pinanediol (2.845 g, 16.71 mmol) and methylboronic acid (1.00 g, 16.71 mmol) in THF (15 mL) was stirred for 20 min, concentrated, and then purified by chromatography (light petroleum/diethyl ether 9: 1), affording GBS27 as a colourless oil (3.07 g, 95% yield). [a]D +31.3 (c 1.1, MeOH). XH-NMR (400 MHz, CDC13): δ 0.31 (3H, s, BCH3), 0.87 (3Η, s, pinanyl CH3), 1.15 (1Η, d, J 10.9, pinanyl Hendo), 1-32 (3Η, s, pinanyl C¾), 1.47 (3Η, s, pinanyl G¾), 1.85-2.39 (5Η, m, pinanyl protons), 4.28 (1Η, dd, J 8.7, 1.8, CHOB). 13C-NMR (100 MHz, CDC13): δ -6.2 (br, CB), 24.0, 26.3, 26.5, 27.1, 28.7, 35.5, 38.1, 39.5, 51.3, 85.4. GC-MS, m/z: 194 (9%, M+), 179 (59%), 153 (30%), 137 (27%), 125 (base peak), 119 (15.5%), 111 (59%), 98 (71%), 91 (17.5%), 83 (92%), 77 (19%), 67 (57%), 55 (45%), 43 (57%).
93%	In diethyl ether
	In diethyl ether at 20℃;

In diethyl ether at 20℃;

Reference： [1]Current Patent Assignee: UNIVERSITY OF CALIFORNIA; UNIVERSITY OF MODENA AND REGGIO EMILIA - WO2013/56163, 2013, A1 Location in patent: Paragraph 0441
[2]Location in patent: scheme or table Li, Xianfeng; Zhang, Yong-Kang; Liu, Yang; Ding, Charles Z.; Li, Qun; Zhou, Yasheen; Plattner, Jacob J.; Baker, Stephen J.; Qian, Xuelei; Fan, Dazhong; Liao, Liang; Ni, Zhi-Jie; White, Gemma V.; Mordaunt, Jackie E.; Lazarides, Linos X.; Slater, Martin J.; Jarvest, Richard L.; Thommes, Pia; Ellis, Malcolm; Edge, Colin M.; Hubbard, Julia A.; Somers, Don; Rowland, Paul; Nassau, Pamela; McDowell, Bill; Skarzynski, Tadeusz J.; Kazmierski, Wieslaw M.; Grimes, Richard M.; Wright, Lois L.; Smith, Gary K.; Zou, Wuxin; Wright, Jon; Pennicott, Lewis E. [Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 12, p. 3550 - 3556]
[3]Shreder, Kevin R.; Wong, Melissa S.; Corral, Sergio; Yu, Zhizhou; Winn, David T.; Wu, Min; Hu, Yi; Nomanbhoy, Tyzoon; Alemayehu, Senaiet; Fuller, Stacy R.; Rosenblum, Jonathan S.; Kozarich, John W. [Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 19, p. 4256 - 4260]
[4]Carmes, Laurence; Carreaux, Francois; Carboni, Bertrand [Journal of Organic Chemistry, 2000, vol. 65, # 17, p. 5403 - 5408]

5
[ 80041-89-0 ]
[ 18680-27-8 ]
[ 90084-26-7 ]

Yield	Reaction Conditions	Operation in experiment
83%	In diethyl ether; at 23℃; for 16h;Inert atmosphere;	Into a 250 mL round-bottom flask equipped with a magnetic stir bar and under nitrogen was weighed isopropyl boronic acid (12.5 g, 142 mmol, 1.1 equiv). The solid was taken up in diethyl ether (100 mL), affording a yellow suspension. To this suspension was added over 4 equal portions (1S,2S,3R,5S)-2,6,6-trimethylbicyclo[3 .1.1 ]heptane-2,3 -diol (22.0 g, 129 mmol, 1.0 equiv) [NOTE: Slight exotherm observed]. The resulting yellow suspension became a light white opaque solution. The reaction mixture was stirred for 16 h. The mixture was concentrated under reduced pressure and the crude yellow oil poured onto a pad of silica gel (10 cm wide x 6 cm high) on a sintered glass funnel and the product eluted with 2% EtOAc in hexanes (500 mL). The clear filtrate was concentration under reduced pressure to afford a clear oil (23.7 g, 83%).

Reference： [1]Patent: WO2016/100555,2016,A1 .Location in patent: Paragraph 0129
[2]Journal of Organic Chemistry,2000,vol. 65,p. 5403 - 5408
[3]Journal of Medicinal Chemistry,2019,vol. 62,p. 7160 - 7184

6
[ 16343-08-1 ]
[ 18680-27-8 ]
[ 289709-75-7 ]

Yield	Reaction Conditions	Operation in experiment
94%	In diethyl ether at 20℃;
71%	In diethyl ether at 20℃;
71%	In diethyl ether portionwise adding of pinanediol to ether soln. of boronic acid deriv. in ether at room temp.; rotary evapn. under reduced pressure, chromy. (silica gel,light petroleum-ethyl acetate 80:20); elem. anal.;

Reference： [1]Carmes, Laurence; Carreaux, Francois; Carboni, Bertrand [Journal of Organic Chemistry, 2000, vol. 65, # 17, p. 5403 - 5408]
[2]Davoli, Paolo; Spaggiari, Alberto; Castagnetti, Luca; Prati, Fabio [Organic and Biomolecular Chemistry, 2004, vol. 2, # 1, p. 38 - 47]
[3]Davoli, Paolo; Spaggiari, Alberto; Castagnetti, Luca; Prati, Fabio [Organic and Biomolecular Chemistry, 2004, vol. 2, # 1, p. 38 - 47]
[4]Priestley; De Lucca, Indawati; Ghavimi, Bahman; Erickson-Viitanen, Susan; Decicco, Carl P. [Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 21, p. 3199 - 3202]

7
[ 18680-27-8 ]
[ 40218-49-3 ]
[ 85167-09-5 ]

Reference： [1]Journal of the Chemical Society. Perkin Transactions 1 (2001),2000,p. 4505 - 4511

8
[ 18680-27-8 ]
[ 98-80-6 ]
[ 76110-78-6 ]

Yield	Reaction Conditions	Operation in experiment
93%	In diethyl ether at 20℃;	8.1 Step 1: Synthesis of phenylboronic acid-(1S,2S,3R,5S)-(+)-2,3-decanediol ester (F-2) Compound F-1 phenylboronic acid (lg, 8 · 20 mmol) was dissolved in diethyl ether (20 mL).After adding (IS, 2S, 3R, 5S)-(+)-2,3-decanediol (1.4 g, 8.20 mmol), it was allowed to react at room temperature overnight. The reaction mixture was washed twice with water and then brine, brinePurified by silica gel column chromatography (eluent: PE/EtOAc = 100:1)Obtained 1.96 g of white solid product, yield 93%
91%	With magnesium sulfate In diethyl ether
90%	With 1H-imidazole; iron(III) chloride In water; acetonitrile at 20℃; for 0.5h; Inert atmosphere;	2.2. General Procedure B : Transformation of Boronic Acids into Boronates General procedure: To a solution of aryl boronic acid (1 mmol) in MeCN (4 mL) was added, sequentially, asolution of FeCl3 (8 mg, 0.05 mmol, 5 mol%) in H2O (1 mL), imidazole (204 mg, 3 mmol)and pinacol (118 mg, 1 mmol). The resulting cloudy orange mixture was stirred at roomtemperature for 30 min. The reaction was then diluted with H2O (5 mL) and extracted withEt2O (3 x 8 mL). The combined organic extracts were dried (Na2SO4) and concentrated invacuo. The resulting oil was then purified by a filtration through a silica gel plug (eluting withEt2O), affording the title compound.

88%	In tetrahydrofuran for 0.166667h;
88%	In tetrahydrofuran for 0.166667h;	2; 8 (+)-pinanediolphenylboronate (19). A solution of (+)-pinanediol (665 mg, 3.9 mmol) and phenylboronic acid (18) (476 mg, 3.9 mmol) in THF (5 mL) was stirred for 10 min, concentrated and distilled to yield 21 (879 mg, 88%) bp 135° C. (1.5 mmHg) as a viscous colorless oil which solidified on standing, mp 50° C., []D=+14.9 (c 2.3, CHCl3). IR (KBr): 2910, 1361, 1094, 701 cm-1. 1HNMR (CDCl3): δ 0.92 (3H, s, pinanyl CH3), 1.25 (1H, d, J=10.5 Hz, pinanyl Hendo), 1.34 (3H, s, pinanyl CH3), 1.50 (3H, s, pinanyl CH3), 1.9-2.6 (5H, m, pinanyl protons), 4.48 (1H, dd, J=8.8, 2.0 Hz, pinanyl CHOB), 7.34-7.54 (3H, m, Hm-Hp), 7.85 (2H, dd, J=7.9 Hz, 1.6, Ho). 13C NMR (CDCl3): δ 24.4, 26.9, 27.5, 29.1, 36.0, 38.6, 40.0, 51.9, 78.7, 86.6, 128.1, 131.5, 135.2. Aromatic CB not seen. EI-MS: m/z 256 (M+), 241, 215, 187, 173, 108 (base peak), 93, 77. Anal. Calcd for C16H21BO2: C, 75.02; H, 8.26. Found: C, 74.77; H, 8.53.
	In diethyl ether at 20℃;
	In diethyl ether at 25℃; for 7h;	General procedure: At 25, boronic acids4a-4c(98.10 mmol) was dissolved in 150 mLether, (+)-pinanediol was at once. The reaction was stired at room temperature and determined by TLC analysis. Concentration and flash chromatography over silica gel (EtOAC: petroleum 1:40) produced5a-5c, yields 94%-97%.
	In diethyl ether at 20℃; Inert atmosphere;
	With water In acetonitrile at 25℃;

Reference： [1]Current Patent Assignee: SICHUAN UNIVERSITY - CN110156820, 2019, A Location in patent: Paragraph 0114-0117
[2]Debaene, François; Da Silva, Julien A.; Pianowski, Zbigniew; Duran, Fernando J.; Winssinger, Nicolas [Tetrahedron, 2007, vol. 63, # 28, p. 6577 - 6586]
[3]Wood, John L.; Marciasini, Ludovic D.; Vaultier, Michel; Pucheault, Mathieu [Synlett, 2014, vol. 25, # 4, p. 551 - 555]
[4]Morandi, Federica; Caselli, Emilia; Morandi, Stefania; Focia, Pamela J.; Blazquez, Jesus; Shoichet, Brian K.; Prati, Fabio [Journal of the American Chemical Society, 2003, vol. 125, # 3, p. 685 - 695]
[5]Current Patent Assignee: UNIVERSITY OF MODENA AND REGGIO EMILIA; NORTHWESTERN UNIVERSITY (ILLINOIS) - US7271186, 2007, B1 Location in patent: Page/Page column 7; 34
[6]Priestley; De Lucca, Indawati; Ghavimi, Bahman; Erickson-Viitanen, Susan; Decicco, Carl P. [Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 21, p. 3199 - 3202]
[7]Carmes, Laurence; Carreaux, Francois; Carboni, Bertrand [Journal of Organic Chemistry, 2000, vol. 65, # 17, p. 5403 - 5408]
[8]Shi, Jingmiao; Lei, Meng; Wu, Wenkui; Feng, Huayun; Wang, Jia; Chen, Shanshan; Zhu, Yongqiang; Hu, Shihe; Liu, Zhaogang; Jiang, Cheng [Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 8, p. 1958 - 1962]
[9]Wang, Yao-Ling; Liu, Sha; Yu, Zhu-Jun; Lei, Yuan; Huang, Meng-Yi; Yan, Yu-Hang; Ma, Qiang; Zheng, Yang; Deng, Hui; Sun, Ying; Wu, Chengyong; Yu, Yamei; Chen, Qiang; Wang, Zhenling; Wu, Yong; Li, Guo-Bo [Journal of Medicinal Chemistry, 2019, vol. 62, # 15, p. 7160 - 7184]
[10]Flores-Alamo, Marcos; Martínez-Aguirre, Mayte A.; Medrano, Felipe; Yatsimirsky, Anatoly K. [Organic and biomolecular chemistry, 2020, vol. 18, # 14, p. 2716 - 2726]

9
[ 84110-40-7 ]
[ 18680-27-8 ]
[ 84110-34-9 ]

Yield	Reaction Conditions	Operation in experiment
95%	In diethyl ether; at 40℃; for 8h;	The (+) - Pinanediol (17.0g,0.10mol) with 2-methylpropylBoric acid(11.2g,0.11mol) sequentially added into 200ml of Ethylene ether then themixture was heated to 40 C, stirred for 8 hours; after Completion of thereaction, the mixture was dried using anhydrous magnesium sulfate; filtrated;The filtrate was concentrated under reduced pressure to dryness; With 200mLisopropyl ether beating of the reaction for two hours; again filteredthen filtrate was concentrated under reduced pressure to dryness to obtainformula 3 compound 22.4g (0.095mol, Molar yield 95%).
94%	In diethyl ether; at 20℃; for 24h;	A mixture of (+) -pinanediol (23.9 g, 0.140 mol) and 2- methylpropylboronic acid (15 g, 0.147 mol) in diethyl ether (300 ml) was stirred at room temperature for 24h. The mixture was dried over anhydrous sodium sulfate and purified by column chromatography (Silica gel 230-400 mesh), eluting with hexane: ethyl acetate 90: 10 mixture. The product was obtained as a clear oil (32.6 g, 94% yield). 1H NMR (DMSO-d6) : 4. 28 (1H, dd, J=8.8 Hz, 2.0) ; 2.30 (1H, M) ; 2.18 (1H, M) ; 1.96 (1H, t, J=5.3) ; 1.86 (1H, M) ; 1.78 (1H, set, J=6.8) ; 1.68 (1H, M) ; 1.30 (3H, s); 1.25 (3H, s); 1.01 (1H, d); 0.9 (6H, d, J=6.6) ; 0.81 (3H, s); 0.69 (2H, M).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 3220 - 3224
[2]Patent: CN103421033,2016,B .Location in patent: Paragraph 0047-0050
[3]Tetrahedron,2007,vol. 63,p. 6577 - 6586
[4]Patent: WO2005/21558,2005,A2 .Location in patent: Page/Page column 52
[5]Patent: US2006/189806,2006,A1 .Location in patent: Page/Page column 29
[6]Journal of Medicinal Chemistry,2008,vol. 51,p. 1068 - 1072
[7]Patent: EP3476850,2019,A1 .Location in patent: Paragraph 0038; 0041
[8]Journal of Organic Chemistry,2010,vol. 75,p. 468 - 471
[9]Chemistry Letters,2009,vol. 38,p. 750 - 751
[10]Organic Letters,2019,vol. 21,p. 3048 - 3052
[11]Journal of Medicinal Chemistry,2019,vol. 62,p. 6377 - 6390
[12]Organometallics,1983,vol. 2,p. 236 - 241
[13]Bioorganic and Medicinal Chemistry Letters,2002,vol. 12,p. 3199 - 3202
[14]Journal of labelled compounds and radiopharmaceuticals,2007,vol. 50,p. 402 - 406
[15]Patent: WO2009/36281,2009,A2 .Location in patent: Page/Page column 33
[16]Chemistry Letters,2009,vol. 38,p. 750 - 751
[17]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 1958 - 1962
[18]Journal of Medicinal Chemistry,2019,vol. 62,p. 7160 - 7184

10
[ 4737-50-2 ]
[ 18680-27-8 ]
[ 476335-09-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2002,vol. 12,p. 3199 - 3202

11
[ 18680-27-8 ]
[ 34420-17-2 ]
[ 244782-33-0 ]

Yield	Reaction Conditions	Operation in experiment
	In diethyl ether; at 25℃; for 7h;	General procedure: At 25, boronic acids4a-4c(98.10 mmol) was dissolved in 150 mLether, (+)-pinanediol was at once. The reaction was stired at room temperature and determined by TLC analysis. Concentration and flash chromatography over silica gel (EtOAC: petroleum 1:40) produced5a-5c, yields 94percent-97percent.

Reference： [1]Journal of Organic Chemistry,2010,vol. 75,p. 468 - 471
[2]Chemistry Letters,2009,vol. 38,p. 750 - 751
[3]Bioorganic and Medicinal Chemistry Letters,2002,vol. 12,p. 3199 - 3202
[4]Chemistry Letters,2009,vol. 38,p. 750 - 751
[5]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 1958 - 1962

12
[ 18680-27-8 ]
C₁₃H₁₈BNO₃ [ No CAS ]
[ 497258-60-3 ]

Yield	Reaction Conditions	Operation in experiment
1.14 g	In tetrahydrofuran; diethyl ether; hexane at 20℃;
	With n-butyllithium In tetrahydrofuran; diethyl ether; hexane at 20℃;	1 (+)-pinanediol 3-(4,4-dimethyl-4,5-dihydro-oxazol-2-yl)phenylboronate (7). n-BuLi (2.5 mL of a 2.5 M solution in hexane, 6.23 mmol) was added dropwise with stirring to a solution of 6 (1.51 g, 5.93 mmol) in THF (9.5 mL) at -78° C. under argon. After 30 min a solution of trimethylborate (0.7 mL, 5.93 mmol) in THF (2 mL) was added and the mixture stirred for 1.5 h; thereafter, the resulting yellow solution was quenched with TMSCl (0.75 mL, 5.93 mmol) and allowed to reach rt. After 1 h (+)-pinanediol (1.01 g, 5.93 mmol) dissolved in a minimum amount of anhydrous Et2O was added one portion to the solution, and then stirred overnight. The reaction mixture was partitioned in Et2O (16 mL) and H2O (10 mL) and the aqueous phase extracted with Et2O (2×10 mL). The combined organic phases were dried on MgSO4, filtered and concentrated to give an orange oil, which was purified by chromatography (7:3 EtPet/EtOAc) and crystallization (EtPet), affording 7 (1.14 g, 54%) as a white crystalline solid, mp 98-101° C., [α]D=+11.2 (c 1.5, CHCl3). IR (KBr): 1646 cm-1. 1H NMR (CDCl3): δ 0.81 (3H, s, pinanyl CH3), 1.22 (1H, d, J=10.5 Hz, pinanyl Hendo), 1.33 (3H, s, pinanyl CH3), 1.40 (6H, s, 2CH3), 1.50 (3H, s, pinanyl CH3), 1.5-2.5 (5H, m, pinanyl protons), 4.22 (2H, s, CH2O), 4.47 (1H, dd, J=8.8, 2.0 Hz, pinanyl CHOB), 7.43 (1H, t, J=7.7 Hz, H5 arom.), 7.92 (1H, dt, J=7.7, 1.5 Hz, H6 arom.), 8.05 (1H, dt, J=7.7, 1.5 Hz, H4 arom.), 8.43 (1H, br s, H2 arom.). 13C NMR (CDCl3): δ 24.4, 26.9, 27.5, 28.8 (2C), 29.1, 35.9, 38.6, 40.0, 51.9, 68.0, 78.8, 79.5, 86.8, 128.1, 131.2, 135.0, 137.8, 162.5, (CB and aromatic quaternary C not seen). EI-MS: m/z 353 (M+), 338 (base peak), 323, 282, 242, 202, 186, 130, 103, 67, 55. Anal. Calcd for C21H28NO3B: C, 71.39; H, 7.99; N 3.96. Found: C, 71.01; H, 8.65; N, 3.89.

Reference： [1]Morandi, Federica; Caselli, Emilia; Morandi, Stefania; Focia, Pamela J.; Blazquez, Jesus; Shoichet, Brian K.; Prati, Fabio [Journal of the American Chemical Society, 2003, vol. 125, # 3, p. 685 - 695]
[2]Current Patent Assignee: UNIVERSITY OF MODENA AND REGGIO EMILIA; NORTHWESTERN UNIVERSITY (ILLINOIS) - US7271186, 2007, B1 Location in patent: Page/Page column 5-6; 30-31

13
[ 5419-55-6 ]
[ 18680-27-8 ]
[ 819816-59-6 ]

Yield	Reaction Conditions	Operation in experiment
100%	In dichloromethane at 0 - 20℃;	Synthesis of 2-isopropoxy-3a,5,5-trimethylhexahydro-4,6-methanobenzo[d][1,3,2]dioxaborole Synthesis of 2-isopropoxy-3a,5,5-trimethylhexahydro-4,6-methanobenzo[d][1,3,2]dioxaboroleTo a stirred at 0° C. solution of (1S,2S,3R,5S)-(+)-pinanediol (or (1R,2R,3S,5R)-(-) pinanediol) in dichloromethane, triisopropylborate (1 equiv.) was added and then the reaction was allowed to warm up to room temperature overnight. The reaction was concentrated under reduced pressure to obtain the product as clear oil in quantitative yield. For (1S,2S,3R,5S)-(+)-pinanediol derivative in chloroform [D]20c=0.1=-18.16, 1H NMR (400 MHz, CDCl3): δ 4.36-4.29 (m, 1H), 4.25-4.23 (m, 1H), 2.34-2.26 (m, 1H), 2.25-2.18 (m, 1H), 2.03-1.99 (m, 1H), 1.92-1.82 (m, 2H), 1.39-1.36 (m, 4H), 1.26 (s, 3H), 1.19 (d, J=6.3 Hz, 6H), 0.81 (s, 3H). 11B NMR (128.3 MHz, CDCl3): δ 22.0. 13C NMR (100.6 MHz, CDCl3): δ 84.4, 77.2, 67.7, 51.8, 39.7, 38.5, 36.0, 28.8, 27.3, 26.6, 24.6, 24.5, 24.20. For (1R,2R,3S,5R)-(-)-pinanediol derivative in chloroform [D]20c=0.1=19.44.
93%	In toluene for 0.5h; Heating;
90%	In tetrahydrofuran at 0℃; for 2h;	A.2.1 To a solution of (1S, 2S, 3R, 5S)- (+)-Pinanediol (50.0 g, 0.293 mol) in anhydrous tetrahydrofuran (350 ml) triisopropoxy borane was slowly added while stirring at 0°C under nitrogen. After 2h the solvent was removed by rotary evaporation. The oily residue was redissolved in hexane (150 ml) and the solution was filtered to remove a very small amount of a white solid. The filtrate was concentrated by rotary evaporation affording the product as a clear oil (62.6 g, 90% yield). 'H NMR (DMSO-d6): 4.31-4. 20 (2H, M) ; 2.34-2. 16 (2H, M) ; 1.96 (1H, t, J=5.5) ; 1.90- 1.85 (1H, M) ; 1.74-1. 67 (1H, M) ; 1.32 (3H, s); 1.31 (1H, d, J=7.6) ; 1.25 (3H, s); 1.14 (3H, d, J=6.1) ; 1.13 (3H, d, J=6.1) ; 0.81 (3H, s).

90%	In tetrahydrofuran at 0℃; for 2h;	A.2.1 Step 1: 2-(1-methylethoxy)-(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methano-1,3,2-benzodioxaborole To a solution of (1S,2S,3R,5S)-(+)-pinanediol (50.0 g, 0.293 mol) in anhydrous tetrahydrofuran (350 ml) triisopropoxy borane was slowly added while stirring at 0° C. under nitrogen. After 2 h the solvent was removed by rotary evaporation. The oily residue was redissolved in hexane (150 ml) and the solution was filtered to remove a very small amount of a white solid. The filtrate was concentrated by rotary evaporation affording the product as a clear oil (62.6 g, 90% yield). 1H NMR (DMSO-d6): 4.31-4.20 (2H, m); 2.34-2.16 (2H, m); 1.96 (1H, t, J=5.5); 1.90-1.85 (1H, m); 1.74-1.67 (1H, m); 1.32 (3H, s); 1.31 (1H, d, J=7.6); 1.25 (3H, s); 1.14 (3H, d, J=6.1); 1.13 (3H, d, J=6.1); 0.81 (3H, s).
	In dichloromethane at 0 - 23℃;

Reference： [1]Current Patent Assignee: MITSUI CHEMICALS,INC. - US2012/289733, 2012, A1 Location in patent: Page/Page column 4
[2]Simov, Biljana Peric; Rohn, Agnieszka; Brecker, Lothar; Giester, Gerald; Hammerschmidt, Friedrich [Synthesis, 2004, # 16, p. 2704 - 2710]
[3]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2005/21558, 2005, A2 Location in patent: Page/Page column 55
[4]Current Patent Assignee: TEVA PHARMACEUTICAL INDUSTRIES LTD. - US2006/189806, 2006, A1 Location in patent: Page/Page column 30
[5]Lira, Ricardo; Roush, William R. [Organic Letters, 2007, vol. 9, # 21, p. 4315 - 4318]

14
[ 18680-27-8 ]
[ 115921-03-4 ]
[ 87249-60-3 ]

Yield	Reaction Conditions	Operation in experiment
91%	In tetrahydrofuran at 20℃; for 18h; Inert atmosphere;	4 Example 4:Dichloro methylene boronic acid - (+) - α-pinane diol ester(Compound III-5-a)Of the preparation Compound No. III-3 of Example 2 was added to 150 mL of anhydrous tetrahydrofuran(10 g, 63 mmol) and Example 3 Compound III-4-a (7.2 g, 42 mmol)At room temperature, the TLC assay showed complete reaction after 18 hours,The use of rotary evaporator in addition to solvent,Column chromatography separation (petroleum ether: ethyl acetate = 10: 1)To give 10 g of a colorless oily liquid in a yield of 91%
	In tetrahydrofuran at 20℃;
4.92 g	In diethyl ether at 20℃; for 18h;

	In tetrahydrofuran at 20℃;
4.8 g	In diethyl ether at 20℃; for 24h;	A solution of the crude product 15 (6.3 g, 0.04 mmol) and (+)-pinanediol (3.4 g, 0.02 mmol) in 100 mL ether was stirred at rt for 24 h. The solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography to yield 4.8 g (91% yield) of (+)-pinanediol dichloromethaneboronate 16 as a colorless oil. 1H NMR (CDCl3, 400 MHz) δ 5.39 (s, 1H), 4.46 (d, 1H, J=8.8Hz), 2.33 (m, 2H), 2.12 (t, 1H, J=5.2Hz), 1.94 (m, 2H), 1.46 (s, 3H), 1.30 (s, 3H), 1.21 (d, 1H, J=11.2Hz), 0.84 (s, 3H).

Reference： [1]Current Patent Assignee: FUDAN UNIVERSITY - CN107151255, 2017, A Location in patent: Paragraph 0167; 0168; 0169
[2]Purandare, Ashok V.; Wan, Honghe; Laing, Naomi; Benbatoul, Khalid; Vaccaro, Wayne; Poss, Michael A. [Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 18, p. 4701 - 4704]
[3]Location in patent: scheme or table Venkatraman, Srikanth; Wu, Wanli; Prongay, Andrew; Girijavallabhan, Viyyoor; George Njoroge [Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 1, p. 180 - 183]
[4]Zhu, Yongqiang; Zhao, Xin; Zhu, Xinrong; Wu, Gang; Li, Yuejie; Ma, Yuheng; Yuan, Yunxia; Yang, Jie; Hu, Yang; Ai, Li; Gao, Qingzhi [Journal of Medicinal Chemistry, 2009, vol. 52, # 14, p. 4192 - 4199]
[5]Zhu, Yongqiang; Zhu, Xinrong; Wu, Gang; Ma, Yuheng; Li, Yuejie; Zhao, Xin; Yuan, Yunxia; Yang, Jie; Yu, Sen; Shao, Feng; Li, Runtao; Ke, Yanrong; Lu, Aijun; Liu, Zhenming; Zhang, Liangren [Journal of Medicinal Chemistry, 2010, vol. 53, # 5, p. 1990 - 1999]
[6]Xu, Yulong; Yang, Xicheng; Chen, Yiyi; Chen, Hao; Sun, Huijiao; Li, Wei; Xie, Qiong; Yu, Linqian; Shao, Liming [Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 12, p. 2148 - 2152]

15
[ 18680-27-8 ]
[ 98-59-9 ]
[ 22553-34-0 ]

Yield	Reaction Conditions	Operation in experiment
93%	With pyridine at 20℃; Inert atmosphere;	Synthesis of PiTs (1S,2S,3R,5S)-(+)-Pinanediol (3.61 g, 21.2 mmol) and 20 mL anhydrous pyridine were placed in a 50 mL round bottomed flask and stirred under nitrogen. Next, p-Toluenesulfonyl chloride (4.45 g, 23.3 mmol) was added to the mixture, which was stirred overnight at room temperature. The reaction mixture was poured into 200 mL deionized water and the product was extracted into ethyl acetate (3×75 mL). The combined organic layers were quickly washed with 10% hydrochloric acid (3×), deionized water (2×), saturated aqueous sodium bicarbonate, and brine and then dried over anhydrous magnesium sulfate. After filtering, 5 g of basic alumina was added and the slurry was stirred for 1 hour. The alumina was removed by filtration and the solution was rotary evaporated to dryness to yield 6.38 g of crystals (93% yield) of pinane tosylate (PiTs). 1H-NMR (CDCl3) (δ, ppm): 7.86 (d, 2H, ArH), 7.39 (d, 2H, ArH), 4.92-4.87 (m, 1H, CH-OTs), 2.48 (s, 3H, CH3), 2.28-2.21 (m, 2H, C-H), 2.02 (m, 1H, C-H), 1.91 (m, 1H, C-H), 1.83 (m, 1H, C-H), 1.56 (m, 2H, CH), 1.28 (s, 3H, CH3), 1.23 (s, 3H, CH3), 0.94 (s, 3H, CH3)
46%	With pyridine at 20℃;

Reference： [1]Current Patent Assignee: INTERNATIONAL BUSINESS MACHINES CORP; JSR CORPORATION - US8614047, 2013, B2 Location in patent: Page/Page column 12; 13
[2]Suzuki, Toshiaki; Shibata, Akira; Morohashi, Naoya; Ohba, Yoshihiro [Chemistry Letters, 2005, vol. 34, # 11, p. 1476 - 1477]

16
[ 5419-55-6 ]
[ 18680-27-8 ]
[ 74-95-3 ]
[ 172791-94-5 ]

Yield	Reaction Conditions	Operation in experiment
79%	Stage #1: Triisopropyl borate; 1,1-dibromomethane With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1h; Inert atmosphere; Stage #2: With trimethylsilyl bromide In tetrahydrofuran; hexane at -78 - 20℃; Inert atmosphere; Stage #3: pinanediol In tetrahydrofuran; hexane at 20℃; for 1h; Inert atmosphere;	VII.B.2 (+)-Pinanediol bromomethaneboronate (CR158). MW: 272.97. w-Butyllithium (2.5 M solution in w-hexane, 1 1.75 niL, 29.37 mmol) was added dropwise to a stirred solution of dibromomethane (2.26 mL, 32.45 mmol) and triisopropyl borate (6.5 mL, 27.97 mmol) in THF (20 mL) at -78 °C under argon atmosphere. After one hour bromotrimethylsilane (4.28 mL, 32.45 mmol) was slowly added at the same temperature. The mixture was allowed to gradually reach room temperature overnight. A solution of (15,,25',3R,55)-(+)-pinanediol (4.76 g, 27.97 mmol) in dry THF (10 mL) was then added at rt and left to react for 1 h. The reaction mixture was partitioned between ethyl acetate (100 mL) and water (40 mL), and the aqueous phase was extracted with ethyl acetate (2 x 80 mL). The combined organic phases were washed with brine, dried over Na2S04, filtered and concentrated in vacuo. The crude residue was purified by chromatography (light petroleum/ethyl acetate 9: 1), affording CR158 as a colourless oil (6.010 g, 79% yield). [a]D +22.5 (c 2.8, CHC13). ¾-NMR (200 MHz, CDC13): δ 0.80 (3H, s, pinanyl G¾), 1.16 (1H, d, J 1 1.0, pinanyl Hendo), 1.25 (3H, s, pinanyl CH3), 1.37 (3Η, s, pinanyl CH3), 1.71- 2.39 (5Η, m, pinanyl protons), 2.57 (2Η, s, BCH2), 4.32 (1Η, dd, J 8.7, 1.8, CHOB). 13C-NMR (50 MHz, CDCI3): δ 8.2 (br, CB), 23.9, 26.2, 27.0, 28.4, 35.2, 38.2, 39.3, 51.2, 78.5, 86.7. IR (neat): vmax 1242, 1340, 1416. GC-MS, m/z: 272-274 (1 : 1, M+, 1 1), 257-259 (1 : 1, 32), 231 (33), 216-218 (1 : 1, 30), 203-205 (1 : 1, 52), 189 (25), 176 (26), 152 (25), 134 (74), 1 19 (30), 109 (30), 96 (80), 83 (100), 81 (66), 67 (62), 55 (51). Anal. Calcd for CnH18BBr02: C, 48.40; H, 6.65. Found: C, 48.48; H, 6.71.
63.7%	Stage #1: Triisopropyl borate; 1,1-dibromomethane With n-butyllithium; trimethylsilyl bromide In tetrahydrofuran at -78 - 20℃; Stage #2: pinanediol In tetrahydrofuran at 20℃; for 4h;	64.3 Step 3. Synthesis of (((3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-4,6-methanobenzo[d][1,3,2]dioxaborol-2-yl)methyl)zinc(II) iodide. To a solution of dibromomethane (47.20 g, 271 mmol) and triisopropyl borate (39.85 g, 212 mmol) in THF (200 mL) at -78oC under argon was added n-BuLi (2.5 M in hexane, 93.5 mL, 234 mmol) dropwise over 50 min. After the resulting mixture was stirred at -78oC for 1.5 h, bromotrimethylsilane (31 mL, 235 mmol) was added dropwise. The reaction mixture was allowed to slowly warm to room temperature overnight. To the reaction mixture was then added (+)-pinanediol (36.03 g, 212 mmol) and stirred at room temperature for 4 h. The reaction mixture was then quenched with water, extracted with ethyl acetate (3x). The combined organic phase was dried over Na2SO4. After the solvent was evaporated under reduced pressure, the residue was purified by flash chromatography on silica gel (340 g column) eluted with 0 to 20% ethyl acetate/hexanes to afford 36.84 g (63.7%) of (3aS,4S,6S,7aR)-2-(bromomethyl)-3a,5,5-trimethylhexahydro-4,6-methanobenzo[d][1,3,2]dioxaborole as a clear liquid. ESI-MS m/z 273.1, 275.0 (M+H)+.
	With n-butyllithium; trimethylsilyl bromide

Reference： [1]Current Patent Assignee: UNIVERSITY OF CALIFORNIA; UNIVERSITY OF MODENA AND REGGIO EMILIA - WO2013/56163, 2013, A1 Location in patent: Paragraph 0416
[2]Current Patent Assignee: VENATORX PHARMACEUTICALS INC - WO2021/108023, 2021, A1 Location in patent: Paragraph 00300
[3]Reddy, Venkata Jaganmohan; Chandra, J. Subash; Reddy, M. Venkat Ram [Organic and Biomolecular Chemistry, 2007, vol. 5, # 6, p. 889 - 891]

17
1,1-d2-isobutylboronic acid [ No CAS ]
[ 18680-27-8 ]
1,1-d2-2-methylpropylboronic acid-(+)-pinanediol ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94.2%	In n-heptane at 20℃; for 2h;	3.4 Step 4: Synthesis of 1,1-d2-2-methylpropylboronic acid-(+)-pinanediol ester (Compound 22). The compound 21 (110 mg, 1.06 mmol) and (1S, 2S, 3R, 5S)-(+)-2,3-pinanediol (179.8 mg, 1.06 mmol) were added to a reaction flask, and dissolved by adding 3 mL of n-heptane. The reaction was stirred at room temperature for 2 hours. After TLC detected the reaction was completed, the mixture was washed with brine, dried over anhydrous sodium sulfate, filtered, concentrated, and dried in vacuo to give a product (238 mg, yield: 94.2%).
	With tert-butyl methyl ether at 0℃;

Reference： [1]Current Patent Assignee: SHENZHEN TARGETRX INC - EP3476850, 2019, A1 Location in patent: Paragraph 0056; 0060
[2]Li, Yuexian; Plesescu, Mihaela; Sheehan, Patrick; Daniels, J. Scott; Prakash, Shimoga R. [Journal of labelled compounds and radiopharmaceuticals, 2007, vol. 50, # 5-6, p. 402 - 406]

18
[ 149682-75-7 ]
[ 18680-27-8 ]
[ 205116-75-2 ]

Yield	Reaction Conditions	Operation in experiment
76%	In tert-butyl methyl ether; at 20℃; for 18.0h;	Example 1; Synthesis of (2R)-boroPro- (lS, 2S, 3R, 5S)-pinanediol ester, hydrochloride (2); [0280] A flame dried round bottom flask equipped with a magnetic stir bar was charged with N-Boc-pyrrolidine (20 g, 117 mmol, 1 eq) and dry THF (60 mL) under a nitrogen atmosphere. The clear colorless solution was cooled to-78C and a solution of s- BuLi (100 mL of a 1.4 M solution in cyclohexane, 140 mmol) was added slowly over a 30 minute period. The light orange colored solution was stirred at-78C for 3 hours followed by treatment with B (OMe) 3 (39 mL, 350 mmol) after which the cooling bath was removed and the clear colorless solution slowly warmed to 0C. Upon reaching 0C, the reaction was quenched with a small amount of water (-2 mL), allowed to warm to room temp then extracted into 2 N NaOH (250 mL) and backwashed with additional EtOAc (150 mL). The aqueous phase was acidified to pH 3 by the addition of 2 N HCl and then extracted with EtOAc (3 x 120 mL). The organic extracts were combined and dried over Na2SO4 and concentrated to produce the free boronic acid (22.08 g, 103 mmol) as a sticky white solid in 88% yield. Without further purification the boronic acid was dissolved in tert-butyl methyl ether (150 mL) and with constant stirring (+) -pinanediol (17.5 g, 103 mmol) was added at room temperature. After 18 hr the ether was removed and the (+) -pinanediol boronic ester was purified by column chromatography (silica gel, 1: 3 hexanes/EtOAc) to give a clear thick oil (26.84 g, 76.8 mmol, 76% yield, Rf= 0.6 using a 2: 1 hexane/ethyl acetate eluant, made visual via 12 and/or PMA stain). Removal of the Boc protecting group was achieved by dissolving the oil in dry ether, cooling to 0C in an ice bath and with constant stirring dry HCl (g) was bubbled into the solution for 10 minutes. After 2 hours a white precipitate developed in the flask and the ether and excess HCl were removed in vacuo to afford the racemic HCl salt as a white solid. Crystallization and isolation of the desired isomer was performed by dissolving the HCI salt in a minimal amount of dichloromethane (250 mL) with gentle heating to facilitate a homogenous solution followed by continuous stirring for 8 hours to yield a fluffy white precipitate that was collected by vacuum filtration, dried and then dissolved in minimal 2-propanol (-200 mL) with gentle heating until homogenous. The alcoholic solution was stirred over night and the resulting white precipitate was collected by vacuum filtration affording isomerically pure 1 as a white solid. (7.0 g, 27 mmol, 23% yield).'H NMR (400 MHz, D20) 8 4.28 (d, J= 8.0 Hz, lH), 3.06 (m, 3H), 2.18 (m, 1H), 1.96 (m, 2H), 1.78 (m, 3 H), 1.62 (m, 2H), 1.21 (s, 3H), 1.05 (m, 5H), 0.84 (d, J=12 Hz, 2H), 0.71 (s, 2H), 0.62 (s, 3H).
12.1%	In ethyl acetate; at 20℃; for 18.0h;	General procedure: A flame dried round bottom flask equipped with a magnetic stir bar was charged with N-Boc-pyrrolidine (10g, 58mmol, 1eq) and dry THF (40mL) under a nitrogen atmosphere. The clear colorless solution was cooled to -78C and a solution of s-BuLi (64mL of a 1.0M solution in cyclohexane, 64mmol) was added slowly over a 30min period. The light orange colored solution was stirred at -78C for 3h followed by treatment with B(OMe)3 (15mL, 175mmol) after which the cooling bath was removed and the clear colorless solution slowly warmed to 0C. Upon reaching 0C, the reaction was quenched with a small amount of water (?2mL), allowed to warm to room temp then extracted into 2N NaOH (100mL) and backwashed with additional EtOAc (60mL). The aqueous phase was acidified to pH 3 by the addition of 2N HCl and then extracted with EtOAc (3×60mL). The organic extracts were combined and dried over Na2SO4 and concentrated to produce the free boronic acid 9g as a sticky white solid. Without further purification the boronic acid was dissolved in EtOAc (60mL) and with constant stirring (+)-pinanediol (7.0g, 41mmol) was added at room temperature. After 18h the ester was removed and the (+)-pinanediol boronic ester was purified by column chromatography (silica gel, 6:1 hexanes/EtOAc) to give a clear thick oil (12.1g, 34.8mmol) 60% yield in two steps. 1H NMR (400MHz, CDCl3) delta 4.50-4.15 (m, 1H), 3.38 (dt, J=13.8, 6.1Hz, 2H), 3.12 (ddd, J=25.1, 15.8, 8.4Hz, 1H), 2.33 (dd, J=12.3, 10.3Hz, 1H), 2.20 (s, 1H), 2.10-1.69 (m, 7H), 1.45 (d, J=7.3Hz, 9H), 1.41 (s, 3H), 1.28 (s, 3H), 0.84 (s, 3H).
2.52 g	In tert-butyl methyl ether; at 20℃; for 12.0h;	Free boric acid C1 of Example 1 (2.1 g, 9.36 mmol)Soluble in 20mL methyl tert-butyl ether,Add (+)-pinanediol (1.75 g, 10 mmol) at room temperatureStirring was continued, and the reaction was completed after 12 hours.The solvent was distilled off and directly subjected to column chromatography (petroleum ether: ethyl acetate = 10:1)A clear viscous oil of 2.52 g was obtained in a yield of 76%.

331 g

With magnesium sulfate; In tetrahydrofuran; for 2.0h;

(1) N-Boc-2-pyrrolidine boronic acid (215g, 1mol) is dissolved in tetrahydrofuran (1.5L),Add anhydrous magnesium sulfate (240g, 2mol) with stirring,Was then added (1S, 2S, 3R, 5S) -2,3- pinanediol (170g, 1mol),After two hours of reaction, it was filtered, washed, and the organic phase was concentrated and dried.331 g gave intermediate A1.

Reference： [1]Journal of Organic Chemistry,2007,vol. 72,p. 6276 - 6279
[2]Patent: WO2005/47297,2005,A1 .Location in patent: Page/Page column 114-115
[3]Bioorganic and Medicinal Chemistry,2017,vol. 25,p. 4031 - 4044
[4]Patent: CN108929340,2018,A .Location in patent: Paragraph 0042; 0043
[5]Patent: CN110452258,2019,A .Location in patent: Paragraph 0087; 0090; 0091; 0100-0102

19
[ 18680-27-8 ]
[ 2704-78-1 ]

Yield	Reaction Conditions	Operation in experiment
80%	With 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione In trifluoroacetic acid at 30℃; for 0.1h;

Reference： [1]Moorthy, Jarugu Narasimha; Singhal, Nidhi; Senapati, Kalyan [Organic and Biomolecular Chemistry, 2007, vol. 5, # 5, p. 767 - 771]

20
C₁₁H₁₇BO₄ [ No CAS ]
[ 18680-27-8 ]
[ 643767-30-0 ]

Yield	Reaction Conditions	Operation in experiment
	With n-butyllithium In tetrahydrofuran; diethyl ether; hexane at 20℃;	20c (+)-Pinanediol (3-Dimethoxymethyl)phenylboronate (23b). n-BuLi (5.72 mL of a 2.5 M solution in hexane, 14.3 mmol) was added dropwise with stirring to a solution of 22b (3.00 g, 13.0 mmol) in THF (8 mL) at -78° C. under argon. After 30 min, a solution of trimethylborate (1.50 mL, 13.0 mmol) in THF (4 mL) was added, and the mixture was stirred for 1.5 h. The resulting turbid solution was quenched with TMSCl (1.65 mL, 13.0 mmol) and allowed to reach rt. After 4 h a clear yellow solution is obtained and (+)-pinanediol (2.21 g, 13.0 mmol) dissolved in a minimum amount of anhydrous Et2O was added and stirred overnight. The reaction mixture was partitioned in Et2O (75 mL) and H2O (25 mL), and the aqueous phase was extracted with Et2O (3×25 mL). The combined organic phases were dried on MgSO4, filtered, and concentrated to give an orange oil, which was purified by gradient chromatography (9:1 to 7:3 EtPet/EtOAc), affording 23b (3.21 g, 75%) as a yellow liquid, [α]D=+7.80 (c 2.78, CHCl3). 1H NMR (CDCl3): δ 0.88 (3H, s, pinanyl CH3), 1.22 (1H, d, J=10.5 Hz, pinanyl Hendo), 1.30 (3H, s, pinanyl CH3), 1.47 (3H, s, pinanyl CH3), 1.8-2.6 (5H, m, pinanyl protons), 3.33 (6H, s, CH(OCH3)2), 4.44 (1H, dd, J=8.8, 1.8 Hz, pinanyl CHOB), 5.40 (1H, s, CH(OCH3)2), 7.37 (1H, t, J=7.6 Hz, H5 Ph), 7.55 (1H, d, J=7.6 Hz, H6 Ph), 7.78 (1H, d, J=7.6 Hz, H4 Ph), 7.90 (1H, s, H2 Ph). 13C NMR (CDCl3): δ 25.4, 27.9, 28.5, 30.1, 36.9, 39.6, 40.9, 52.8, 54.1, 79.7, 87.6, 104.7, 129.0, 130.8, 134.5, 136.3, 138.8 (CB and aromatic quaternary C not seen). EIMS: m/z 330 (M+), 315, 299 (base peak), 289, 261, 247, 203, 147, 121, 105, 93, 91, 83, 75, 67.

Reference： [1]Current Patent Assignee: UNIVERSITY OF MODENA AND REGGIO EMILIA; NORTHWESTERN UNIVERSITY (ILLINOIS) - US7271186, 2007, B1 Location in patent: Page/Page column 39

21
[ 18680-27-8 ]
(+)-pinanediol 1-cyclobutylmethyl-1-boronate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38%	Stage #1: (Bromomethyl)cyclobutane With magnesium In diethyl ether for 1.16667h; Heating / reflux; Stage #2: With Triisopropyl borate In diethyl ether at 0 - 20℃; for 4h; Stage #3: pinanediol With sulfuric acid more than 3 stages;	3 To a flame dried 2-necked round bottom flask equipped with a reflux condenser and magnetic stir bar charged with Et2O (15 mL) and Mg° (200 mg, 8.37 mmol, 1.25 eq.). The suspension was stirred under a blanket OfN2 and an ethereal solution of 5 (1.Og. 6.7 mmol) was slowly dripped into the flask until the suspension began to reflux. The remaining solution of 5 was added over a 10 min period and the reaction was heated at reflux for an additional 60 min. The resulting metallic grey suspension was cooled to rt, diluted with Et2O (50 mL) and slowly dripped into a O0C solution of triisopropyl borate (1.43 mL, 6.7 mmol) in Et2O (50 mL). The resulting cloudy solution was allowed to warm to rt and stirred for 4 hr followed by addition of 10% H2SO4 (50 mL). The biphasic solution was extracted with additional Et2O (2 x 30 mL), washed with H2O (50 mL), and brine (50 mL), dried over Na2SO4, and concentrated to approx half the original volume followed by addition of (+)-pinanediol (1.14g, 6.7 mmol). The solution was stirred overnight, concentrated, and purified by flash column chromatography (silica gel, 1.5% EtOAc in hexanes) to give 6 (631 mg, 2.54 mmol, 38% yield) as a clear colorless oil. 1H NMR (400 MHz, CDCl3) δ 4.23 (dd, IH); 2.48 (m, IH); 2.18 (m, IH); 2.10 (m, 2H), 2.04 (dd, IH); 1.9 (m, IH); 1.8 (m, 3H); 1.61 (m, 2H); 1.6 (s, 3H); 1.28 (s, 3H); 1.11 (d, IH); 1.0 (d, 2H); 0.85 (s, 3H).

Reference： [1]Current Patent Assignee: PHENOMIX - WO2007/89618, 2007, A2 Location in patent: Page/Page column 67-68

22
[ 18680-27-8 ]
[ 478375-42-7 ]
[ 1017233-77-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2008,vol. 16,p. 1195 - 1205

23
[ 18680-27-8 ]
[ 1104197-00-3 ]
[ 87249-60-3 ]

Yield	Reaction Conditions	Operation in experiment
60%	With n-butyllithium In diethyl ether at 20℃; for 1.5h;	1.1 Step 1: (3aS,4S,6S)-2-(dichloromethyl)-3a,5,5-trimethylhexahydro-4,6-methano-1,3,2-benzodioxaborole Intermediate 1To a solution of DCM (80 mL, 1.2 mol) in THF (800 mL) at -80° C. to -90° C. was added n-BuLi (2.5 M in hexane, 480 mL, 1.2 mol) under N2, and the reaction mixture was stirred for 1.5 h below -80° C. B(OEt)3 (200 mL, 1.2 mol) was added in one portion and the mixture was stirred for 1 h at -45° C. to -30° C. Aqueous HCl (5 M, 240 mL, 1.2 mol) was then added dropwise while maintaining the temperature below -20° C. and the resulting mixture was stirred at -20° C. for 4 h. The organic layer was separated, and the water layer was extracted with diethyl ether (100 mL×2). The combined organic layers were dried over anhydrous Na2SO4 and concentrated to give an intermediate. The intermediate was re-dissolved in diethyl ether (800 mL) and pinanediol (188 g, 1.1 mol) was added to the solution. The reaction mixture was stirred overnight at room temperature and then concentrated in vacuo. The residue was purified by column chromatography (petroleum ether:EtOAc 10:1 to 1:1) to afford Intermediate 1 (190 g, 60% yield).
	In diethyl ether at 20℃;	1.1 Step 1: (3aS,4S,6S)-2-(dichloromethyl)-3a,5,5-trimethylhexahydro-4,6-methano-1,3,2-benzodioxaborole (intermediate 1) To a solution of CH2Cl2 (80 mL, 1.2 mol) in THF (800 mL) at -80° C. to -90° C. was added n-BuLi (2.5 M in hexane, 480 mL, 1.2 mol) under N2 and the reaction mixture was stirred for 1.5 h below -80° C. B(OEt)3 (200 mL, 1.2 mol) was added in one portion and the mixture was stirred for 1 h at -45° C. to -30° C. Aqueous HCl (5 M, 240 mL, 1.2 mol) was then added dropwise at temperature below -20° C. and the resulting mixture was stirred at -20° C. for 4 h. The organic layer was separated, and the water layer was extracted with Et2O (100 mL*2). The combined organic layer was dried over anhydrous Na2SO4 and concentrated to give an intermediate. The intermediate was re-dissolved in Et2O (800 mL), and pinanediol (188 g, 1.1 mol) was added to the solution. The reaction mixture was stirred overnight at room temperature and then concentrated in vacuo. The residue was purified by column chromatography (petroleum ether: ethyl acetate=10:1~1:1) to afford intermediate 1 (190 g, 60% yield).

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - US2011/245203, 2011, A1 Location in patent: Page/Page column 28
[2]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - US2010/81633, 2010, A1 Location in patent: Page/Page column 27-28

24
[ 220210-56-0 ]
[ 18680-27-8 ]
[ 1154427-21-0 ]

Yield	Reaction Conditions	Operation in experiment
> 99%	With magnesium sulfate; In diethyl ether; at 20℃; for 3h;Inert atmosphere;	(3-(tert-Butoxycarbonyl)phenyl)boronic acid (978 mg, 4,40 mmol) was suspended in 40 mL Et20 and mixed with (+)-pinanediol (750 mg, 4,40 mmol) and anhydrous MgS04 (1 gram, 8,30 mmol). The mixture was stirred at room temperature under argon for 3 hours before the inorganic material was filtered off and the filtrate concentrated under reduced pressure. This gave a sticky clear oil (1568 mg, 4.40 mmol, >99%) which solidified overnight at room temperature. 1H NMR (600 MHz, Chloroform-d) delta 8.41 (t, J- 1.5 Hz, 1H), 8.07 (dt, J= 7.8, 1.6 Hz, 1H), 7.95 (dt, J= 7.4, 1.4 Hz, 1H), 7.42 (t, J= 7.6 Hz, 1H), 4.47 (dd, J= 8.8, 1.9 Hz, 1H), 2.42 (ddt, J= 14.8, 8.8, 2.4 Hz, 1H), 2.30 - 2.20 (m, 1H), 2.16 (t, J= 5.5 Hz, 1H), 2.05 - 1.89 (m, 2H), 1.60 (s, 10H), 1.49 (s, 3H), 1.31 (s, 3H), 1.19 (s, 1H), 0.89 (s, 3H). 13C NMR (151 MHz, CDC13) delta 166.04, 138.84, 135.78, 132.22, 131.60, 127.79, 86.62, 81.12, 78.57, 77.37, 77.16, 76.95, 66.00, 51.53, 39.67, 38.35, 35.64, 28.84, 28.37, 27.25, 26.65, 24.20, 15.43. MS (ESI positive mode): m/z 379.2 (M+Na+)
85%	In tetrahydrofuran; at 20℃; for 0.5h;	A solution of (+)- pinanediol (10.0 g, 58.7 mmole) and 3-tert-Butoxycarbonylphenylboronic acid (13.0 g, 58.7 mmole) in tetrahydrofuran (THF, 78 ml_) was stirred for 30 min at room temperature. The solution was concentrated in vacuo, and the residue chromatographed on SiO2 using a gradient of 20% dichloromethane (DCM) in hexane to 70% DCM/hexane to afford 17.76 g (85%) of the product as a slowly crystallizing white solid. Electrospray Ionization Mass Spectrum (ESI-MS) m/z

Reference： [1]Patent: WO2018/33719,2018,A1 .Location in patent: Page/Page column 154
[2]Patent: WO2009/64413,2009,A1 .Location in patent: Page/Page column 64

25
[ 18680-27-8 ]
[ 18295-60-8 ]
[ 1329020-55-4 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: allenylmagnesium bromide With Trimethyl borate In diethyl ether at -78 - 0℃; Inert atmosphere; Stage #2: With hydrogenchloride In diethyl ether; water for 1h; Inert atmosphere; Stage #3: pinanediol With magnesium sulfate In diethyl ether at 20℃; for 42h; Inert atmosphere;	5.2. Procedure for the preparation of the allenyl boronic esters (6, 20, and ent-39) General procedure: Freshly distilled trimethyl borate (21.7 mL, 196 mmol) was added to a round bottom flask containing 150 mL of ether placed in a -78 °C cold bath. A 0 °C solution of allenylmagnesium bromide (1 M in ether, 196 mmol) was added via syringe or cannula at a rate as to keep the internal reaction temperature below -65 °C. A white precipitate formed during this addition. The reaction mixture was stirred 3 h at -78 °C, then was warmed to 0 °C over 1 h and stirred at 0 °C for an additional hour. Aqueous HCl (2 M, 392 mmol) was added via an addition funnel. This mixture was stirred for 1 h and then the organic layer was separated using a separatory funnel. The aqueous layer was washed with ether (2×200 mL) and the combined organic phases were dried over Na2SO4 for 30 min. The solution was filtered under nitrogen and solvent removed in vacuo until 250 mL of solvent remained (the rotary evaporator was flushed and backfilled using an argon balloon). The appropriate diol (137 mmol) was added to the flask and reaction stirred for 24 h at room temperature, at which time 10 g of MgSO4 was added and the mixture stirred for an additional 18 h at room temperature. The reaction was filtered under nitrogen using a coarse fritted funnel and solvent removed in vacuo using argon to backfill the rotary evaporator.

Reference： [1]Location in patent: experimental part Nuhant, Philippe; Kister, Jeremy; Lira, Ricardo; Sorg, Achim; Roush, William R. [Tetrahedron, 2011, vol. 67, # 35, p. 6497 - 6512]

26
[ 18680-27-8 ]
[ 1360458-62-3 ]
[ 1360458-63-4 ]

Yield	Reaction Conditions	Operation in experiment
84.6%	In tetrahydrofuran at 20℃; for 16h;	1.2 To a solution of tert-butyl 3-(tert-butyldimethylsilyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pentanoate XXXVIII (5.4 g, 13 mmol) in THF (25 mL) was added (1S,2S,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]heptane-2,3-diol (2.4 g, 14.3 mol) at room temperature. The reaction mixture was stirred for 16 h and then was concentrated under vacuum. The residue was purified by column chromatography (100% hexane→40% EtOAc/hexane) on silica gel to give 1-(tert-butoxy)-3-[(tert-butyldimethylsilyl)oxy]-1-oxo-6-[(2S,6R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]hexan-3-yl XXXIX (5.5 g, 11 mmol, 84.6% yield).

Reference： [1]Current Patent Assignee: MELINTA THERAPEUTICS INC. - US2012/40932, 2012, A1 Location in patent: Page/Page column 32

27
[ 18680-27-8 ]
[ 1360458-67-8 ]
tert-butyl (4Z)-3-hydroxy-6-[6,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]hex-4-enoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
59.9%	In tetrahydrofuran at 20℃; for 16h;	4.1 To a stirred solution of tert-butyl 2-(2-hydroxy-3,6-dihydro-2H-1,2-oxaborinin-6-yl)acetate XLVII (770 mg, 4.58 mmol) in THF (25 mL) was added (1S,2S,3R,55)-2,6,6-trimethylbicyclo[3.1.1]heptane-2,3-diol (980 mg, 4.58 mmol) at room temperature. The reaction mixture was stirred for 16 h and concentrated under vacuum. The residue was purified by column chromatography (100% hexane→30% EtOAc/hexane) on silica gel to give tert-butyl (4Z)-3-hydroxy-6-[(1R,2R,6S,8R)-6,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]hex-4-enoate LIV (1 g, 2.75 mmol, 59.9% yield).

Reference： [1]Current Patent Assignee: MELINTA THERAPEUTICS INC. - US2012/40932, 2012, A1 Location in patent: Page/Page column 42

28
[ 18680-27-8 ]
[ 1360458-68-9 ]
tert-butyl 3-hydroxy-6-[6,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]hexanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71.9%	In tetrahydrofuran at 20℃; for 12h;	3.3 To a solution of tert-butyl 2-(2-hydroxy-1,2-oxaborinan-6-yl)acetate XLVIII (641 mg, 3.00 mmol) in THF (20 mL) was added (1S,2S,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]heptane-2,3-diol (509 mg, 3 mol) at room temperature. The reaction mixture was stirred for 16 h and concentrated under vacuum. The residue was purified by column chromatography (100% hexane→40% EtOAc/hexane) on silica gel to give tert-butyl 3-hydroxy-6-[(1R,2R,6S,8R)-6,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]hexanoate XLIX (790 mg, 2.16 mmol, 71.9% yield).

Reference： [1]Current Patent Assignee: MELINTA THERAPEUTICS INC. - US2012/40932, 2012, A1 Location in patent: Page/Page column 41

29
aqueous NaCl [ No CAS ]
[ 177698-18-9 ]
Me₃NO_.2H₂O [ No CAS ]
[ 75-65-0 ]
[ 18680-27-8 ]

Yield	Reaction Conditions	Operation in experiment
92.9%	With pyridine; sodium hydrogen sulfate; osmium(VIII) oxide In water	P.38 (1S,2S,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]heptane-2,3-diol Preparation Example 38 (1S,2S,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]heptane-2,3-diol Me3NO.2H2O (11.3 g, 102 mmol) was dissolved with 16 ml of water, α-pinene (13.2 g, 96.9 mmol), 74 ml of tert-butyl alcohol, 7.4 ml of pyridine and osmium tetroxide (60 mg, 0.236 mmol) were added under stirring. Then nitrogen gas was purged, 10 min later, the reaction mixture was heated to reflux. The reaction was monitored by TLC and finished after 15 h. Spontaneously cooled down to room temperature, NaHSO3 (1.2 g, 11.5 mmol) and an appropriate amount of saturated aqueous NaCl solution were added. The organic phase was separated out, and the water layer was extracted with diethyl ether (3*20 ml), the organic phase was combined and dried over anhydrous sodium sulfate. The product was concentrated and the residue was purified by column chromatography (ethyl acetate:petroleum ether=1:30), 15.33 g of white solid was obtained, and the yield was 92.9%, [α]D20=-10.79° (c=5.5, toluene), m.p.: 52-54° C. 1H-NMR (CDCl3, 300 MHz): δ 0.94 (-CH3, s, 3H), 1.28 (-CH3, s, 3H), 1.32 (-CH3, s, 3H), 1.34~1.38 (-CH2, d, 1H), 1.66 (-CH2, m, 1H), 1.93 (-CH, m, 1H), 2.01 (-CH2, t, 1H), 2.20 (-CH, m, 1H), 2.33 (H2O, s, 2H), 2.49 (-CH2, m, 1H), 4.00 (-CH, q, 1H); 13C-NMR (CDCl3, 300 MHz): δ 24.11, 27.80, 28.00, 29.54, 38.21, 38.99, 40.51, 53.98, 69.26, 73.88; Elemental analysis: C10H18O2, Calculated values C, 70.55; H, 10.66; Measured values C, 70.55; H, 10.67.

Reference： [1]Current Patent Assignee: PEKING UNIVERSITY - US2012/135921, 2012, A1

30
[ 5419-55-6 ]
[ 18680-27-8 ]
[ 69038-74-0 ]
[ 1154427-21-0 ]

Yield	Reaction Conditions	Operation in experiment
89%		(+)-Pinanediol 3-(teri-butoxycarbonyl)benzeneboronate (12b). A solution of tert- butyl 3-bromo-benzoate (1.70 g, 6.61 mmol), obtained from 3-bromobenzoic acid, (Wright, S. W. et al, Tetrahedron Lett. 1997, 38, 7345-7348) and freshly distilled triisopropyl borate (1.53 mL, 6.61 mmol) in THF (17 mL) was cooled to -100 °C under argon flow and w-butyllithium (2.5 M soln in hexane, 2.91 mL, 7.27 mmol) was added dropwise over 15 min, during which the solution turned cherry red. After 1 h at -100 °C, trimethylsilyl chloride (0.84 mL, 6.61 mmol) was dropped into the reactor and the resulting colorless solution was allowed to warm to room temperature and stirred overnight. Finally, (+)-pinanediol (1.12 g, 6.61 mmol) was added and the solution stirred 1 h at room temperature. The mixture was partitioned between ethyl acetate (100 mL) and water (40 mL) and the aqueous phase was extracted with ethyl acetate (2 x 50 mL). The combined organic phases were washed with brine, dried over MgS04, filtered and concentrated in vacuo. The crude residue was purified by column chromatography (light petroleum/ethyl ether 95:5), affording 12b as a yellowish solid (2.10 g, 89percent yield). Mp 70-71 °C. [CC]D +7.3 (c 1.1, CHCI3). XH-NMR (400 MHz, CDC13): delta 0.94 (3H, s, pinanyl CH»), 1.24 (1H, d, J 10.9, pinanyl Hendo), 1.36 (3H, s, pinanyl G¾), 1.53 (3H, s, pinanyl CH3), 1.64 (9H, s, f-Bu), 1.98-2.30 (5H, m, pinanyl protons), 4.51 (1H, dd, J 8.5, 2.0, CHOB), 7.46 (1Eta, t, J7.6, ¾), 8.0 (1Eta, d, J 7.6, H4), 8.12 (1H, d, J7.6, H6), 8.45 (1H, s, H2). 13C-NMR (100 MHz, CDCI3): delta 24.0, 26.5, 27.1, 28.2, 28.7, 35.5, 38.2, 39.5, 51.4, 78.4, 80.9, 86.5, 127.6, 131.5, 132.1, 135.7, 138.7, 169.5, CB not seen. EI-MS: m/z 356 (M+, 10percent), 300 (36), 283 (41), 231 (50), 204 (38), 83 (65), 67 (59), 57 (100). Anal. Calcd. for C2iH29B04: C, 70.80; H, 8.20. Found: C, 70.55; H, 8.22.

Reference： [1]Patent: WO2013/56163,2013,A1 .Location in patent: Paragraph 0404

31
[ 18680-27-8 ]
(E)-propenylboronic acid [ No CAS ]
(+)-pinanediol trans-1-propen-1-ylboronate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	In tetrahydrofuran for 0.5h;	4.2 General procedure for the synthesis of (+)-pinanediol boronate General procedure: A solution of the starting boronic acid (3.00 mmol) and (+)-pinanediol (3.00 mmol) in THF (6mL) was stirred for 30min and then concentrated in vacuo. The crude was purified by chromatography (light petroleum/ diethyl ether 7:3), affording the expected compounds with good yields.

Reference： [1]D'Annibale, Andrea; D'Auria, Maurizio; Prati, Fabio; Romagnoli, Chiara; Stoia, Sonia; Racioppi, Rocco; Viggiani, Licia [Tetrahedron, 2013, vol. 69, # 19, p. 3782 - 3795]

32
[ 18680-27-8 ]
(E)-1-pentenylboronic acid [ No CAS ]
[ 1429441-93-9 ]

Yield	Reaction Conditions	Operation in experiment
97%	In tetrahydrofuran for 0.5h;	4.2 General procedure for the synthesis of (+)-pinanediol boronate General procedure: A solution of the starting boronic acid (3.00 mmol) and (+)-pinanediol (3.00 mmol) in THF (6mL) was stirred for 30min and then concentrated in vacuo. The crude was purified by chromatography (light petroleum/ diethyl ether 7:3), affording the expected compounds with good yields.

Reference： [1]D'Annibale, Andrea; D'Auria, Maurizio; Prati, Fabio; Romagnoli, Chiara; Stoia, Sonia; Racioppi, Rocco; Viggiani, Licia [Tetrahedron, 2013, vol. 69, # 19, p. 3782 - 3795]

33
[ 13331-23-2 ]
[ 18680-27-8 ]
[ 1429441-94-0 ]

Yield	Reaction Conditions	Operation in experiment
89%	In tetrahydrofuran for 0.5h;	4.2 General procedure for the synthesis of (+)-pinanediol boronate General procedure: A solution of the starting boronic acid (3.00 mmol) and (+)-pinanediol (3.00 mmol) in THF (6mL) was stirred for 30min and then concentrated in vacuo. The crude was purified by chromatography (light petroleum/ diethyl ether 7:3), affording the expected compounds with good yields.

Reference： [1]D'Annibale, Andrea; D'Auria, Maurizio; Prati, Fabio; Romagnoli, Chiara; Stoia, Sonia; Racioppi, Rocco; Viggiani, Licia [Tetrahedron, 2013, vol. 69, # 19, p. 3782 - 3795]

34
[ 18680-27-8 ]
[ 1444010-69-8 ]
[ 1444010-70-1 ]

Yield	Reaction Conditions	Operation in experiment
88%	In diethyl ether at 20℃; for 12h;	1a.4 Step 4: 2-(3-ethylbenzyl)boronic acid (+)-pinanediol ester A solution of 2-(3-ethylbenzyl)-4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane (8.7 g, 28.0 mmol) in diethyl ether (90 ml) was treated with (1S, 2S, 3R, 5S)-(+)-pinanediol (7.2 g, 42.0 mmol). The reaction mixture was stirred at room temperature for 12 h then the mixture was washed with water twice, then with brine and dried over anhydrous sodium sulphate, then concentrated. The crude product was purified by flash column chromatography on silica gel, eluting with 3% of ethyl acetate in petroleum ether, to afford the title compound (9.4 g, colourless liquid, 88%). 1H NMR (400 MHz, CDCI3): δ 7.19-7.16 (m, 1H), 7.04-6.97 (m, 3H), 4.29 (dd, J = 1.88, 8.74 Hz, 1H), 2.65-2.59 (m, 2H), 2.35-2.31 (m, 3H), 2.21-2.17 (m, 1 H), 2.06 (t, J = 5.84 Hz, 1H), 1.90-1.82 (m, 2H), 1.40 (s, 3H), 1.29 (s, 3H), 1.10-1.07 (m, 1H), 0.84 (s, 3H). GCMS: m/z: 298.1.
88%	In diethyl ether at 20℃; for 12h;	Step 4: 2-(3-ethylbenzyl)boronic acid (+)-pinanediol ester Step 4: 2-(3-ethylbenzyl)boronic acid (+)-pinanediol ester A solution of 2-(3-ethylbenzyl)-4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane (8.7 g, 28.0 mmol) in diethyl ether (90 ml) was treated with (1 S, 2S, 3R, 5S)-(+)-pinanediol (7.2 g, 42.0 mmol). The reaction mixture was stirred at room temperature for 12 h then the mixture was washed with water twice, then with brine and dried over anhydrous sodium sulphate, then concentrated. The crude product was purified by flash column chromatography on silica gel, eluting with 3% of ethyl acetate in petroleum ether, to afford the title compound (9.4 g, colourless liquid, 88%). 1H NMR (400 MHz, CDCI3): δ 7.19-7.16 (m, 1 H), 7.04-6.97 (m, 3H), 4.29 (dd, J = 1.88, 8.74 Hz, 1 H), 2.65-2.59 (m, 2H), 2.35-2.31 (m, 3H), 2.21-2.17 (m, 1 H), 2.06 (t, J = 5.84 Hz, 1H), 1.90-1.82 (m, 2H), 1.40 (s, 3H), 1.29 (s, 3H), 1.10-1.07 (m, 1 H), 0.84 (s, 3H). GCMS: m/z: 298.1
84%	In diethyl ether at 20℃; for 12h;	2.4 Step 4: (3-ethylbenzyl)boronic acid (+)-pinanediol ester A solution of 2-(3-ethylbenzyl)-4 ,4,5, 5-tetramethyl-1 ,3,2-dioxaborolane (1.4 g, 5.68 mmol) in diethyl ether (30 ml) was treated with (1 S, 2S, 3R, 5S)-(+)-pinanediol (1 .45 g, 8.53 mmol). The reaction mixture was stirred at room temperature for 12 h then the mixture was washed with water twice, then with brine and dried over anhydrous sodium sulphate, then concentrated. The crude product was purified by column chromatography on silica gel, eluting with 5% of ethyl acetate in petroleum ether, to afford the title compound (1 .43 g, 84%). 1H NMR (400 MHz, CDCI3) δ 7.19-7.15 (m, 1 H), 7.04-7.01 (m, 2H), 6.98-6.96 (m, 1 H), 4.29-4.27 (m, 1 H), 2.64-2.58 (m, 2H), 2.34-2.28 (m, 3H), 2.20-2.19 (m, 1 H), 2.07-2.04 (m, 1 H), 1.89-1 .81 (m, 2H), 1 .29 (s, 3H), 1 .25-1.21 (m, 3H), 1.1 -1.08 (m, 1 H), 0.84 (s, 3H). GCMS: m/z: 298

63%	In diethyl ether at 20℃;	30 A solution of 2-(3-ethylbenzyl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (4 g, 16 mmol) in diethyl ether (30 mL) was treated with (lS,2S,3R,5S)-2,6,6-trimethylbicyclo[3. l.l]heptane-2,3- diol (3.5 g, 20.8 mmol). The mixture was stirred at rt for 12 h. Then the mixture was concentrated and the crude was purified by column chromatography on silica gel, eluting with 5% of EtOAc in petroleum ether to afford (3aS,4S,6S,7aR)-2-(3-ethylbenzyl)-3a,5,5-trimethylhexahydro-4,6- methanobenzo[d] [l,3,2]dioxaborole (3 g, 63%) as a yellow oil.
	In tert-butyl methyl ether at 20℃; Inert atmosphere;

Reference： [1]Current Patent Assignee: MERCK KGAA - WO2016/50355, 2016, A1 Location in patent: Page/Page column 66
[2]Current Patent Assignee: MERCK KGAA - WO2016/50356, 2016, A1 Location in patent: Page/Page column 73; 74
[3]Current Patent Assignee: MERCK KGAA - WO2013/92979, 2013, A1 Location in patent: Page/Page column 45; 46
[4]Current Patent Assignee: SANOFI - WO2019/99582, 2019, A1 Location in patent: Paragraph 0313; 0314; 0318
[5]Klein, Markus; Busch, Michael; Friese-Hamim, Manja; Crosignani, Stefano; Fuchss, Thomas; Musil, Djordje; Rohdich, Felix; Sanderson, Michael P.; Seenisamy, Jeyaprakashnarayanan; Walter-Bausch, Gina; Zanelli, Ugo; Hewitt, Philip; Esdar, Christina; Schadt, Oliver [Journal of Medicinal Chemistry, 2021, vol. 64, # 14, p. 10230 - 10245]

35
[ 18680-27-8 ]
[ 1190235-39-2 ]
[ 1444010-73-4 ]

Yield	Reaction Conditions	Operation in experiment
99%	In diethyl ether; at 20℃; for 12h;	A solution of 2-(3-trifluoromethylbenzyl)-4,4, 5, 5-tetramethyl-1 ,3,2-dioxaborolane (5.10 g, 17.8 mmol) in diethyl ether (50 ml) was treated with (1 S, 2S, 3R, 5S)-(+)-pinanediol (4.55 g, 26.7 mmol). The reaction mixture was stirred at room temperature for 12 h, then the mixture was washed with water twice, then with brine and dried over sodium sulphate, then concentrated. The crude product was purified by column chromatography on silica gel, eluting with 2% of ethyl acetate in petroleum ether to afford the title compound (6.0 g, 99%) as a colourless liquid. 1H NMR (400 MHz, CDCI3): delta 7.40 (s, 1 H), 7.35-7.38 (m, 3H), 4.29 (dd, J= 2.0, 8.8 Hz, 1 H), 2.40 (s, 2H), 2.31 -2.36 (m, 1 H), 2.17-2.21 (m, 1 H), 2.05 (t, J= 5.8 Hz, 1 H), 1 .90-1.92 (m, 1 H), 1.80-1 .85 (m, 1 H), 1 .39 (s, 3H), 1 .29 (s, 3H), 1.02-1.05 (m, 1 H), 0.84 (s, 3H). GCMS: m/z=338

Reference： [1]Patent: WO2013/92979,2013,A1 .Location in patent: Page/Page column 47; 48

36
[ 18680-27-8 ]
[ 1444010-65-4 ]
[ 1444010-66-5 ]

Yield	Reaction Conditions	Operation in experiment
90%	In diethyl ether at 20℃; for 48h;	1.3 Step 3: (3-thienylmethyl)boronic acid (+)-pinanediol ester A solution of 4,4,5,5-tetramethyl-2-(3-thienylmethyl)-1 ,3,2-dioxaborolane (3.55 g, 15.8 mmol) in diethyl ether (40 ml) was treated with (1 S, 2S, 3R, 5S)-(+)-pinanediol (3.1 g, 18 mmol). The reaction mixture was stirred at room temperature for 2 days. The reaction mass was washed with water (2 x 15 ml), brine and dried over anhydrous sodium sulphate and concentrated to get a crude product which was purified by column chromatography on silica gel, eluting with 5% of ethyl acetate in petroleum ether, to afford the title compound (4.0 g, 90%) 1H NMR (400 MHz, CDCI3) δ 7.23 (dd, J= 7.8, 3.2 Hz, 1 H), 6.97-6.95 (m, 2H), 4.31 (dd, J= 8.8, 2.0 Hz, 1 H), 2.36-2.30 (m, 3H), 2.2-2.18 (m, 1 H), 2.07 (t, J= 5.2Hz, 1 H), 1.92-1.90 (m, 1 H), 1.87-1 .84 (m, 1 H) 1.40 (s, 3H), 1.32 (s, 3H), 1.10 (d, J= 10.9 Hz, 1 H), 0.84 (s, 3H).

Reference： [1]Current Patent Assignee: MERCK KGAA - WO2013/92979, 2013, A1 Location in patent: Page/Page column 42; 43

37
[ 18680-27-8 ]
[ 1444010-79-0 ]
[ 1444010-80-3 ]

Yield	Reaction Conditions	Operation in experiment
88%	In diethyl ether at 20℃;	6.7 Step 7: Synthesis of 1-(3'-benzofuran)methylboronic acid-(1S,2S,3R,5S)-(+)-2,3-decanediol ester (E-8) Compound E-7 (2 g, 7.74 mmol) was dissolved in diethyl ether (25 mL) and (1S,2S,3R,5S)-(+)-2,3-decanediol (1.45 g, 8.51 mmol) After that, it was reacted overnight at room temperature. The reaction mixture was washed twice with water and then brine, dried over anhydrous sodium sulfateThe product was obtained as a colorless oil, 2.11 g, yield 88%
82%	In diethyl ether at 20℃; for 12h;	18.4 Step 4: 2-(benzofuran-3-ylmethyl)boronic acid (+)-pinanediol ester A solution of 2-(benzofuran-3-ylmethyl)-4,4, 5, 5-tetramethyl-1 ,3,2-dioxaborolane (6.1 g, 23.6 mmol) in diethyl ether (60 ml) was treated with (1 S, 2S, 3R, 5S)-(+)-pinanediol (6.0 g, 35.4 mmol). The reaction mixture was stirred at room temperature for 12 h then the mixture was washed with water twice, then with brine and dried over anhydrous sodium sulphate, then concentrated. The crude product was purified by column chromatography on silica gel, eluting with 5% of ethyl acetate in petroleum ether, to afford the title compound (6.3 g, 82%). 1H NMR (400 MHz, CDCI3): δ 7.56-7.58 (m, 1 H), 7.53-7.55 (m, 1 H), 7.44-7.46 (m, 1 H), 7.23-7.28 (m, 2H), 4.33 (dd, J = 1.88, 8.76 Hz, 1 H), 2.32-2.34 (m, 1 H), 2.28 (s, 2H), 2.21 - 2.22 (m, 1 H), 2.08 (t, J = 5.88 Hz, 1 H), 1.42 (s, 3H), 1.29 (s, 3H), 1.13 (d, J = 10.92 Hz, 1 H), 0.85 (s, 3H). GCMS: m/z: 310
82%	In diethyl ether at 20℃; for 12h;	4 Step 4: 2-(benzofuran-3-ylmethyl)boronic acid (+)-pinanediol ester A solution of 2-(benzofuran-3-ylmethyl)-4,4,5, 5-tetramethyl-1 , 3,2-dioxaborolane (6.1 g, 23.6 mmol) in diethyl ether (60 ml) was treated with (iS, 2S, 3R, 5S)-(+)- pinanediol (6.0 g, 35.4 mmol). The reaction mixture was stirred at room temperature for 12 h then the mixture was washed with water twice, then withbrine and dried over anhydrous sodium sulphate, then concentrated. The crude product was purified by flash column chromatography on silica gel, eluting with 5% of ethyl acetate in petroleum ether, to afford the title compound (6.3 g, 82%). 1H NMR (400 MHz, CDCI3): 67.58-7.56 (m, IH), 7.55-7.53 (m, 1H), 7.46-7.44 (m,1H), 7.28-7.23 (m, 2H), 4.33 (dd, J = 1.88, 8.76 Hz, 1H), 2.34-2.32 (m, 1H), 2.28 (s, 2H), 2.22-2.21 (m, IH), 2.08 (t, J = 5.88 Hz, 1H), 1.42 (s, 3H), 1.29 (s, 3H), 1.13 (d, J= 10.92 Hz, 1H), 0.85 (s, 3H). GCMS: m/z: 310.

82%	In diethyl ether at 20℃; for 12h;	1a.4 Step 4: 2-(benzofuran-3-ylmethyl)boronic acid (+)-pinanediol ester Step 4: 2-(benzofuran-3-ylmethyl)boronic acid (+)-pinanediol ester A solution of 2-(benzofuran-3-ylmethyl)-4,4l5,5-tetramethyl-1,3>2-dioxaborolane (6.1 g, 23.6 mmol) in diethyl ether (60 ml) was treated with (1S, 2S, 3R, 5S)-(+)-pinanediol (6.0 g, 35.4 mmol). The reaction mixture was stirred at room temperature for 12 h then the mixture was washed with water twice, then with brine and dried over anhydrous sodium sulphate, then concentrated. The crude product was purified by flash column chromatography on silica gel, eluting with 5% of ethyl acetate in petroleum ether, to afford the title compound (6.3 g, 82%). 1H NMR (400 MHz, CDC ): δ 7.58-7.56 (m, 1 H), 7.55-7.53 (m, 1 H), 7.46-7.44 (m, 1H), 7.28-7.23 (m, 2H), 4.33 (dd, J = 1.88, 8.76 Hz, 1 H), 2.34-2.32 (m, 1 H), 2.28 (s, 2H), 2.22- 2.21 (m, 1H), 2.08 (t, J = 5.88 Hz, 1 H), 1.42 (s, 3H), 1.29 (s, 3H), 1.13 (d, J = 10.92 Hz, 1H), 0.85 (s, 3H). GCMS: m/z: 310.
82%	In diethyl ether at 20℃; for 12h;	2.4 Step 4: 2-(benzofuran-3-ylmethyl)boronic acid (+)-pinanediol ester A solution of 2-(benzofuran-3-ylmethyl)-4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane (6.1 g, 23.6 mmol) in diethyl ether (60 ml) was treated with (1S, 2S, 3R, 5S)-(+)-pinanediol (6.0 g, 35.4 mmol). The reaction mixture was stirred at room temperature for 12 h then the mixture was washed with water twice, then with brine and dried over anhydrous sodium sulphate, then concentrated. The crude product was purified by flash column chromatography on silica gel, eluting with 5% of ethyl acetate in petroleum ether, to afford the title compound (6.3 g, 82%). 1H NMR (400 MHz, CDCI3): δ 7.58-7.56 (m, 1 H), 7.55-7.53 (m, 1 H), 7.46-7.44 (m, 1 H), 7.28-7.23 (m, 2H), 4.33 (dd, J = 1.88, 8.76 Hz, 1 H), 2.34-2.32 (m, 1H), 2.28 (s, 2H), 2.22- 2.21 (m, 1H), 2.08 (t, J = 5.88 Hz, 1 H), 1.42 (s, 3H), 1.29 (s, 3H), 1.13 (d, J = 10.92 Hz, 1 H), 0.85 (s, 3H). GCMS: m/z: 310.
82%	In diethyl ether at 20℃; for 12h;	4 Step 4: 2-(benzofuran-3-ylmethyl)boronic acid (+)-pinanediol ester A solution of 2-(benzofuran-3-ylmethyl)-4,4,5,5-tetramethyl-1 ,3,2- dioxaborolane (6.1 g, 23.6 mmol) in diethyl ether (60 ml) is treated with (1 S, 2S, 3R, 5S)-(+)-pinanediol (6.0 g, 35.4 mmol). The reaction mixture is stirred at room temperature for 12 h then the mixture is washed with water twice, then with brine and dried over anhydrous sodium sulphate, then concentrated. The crude product is purified by flash column chromatography on silica gel, eluting with 5% of ethyl acetate in petroleum ether, to afford the title compound (6.3 g, 82%). 1H NMR (400 MHz, CDCI3): δ 7.58-7.56 (m, 1 H), 7.55-7.53 (m, 1 H), 7.46- 7.44 (m, 1 H), 7.28-7.23 (m, 2H), 4.33 (dd, J = 1 .88, 8.76 Hz, 1 H), 2.34-2.32 (m, 1 H), 2.28 (s, 2H), 2.22-2.21 (m, 1 H), 2.08 (t, J = 5.88 Hz, 1 H), 1 .42 (s, 3H), 1 .29 (s, 3H), 1 .13 (d, J = 10.92 Hz, 1 H), 0.85 (s, 3H). GCMS: m/z: 310.
82%	In diethyl ether at 20℃; for 12h;	1.4 Step 4: 2-(benzofuran-3-ylmethyl)boronic acid (+)-pinanediol ester. A solution of 2-(benzofuran-3-ylmethyl)-4,4,5,5-tetramethyl-1,3,2- dioxaborolane (6.1 g, 23.6 mmol) in diethyl ether (60 ml_) is treated with (1S,2S,3R,5S)-(+)-pinanediol (6.0 g, 35.4 mmol). The reaction mixture is stirred at room temperature for 12 h then the mixture is washed with water (twice), then with brine and resulting solution is dried over anhydrous sodium sulphate and concentrated. The crude product is purified by flash column chromatography on silica gel, eluting with 5% of ethyl acetate in petroleum ether to obtain 2-(benzofuran-3-ylmethyl)boronic acid (+)-pinanediol ester (6.3 g, 82%). 1H NMR (400 MHz, CDCIs): d 7.58-7.56 (m, 1H), 7.55-7.53 (m, 1H), 7.46-7.44 (m, 1H), 7.28-7.23 (m, 2H), 4.33 (dd, J = 1.88, 8.76 Hz, 1H), 2.34-2.32 (m, 1H), 2.28 (s, 2H), 2.22-2.21 (m, 1H), 2.08 (t, J = 5.88 Hz, 1H), 1.42 (s, 3H), 1.29 (s, 3H), 1.13 (d, J = 10.92 Hz, 1H), 0.85 (s, 3H). GCMS: m/z: 310.
82%	In diethyl ether at 20℃; for 12h; Inert atmosphere;
80%	In diethyl ether at 20℃;	31; 41; 47 A solution of 2-(benzofuran-3-ylmethyl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (4.58 g, 17.7 mmol) in diethyl ether (30 mL) was treated with (lS,2S,3R,5S)-2,6,6- trimethylbicyclo[3.l.l]heptane-2,3-diol (3.9 g, 23.1 mmol), the mixture was stirred at rt for 12 h. Then the mixture was concentrated and the crude was purified by column chromatography on silica gel, eluting with 5% of ethylacetate in petroleum ether to afford (3aS,4S,6S,7aR)-2-(benzofuran-3-ylmethyl)-3a,5,5- trimethylhexahydro-4,6-methanobenzo[d][l,3,2]dioxaborole (4.5 g, 80%) as a yellow oil.
34%	In diethyl ether at 20℃;	16.4 Into a 50-mL round-bottom flask, was placed a solution of 2-(I -benzofuran-3- ylmethyl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (490 mg, 1.90 mmol, 1.00 eq.) in ether (5 mL), and ( lS,2S,3R,5S)-2,6,6-tiimethylbicyclo[3.1.1]heptane-2,3~diol (420 mg, 2.47 mmol, 1.30 eq.). The resulting solution was stirred overnight at rt. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (3:97). This resulted in 200 mg (34%) of (lS,2S,6R,8S)-4-( l-benzofuran-3-ylmethyl)-2,9,9-trimethyl-3,5-dioxa-4- boratricyclo[6.1.1.0A[2,6]]decane as a yellow oil.
	In diethyl ether at 20℃; Inert atmosphere;
10.5 g	In diethyl ether at 20℃;	1.D Step D: Benzofuran-3-ylmethylboronic acid (1S,2S,3R,5S)-(+)-pinane-2,3-diol ester Pinacol benzofuran-3-ylmethylboronic acid (14.0g)And (1S, 2S, 3R, 5S)-(+)-Pinane-2,3-diol (18.4g) were added to anhydrous ether (200mL),The suspension was stirred overnight at room temperature,After the detection reaction is completed, wash with water three times, dry the organic phase with anhydrous sodium sulfate, evaporate the solvent after filtration, and purify the residue by silica gel column chromatography (50% dichloromethane/petroleum ether) to obtain the product (10.5 g).
10.5 g	In diethyl ether at 20℃;	1.D Step D: Benzofuran-3-ylmethylboronic acid-(1S,2S,3R,5S)-(+)-pinene-2,3-diol ester Pinacol benzofuran-3-ylmethylboronic acid (14.0g)And (1S, 2S, 3R, 5S)-(+)-Pinane-2,3-diol (18.4g) were added to anhydrous ether (200mL),The suspension was stirred overnight at room temperature. After the LC/MS detection of the reaction was completed,Wash three times with water, dry the organic phase with anhydrous sodium sulfate,After filtration, the solvent was evaporated to dryness, and the residue was purified by silica gel column chromatography (50% dichloromethane/petroleum ether) to obtain the product (10.5 g).

Reference： [1]Current Patent Assignee: SICHUAN UNIVERSITY - CN110156820, 2019, A Location in patent: Paragraph 0090; 0091; 0104; 0105
[2]Current Patent Assignee: MERCK KGAA - WO2013/92979, 2013, A1 Location in patent: Page/Page column 58
[3]Current Patent Assignee: MERCK KGAA - WO2016/50358, 2016, A1 Location in patent: Page/Page column 75; 76
[4]Current Patent Assignee: MERCK KGAA - WO2016/50359, 2016, A1 Location in patent: Page/Page column 65-67
[5]Current Patent Assignee: MERCK KGAA - WO2016/50355, 2016, A1 Location in patent: Page/Page column 81; 82
[6]Current Patent Assignee: MERCK KGAA - WO2019/38250, 2019, A1 Location in patent: Page/Page column 79; 81
[7]Current Patent Assignee: MERCK KGAA - WO2020/20858, 2020, A1 Location in patent: Page/Page column 62-63
[8]Klein, Markus; Busch, Michael; Friese-Hamim, Manja; Crosignani, Stefano; Fuchss, Thomas; Musil, Djordje; Rohdich, Felix; Sanderson, Michael P.; Seenisamy, Jeyaprakashnarayanan; Walter-Bausch, Gina; Zanelli, Ugo; Hewitt, Philip; Esdar, Christina; Schadt, Oliver [Journal of Medicinal Chemistry, 2021, vol. 64, # 14, p. 10230 - 10245]
[9]Current Patent Assignee: SANOFI - WO2019/99582, 2019, A1 Location in patent: Paragraph 0323; 0327; 0374; 0377; 0399; 0402
[10]Current Patent Assignee: SANOFI - WO2018/136401, 2018, A1 Location in patent: Paragraph 0189
[11]Wang, Yao-Ling; Liu, Sha; Yu, Zhu-Jun; Lei, Yuan; Huang, Meng-Yi; Yan, Yu-Hang; Ma, Qiang; Zheng, Yang; Deng, Hui; Sun, Ying; Wu, Chengyong; Yu, Yamei; Chen, Qiang; Wang, Zhenling; Wu, Yong; Li, Guo-Bo [Journal of Medicinal Chemistry, 2019, vol. 62, # 15, p. 7160 - 7184]
[12]Current Patent Assignee: SHOUYAO HOLDINGS BEIJING CO LTD - CN113135943, 2021, A Location in patent: Paragraph 0098; 0113-0116
[13]Current Patent Assignee: SHOUYAO HOLDINGS BEIJING CO LTD - CN113135944, 2021, A Location in patent: Paragraph 0113; 0128-0131

38
[ 18680-27-8 ]
[ 1360458-62-3 ]
C₂₆H₄₉BO₅Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84.6%	In tetrahydrofuran at 20℃; for 16h;	1.2 [0162] To a solution of tert-butyl 3-(tert-butyldimethylsilyloxy)-5-(4,4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)pentanoate XXXVIII (5.4 g, 13 mmol) in THF (25 mL) was added (1 S,2S,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]heptane-2,3-diol (2.4 g, 14.3 mol) at room temperature. The reaction mixture was stirred for 16 h and then was concentrated under vacuum. The residue was purified by column chromatography (100% hexane→40% EtOAc/hexane) on silica gel to give l-(tert-butoxy)-3-[(tert-butyldimethylsilyl)oxy]-l-oxo-6- [(2S,6R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo [6.1.1.02,6]decan-4-yl]hexan-3-yl XXXIX (5.5 g, 11 mmol, 84.6% yield).

Reference： [1]Current Patent Assignee: MELINTA THERAPEUTICS INC. - WO2013/122888, 2013, A2 Location in patent: Paragraph 0162

39
[ 18680-27-8 ]
[ 1360458-67-8 ]
C₂₀H₃₃BO₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
59.9%	In tetrahydrofuran at 20℃; for 16h;	4.1 [0225j To a stirred solution of tert-butyl 2-(2-hydroxy-3,6-dihydro-2H-1,2- oxaborinin-6-yl)acetate XLVII (770 mg, 4.58 mmol) in THF (25 mL) was added (1 S,25,3R,55)-2,6,6-trimethylbicyclo[3.1.1]heptane-2,3-diol (980 mg, 4.58 mmol) at room temperature. The reaction mixture was stirred for 16 h and concentrated under vacuum. The residue was purified by column chromatography (100% hexane-*30% EtOAc/hexane) on silica gel to give tert-butyl (4Z)-3 -hydroxy-6- [(1 R,2R,65 , 8R)-6,9,9- trimethyl-3 ,5 -dioxa-4- boratricyclo[6.1.1.02,6]decan-4-yl]hex-4-enoate LIV (1 g, 2.75 mmol, 59.9% yield).
59.9%	In tetrahydrofuran at 20℃; for 16h;	2-[(3R)-2-hydroxy-3-[[2-(2-thienyl)acetyl]amino]-4,7-dihydro-3H-oxaborepin-7-yl]acetic acid (15) tert-Butyl (Z)-3-[tert-butyl(dimethyl)silyl]oxy-6-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]hex-4-enoate (10). To a stirred solution of compound 2 (770mg, 4.58mmol) in THF (25mL) was added (+)-pinanediol (980mg, 4.58mmol) at room temperature. The reaction mixture was stirred for 16h and concentrated under vacuum. The residue was purified by column chromatography (100% hexane→30% EtOAc/hexane) on silica gel to give compound 10 (1g, 2.75mmol, 59.9% yield).
59.9%	In tetrahydrofuran at 20℃; for 16h;	2-[(3R)-2-hydroxy-3-[[2-(2-thienyl)acetyl]amino]-4,7-dihydro-3H-oxaborepin-7-yl]acetic acid (15) tert-Butyl (Z)-3-[tert-butyl(dimethyl)silyl]oxy-6-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]hex-4-enoate (10). To a stirred solution of compound 2 (770mg, 4.58mmol) in THF (25mL) was added (+)-pinanediol (980mg, 4.58mmol) at room temperature. The reaction mixture was stirred for 16h and concentrated under vacuum. The residue was purified by column chromatography (100% hexane→30% EtOAc/hexane) on silica gel to give compound 10 (1g, 2.75mmol, 59.9% yield).

Reference： [1]Current Patent Assignee: MELINTA THERAPEUTICS INC. - WO2013/122888, 2013, A2 Location in patent: Paragraph 0225
[2]Clifton, Matthew C.; Griffith, David C.; Hecker, Scott J.; Lomovskaya, Olga; Raja Reddy, K.; Tarazi, Ziad; Totrov, Maxim [Bioorganic and Medicinal Chemistry, 2022, vol. 62]
[3]Clifton, Matthew C.; Griffith, David C.; Hecker, Scott J.; Lomovskaya, Olga; Raja Reddy, K.; Tarazi, Ziad; Totrov, Maxim [Bioorganic and Medicinal Chemistry, 2022, vol. 62]

40
[ 18680-27-8 ]
[ 1360458-68-9 ]
tert-butyl 3-hydroxy-6-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]hexanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71.9%	In tetrahydrofuran at 20℃; for 16h;	3.3 Step 3 [0218] To a solution of tert-butyl 2-(2-hydroxy-l,2-oxaborinan-6-yl)acetate XL VIII (641 mg, 3.00 mmol) in THF (20 mL) was added (1 S,2S,3R,5S)-2,6,6- trimethylbicyclo[3.1.1]heptane-2,3-diol (509 mg, 3 mol) at room temperature. The reaction mixture was stirred for 16 h and concentrated under vacuum. The residue was purified by column chromatography (100% hexane→40% EtOAc/hexane) on silica gel to give tert-butyl 3- hydroxy-6-[(lR,2R,6S,8R)-6,9,9- trimethyl-3,5-dioxa-4- boratricyclo[6.1.1.02'6]decan-4- yl]hexanoate XLIX (790 mg, 2.16 mmol, 71.9% yield).
71.9%	In tetrahydrofuran at 20℃; for 16h;	tert-Butyl 3-hydroxy-6-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]hexanoate (4). To a solution of tert-butyl 2-(2-hydroxyoxaborinan-6-yl)acetate 3 (641mg, 3.00mmol) in THF (20mL) was added (+)-pinanediol (509mg, 3mol) at room temperature. The reaction mixture was stirred for 16h and concentrated under vacuum. The residue was purified by column chromatography (100% hexane→40% EtOAc/hexane) on silica gel to give compound 4 (790mg, 2.16mmol, 71.9% yield).
71.9%	In tetrahydrofuran at 20℃; for 16h;	tert-Butyl 3-hydroxy-6-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]hexanoate (4). To a solution of tert-butyl 2-(2-hydroxyoxaborinan-6-yl)acetate 3 (641mg, 3.00mmol) in THF (20mL) was added (+)-pinanediol (509mg, 3mol) at room temperature. The reaction mixture was stirred for 16h and concentrated under vacuum. The residue was purified by column chromatography (100% hexane→40% EtOAc/hexane) on silica gel to give compound 4 (790mg, 2.16mmol, 71.9% yield).

Reference： [1]Current Patent Assignee: MELINTA THERAPEUTICS INC. - WO2013/122888, 2013, A2 Location in patent: Paragraph 0218
[2]Clifton, Matthew C.; Griffith, David C.; Hecker, Scott J.; Lomovskaya, Olga; Raja Reddy, K.; Tarazi, Ziad; Totrov, Maxim [Bioorganic and Medicinal Chemistry, 2022, vol. 62]
[3]Clifton, Matthew C.; Griffith, David C.; Hecker, Scott J.; Lomovskaya, Olga; Raja Reddy, K.; Tarazi, Ziad; Totrov, Maxim [Bioorganic and Medicinal Chemistry, 2022, vol. 62]

41
[ 18680-27-8 ]
[ 913836-10-9 ]
[ 1155425-58-3 ]

Yield	Reaction Conditions	Operation in experiment
100%	In tetrahydrofuran at 20℃; for 91h;	1.1 Synthesis of 2-Methoxy-3-(2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]dec-4-yl)benzoic acid A solution of 3-borono-2-methoxybenzoic acid (Combi-Blocks, 7.42 g, 37.9 mmol) and (+)-pinanediol (6.44 g, 37.8 mmol) in tetrahydrofuran (THF, 56 mL) was stirred at room temperature for 91 h. The solution was concentrated in vacuo and triturated twice with hexanes to afford 12.50 g (-100%) of product as a white solid. ESI-MS m/z 331 (MH)+
	In toluene for 3h;	48.1.1a Step la: Synthesis of 3-carboxy-2-methoxy-phenyl boronic acid (+) pinandiolato diester Step la: Synthesis of 3-carboxy-2-methoxy-phenyl boronic acid (+) pinandiolato diester. [00305] To a mixture of 3-carboxy-2-methoxy-phenyl boronic acid (35. Og, 178.5 mmol,) and (+) pinanediol (30.35g, 178.5 mmol) was added toluene (400mL). The resulting mixture was stirred for 3 hr then concentrated under vacuum (28 mmHg, bath temperature 40°C). The resulting solid was dried by toluene azeotrope (2 times, approximately lOOmL). This residue was dried under high vacuum (approx. 1 mmHg) at room temperature for 17.5 hr to give the crude title compound which can be used without further purification. 48.06g of this crude product was recrystallized from 150 mL of chloroform/hexane (1 :5 v/v) to give the pure title compound. The mother liquor from the crystallization was concentrated and purified by silica chromatography (120g silica eluted with 40-100% ethyl acetate in hexane) to give an additional batch of the title compound.
	In n-heptane Reflux;	1.4 Step 4: Pinanediol ester formation [00185] The pinanediol ester formation was performed in the same reactor used for isolation of intermediate 3 without cleaning. The intermediate 3 sticking to walls of the reactor in the reaction (estimated up to 3 kg; 15.3 mol). Additionally, 36.5 kg damp intermediate 3 (approx. 29.6 kg pure intermediate, 151.0 mol) and 30.0 kg (+)-pinanediol (176.2 mol, 1.1 eq) were charged. Solids were suspended in n-heptane (290 kg), the mixture was heated to reflux and water was removed by distillation. After stirring overnight, there was remaining intermediate 3 on the walls of the reactor. Additional n-heptane (210 kg) was added to increase the filling level and refluxing was continued at reduced pressure. However, there was still remaining intermediate 3, which was not taken up in n-heptane. A sample taken after crystallization showed no remaining intermediate 3. Q-NMR of the mother liquor (approx. 500 kg) showed an excess of approx. 3.8 kg unreacted pinanediol and 4.3 kg product. Based on the amount of pinanediol used, 50.9 kg of the desired product 4 was formed. (0271) Accordingly, there was approx. 46.6 kg product suspended. (0272) [00186] The product 4 was filtered and washed with heptane (30 kg). Drying on the filter overnight provided 44.1 kg desired product (LOD: 0.04%, 88% yield based on damp product used). (0273) [00187] After completion, the reactor was cleaned with THF showing approx. 2 kg desired product 4 and a minor amount of intermediate 3 (approx. 0.5 kg) in the wash solution.

Reference： [1]Current Patent Assignee: VENATORX PHARMACEUTICALS INC - WO2014/151958, 2014, A1 Location in patent: Paragraph 00172
[2]Current Patent Assignee: VENATORX PHARMACEUTICALS INC - WO2014/89365, 2014, A1 Location in patent: Paragraph 00305
[3]Current Patent Assignee: VENATORX PHARMACEUTICALS INC - WO2022/76070, 2022, A1 Location in patent: Paragraph 00185-00187

42
[ 18680-27-8 ]
[ 24067-17-2 ]
[ 1609633-45-5 ]

Yield	Reaction Conditions	Operation in experiment
97%	With 1H-imidazole; iron(III) chloride In water; acetonitrile at 20℃; for 0.5h; Inert atmosphere;	2.2. General Procedure B : Transformation of Boronic Acids into Boronates General procedure: To a solution of aryl boronic acid (1 mmol) in MeCN (4 mL) was added, sequentially, asolution of FeCl3 (8 mg, 0.05 mmol, 5 mol%) in H2O (1 mL), imidazole (204 mg, 3 mmol)and pinacol (118 mg, 1 mmol). The resulting cloudy orange mixture was stirred at roomtemperature for 30 min. The reaction was then diluted with H2O (5 mL) and extracted withEt2O (3 x 8 mL). The combined organic extracts were dried (Na2SO4) and concentrated invacuo. The resulting oil was then purified by a filtration through a silica gel plug (eluting withEt2O), affording the title compound.

Reference： [1]Wood, John L.; Marciasini, Ludovic D.; Vaultier, Michel; Pucheault, Mathieu [Synlett, 2014, vol. 25, # 4, p. 551 - 555]

43
[ 18680-27-8 ]
[ 123088-59-5 ]
[ 1609633-46-6 ]

Yield	Reaction Conditions	Operation in experiment
99%	With 1H-imidazole; iron(III) chloride; In water; acetonitrile; at 20℃; for 0.5h;Inert atmosphere;	General procedure: To a solution of aryl boronic acid (1 mmol) in MeCN (4 mL) was added, sequentially, asolution of FeCl3 (8 mg, 0.05 mmol, 5 mol%) in H2O (1 mL), imidazole (204 mg, 3 mmol)and pinacol (118 mg, 1 mmol). The resulting cloudy orange mixture was stirred at roomtemperature for 30 min. The reaction was then diluted with H2O (5 mL) and extracted withEt2O (3 x 8 mL). The combined organic extracts were dried (Na2SO4) and concentrated invacuo. The resulting oil was then purified by a filtration through a silica gel plug (eluting withEt2O), affording the title compound.

Reference： [1]Synlett,2014,vol. 25,p. 551 - 555

44
[ 18680-27-8 ]
C₂₄H₃₅BO₇ [ No CAS ]
C₂₈H₃₉BO₇ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	In tetrahydrofuran at 20℃;	22.7 Synthesis of compound 22H The solution of compound 22G (720 mg, 1.6 mmol) and (+)-pinanediol (412 mg, 2.4 mmol) in THF (15 mL) was stirred at room temperature for overnight before it was concentrated to dryness. The residue was purified by column chromatography (ethyl acetate/hexanes, v/v, 1/40 to 1/20) to give the titled compound 22H (756 mg, 95%) as yellow solid. MS calcd for (C28H39B07): 498 MS (ESI, positive) found: (M+l): 499

Reference： [1]Current Patent Assignee: QPEX BIOPHARMA INC - WO2016/3929, 2016, A1 Location in patent: Paragraph 0247

45
[ 18680-27-8 ]
[ 356570-52-0 ]
2-(4-methylbenzyl)boronic acid (+)-pinanediol ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	In diethyl ether at 20℃; for 12h;	2 Step 2: 2-(4-methylbenzyl)boronic acid (+)-pinanediol ester A solution of 4,4,5,5-tetramethyl-2-(4-methylbenzyl)-1 ,3,2-dioxaborolane (9.3g,37.6 mmol) in diethyl ether (90 ml) was treated with (iS, 2S, 3R, 5S)-(+)-pinanediol (9.7 g, 56.4 mmol). The reaction mixture was stirred at room temperature for 12 h then the mixture was washed with water twice, then with brine and dried over anhydrous sodium sulphate, then concentrated. The crude product was purified by flash column chromatography on silica gel, eluting with3% of ethyl acetate in petroleum ether, to afford the title compound (11.0 g, colourless liquid, 93%).1H NMR (400 MHz, CDCI3): 6400 MHz, CDCI3: 6 7.08 (s, 4H), 4.28 (dd, J = 1.88,8.74 Hz, 1H), 2.34-2.28 (m, 6H), 2.21-2.17 (m, 1H), 2.06 (t, J = 5.80 Hz, 1H),1.91-1.81 (m, 2H), 1.39 (s, 3H), 1.29 (5, 3H), 1.07-0.91 (m, 1H), 0.84 (s, 3H). GCMS: m/z: 284.3.
93%	In diethyl ether at 20℃; for 12h;	2.2 Step 2: 2-(4-methylbenzyl)boronic acid (+)-pinanediol ester Step 2: 2-(4-methylbenzyl)boronic acid (+)-pinanediol ester A solution of 4,4,5,5-tetramethyl-2-(4-methylbenzyl)-1 ,3,2-dioxaborolane (9.3g, 37.6 mmol) in diethyl ether (90 ml) was treated with (1S, 2S, 3R, 5S)-(+)-pinanediol (9.7 g, 56.4 mmol). The reaction mixture was stirred at room temperature for 12 h then the mixture was washed with water twice, then with brine and dried over anhydrous sodium sulphate, then concentrated. The crude product was purified by flash column chromatography on silica gel, eluting with 3% of ethyl acetate in petroleum ether, to afford the title compound ( 1.0 g, colourless liquid, 93%). 1H NMR (400 MHz, CDCI3): δ 400 MHz, CDCI3: δ 7.08 (s, 4H), 4.28 (dd, J = 1.88, 8.74 Hz, 1 H), 2.34-2.28 (m, 6H), 2.21-2.17 (m, 1 H), 2.06 (t, J = 5.80 Hz, 1 H), 1.91-1.81 (m, 2H), 1.39 (s, 3H), 1.29 (s, 3H), 1.07-0.91 (m, 1H), 0.84 (s, 3H). GCMS: m/z: 284.3.
93%	In diethyl ether at 20℃; for 12h;	3.2 Step 2: 2-(4-methylbenzyl)boronic acid (+)-pinanediol ester A solution of 4,4,5,5-tetramethyl-2-(4-methylbenzyl)-1,3,2-dioxaborolane (9.3g, 37.6 mmol) in diethyl ether (90 ml) was treated with (1S, 2S, 3R, 5S)-(+)-pinanediol (9.7 g, 56.4 mmol). The reaction mixture was stirred at room temperature for 12 h then the mixture was washed with water twice, then with brine and dried over anhydrous sodium sulphate, then concentrated. The crude product was purified by flash column chromatography on silica gel, eluting with 3% of ethyl acetate in petroleum ether, to afford the title compound (11.0 g, colourless liquid, 93%). 1H NMR (400 MHz, CDCfe): δ 400 MHz, CDCI3 : δ 7.08 (s, 4H), 4.28 (dd, J = 1.88, 8.74 Hz, 1H), 2.34-2.28 (m, 6H), 2.21-2.17 (m, 1 H), 2.06 (t, J = 5.80 Hz, 1 H), 1.91-1.81 (m, 2H), 1.39 (s, 3H), 1.29 (s, 3H), 1.07-0.91 (m, 1H), 0.84 (s, 3H). GCMS: m/z: 284.3

In tert-butyl methyl ether at 20℃; Inert atmosphere;

Reference： [1]Current Patent Assignee: MERCK KGAA - WO2016/50358, 2016, A1 Location in patent: Page/Page column 89
[2]Current Patent Assignee: MERCK KGAA - WO2016/50359, 2016, A1 Location in patent: Page/Page column 79
[3]Current Patent Assignee: MERCK KGAA - WO2016/50355, 2016, A1 Location in patent: Page/Page column 83; 84
[4]Klein, Markus; Busch, Michael; Friese-Hamim, Manja; Crosignani, Stefano; Fuchss, Thomas; Musil, Djordje; Rohdich, Felix; Sanderson, Michael P.; Seenisamy, Jeyaprakashnarayanan; Walter-Bausch, Gina; Zanelli, Ugo; Hewitt, Philip; Esdar, Christina; Schadt, Oliver [Journal of Medicinal Chemistry, 2021, vol. 64, # 14, p. 10230 - 10245]

46
[ 18680-27-8 ]
7-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-ylmethyl)-benzofuran [ No CAS ]
(1S,2S,6R,8S)-2,9,9-trimethyl-4-(7-methylbenzofuran-3-ylmethyl)-3,5-dioxa-4-bora-tricyclo[6.1.1.0^2,6]decane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70.7%	In diethyl ether at 20℃; for 14h; Cooling with ice; Inert atmosphere;	5 Step 5: Trimethyl-4-(7-methyl-benzofuran-3-ylmethyl)-3,5-dioxa-4-bora-tricyclo [6.1.1 .02,6]decane To an ice-cooled solution of 7-Methyl-3-(4,4,5,5-tetramethyl-[1 ,3,2]dioxaborolan- 2-ylmethyl)-benzofuran (5.00 g; 18.37 mmol; 1.00 eq.) in Et20 (50.00 ml; 10.00 V) under nitrogen atmosphere was added IS, 2S, 3R, 5S-(+)-2,3-pinane diol (4.69 g;27.56 mmol; 1.50 eq.) and the reaction mixture was stirred at RT for 14 h. TLC analysis showed completion of reaction. The reaction mixture was washed with brine. The organic layer was dried over anhydrous Na2SO4 and concentrated. The crude was purified by flash column chromatography using 2 % ethyl acetate in petroleum ether to get (1S,2S,6R,8S)-2,9,9-Trimethyl-4-(7-methyl-benzofuran-3-ylmethyl)-3,5-dioxa-4-bora-tricyclo[6. 1.1.02,6] decane (5.00 g; 13.00 mmol;70.7 %; colorless liquid; Purified Product).GCMS: mlz: 324.21H NMR, 400 MHz, CDCI3: 7.53-7.55 (m, 1H), 7.39-7.40 (m, 1H), 7.12-7.27 (m,1H), 7.06-7.08 (m, IH), 4.31-4.34 (m, IH), 2.53 (s, 3H), 2.30-2.37 (m, 1H), 2.26 (s, 2H), 2.18-2.23 (m, IH), 2.07 (t, J = 5.76 Hz, 1H), 1.84-1.93 (m, 2H), 1.42 (s, 3H), 1.29 (s, 3H), 1.12-1.15 (m, 1H), 0.85 (s, 3H).
70.7%	In diethyl ether at 20℃; for 14h; Inert atmosphere; Cooling with ice;	1b.5 Step 5: TrimethyI-4-(7-methyl-benzofuran-3-ylmethyl)-3,5-dioxa-4-bora- tricyclo [6.1.1.02,6]decane Step 5: TrimethyI-4-(7-methyl-benzofuran-3-ylmethyl)-3,5-dioxa-4-bora- tricyclo [6.1.1.02,6]decane To an ice-cooled solution of 7-Methyl-3-(4l4,5>5-tetramethyl-[1,3,2]dioxaborolan-2- ylmethyl)-benzofuran (5.00 g; 18.37 mmol; 1.00 eq.) in Et20 (50.00 ml; 10.00 V) under nitrogen atmosphere was added 1S, 2S, 3R, 5S-(+)-2,3-pinane diol (4.69 g; 27.56 mmol; 1.50 eq.) and the reaction mixture was stirred at RT for 14 h. TLC analysis showed completion of reaction. The reaction mixture was washed with brine. The organic layer was dried over anhydrous Na2S04 and concentrated. The crude was purified by flash column chromatography using 2 % ethyl acetate in petroleum ether to get (1S,2S,6R,8S)-2,9,9-Trimethyl-4-(7-methyl-benzofuran-3-ylmethyl)-3,5-dioxa-4-bora- tricyclo[6.1.1.02,6] decane (5.00 g; 13.00 mmol; 70.7 %; colorless liquid; Purified Product). GCMS: m/z: 324.2 1H NMR, 400 MHz, CDCI3: 7.53-7.55 (m, 1H), 7.39-7.40 (m, 1 H), 7.12-7.27 (m, 1H), 7.06-7.08 (m, 1H), 4.31-4.34 (m, 1 H), 2.53 (s, 3H), 2.30-2.37 (m, 1H), 2.26 (s, 2H), 2.18- 2.23 (m, 1H), 2.07 (t, J = 5.76 Hz, 1H), 1.84-1.93 (m, 2H), 1.42 (s, 3H), 1.29 (s, 3H), 1.12-1.15 (m, 1 H), 0.85 (s, 3H).
70.7%	In diethyl ether at 20℃; for 14h; Cooling with ice; Inert atmosphere;	1b.5 Step 5: Trimethyl-4-(7-methyI-benzofuran-3-ylmethyl)-3,5-dioxa-4-bora- tricyclo [6.1.1.02,6]decane To an ice-cooled solution of 7-Methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2- ylmethyl)-benzofuran (5.00 g; 18.37 mmol; 1.00 eq.) in Et20 (50.00 ml; 10.00 V) under nitrogen atmosphere was added 1S, 2S, 3R, 5S-(+)-2,3-pinane diol (4.69 g; 27.56 mmol; 1.50 eq.) and the reaction mixture was stirred at RT for 14 h. TLC analysis showed completion of reaction. The reaction mixture was washed with brine. The organic layer was dried over anhydrous Na2S04 and concentrated. The crude was purified by flash column chromatography using 2 % ethyl acetate in petroleum ether to get (1S,2S,6R,8S)-2,9l9-Trimethyl-4-(7-methyl-benzofuran-3-ylmethyl)-3,5-dioxa-4-bora- tricyclo[6.1.1.02,6] decane (5.00 g; 13.00 mmol; 70.7 %; colorless liquid; Purified Product). GCMS: m/z: 324.2 1H NMR, 400 MHz, CDCI3: 7.53-7.55 (m, 1 H), 7.39-7.40 (m, 1 H), 7.12-7.27 (m, 1 H), 7.06-7.08 (m, 1 H), 4.31-4.34 (m, 1H), 2.53 (s, 3H), 2.30-2.37 (m, 1 H), 2.26 (s, 2H), 2.18- 2.23 (m, 1 H), 2.07 (t, J = 5.76 Hz, 1H), 1.84-1.93 (m, 2H), 1.42 (s, 3H), 1.29 (s, 3H), 1.12-1.15 (m, 1H), 0.85 (s, 3H).

70.7%	In diethyl ether at 20℃; for 14h; Inert atmosphere; Cooling with ice;	Step 5: Trimethyl-4-(7-methyl-benzofuran-3-ylmethyl)-3,5-dioxa-4-bora- tricyclo [6.1.1.02,6]decane Step 5: Trimethyl-4-(7-methyl-benzofuran-3-ylmethyl)-3,5-dioxa-4-bora- tricyclo [6.1.1.02,6]decane To an ice-cooled solution of 7-Methyl-3-(4,4,5,5-tetramethyl-[1 ,3,2]dioxaborolan-2- ylmethy -benzofuran (5.00 g; 18.37 mmol; 1.00 eq.) in Et20 (50.00 ml; 10.00 V) under nitrogen atmosphere was added 1 S, 2S, 3R, 5S-(+)-2,3-pinane diol (4.69 g; 27.56 mmol; 1.50 eq.) and the reaction mixture was stirred at RT for 14 h. TLC analysis showed completion of reaction. The reaction mixture was washed with brine. The organic layer was dried over anhydrous a2S04 and concentrated. The crude was purified by flash column chromatography using 2 % ethyl acetate in petroleum ether to get (1S,2S,6R,8S)-2,9,9-Trimethyl-4-(7-methyl-benzofuran-3-ylmethyl)-3,5-dioxa-4-bora- tricyclo[6.1.1.02,6] decane (5.00 g; 13.00 mmol; 70.7 %; colorless liquid; Purified Product). GCMS: m/z: 324.2 1H NMR, 400 MHz, CDCI3: 7.53-7.55 (m, 1 H), 7.39-7.40 (m, 1 H), 7.12-7.27 (m, 1 H), 7.06-7.08 (m, 1 H), 4.31-4.34 (m, 1 H), 2.53 (s, 3H), 2.30-2.37 (m, 1 H), 2.26 (s, 2H), 2.18- 2.23 (m, 1 H), 2.07 (t, J = 5.76 Hz, 1 H), 1.84-1.93 (m, 2H), 1.42 (s, 3H), 1.29 (s, 3H), 1.12-1.15 (m, 1 H), 0.85 (s, 3H).
70.7%	In diethyl ether at 20℃; for 14h; Inert atmosphere; Cooling with ice;	3.5 Step 5: Trimethyl-4-(7-methyl-benzofuran-3-ylmethyl)-3,5-dioxa-4-bora-tricyclo[6.1.1.02,6]decane. To an ice-cooled solution of 7-Methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-ylmethyl)-benzofuran (5.00 g; 18.37 mmol; 1.00 eq.) in Et20 (50.00 ml_) under nitrogen atmosphere is added 1S, 2S, 3R, 5S-(+)-2,3-pinane diol (4.69 g; 27.56 mmol; 1.50 eq.) and the reaction mixture is stirred at rt for 14 h. TLC analysis showed completion of reaction. The reaction mixture is washed with brine. The organic layer is dried over anhydrous Na2S04 and concentrated. The crude is purified by flash column chromatography using 2 % ethyl acetate in petroleum ether to get (1S,2S,6R,8S)-2,9,9-Trimethyl-4-(7-methyl-benzofuran-3-ylmethyl)-3,5-dioxa-4-bora-tricyclo[6.1.1.02,6]decane (5.00 g; 13.00 mmol; 70.7 %; colorless liquid). GCMS: m/z: 324.2 1H NMR, 400 MHz, CDCI3: 7.53-7.55 (m, 1H), 7.39-7.40 (m, 1H), 7.12-7.27 (m, 1H), 7.06-7.08 (m, 1H), 4.31 -4.34 (m, 1H), 2.53 (s, 3H), 2.30-2.37 (m, 1H), 2.26 (s, 2H), 2.18-2.23 (m, 1H), 2.07 (t, J = 5.76 Hz, 1H), 1.84-1.93 (m, 2H), 1.42 (s, 3H), 1.29 (s, 3H), 1.12-1.15 (m, 1H), 0.85 (s, 3H).
	In tert-butyl methyl ether at 20℃; Inert atmosphere;

Reference： [1]Current Patent Assignee: MERCK KGAA - WO2016/50358, 2016, A1 Location in patent: Page/Page column 81
[2]Current Patent Assignee: MERCK KGAA - WO2016/50359, 2016, A1 Location in patent: Page/Page column 71
[3]Current Patent Assignee: MERCK KGAA - WO2016/50355, 2016, A1 Location in patent: Page/Page column 71
[4]Current Patent Assignee: MERCK KGAA - WO2016/50356, 2016, A1 Location in patent: Page/Page column 77; 78
[5]Current Patent Assignee: MERCK KGAA - WO2020/20858, 2020, A1 Location in patent: Page/Page column 72
[6]Klein, Markus; Busch, Michael; Friese-Hamim, Manja; Crosignani, Stefano; Fuchss, Thomas; Musil, Djordje; Rohdich, Felix; Sanderson, Michael P.; Seenisamy, Jeyaprakashnarayanan; Walter-Bausch, Gina; Zanelli, Ugo; Hewitt, Philip; Esdar, Christina; Schadt, Oliver [Journal of Medicinal Chemistry, 2021, vol. 64, # 14, p. 10230 - 10245]

47
[ 5162-44-7 ]
[ 18680-27-8 ]
[ 274-07-7 ]
[ 165881-36-7 ]

Yield	Reaction Conditions	Operation in experiment
70%	Stage #1: 1-bromo-4-butene; benzo[1,3,2]dioxaborole at 110℃; for 18h; Inert atmosphere; Stage #2: pinanediol In tetrahydrofuran at 23℃; for 18h;	1 Step 1: Preparation of (3 aS,4S, 6S,7aR)-2-(4-bromobutyl)-3 a, 5,5 -trimethylhexahydro4,6-methanobenzo[d][1,3,2]dioxaborolej Into a 40 mL vial equipped with a magnetic stir bar and under nitrogenwas added catechol borane (8.79 g, 72 mmol, 1.0 equiv) and 4-bromo-1-butene (10 g, 72mmol, 1.0 equiv). The solution turned slightly cloudy and was heated to 110 °C for 18 hovernight. The contents of the vial were cooled to room temperature and transferred into a 250 mL round-bottom flask using THF (60 mL). To the flask was added (1S,2S,3R,5S’)-2,6,6-trimethylbicyclo[3.1.1]heptane-2,3-diol (12.5 g, 72 mmol, 1.0 equiv) and the mixture stirred at room temperature for 18 h. The solution was concentrated under reduced pressure and loaded onto a silica gel column (240 g) and eluted with 100:0 to 90:10 Hexanes:EtOAc as a gradient. The product fractions were concentrated under reduced pressure to afford a clear oil (15.8 g, 70%).

Reference： [1]Current Patent Assignee: OPHTHOTECH CORPORATION - WO2016/100555, 2016, A1 Location in patent: Paragraph 0133

48
[ 18680-27-8 ]
[ 106-95-6 ]
[ 274-07-7 ]
[ 90084-37-0 ]

Yield	Reaction Conditions	Operation in experiment
64%	Stage #1: allyl bromide; benzo[1,3,2]dioxaborole at 100℃; for 3h; Inert atmosphere; Stage #2: pinanediol In tetrahydrofuran at 0 - 20℃; Inert atmosphere;
57%	Stage #1: allyl bromide; benzo[1,3,2]dioxaborole at 110℃; for 8h; Inert atmosphere; Stage #2: pinanediol In tetrahydrofuran at 23℃; for 18h;	1 Step 1: Preparation of (3aS,4S,6S,7a]?)-2-(3-bromopropyl)-3a,5,5-trimethylhexahydro-4, 6-methanobenzo[d] [1,3,2] dioxaborole Into a round-bottom flask equipped with a magnetic stir bar and under nitrogen was added catechol borane (6.2 mL, 58 mmol, 1.0 equiv) and ally bromide (5 mL, 58 mmol, 1.0 equiv). The solution was heated to 110 °C for 8 h. The contents of the vial were cooled to room temperature and transferred with THF (100 mL). To the flask was added (1S,2S,3R, 5S)-2,6,6-trimethylbicyclo[3. 1.1 ]heptane-2,3 -diol (9.8 g, 58 mmol, 1.0 equiv) and the mixture stirred at room temperature for 18 h. The solution was concentrated under reduced pressure, loaded onto a silica gel column (220 g) and eluted with 100:0 to 90:10 Hexanes:EtOAc as a gradient. The product fractions were concentrated under reduced pressure to afford a clear oil (9.93 g, 57%).

Reference： [1]Nitsche, Christoph; Zhang, Linlin; Weigel, Lena F.; Schilz, Jonas; Graf, Dominik; Bartenschlager, Ralf; Hilgenfeld, Rolf; Klein, Christian D. [Journal of Medicinal Chemistry, 2017, vol. 60, # 1, p. 511 - 516]
[2]Current Patent Assignee: OPHTHOTECH CORPORATION - WO2016/100555, 2016, A1 Location in patent: Paragraph 0137

49
[ 18680-27-8 ]
[ 1119-51-3 ]
[ 274-07-7 ]
(3aS,4S,6S,7aR)-2-(5-bromopentyl)-3a,5,5-trimethylhexahydro-4,6-methanobenzo[d][1,3,2]dioxaborole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	Stage #1: bromopentene; benzo[1,3,2]dioxaborole at 110℃; for 16h; Inert atmosphere; Stage #2: pinanediol In tetrahydrofuran at 23℃; for 16.3333h;	63.1 Step 1: Preparation of (3 aS,4S,6S,7aR)-2-(5-bromopentyl)-3 a, 5,5-trimethylhexahydro-4, 6-methanobenzo[d] [1,3,2] dioxaborole General procedure: Into a 40 mL vial equipped with a magnetic stir bar and under nitrogen was combined 5-bromo-1-pentene (10 g, 66 mmol, 1.0 equiv) and catecholborane (8.1 g, 66 mmol, 1.0 equiv). The neat mixture was heated to 110 °C for 16 h. In a separate 250 mL round bottom flask equipped with a magnetic stir bar was added (1S,2S,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]heptane-2,3-diol (11.4 g, 66 mmol, 1.0 equiv) and THF (60 mL). After the solids had dissolved, the prepared borate was added via syringe over 20 minutes. The mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated under reduced pressure and purified by column chromatography through silica gel, eluting with 100:0 to 90:10 Hexanes:EtOAc as a gradient. The desired product was obtained as a clear oil (6.6 g, 77%).

Reference： [1]Current Patent Assignee: OPHTHOTECH CORPORATION - WO2016/100555, 2016, A1 Location in patent: Paragraph 0211

50
[ 18680-27-8 ]
[ 115921-03-4 ]
dichloromethyl boronic acid-α-pinanediol ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98.5%	In tetrahydrofuran at 20℃; for 18h;	40 Preparation example 40 dichloromethyl boronic acid-α-pinanediol ester Preparation example 40 dichloromethyl boronic acid-α-pinanediol ester To a 25ml of flask was added the product of α-pinanediol of Preparation example 38 (3.23g, 0.019mmol) and the product of dichloromethyl boronic acid dimethyl ester of Preparation example 39 (5.38g, 0.035mmol), then dissolved with 5ml of THF, stirred at room temperature. The reaction was monitored by TLC and finished after 18h. Separated by column chromatography (ethyl acetate: petroleum ether = 1: 20)to give 4.92g of colorless liquid with a yield of 98.5%. 1H-NMR (CDCl3, 300MHz): δ 0.85 (-CH3, s, 3H), 1.21 (-CH2, t, 1H), 1.31 (-CH3, s, 3H), 1.47 (-CH3, s, 3H), 1.92∼1.97 (-CH2, CH, m, 2H), 2.15 (-CH, t, 1H), 2.25∼2.43 (-CH2, m, 2H), 4.47 (-CH, q, 1H), 5.40 (-CH, s, 1H); 13C-NMR (CDCl3, 75MHz): δ 23.92, 26.18, 26.93, 28.18, 34.98, 38.31, 39.16, 51.09, 79.41, 88.08. MS (EI): m/z 262.0 (M+), Calculated value m/z 262.0.

Reference： [1]Current Patent Assignee: PEKING UNIVERSITY - EP2444411, 2016, B1 Location in patent: Paragraph 0074

51
[ 23978-81-6 ]
[ 18680-27-8 ]

Yield	Reaction Conditions	Operation in experiment
92.9%	With pyridine; osmium(VIII) oxide; trimethylamine-N-oxide In water; <i>tert</i>-butyl alcohol for 15h; Inert atmosphere; Reflux;	38 Preparation example 38 (1S,2S,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]heptane-2,3 -diol Preparation example 38 (1S,2S,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]heptane-2,3 -diol Me3NO·2H2O (11.3g, 102mmol) was dissolved with 16ml of water, α-pinene (13.2g, 96.9mmol), 74ml of tert-butyl alcohol, 7.4ml of pyridine and osmium tetroxide (60mg, 0.236mmol) were added under stirring. Then nitrogen gas was purged, 10 min later, the reaction mixture was heated to reflux. The reaction was monitored by TLC and finished after 15 h. Spontaneously cooled down to room temperature, NaHSO3 (1.2g, 11.5mmol) and an appropriate amount of saturated aqueous NaCl solution were added. The organic phase was separated out, and the water layer was extracted with diethyl ether (3*20ml), the organic phase was combined and dried over anhydrous sodium sulfate. The product was concentrated and the residue was purified by column chromatography (ethyl acetate: petroleum ether= 1: 30), 15.33g of white solid was obtained, and the yield was 92.9%, [α]D20=-10.79° (c=5.5, toluene), m.p.: 52-54°C. 1H-NMR (CDCl3, 300MHz): δ 0.94 (-CH3, s, 3H), 1.28 (-CH3, s, 3H), 1.32 (-CH3, s, 3H), 1.34∼1.38 (-CH2, d, 1H), 1.66 (-CH2, m, 1H), 1.93 (-CH, m, 1H), 2.01 (-CH2, t, 1H), 2.20 (-CH, m, 1H), 2.33 (H2O s, 2H), 2.49 (-CH2, m, 1H), 4.00 (-CH, q, 1H); 13C-NMR (CDCl3, 300MHz): δ 24.11, 27.80, 28.00, 29.54, 38.21, 38.99, 40.51, 53.98, 69.26, 73.88; Elemental analysis: C10H18O2, Calculated values C, 70.55; H, 10.66; Measured values C, 70.55; H, 10.67.

Reference： [1]Current Patent Assignee: PEKING UNIVERSITY - EP2444411, 2016, B1 Location in patent: Paragraph 0072

52
[ 5419-55-6 ]
[ 593-71-5 ]
[ 18680-27-8 ]
[ 110744-85-9 ]

Yield	Reaction Conditions	Operation in experiment
69.5 g	Stage #1: Triisopropyl borate; Chloroiodomethane With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1.5h; Stage #2: With chloro-trimethyl-silane In tetrahydrofuran; hexane for 18h; Stage #3: pinanediol In tetrahydrofuran; hexane for 4h;	1.1.A-2 Step 1A-2: Synthesis of 4-chloromethyl-2,9,9-trimethyl-3,5-dioxa-4-bora- tricycloj6.1.1.02,61 -decane (lAc). To a solution of chloroiodomethane (27.0 mL, 367 mmol) in THE (367 mL) at -78 °C was added triisopropyl borate (78.5 mL, 340 mmol) followed by slowly addition of n-BuLi solution (147 mL, 367 mmol, 2.5 M in hexanes), down the side of the flask over 50 mm, and stirring was continued for additional 40 mm. To the resulted milky mixture was added chlorotrimethylsilane (46.6 mL, 367 mmol) over 5 mm. The cold bath was removed, and stirring continued for 18 hr. To the resulted mixture was added a solution of(1S, 2S, 3R, 5S)-(+)-2,3- pinanediol (57.87 g, 340 mmol) in THF (170 mL) over 5 mm, and stirring continued for 4 hr. The resulted yellow solution was diluted with ether (1.5 L) and washed H20 (400 mL). The organic layer was separated and washed with brine, dried over Na2 SO4, concentrated, and flash chromatographed on a silica gel (1040 g) column, eluted with hexanes/EtOAc (0-4%) to give an oil (69.5 g). The compound was immediately used in next step of reaction.

Reference： [1]Current Patent Assignee: VENATORX PHARMACEUTICALS INC - WO2017/44828, 2017, A1 Location in patent: Paragraph 0312

53
[ 19902-08-0 ]
[ 18680-27-8 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium permanganate; tetrabutyl-ammonium chloride; potassium hydroxide In dichloromethane at -40 - -15℃; for 10h; Large scale;	2.1 Example 2 Synthesis of (IS, 2S, 3R, 5S) - (+) _2,3-pinanediol (1) L-pinene 272kg into the 5000L reactor, Under stirring, methylene chloride (800 L) was added, Then add potassium hydroxide 16kg, at -40 ° C to _15 ° C temperature, 4 kg of tetrabutylammonium chloride was added and an aqueous solution of potassium permanganate (320 kg) was added in portions. After l0 h, the solid residue was removed by filtration. The reaction solution was concentrated to remove the solvent and the remaining very small amount of piniophene, (1S, 2S, 3R, 5S) - (+) -2,3-pinanediol

Reference： [1]Current Patent Assignee: SHANGHAI SCIENTIA PHARMACEUTICAL TECH - CN105859519, 2016, A Location in patent: Paragraph 0039-0040

54
[ 18680-27-8 ]
C₂₁H₂₆BFN₂O₇ [ No CAS ]
5-fluoro-2,2-dimethyl-8-[(1S,2R)-2-[(2S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]-cyclopropyl]-1,3-benzodioxin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
6.8 g	With magnesium sulfate In tetrahydrofuran at 20℃; for 12h;	13.5 Step 5: Synthesis of 12B To a solution of crude compound 13E (~ 45 mmol, 1.0 eq) in THF (~ 150 mL) was added (+)-pinanediol (23.0 g, 135 mmol, 3.0 eq) and MgS04 (20 g). The resulting reaction mixture was stirred at rt for 12 hours before it was filtered and concentrated to dryness. The obtained residue was purified by column chromatography (hexanes/EtOAc= 5/1 to 3/1) to give compound 12B (12.1 g, ~ 90% purity and ~ 93% de) as yellow solid. The product was further purified by re-crystallization in 10% ethyl acetate in hexanes to give 6.8 g pure 12B (> 99% purity and > 99% de). JH NMR(CDC13, 400 MHz) for 12B: δ 7.32-7.25 (m, 1H), 6.72 (t, / = 9.2 Hz, 1H), 4.00 (dd, / = 1.6, 1.6 Hz, 1H), 2.28-2.24 (m, 1H), 2.17-2.14 (m, 1H), 1.86-1.81 (m, 2H), 1.75 (s, 8H), 1.62 (d, / = 1.2 Hz, 1H), 1.21-1.19 (m, 1H), 1.18 (s, 3H), 1.17 (s, 3H), 1.16-1.13 (m, 1H), 0.72 (s, 3H), 0.53-0.47 (m, 2H).

Reference： [1]Current Patent Assignee: QPEX BIOPHARMA INC - WO2018/5662, 2018, A1 Location in patent: Paragraph 0257

55
[ 18680-27-8 ]
C₂₂H₂₆BNO₅ [ No CAS ]
C₂₆H₃₀BNO₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	In tetrahydrofuran at 20℃;	20.9 Step 9: Synthesis of compound 20.J A mixture of 201 (4.75 g, 12.0 mmol, 1.0 eq) and (+)-pinanediol (4.08 g, 24.0 mmol, 2.0 eq) in THF (50 mL) was stirred at rt overnight. The reaction was concentrated and purified by flash column chromatography (ethyl acetate : hexane = 1:3 to 1:2) to give compound 20J (4.0 g, 75%) as light yellow oil.
75%	In tetrahydrofuran at 20℃;

Reference： [1]Current Patent Assignee: QPEX BIOPHARMA INC - WO2018/5662, 2018, A1 Location in patent: Paragraph 0298
[2]Hecker, Scott J.; Reddy, K. Raja; Lomovskaya, Olga; Griffith, David C.; Rubio-Aparicio, Debora; Nelson, Kirk; Tsivkovski, Ruslan; Sun, Dongxu; Sabet, Mojgan; Tarazi, Ziad; Parkinson, Jonathan; Totrov, Maxim; Boyer, Serge H.; Glinka, Tomasz W.; Pemberton, Orville A.; Chen, Yu; Dudley, Michael N. [Journal of Medicinal Chemistry, 2020, vol. 63, # 14, p. 7491 - 7507]

56
[ 18680-27-8 ]
[ 71628-89-2 ]

Yield	Reaction Conditions	Operation in experiment
90%	With C₂₁H₁₂Cl₆NO₄V; oxygen In toluene at 1000℃; for 1.5h; chemoselective reaction;
98 %Spectr.	With N-Bromosuccinimide; (oxybis(2,1-phenylene))bis(diphenylbismuthane); potassium carbonate In [D₃]acetonitrile at 23℃; for 0.5h; Schlenk technique;

Reference： [1]Amadio, Emanuele; González-Fabra, Joan; Carraro, Davide; Denis, William; Gjoka, Blerina; Zonta, Cristiano; Bartik, Kristin; Cavani, Fabrizio; Solmi, Stefania; Bo, Carles; Licini, Giulia [Advanced Synthesis and Catalysis, 2018, vol. 360, # 17, p. 3286 - 3296]
[2]Magre, Marc; Kuziola, Jennifer; Nöthling, Nils; Cornella, Josep [Organic and Biomolecular Chemistry, 2021, vol. 19, # 22, p. 4922 - 4929]

57
[ 18680-27-8 ]
[ 475250-52-3 ]
[ 243145-80-4 ]

Yield	Reaction Conditions	Operation in experiment
75%	In diethyl ether; at 20℃;	A solution of (l S,2S,3 ,5S)-2,6,6-irimeihylbicyclo[3.1.1]heptane-2,3-diol (4.9 g, 28.8 mmol) in diethyl ether (100 mL) was treated with 2-(4-niethoxybenzyl)-4,4,5,5~tetramethyl-l,3,2- dioxaborolane (5 g, 20 mmol), the mixture was stirred at rt for 12 h. Then the mixture was concentrated and the crude was purified by column chromatography on silica gel, eluting with 5% of ethyl acetate in petroleum ether to afford the (3aS,4S,6S,7aR)-2-(4-methoxybenzyl)-3a,5,5-irimethylhexaliydro-4,6- methanobenzo[d] \| 1,3,2 jdioxaborole (4.5 g, 75%) as a colorless oil.

Reference： [1]Patent: WO2018/136401,2018,A1 .Location in patent: Paragraph 0366
[2]Journal of Medicinal Chemistry,2019,vol. 62,p. 7160 - 7184

58
[ 18680-27-8 ]
C₁₁H₇⁽²⁾H₂ClO₂ [ No CAS ]
(1S,2S,3R,5S)-2-hydroxy-2,6,6-trimethylbicyclo[3.1.1]heptan-3-yl (1R,2R,3S,4S)-2,3-dideuterium-2,3-dihydro-1,4-epoxynaphthalene-1(4H)-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.0326 g	With dmap; triethylamine In dichloromethane at 20℃; Inert atmosphere;	General procedure II: preparation of THENA-d2 ester 8-27. General procedure: Oxalyl chloride and DMF (1-2 drops) were added slowly to THENA-d2 (R)-(-)-2 or (S)-(+)-2 in dry CH2Cl2 under a nitrogen atmosphere at room temperature. The reaction mixture was stirred continuously for 3 h followed by evaporation to dryness under vacuum for 1 h to give the corresponding acid chloride. A solution of the acid chloride in dry CH2Cl2 was transferred to a mixture of the chiral secondary alcohol, triethylamine, and DMAP in dry CH2Cl2, then the resulting solution was stirred overnight. After the reaction was quenched with sat. NaHCO3 solution, the crude reaction mixture was extracted 3 times with CH2Cl2 and the organic layer was collected, dried over anh. Na2SO4, filtered, and evaporated to dryness. The crude product was purified by PLC (silica gel, hexane:EtOAc as eluents) to give the corresponding THENA-d2 ester.

Reference： [1]Soponpong, Jakapun; Dolsophon, Kulvadee; Thongpanchang, Chawanee; Linden, Anthony; Thongpanchang, Tienthong [Tetrahedron Letters, 2019, vol. 60, # 6, p. 497 - 500]

59
[ 18680-27-8 ]
C₁₁H₇⁽²⁾H₂ClO₂ [ No CAS ]
(1S,2S,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]heptan-3-yl (1S,2S,3R,4R)-2,3-dideuterium-2,3-dihydro-1,4-epoxynaphthalene-1(4H)-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.0339 g	With dmap; triethylamine In dichloromethane at 20℃; Inert atmosphere;	General procedure II: preparation of THENA-d2 ester 8-27. General procedure: Oxalyl chloride and DMF (1-2 drops) were added slowly to THENA-d2 (R)-(-)-2 or (S)-(+)-2 in dry CH2Cl2 under a nitrogen atmosphere at room temperature. The reaction mixture was stirred continuously for 3 h followed by evaporation to dryness under vacuum for 1 h to give the corresponding acid chloride. A solution of the acid chloride in dry CH2Cl2 was transferred to a mixture of the chiral secondary alcohol, triethylamine, and DMAP in dry CH2Cl2, then the resulting solution was stirred overnight. After the reaction was quenched with sat. NaHCO3 solution, the crude reaction mixture was extracted 3 times with CH2Cl2 and the organic layer was collected, dried over anh. Na2SO4, filtered, and evaporated to dryness. The crude product was purified by PLC (silica gel, hexane:EtOAc as eluents) to give the corresponding THENA-d2 ester.

Reference： [1]Soponpong, Jakapun; Dolsophon, Kulvadee; Thongpanchang, Chawanee; Linden, Anthony; Thongpanchang, Tienthong [Tetrahedron Letters, 2019, vol. 60, # 6, p. 497 - 500]

60
[ 18680-27-8 ]
[ 1155425-66-3 ]
2-methoxy-3-(2,9,9-trimethyl-3,5-dioxo-4-borotricyclic(6,1,1,0<SUP>2,6</SUP>)-3,5-decyl-4-benzoic acid) tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	In tetrahydrofuran at 20℃; for 15h;	1.II.2 Step 2. Synthesis of 2-methoxy-3-(2,9,9-trimethyl-3,5-dioxo-4-boro-tricyclic (6,1,1,0^{2, 6}) decyl-4-benzoic acid-tert-butyl ester (Compound B-3) (+)-2,3-pinanediol (2.70 g, 15.9 mmol) and tert-butyl 3-dihydroxyboryl-2-methoxybenzoate (compound B-2, 4.0 g, 15.9 mmol) dissolved in tetrahydrofuran (THF, 21 mL) were mixed and stirred at room temperature for 15 h. The solution was concentrated in vacuo and the residue was washed with hexane to obtain 5.0 g (86%) of a slowly crystallized white solid, ESI-MS M/Z 409 (M+Na)+.

Reference： [1]Current Patent Assignee: WUHAN VISION PHARMACEUTICAL TECHNOLOGY; WUHAN VISION PHARMACEUTICAL TECH - US2019/48027, 2019, A1 Location in patent: Paragraph 0047

61
[ 18680-27-8 ]
[ 1160367-20-3 ]
C₂₇H₃₀O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
59%	With Echavarren's catalyst In 1,2-dichloro-ethane at 80℃; for 3h;

Reference： [1]Zhang, Cheng; Li, Hongli; Pei, Chao; Qiu, Lihua; Hu, Wenhao; Bao, Xiaoguang; Xu, Xinfang [ACS Catalysis, 2019, vol. 9, # 3, p. 2440 - 2447]

62
[ 18680-27-8 ]
2-(2,4-dimethylbenzyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane [ No CAS ]
(1S,2S,6R,8S)-4-(2,4-dimethylbenzyl)-2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.0^2,6]decane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	In diethyl ether at 20℃; for 14h; Cooling with ice; Inert atmosphere;	2 Step 2: (1S,2S,6R,8S)-4-(2,4-Dimethyl-benzyl)-2,9,9-trimethyl-3,5- dioxa-4-bora-tricyclo[6.1.1.0²'⁶]decane To an ice-cooled solution of 2-(2,4-Dimethyl-benzyl)-4,4,5,5-tetramethyl- [1 ,3,2]dioxaborolane (24.00g; 79.3 mmol; 1 .0 eq.) in Diethyl ether (240.00 ml) under nitrogen atmosphere, (1 S,2S,3R,5S)-2,6,6-Trimethyl- bicyclo[3.1 .1 ]heptane-2,3-diol (20.68g; 1 19.07 mmol; 1 .50 eq.) is added and the reaction mixture is stirred at rt for 14 h. TLC analysis showed completion of reaction. The reaction mixture is washed with brine. The organic layer is dried over anhydrous Na2SO4 and concentrated. The crude is purified by flash column chromatography using 2 % ethyl acetate in petroleum ether to get (1 S,2S,6R,8S)-4-(2,4-Dimethyl-benzyl)-2,9,9-trimethyl-3,5-dioxa-4- bora-thcyclo[6.1 .1 .02'6]decane (28.00g; 82.96 mmol; 90.0 %) as colorless oil. 1H NMR (400 MHz, CDCI3): δ 7.05-7.03 (m, 1 H), 6.95-6.94 (m, 1 H), 6.92- 6.90 (m, 1 H), 4.27-4.25 (m, 1 H), 2.33-2.30 (m, 9H), 2.27-2.17 (m, 1 H), 2.05 (t, J = 5.76 Hz, 1 H), 1 .90-1 .89 (m, 1 H), 1 .84-1 .80 (m, 1 H), 1 .38 (s, 3H), 1 .28 (s, 3H), 1 .1 1 -1 .09 (m, 1 H), 0.91 (s, 3H) GCMS: m/z: 298.3.
90%	In diethyl ether at 20℃; for 14h; Inert atmosphere; Cooling with ice;	2.2 Step 2: (1S,2S,6R,8S)-4-(2,4-Dimethyl-benzyl)-2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.02,6]decane. To an ice-cooled solution of 2-(2,4-Dimethyl-benzyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (24.00g; 79.3 mmol; 1.0 eq.) in diethyl ether (240.00 ml_) under nitrogen atmosphere, (1S,2S,3R,5S)-2,6,6-Trimethyl-bicyclo[3.1.1]heptane-2,3-diol (20.68g; 1 19.07 mmol; 1.50 eq.) is added and the reaction mixture is stirred at rt for 14 h. TLC analysis shows completion of reaction. The reaction mixture is washed with brine. The organic layer is dried over anhydrous Na2S04 and concentrated. The crude is purified by flash column chromatography using 2 % ethyl acetate in petroleum ether to obtain (1S,2S,6R,8S)-4-(2,4-Dimethyl-benzyl)-2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.02,6]decane (28.00g; 82.96 mmol; 90.0 %) as colorless oil. 1H NMR (400 MHz, CDCIs): d 7.05-7.03 (m, 1H), 6.95-6.94 (m, 1H), 6.92-6.90 (m, 1H), 4.27-4.25 (m, 1H), 2.33-2.30 (m, 9H), 2.27-2.17 (m, 1H), 2.05 (t, J = 5.76 Hz, 1H), 1.90-1.89 (m, 1H), 1.84-1.80 (m, 1H), 1.38 (s, 3H), 1.28 (s, 3H), 1.1 1 -1.09 (m, 1H), 0.91 (s, 3H) GCMS: m/z: 298.3.
	In tert-butyl methyl ether at 20℃; Inert atmosphere;

Reference： [1]Current Patent Assignee: MERCK KGAA - WO2019/38250, 2019, A1 Location in patent: Page/Page column 74; 75; 76
[2]Current Patent Assignee: MERCK KGAA - WO2020/20858, 2020, A1 Location in patent: Page/Page column 65-66
[3]Klein, Markus; Busch, Michael; Friese-Hamim, Manja; Crosignani, Stefano; Fuchss, Thomas; Musil, Djordje; Rohdich, Felix; Sanderson, Michael P.; Seenisamy, Jeyaprakashnarayanan; Walter-Bausch, Gina; Zanelli, Ugo; Hewitt, Philip; Esdar, Christina; Schadt, Oliver [Journal of Medicinal Chemistry, 2021, vol. 64, # 14, p. 10230 - 10245]

63
[ 18680-27-8 ]
[ 30418-59-8 ]
3-aminophenylboronic acid pinanediol ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	With magnesium sulfate In toluene at 20℃;

Reference： [1]Hinkes, Stefan P.A.; Klein, Christian D.P. [Organic Letters, 2019, vol. 21, # 9, p. 3048 - 3052]

64
4,4,5,5-tetramethyl-2-[[4-(trifluoromethyl)phenyl]methyl]-1,3,2-dioxaborolane [ No CAS ]
[ 18680-27-8 ]
(1S,2S,6R,8S)-2,9,9-trimethyl-4-[[4-(trifluoromethyl)phenyl]methyl]-3,5-dioxa-4-boratricyclo[6.1.1.0^[2,6]]decane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	In diethyl ether at 20℃;	66 Into a 250-mL round-bottom flask, was placed 4,4,5,5-tetramethyl-2-[[4-(trifluoro methyl)phenyl] methyl] -1,3, 2-dioxaborolane (2.36 g, 8.25 mmol, 1 eq.), Et20 (30 mL), and (1S,2S,3R,5S)- 2,6,6-trimethylbicyclo[3.1.1]heptane-2,3-diol (2.8 g, 16.5 mmol, 2 eq.). The resulting solution was stirred for 16 h at rt. The resulting mixture was concentrated. The residue was applied onto a silica gel column with ethyl acetate :petroleum ether (0: 100-3:97). This resulted in 2.2 g (79%) of (lS,2S,6R,8S)-2,9,9- trimethyl-4-[[4-(trifluoromethyl)phenyl]methyl]-3,5-dioxa-4-boratricyclo[6.1.1.0A[2,6]]decane as a solid.

Reference： [1]Current Patent Assignee: SANOFI - WO2019/99582, 2019, A1 Location in patent: Paragraph 0488; 0489

65
[ 18680-27-8 ]
[ 243145-83-7 ]
(1S,2S,6R,8S)-4-[(4-fluorophenyl)methyl]-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0^[2,6]]decane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	In diethyl ether; at 20℃; for 16h;Inert atmosphere;	In a 500-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed 2-[(4-fluorophenyl)methyl]-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (15.3 g, 64.8 mmol, 1 eq.), (lS,2S,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]heptane-2,3-diol (14.3 g, 84 mmol, 1.3 eq.) and ethoxyethane (153 mL). The resulting solution was stirred 16 h at rt. The resulting mixture was washed with brine (160 mL). The aqueous layer was extracted with ethyl acetate (2 x 100 mL). The combined organic layers were dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by flash silica gel column with pure petroleum ether increasing to ethyl acetate:petroleum ether (1:3). This resulted in 16.7 g (89%) of (lS,2S,6R,8S)-4-[(4-fluorophenyl)methyl]-2,9,9-trimethyl-3,5- dioxa-4-boratricyclo[6.1.1.0A[2,6]]decane as a colorless oil.

Reference： [1]Patent: WO2019/99582,2019,A1 .Location in patent: Paragraph 0506; 0507
[2]Journal of Medicinal Chemistry,2019,vol. 62,p. 7160 - 7184

66
[ 18680-27-8 ]
[ 87100-28-5 ]
[ 78922-83-5 ]

Yield	Reaction Conditions	Operation in experiment
96%	In diethyl ether at 20℃; for 24h;
91%	In diethyl ether at 20℃;	2.2 Step 2:Synthesis of benzylboronic acid-(1S,2S,3R,5S)-(+)-2,3-decanol ester (B-3) Compound B-2 (1 g, 4.58 mmol) was dissolved in diethyl ether (20 mL).After adding (1S, 2S, 3R, 5S)-(+)-2,3-decanediol (859 mg, 5.04 mmol), it was allowed to react at room temperature overnight. The reaction solution was washed twice with water, and then washed twice with saturated brine.After drying with anhydrous sodium sulfate, concentration is reduced.Purified by silica gel column chromatography (eluent: PE/EtOAc = 50:1)The product was obtained as a colorless oil, 1.13 g, yield 91%
91%	In diethyl ether at 20℃; Inert atmosphere;

In tert-butyl methyl ether at 20℃; Inert atmosphere;

Reference： [1]Dong, Guangbin; Xie, Qiqiang [Journal of the American Chemical Society, 2022]
[2]Current Patent Assignee: SICHUAN UNIVERSITY - CN110156820, 2019, A Location in patent: Paragraph 0070; 0071; 0074; 0075
[3]Wang, Yao-Ling; Liu, Sha; Yu, Zhu-Jun; Lei, Yuan; Huang, Meng-Yi; Yan, Yu-Hang; Ma, Qiang; Zheng, Yang; Deng, Hui; Sun, Ying; Wu, Chengyong; Yu, Yamei; Chen, Qiang; Wang, Zhenling; Wu, Yong; Li, Guo-Bo [Journal of Medicinal Chemistry, 2019, vol. 62, # 15, p. 7160 - 7184]
[4]Klein, Markus; Busch, Michael; Friese-Hamim, Manja; Crosignani, Stefano; Fuchss, Thomas; Musil, Djordje; Rohdich, Felix; Sanderson, Michael P.; Seenisamy, Jeyaprakashnarayanan; Walter-Bausch, Gina; Zanelli, Ugo; Hewitt, Philip; Esdar, Christina; Schadt, Oliver [Journal of Medicinal Chemistry, 2021, vol. 64, # 14, p. 10230 - 10245]

67
[ 517920-59-1 ]
[ 18680-27-8 ]
(+)-pinanediol[(4-chlorophenyl)methyl]boronate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In tert-butyl methyl ether at 20℃; Inert atmosphere;

Reference： [1]Klein, Markus; Busch, Michael; Friese-Hamim, Manja; Crosignani, Stefano; Fuchss, Thomas; Musil, Djordje; Rohdich, Felix; Sanderson, Michael P.; Seenisamy, Jeyaprakashnarayanan; Walter-Bausch, Gina; Zanelli, Ugo; Hewitt, Philip; Esdar, Christina; Schadt, Oliver [Journal of Medicinal Chemistry, 2021, vol. 64, # 14, p. 10230 - 10245]

68
[ 18680-27-8 ]
(2-amino-3,4,5,6-tetrafluorophenyl)boronic acid [ No CAS ]
2,3,4,5-tetrafluoro-6-((3aR,4R,6R)-3a,5,5-trimethylhexahydro-4,6-methanobenzo[d][1,3,2]dioxaborol-2-yl)aniline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87.98%	In toluene at 55℃; for 3h;	4.3 Step 3. 2, 3, 4, 5-tetrafluoro-6- ( (3aR, 4R, 6R) -3a, 5, 5-trimethylhexahydro-4, 6-methanobenzo [d] [1, 3, 2] dioxaborol-2-yl) aniline Into a 250-mL round-bottom flask was placed (2-amino-3, 4, 5, 6-tetrafluorophenyl) boronic acid (11.82 g, 56.58 mmol) , (1S, 3R, 4S, 5S) -4, 6, 6-trimethylbicyclo [3.1.1] heptane-3, 4-diol (9.56 g, 56.58 mmol) and toluene (120 mL) . The mixture was stirred for 3h at 55 . The residue was concentrated under vacuum and purified by a silica gel column eluted with Hex/EA (v/v =20/1) . This resulted 17.08 g (87.98%yield) of 2, 3, 4, 5-tetrafluoro-6- ( (3aR, 4R, 6R) -3a, 5, 5-trimethylhexahydro-4, 6-methanobenzo [d] [1, 3, 2] dioxaborol-2-yl) aniline as brown solid. LCMS: m/z= 344 [M+1] +.

Reference： [1]Current Patent Assignee: JACOBIO PHARMACEUTICALS GROUP CO LTD - WO2021/185233, 2021, A1 Location in patent: Page/Page column 37

69
[ 18680-27-8 ]
(2-amino-3,4,5,6-tetrafluorophenyl)boronic acid [ No CAS ]
2,3,4,5-tetrafluoro-6-((3aR)-3a,5,5-trimethylhexahydro-4,6-methanobenzo[d][1,3,2]dioxaborol-2-yl)aniline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87.98%	In toluene at 55℃; for 3h;	4.3 Step 3. 2, 3, 4, 5-tetrafluoro-6- ( (3aR, 4R, 6R) -3a, 5, 5-trimethylhexahydro-4, 6-methanobenzo [d] [1, 3, 2] dioxaborol-2-yl) aniline Into a 250-mL round-bottom flask was placed (2-amino-3, 4, 5, 6-tetrafluorophenyl) boronic acid (11.82 g, 56.58 mmol) , (1S, 3R, 4S, 5S) -4, 6, 6-trimethylbicyclo [3.1.1] heptane-3, 4-diol (9.56 g, 56.58 mmol) and toluene (120 mL) . The mixture was stirred for 3h at 55 . The residue was concentrated under vacuum and purified by a silica gel column eluted with Hex/EA (v/v =20/1) . This resulted 17.08 g (87.98%yield) of 2, 3, 4, 5-tetrafluoro-6- ( (3aR, 4R, 6R) -3a, 5, 5-trimethylhexahydro-4, 6-methanobenzo [d] [1, 3, 2] dioxaborol-2-yl) aniline as brown solid. LCMS: m/z= 344 [M+1] +.

Reference： [1]Current Patent Assignee: JACOBIO PHARMACEUTICALS GROUP CO LTD - WO2021/185233, 2021, A1 Location in patent: Page/Page column 36-37

70
[ 18680-27-8 ]
[ 475250-52-3 ]
(3aS,4S,6S,7aR)-2-(4-methoxybenzyl)-5,5,7a-trimethylhexahydro-4,6-methanobenzo[d][1,3,2]dioxaborole [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2022,vol. 144,p. 2460 - 2467

71
[ 18680-27-8 ]
[ 1123299-30-8 ]
(3aS,4S,6S,7aR)-2-(benzo[d][1,3]dioxol-5-ylmethyl)-5,5,7a-trimethylhexahydro-4,6-methanobenzo[d][1,3,2]dioxaborole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%	In diethyl ether at 20℃; for 24h; Inert atmosphere; Schlenk technique;