[ CAS No. 1443-80-7 ] {[proInfo.proName]}

Name: 1443-80-7|4-Acetylbenzonitrile|97%
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Quality Control of [ 1443-80-7 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 1443-80-7 ]

CAS No. :	1443-80-7	MDL No. :	MFCD00001825
Formula :	C₉H₇NO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	NLPHXWGWBKZSJC-UHFFFAOYSA-N
M.W :	145.16	Pubchem ID :	74044
Synonyms :

Calculated chemistry of [ 1443-80-7 ]

Physicochemical Properties

Num. heavy atoms :	11
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.11
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	41.35
TPSA :	40.86 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.32 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.56
Log Po/w (XLOGP3) :	1.22
Log Po/w (WLOGP) :	1.76
Log Po/w (MLOGP) :	1.08
Log Po/w (SILICOS-IT) :	2.14
Consensus Log Po/w :	1.55

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-1.85
Solubility :	2.07 mg/ml ; 0.0142 mol/l
Class :	Very soluble
Log S (Ali) :	-1.68
Solubility :	3.07 mg/ml ; 0.0211 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.8
Solubility :	0.232 mg/ml ; 0.0016 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.21

Safety of [ 1443-80-7 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 1443-80-7 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 1443-80-7 ]
Downstream synthetic route of [ 1443-80-7 ]

[ 1443-80-7 ] Synthesis Path-Upstream 1~9

1
[ 1443-80-7 ]
[ 20099-89-2 ]

Yield	Reaction Conditions	Operation in experiment
61%	With N-Bromosuccinimide In ethyl acetate at 40℃;	In a 100 mL round bottom flask, 10 mmol of 4-cyanoacetophenone and 11 mmol of N-bromosuccinimide (NBS) were added.35mL of ethyl acetate dissolved,Then add 1g of Amberlyst 15 ion exchange resin as catalyst.The reaction was warmed to 40°C and reacted. After TLC tracks the reaction,The reaction solution was filtered to remove Amberlyst 15 ion exchange resin,The filtrate was spin-dried and separated by column chromatography (eluent: petroleum ether/ethyl acetate) to give a white solid with a yield of 61percent.
61%	With N-Bromosuccinimide In ethyl acetate at 40℃;	In a 100 mL round bottom flask, 10 mmol of 4-cyanoacetophenone and 11 mmol of N-bromosuccinimide (NBS) were added.35mL of ethyl acetate dissolved,Then add 1g of Amberlyst 15 ion exchange resin as catalyst.The reaction was warmed to 40°C and reacted. After TLC tracks the reaction,The reaction solution was filtered to remove Amberlyst 15 ion exchange resin, and the filtrate was spin-dried.Column chromatography (eluent: petroleum ether/ethyl acetate) afforded a white solid in 61percent yield.
38%	With Oxone; ammonium bromide In methanol at 20℃; for 48 h;	General procedure: Oxone (1.352 g, 2.2 mmol) was added to the well stirred solution of substrate (2 mmol) and NH₄Br (0.215 g, 2.2 mmol) in methanol (10 ml) and the reaction mixture was allowed to stir at room temperature (or reflux temperature). After completion of the reaction, as monitored by TLC, the reaction mixture was quenched with aqueous sodium thiosulfate, and extracted with ethyl acetate (3.x.25 ml). Finally, the combined organic layer was washed with water, dried over anhydrous sodium sulfate, filtered and removal of solvent in vacuo yielded a crude residue, which was further purified by column chromatography over silica gel (finer than 200 mesh) to afford pure products. All the products were identified on the basis of ¹H NMR and mass spectral data.

29%	With hydrogen bromide; bromine In chloroform	j) Preparation of 2-Bromo-4'-cyanoacetophenone To a mixture of para-cyanoacetophenone (52 g, 0.36 mol) in chloroform (520 ml) and 48percent HBr (5.2 ml), a solution of bromine (19.3 ml) in chloroform (52 ml) was added dropwise over a period of 20 min. The mixture was stirred for 3 h at room temperature and neutralized to pH7 with sat. NaHCO₃. The organic layer was washed with sat. NaCl and dried over anhydrous Na₂SO₄ and concentrated. The residue was chromatographed on silica gel (AcOEt/n-hexane=1/3 as an eluent) and recrystallized to obtain 2-bromo-4'-cyanoacetophenone as a colourless plate (23.4 g, 29percent). EI-MS(+): m/z 223 (M+) 1H-NMR(CDCl₃): 4.43(2H,s), 7.80(2H,d,J=6.6 Hz), 8.09(2H,d,J=6.6 Hz)
29%	With hydrogen bromide; bromine In chloroform	g) Preparation of 2-bromo-4'-cyanoacetophenone To a mixture of para-cyanoacetophenone (52 g, 0.36 mol) in chloroform (520 ml) and 48percent HBr (5.2 ml), a solution of bromine (19.3 ml) in chloroform (52 ml) was added dropwise over a period of 20 min. The mixture was stirred for 3 h at room temperature and neutralized to pH7 with sat. NaHCO₃. The organic layer was washed with sat. NaCl and dried over anhydrous Na₂SO₄ and concentrated. The residue was chromatographed on silica gel (AcOEt/n-hexane=1/3 as an eluent) and recrystallized to obtain 2-bromo-4'-cyanoacetophenone as a colourless plate (23.4 g, 29percent). EI-MS(+): m/z 223 (M+) 1H-NMR(CDCl3) δ4.43(2H,s), 7.80(2H,d,J=6.6 Hz), 8.09(2H,d,J=6.6 Hz)

Reference： [1] Archiv der Pharmazie (Weinheim, Germany), 1980, vol. 313, # 4, p. 315 - 323
[2] European Journal of Organic Chemistry, 2017, vol. 2017, # 43, p. 6390 - 6400
[3] Helvetica Chimica Acta, 2013, vol. 96, # 5, p. 889 - 896
[4] Chemical and Pharmaceutical Bulletin, 1998, vol. 46, # 4, p. 623 - 630
[5] Patent: CN107629023, 2018, A, . Location in patent: Paragraph 0135; 0138; 0139; 0140
[6] Patent: CN107629022, 2018, A, . Location in patent: Paragraph 0212; 0213; 0214; 0215
[7] RSC Advances, 2016, vol. 6, # 42, p. 35602 - 35608
[8] Tetrahedron Letters, 2012, vol. 53, # 2, p. 191 - 195
[9] Patent: US6300353, 2001, B1,
[10] Patent: US6300353, 2001, B1,
[11] Patent: US2784194, 1954, ,
[12] Yakugaku Zasshi, 1952, vol. 72, p. 305,307[13] Chem.Abstr., 1953, p. 2133
[14] Journal of Medicinal Chemistry, 1971, vol. 14, # 10, p. 977 - 982
[15] Journal of Medicinal Chemistry, 1987, vol. 30, # 8, p. 1497 - 1502
[16] Journal of Organic Chemistry USSR (English Translation), 1992, vol. 28, # 7, p. 1162 - 1168[17] Zhurnal Organicheskoi Khimii, 1992, vol. 28, # 7, p. 1472 - 1478
[18] Journal of Physical Chemistry, 1995, vol. 99, # 20, p. 8190 - 8195
[19] Patent: WO2004/85408, 2004, A1, . Location in patent: Page 285
[20] Patent: US5935776, 1999, A,
[21] Patent: US5648372, 1997, A,
[22] Patent: US4812470, 1989, A,
[23] Patent: EP1231210, 2002, A2, . Location in patent: Page 73
[24] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 14, p. 5063 - 5070
[25] European Journal of Medicinal Chemistry, 2012, vol. 57, p. 407 - 416
[26] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 7, p. 2031 - 2034
[27] Advanced Synthesis and Catalysis, 2013, vol. 355, # 18, p. 3570 - 3574
[28] Chemical Communications, 2014, vol. 50, # 51, p. 6726 - 6728
[29] Organic Letters, 2017, vol. 19, # 8, p. 1994 - 1997
[30] Letters in Drug Design and Discovery, 2017, vol. 14, # 5, p. 528 - 539
[31] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 16, p. 3726 - 3732
[32] Organic and Biomolecular Chemistry, 2017, vol. 15, # 38, p. 8134 - 8139
[33] Advanced Synthesis and Catalysis, 2018, vol. 360, # 8, p. 1628 - 1633
[34] Tetrahedron Letters, 2018, vol. 59, # 33, p. 3214 - 3219
[35] Chemical Communications (Cambridge, United Kingdom), 2018, vol. 54, # 86, p. 12182 - 12185

2
[ 1443-80-7 ]
[ 20099-89-2 ]
[ 21661-87-0 ]

Yield	Reaction Conditions	Operation in experiment
45%	With N-Bromosuccinimide; silica gel In methanol for 0.3 h; Reflux	General procedure: The α-bromination reaction was carried out using acetophenone (1200 mg, 10 mmol), N-bromosuccinimide (2136 mg, 12 mmol), 10percent (w/w) silica gel (120mg) in 10 mL of methanol at reflux conditions until the disappearance of the substrate. (Note: 2136mg of N-bromosuccinimide was added portion wise i.e. 356 mg for each time in six portions). The progress of the reaction was monitored by TLC. The reaction mass was filtered after the completion of the reaction as per TLC and the catalyst was collected for reuse. The filtrate was concentrated under vacuum. Double distilled water was added to the reaction mixture and quenched with aqueous sodium thiosulfate and the product extracted with dichloromethane (Caution: Severe burning sensation of eyes was observed during the work-up process). The layers were separated and the organic layer was collected and washed thrice with distilled water (3×50mL). The collected organic layer was dried over anhydrous Na₂SO₄, filtered and concentrated. The obtained crude product was purified by column chromatography over silica gel (60–120 mesh) using n-hexane–EtOAc (99:1 ratio). With the aim of studying the recycling of the catalyst, the isolated catalyst was washed with ethyl acetate (5mL) after its filtration from the reaction medium, collected and dried in vacuum at 70°C to a constant weight. Subsequently it was reused for the α-bromination of acetophenone and achieved 95percent, 86percent and 83percent yields of product (2a) for first, second and third reuse of catalyst respectively. All products gave spectroscopic data in agreement with the literature [15,21,27–30]. The method is also very practical for scale up in process development. We attempted large scale (100 gram scale) synthesis of 2-bromo-1-phenylethanone 2a and obtained fruitful results with isolated yields ranging from 93percent to 96percent.

Reference： [1] Journal of Medicinal Chemistry, 2011, vol. 54, # 12, p. 4042 - 4056
[2] Chinese Chemical Letters, 2014, vol. 25, # 1, p. 179 - 182

3
[ 67-56-1 ]
[ 1443-80-7 ]
[ 20099-89-2 ]
[ 164594-65-4 ]

Yield	Reaction Conditions	Operation in experiment
35%	for 16 h; Reflux	General procedure: Oxone (1.352 g, 2.2 mmol) was added to the well stirred solution of substrate (2 mmol) and NH₄Br (0.215 g, 2.2 mmol) in methanol (10 ml) and the reaction mixture was allowed to stir at room temperature (or reflux temperature). After completion of the reaction, as monitored by TLC, the reaction mixture was quenched with aqueous sodium thiosulfate, and extracted with ethyl acetate (3.x.25 ml). Finally, the combined organic layer was washed with water, dried over anhydrous sodium sulfate, filtered and removal of solvent in vacuo yielded a crude residue, which was further purified by column chromatography over silica gel (finer than 200 mesh) to afford pure products. All the products were identified on the basis of ¹H NMR and mass spectral data.

Reference： [1] Tetrahedron Letters, 2012, vol. 53, # 2, p. 191 - 195

4
[ 25309-65-3 ]
[ 1443-80-7 ]
[ 20099-89-2 ]

Reference： [1] Organic Letters, 2016, vol. 18, # 4, p. 784 - 787

5
[ 1443-80-7 ]
[ 65695-05-8 ]

Reference： [1] Patent: US2003/45546, 2003, A1,

6
[ 623-00-7 ]
[ 108-24-7 ]
[ 1591-30-6 ]
[ 1443-80-7 ]
[ 32446-66-5 ]
[ 100-47-0 ]

Reference： [1] Journal of Organic Chemistry, 2004, vol. 69, # 3, p. 936 - 942

7
[ 1443-80-7 ]
[ 28357-95-1 ]

Reference： [1] Chemical and Pharmaceutical Bulletin, 1979, vol. 27, # 11, p. 2735 - 2742

8
[ 1443-80-7 ]
[ 20099-90-5 ]

Reference： [1] Chemische Berichte, 1934, vol. 67, p. 1209

9
[ 1443-80-7 ]
[ 552846-23-8 ]

Yield	Reaction Conditions	Operation in experiment
93%	at 120℃; for 24 h;	General procedure: A mixture of the required nitrile (1 mmol), sodium azide(1 mmol) and the catalyst MNP (0.05 g) was stirred at 120° C in PEG (1 mL) as solvent. After completion of the reaction, as indicated by TLC, the mixture was cooled to room temperature and diluted with 1:1 H2O:Ethyl acetate(10 mL) and then stirred at ambient temperature (10 min). The catalyst was removed by applying a magnetic field, and the decantate was treated with HCl (4 N, 10 mL). The organic layer was separated, washed with water, dried over sodium sulfate and concentrated to precipitate the crude crystalline solid. The pure tetrazoles were characterized bytheir spectroscopic data and melting points.
93%	With sodium azide; C₁₉H₁₇N₃O₄^(2-)*Cu⁽²⁺⁾ In ethylene glycol at 120℃; for 3 h;	General procedure: In 25mL round-bottomed flask, sodium azide (0.076g, 1.2mmol) and polymeric copper (II) complex (0.005g) were added to a solution of benzonitrile (0.103g, 1mmol) in ethylene glycol (3mL) with stirring at room temperature. The reaction temperature was raised up to 120°C for 3h. The reaction was monitored by TLC at regular intervals. After completion of the reaction, the reaction mixture was cooled to room temperature and treated with 10mL HCl (2N) and extracted with 10mL ethyl acetate. The resulted organic layers were separated and washed with 2×10mL distilled water, dried over anhydrous sodium sulphate and evaporated under reduced pressure. The residue was then purified by column chromatography on silica gel (100–200 mesh) to afford the corresponding products.
91%	at 120℃; for 30 h; Green chemistry	General procedure: In a round-bottomed flask, a mixture of nitrile (1 mmol) and sodium azide (1.2 mmol) in the presence of 40 mg of Fe₃O₄SBTUNi(II) was stirred at 120 °C in PEG for an appropriate time (monitored by TLC). Then, the reaction mixture was cooled down to room temperature. After magnetic separation of catalyst, HCl (4 N, 10 mL) was added to the filtrate and the product extracted with ethyl acetate (2 × 10 mL). The organic layer was washed with water several times, dried with anhydrous Na₂SO₄ and concentrated to give the crude solid crystalline product.

90%	With sodium azide; tetra(n-butyl)ammonium hydrogensulfate In water at 85℃; for 5 h; Green chemistry	General procedure: General Procedure for Preparation of Tetrazoles in Water(Method II). TBAHS (0.25 mmol) was added to a mixture of nitrile (1 mmol), sodium azide (1.5 mmol), and 2 mL H₂O in around-bottomed flask. The reaction mixture was heated to 85 °C. After completion of the reaction (as monitored by TLC), the crude reaction mixture was transferred into a separatory funnel, to which was added 1 N HCl (15 mL) extracted by ethylacetate (EtOAc, 10 mL × 5). The combined organic layers were washed with H₂O and dried over anhydrous sodium sulfate, and were evaporated under reduced pressure to give pure 5-substituted-1H-tetrazole.
87%	With sodium azide; activated Fuller’s earth In dimethyl sulfoxide at 120℃; for 3 h; Green chemistry	General procedure: To a DMSO (3 ml) solution of nitrile (1 mmol), and sodium azide (1.5 mmol), was added catalyst (10 wt percent). The reaction mixture was stirred to 120 ⁰C in an oil bath. The reaction was monitored by TLC. After completion of the reaction, the mixture was filtered to separate the catalyst. The filtrate was quenched with water (30 ml), acidified with 5N HCl (20 ml) to precipitate the product, extracted with ethyl acetate (2 X 20 ml). The combined organic layers were washed with water, dried over sodium sulphate and evaporated under reduced pressure to give the product.
78%	at 120℃; for 10 h;	General procedure: To a stirred mixture of sodium azide (1.2 mmol) in PEG-400(2 mL), a nitrile compound (1 mmol) and NiNP-PNF (200 mL) were added and heated at 120°C under atmospheric conditions.The reaction progress was monitored by TLC. Upon reaction completion, the mixture was allowed to cool to ambient temperature and then filtered and extracted with ethyl acetate. The organic layer was washed with 1N HCl, dried with anhydrous Na₂SO₄, and filtered to afford pure 5-substituted tetrazoles.
57%	With indium(III) chloride; sodium azide In water; isopropyl alcohol at 160℃; Microwave irradiation	General procedure: Synthesis of 4-acetylbenzotetrazole (2c). 4-Acetylbenzonitrile 3c (290 mg, 2 mmol), NaN₃ (260 mg, 4 mmol), InCl₃(89 mg, 0.4 mmol), and 8 mL of a 3:1 isopropanol/water mixture were added to a 30-mL Pyrex microwave vessel and capped. The microwave vessel was then placed in a Milestone Start Synth microwave reactor. The reaction was magnetically stirred and heated for 1 hour at 160 ^oC. The pressure in the vessels was not determined. The reaction was monitored by TLC using an ether/hexane mixture (typically50/50) for development. After cooling, the reaction mixture was diluted with saturated aqueous sodium bicarbonate (20mL) and washed with ethyl acetate (2 x 15 mL). The aqueous sodium bicarbonate layer was cooled to 0 ^oC and acidified to a pH of 2 or less with concentrated hydrochloric acid,which was added drop-wise. The precipitate formed was extracted with ethyl acetate (3 x 15 mL). The combined organic layers were dried over anhydrous sodium sulfate and decanted into a tared round bottom flask. The organic layer was concentrated under reduced pressure. The tetrazole product was recrystallized from ethyl acetate and hexane. All reagents mentioned above were used unpurified

Reference： [1] Applied Organometallic Chemistry, 2017, vol. 31, # 9,
[2] RSC Advances, 2016, vol. 6, # 79, p. 75227 - 75233
[3] Applied Organometallic Chemistry, 2018, vol. 32, # 8,
[4] New Journal of Chemistry, 2018, vol. 42, # 16, p. 13754 - 13762
[5] Journal of Organic Chemistry, 2004, vol. 69, # 8, p. 2896 - 2898
[6] RSC Advances, 2016, vol. 6, # 61, p. 56638 - 56646
[7] Transition Metal Chemistry, 2017, vol. 42, # 2, p. 131 - 136
[8] Journal of Organometallic Chemistry, 2018, vol. 870, p. 16 - 22
[9] Applied Organometallic Chemistry, 2016, vol. 30, # 8, p. 705 - 712
[10] Journal of Sulfur Chemistry, 2018, vol. 39, # 3, p. 237 - 251
[11] Applied Organometallic Chemistry, 2018, vol. 32, # 6,
[12] Bulletin of the Korean Chemical Society, 2015, vol. 36, # 1, p. 198 - 202
[13] Applied Organometallic Chemistry, 2017, vol. 31, # 7,
[14] Applied Organometallic Chemistry, 2017, vol. 31, # 12,
[15] Tetrahedron Letters, 2016, vol. 57, # 51, p. 5815 - 5819
[16] Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 11, p. 3047 - 3054
[17] Australian Journal of Chemistry, 2017, vol. 70, # 10, p. 1127 - 1137
[18] European Journal of Organic Chemistry, 2008, # 23, p. 3928 - 3932
[19] RSC Advances, 2016, vol. 6, # 39, p. 32653 - 32660
[20] Medicinal Chemistry, 2017, vol. 13, # 4, p. 359 - 364
[21] Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 2, p. 483 - 495
[22] Patent: WO2016/187521, 2016, A1, . Location in patent: Paragraph 0020; 0021
[23] Applied Organometallic Chemistry, 2017, vol. 31, # 5,

[ 1443-80-7 ] Synthesis Path-Downstream 1~88

1
[ 1443-80-7 ]
[ 20099-53-0 ]

Yield	Reaction Conditions	Operation in experiment
85%	With selenium(IV) oxide; water In 1,4-dioxane at 90℃; for 12h;	1 Synthesis of4-(2-oxo-acetyl)-benzonitrile 1.7.a; To a mixture of dioxane (75 ml) and water (7.5 ml), selenium oxide (100 mmol) was added. The mixture was stirred at 50°C until the selenium oxide was dissolved. Then para-cyano-acetophenone (100 mmol) was added. The mixture was stirred at 90°C for 12 hours. The warm solution was filtered and the solvent was removed. The residue obtained was dissolved in dichloromethane and water was added. The organic layer was separated, dried on magnesium sulphate and the solvent was removed, yielding intermediate 1.7. a as a solid (85%).
80%	With selenium(IV) oxide In 1,4-dioxane for 20h; Heating / reflux;	1 Synthesis of 4-(2-oxo-acetyl)-benzonitrile 1.6.aTo a solution of 4-cyanoacetophenone 4.1.a (6 g, 41 mmol) in dioxane (250 mL), selenium dioxide (9.1 g, 82 mmol) was added. The reaction mixture was refluxed for 20 hours, cooled to room temperature, filtrated and concentrated. The residue was dissolved in CH2CI2 and filtrated again. The solvent was evaporated and the residue was purified by column chromatography (ethyl acetate/heptane = 1/1), to give 5.2 g of glyoxal 1.6.a (80% yield).
		14 EXAMPLE 14 4-Cyanophenylglyoxal is prepared from 4-cyanoacetophenone.

	Multi-step reaction with 2 steps 1: bromine / dichloromethane 2: dimethyl sulfoxide; water / 20 °C
	With iodine; dimethyl sulfoxide In chlorobenzene at 120℃;
	With 1,4-dioxane; selenium(IV) oxide
	With hydrogen bromide; dimethyl sulfoxide In water at 85℃; for 18h;
	With selenium(IV) oxide; water In 1,4-dioxane Reflux;	Preparation of -Cyanoenones 8b-m; General Procedure General procedure: To a 100 mL two-neck round-bottom flask, SeO2 (2.00 g, 18.0 mmol), H2O (0.31 g, 17.0 mmol) and 1,4-dioxane (10.0 mL) were added and the flask was fitted with a condenser. The mixture was heated to reflux with stirring until the solid dissolved. Then, substituted aryl ketone(10.0 mmol) was added into the solution and the reaction mixture was allowed to reflux. After the reaction was completed, the reaction mixture was cooled to r.t. and filtered through a Celite pad,which was then washed several times with diethyl ether. The combined filtrate was evaporated on a rotary evaporator to afford the crude product, which was used in the next step without further purification. A solution of aryllglyoxal monohydrate (10.0 mmol) in benzene (40 mL) was heated under reflux with azeotropic removal of water (Dean-Stark). Thereafter, cyanomethylidenetriphenylphosphorane(3.80 g, 12.6 mmol) and benzoic acid (211 mg, 1.73 mmol) were added and the mixture was stirred for 10 h under an argon atmosphere at 80 °C. The cooled mixture was concentrated in vacuo and the residue was subjected to column chromatography on silica gel (hexane/EtOAc, 2:1) and recrystallization to give 8 as yellow crystals.
	With selenium(IV) oxide In 1,4-dioxane Reflux;
	With selenium(IV) oxide In 1,4-dioxane for 8h; Inert atmosphere; Reflux;

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2005/105810, 2005, A2 Location in patent: Page/Page column 27
[2]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2006/108828, 2006, A1 Location in patent: Page/Page column 29
[3]Current Patent Assignee: LABORATOIRE ROGER BELLON; ROZHE BELLON LAB - US5053509, 1991, A
[4]Usui, Yoshihiro; Uehara, Fumiaki; Hiki, Shinsuke; Watanabe, Kazutoshi; Tanaka, Hiroshi; Shouda, Aya; Yokoshima, Satoshi; Aritomo, Keiichi; Adachi, Takashi; Fukunaga, Kenji; Sunada, Shinji; Nabeno, Mika; Saito, Ken-Ichi; Eguchi, Jun-ichi; Yamagami, Keiji; Asano, Shouichi; Tanaka, Shinji; Yuki, Satoshi; Yoshii, Narihiko; Fujimura, Masatake; Horikawa, Takashi [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 16, p. 3726 - 3732]
[5]Xu, Liang; Wang, Shengpeng; Chen, Bajin; Li, Meichao; Hu, Xinquan; Hu, Baoxiang; Jin, Liqun; Sun, Nan; Shen, Zhenlu [Synlett, 2018, vol. 29, # 11, p. 1505 - 1509]
[6]Current Patent Assignee: ROCHE HOLDING AG - US2641601, 1950, A
[7]De Toledo, Ian; Grigolo, Thiago A.; Bennett, James M.; Elkins, Jonathan M.; Pilli, Ronaldo A. [Journal of Organic Chemistry, 2019, vol. 84, # 21, p. 14187 - 14201]
[8]Akutsu, Hiroshi; Nakashima, Kosuke; Kanetsuna, Yuta; Kawada, Masahiro; Hirashima, Shin-Ichi; Miura, Tsuyoshi [Synthesis, 2020, vol. 52, # 24, p. 3874 - 3880]
[9]Kuzu, Burak; Tan, Meltem; Gülçin, İlhami; Menges, Nurettin [Archiv der Pharmazie, 2021, vol. 354, # 10]
[10]Nam, Dong Guk; Shim, Su Yong; Jeong, Hye-Min; Ryu, Do Hyun [Angewandte Chemie - International Edition, 2021, vol. 60, # 41, p. 22236 - 22240][Angew. Chem., 2021, vol. 133, # 41, p. 22410 - 22414]

2
[ 1443-80-7 ]
[ 20099-89-2 ]

Yield	Reaction Conditions	Operation in experiment
61%	With N-Bromosuccinimide; In ethyl acetate; at 40℃;	In a 100 mL round bottom flask, 10 mmol of 4-cyanoacetophenone and 11 mmol of N-bromosuccinimide (NBS) were added.35mL of ethyl acetate dissolved,Then add 1g of Amberlyst 15 ion exchange resin as catalyst.The reaction was warmed to 40C and reacted. After TLC tracks the reaction,The reaction solution was filtered to remove Amberlyst 15 ion exchange resin,The filtrate was spin-dried and separated by column chromatography (eluent: petroleum ether/ethyl acetate) to give a white solid with a yield of 61%.
61%	With N-Bromosuccinimide; In ethyl acetate; at 40℃;	In a 100 mL round bottom flask, 10 mmol of 4-cyanoacetophenone and 11 mmol of N-bromosuccinimide (NBS) were added.35mL of ethyl acetate dissolved,Then add 1g of Amberlyst 15 ion exchange resin as catalyst.The reaction was warmed to 40C and reacted. After TLC tracks the reaction,The reaction solution was filtered to remove Amberlyst 15 ion exchange resin, and the filtrate was spin-dried.Column chromatography (eluent: petroleum ether/ethyl acetate) afforded a white solid in 61% yield.
38%	With Oxone; ammonium bromide; In methanol; at 20℃; for 48h;	General procedure: Oxone (1.352 g, 2.2 mmol) was added to the well stirred solution of substrate (2 mmol) and NH4Br (0.215 g, 2.2 mmol) in methanol (10 ml) and the reaction mixture was allowed to stir at room temperature (or reflux temperature). After completion of the reaction, as monitored by TLC, the reaction mixture was quenched with aqueous sodium thiosulfate, and extracted with ethyl acetate (3×25 ml). Finally, the combined organic layer was washed with water, dried over anhydrous sodium sulfate, filtered and removal of solvent in vacuo yielded a crude residue, which was further purified by column chromatography over silica gel (finer than 200 mesh) to afford pure products. All the products were identified on the basis of 1H NMR and mass spectral data.

29%	With hydrogen bromide; bromine; In chloroform;	j) Preparation of 2-Bromo-4'-cyanoacetophenone To a mixture of para-cyanoacetophenone (52 g, 0.36 mol) in chloroform (520 ml) and 48% HBr (5.2 ml), a solution of bromine (19.3 ml) in chloroform (52 ml) was added dropwise over a period of 20 min. The mixture was stirred for 3 h at room temperature and neutralized to pH7 with sat. NaHCO3. The organic layer was washed with sat. NaCl and dried over anhydrous Na2SO4 and concentrated. The residue was chromatographed on silica gel (AcOEt/n-hexane=1/3 as an eluent) and recrystallized to obtain 2-bromo-4'-cyanoacetophenone as a colourless plate (23.4 g, 29%). EI-MS(+): m/z 223 (M+) 1H-NMR(CDCl3): 4.43(2H,s), 7.80(2H,d,J=6.6 Hz), 8.09(2H,d,J=6.6 Hz)
29%	With hydrogen bromide; bromine; In chloroform;	g) Preparation of 2-bromo-4'-cyanoacetophenone To a mixture of para-cyanoacetophenone (52 g, 0.36 mol) in chloroform (520 ml) and 48% HBr (5.2 ml), a solution of bromine (19.3 ml) in chloroform (52 ml) was added dropwise over a period of 20 min. The mixture was stirred for 3 h at room temperature and neutralized to pH7 with sat. NaHCO3. The organic layer was washed with sat. NaCl and dried over anhydrous Na2SO4 and concentrated. The residue was chromatographed on silica gel (AcOEt/n-hexane=1/3 as an eluent) and recrystallized to obtain 2-bromo-4'-cyanoacetophenone as a colourless plate (23.4 g, 29%). EI-MS(+): m/z 223 (M+) 1H-NMR(CDCl3) delta4.43(2H,s), 7.80(2H,d,J=6.6 Hz), 8.09(2H,d,J=6.6 Hz)
	With bromine; In dichloromethane; at 20℃;	To a solution of 4-cyanoacetophenone (11. 32 G, 77. 98 mmol) in dichloromethane (200 mL) was added bromine (4. 00 mL, 78. 0 mmol) dropwise at room temperature. After stirring several minutes, the reaction mixture was washed with water, dried over anhydrous sodium sulfate, and concentrated in vacuo to afford 4-cyanophenacyl bromide (17. 73 g) as a white solid.
	With bromine;AlCl3; In water; acetic acid;	1) Synthesis of alpha-Bromo-4-cyanoacetophenone (Compound 3) A solution of bromine (2.6 ml, 50.0 mmol) in 5 ml acetic acid was added to 4-cyanoacetophenone (7.26 g, 50.0 mmol) in 20 ml acetic acid over 10 min at 0 C. The mixture was warmed to room temperature. AlCl3 (100 mg) was added, after which the red color of bromine disappeared. The reaction mixture was stirred for 25 min at room temperature. Water (5 ml) was added to the mixture, and the resulting white precipitate was filtered off and washed with water and cold 95% alcohol. The yield was 10.24 g (91%). The properties of the alpha-bromo-4-cyanoacetophenone are listed below: M.P. 288.5 C. 1 H NMR (CDCl3, 300 MHz): delta8.08 (m, 2H), 7.81 (m, 2H), 4.43 (s, 2H).
	With hydrogen bromide; bromine; sodium hydrogencarbonate; In chloroform;	Preparation of 2-bromo-4'-cyanoacetophenone Structural formula: STR299 4'-Cyanoacetophenone (10 g) was dissolved in 100 ml of CHCl3, and 1 ml of 48% HBr was added to the resultant solution. To the mixture, a solution of Br2 (3.7 ml) in CHCl3 (10 ml) was added dropwise at room temperature. After stirring for 2 hours at room temperature, a saturated aqueous solution of NaHCO3 was added to the liquid reaction mixture to neutralize it. The CHCl3 layer was washed with H2 O and then a saturated NaCl solution and dried over MgSO4. Thereafter, CHCl3 was distilled out. The resulting solid matter was recrystallized from AcOET-nHex, thereby obtaining the intended compound (3.49 g). Physical properties of this product are described below. mp: 82-84 C. NMR: delta solvent (CDCl3) 4.44(2H,s), 7.81-7.84(2H,m), 8.09(1H,d,J=8 Hz), 8.23(1H,d,J=8 Hz).
	With bromine;aluminium chloride;	Example 21 5-p-Cyanophenyl-2-(1-normon-2-yl) oxazole A 4-Acetylbenzonitrile (14.5 g, 100 mmol) was dissolved in anhydrous ether (150 ml). Aluminium chloride (catalytic amount) was added to the solution. Bromine (5.1 ml, 100 mmol) was added dropwise at room temperature and the solution stirred for 1/2 h. A precipitate formed and was collected and dried to yield p-cyanophenacyl bromide, m.p. 85-86 C. (19.34 g, 86%); deltaH (CDCl3) 7.80 and 8.10 (4H, ABq, aryl), 4.45 (2H, s, CH2).
	With aluminum (III) chloride; bromine; In diethyl ether; at 0℃; for 0.5h;Inert atmosphere;	General procedure: To a stirred solution of substituted acetophenone (1 mmol) in anhydrous diethyl ether (5 mL) cooled at 0 C was added anhydrous aluminium chloride (0.05 mmol) under N2 atmosphere followed by bromine (1 mmol). The reaction mixture was stirred at same temperature for 30 min. After the completion of the starting material as monitored by the TLC, reaction mass quenched with crushed ice. Extracted in diethyl ether (2 × 75 mL), combined extract was washed with 10% NaHCO3 solution, water followed by brine solution and dried over anhydrous Na2SO4. The crude product was purified by recrystallization using pet ether to afford the pure phenacyl bromides as low melting solids.
	With hydrogen bromide; bromine; In acetic acid;Cooling with ice;	General procedure: Corresponding acetophenone (10 mmol) was dissolved in glacial AcOH (50 mL) and HBr (0.5 mL) was added. The solution was taken into ice bath and bromine (12 mmol, 0.62mL) in AcOH (10 mL) was added dropwise. The reaction was routinely checked on LC/MS IT-TOF system. After completion of reaction, the mixture was poured into iced water, participated product was filtered, washed with water, dried and then recrystallized from EtOH.
	With N-Bromosuccinimide; toluene-4-sulfonic acid; In acetonitrile; at 50℃; for 24h;	General procedure: Synthesis of alpha-Aminocarbonyl Compounds by a Two-Step Method. First Step Synthesis of alpha-bromoacetophenone: to a solution of the acetophenone derivative (15.0 mmol, 1 equiv) in 8 mL of acetonitrile were added NBS (2.72 g, 15.3 mmol, 1.02 equiv) and p-toluenesulfonic acid (2.85 g, 15.0 mmol, 1 equiv). The reaction mixture was stirred for 24 h at 50 C. After that time, the solvent was evaporated under reduced pressure. A water solution of saturated NaHCO3 (30 mL) was then added, and the solution was extracted with dichloromethane (3 × 30 mL). The organic layers were combined and dried over Na2SO4. The solvent was evaporated, and the residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate = 25:1, V/V) to afford the desired product in 82% yield as a white solid. After that, alpha-bromoacetophenone (5 mmol) and with aniline (5 mmol) and NaHCO3 (5 mmol) were added to a stirred solution of EtOH (20 ml) at room temperature for 12 h. The crude product was filtered under reduced pressure to give a yellow precipitate, which was recrystallized by EtOH and the yellow solid was isolated in 86% yield.
	With hydrogen bromide; dimethyl sulfoxide; In ethyl acetate; at 60℃; for 6h;	General procedure: General procedure for products 3: ketone 1 (0.3 mmol), HBr (0.36 mmol), DMSO (0.36 mmol) and EtOAc (1.5 mL) were added to a 25 mL tube with magnetic stirrer bar. The reaction mixture was stirred at 60C (oil bath temperature) for 6 h, then added sodium sulfinates (0.6 mmol) and (HOCH2)2 (1.0 mL) to continue the reaction at 80 oC for 17 h. After the reaction was finished (monitored by TLC), the mixture was cooled to room temperature, quenched with solution of NaHCO3 (10 mL) and extracted with EtOAc (3 10 mL). The combined organic layers were dried over anhydrous MgSO4 and the solvent was removed under vacuum. The crude product was purified by column chromatography (EtOAc/hexanes) on silica gel.
	With copper(ll) bromide; In 2-methyltetrahydrofuran; at 20℃; for 24h;	General procedure: To a solution of acetophenones 1-6 (16.65 mmol) in 2-Metetrahydrofuran(20 mL), copper(II)bromide (19.98 mmol)was added (Raghunath et al. 2015). The reaction mixturewas allowed to stir at room temperature for 24 h. Aftercompletion of the reaction (monitored by TLC), reactionmixture was filtered off. The filtrate containing the 2-bromo-1-phenylethanones 7-12 was taken to the next stepwithout isolation. However, to check the purity of theformed phenacyl bromides, two representative compounds(8 and 10) were isolated in standard procedure by evaporatingthe solvent under vacuum and confirmed by spectralanalysis (1H NMR, Mass, and HPLC). As all the derivativeswere pure by TLC, they were preceded to next step withoutpurification/isolation.

Reference： [1]Archiv der Pharmazie,1980,vol. 313,p. 315 - 323
[2]European Journal of Organic Chemistry,2017,vol. 2017,p. 6390 - 6400
[3]Helvetica Chimica Acta,2013,vol. 96,p. 889 - 896
[4]Chemical and Pharmaceutical Bulletin,1998,vol. 46,p. 623 - 630
[5]Advanced Synthesis and Catalysis,2019,vol. 361,p. 4966 - 4982
[6]Patent: CN107629023,2018,A .Location in patent: Paragraph 0135; 0138; 0139; 0140
[7]Patent: CN107629022,2018,A .Location in patent: Paragraph 0212; 0213; 0214; 0215
[8]RSC Advances,2016,vol. 6,p. 35602 - 35608
[9]Tetrahedron Letters,2012,vol. 53,p. 191 - 195
[10]Patent: US6300353,2001,B1
[11]Patent: US6300353,2001,B1
[12]Patent: US2784194,1954,
[13]Journal of Medicinal Chemistry,1971,vol. 14,p. 977 - 982
[14]Journal of Medicinal Chemistry,1987,vol. 30,p. 1497 - 1502
[15]Journal of Organic Chemistry USSR (English Translation),1992,vol. 28,p. 1162 - 1168
Zhurnal Organicheskoi Khimii,1992,vol. 28,p. 1472 - 1478
[16]Journal of Physical Chemistry,1995,vol. 99,p. 8190 - 8195
[17]Patent: WO2004/85408,2004,A1 .Location in patent: Page 285
[18]Patent: US5935776,1999,A
[19]Patent: US5648372,1997,A
[20]Patent: US4812470,1989,A
[21]Patent: EP1231210,2002,A2 .Location in patent: Page 73
[22]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 5063 - 5070
[23]European Journal of Medicinal Chemistry,2012,vol. 57,p. 407 - 416
[24]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 2031 - 2034
[25]Advanced Synthesis and Catalysis,2013,vol. 355,p. 3570 - 3574
[26]Chemical Communications,2014,vol. 50,p. 6726 - 6728
[27]Organic Letters,2017,vol. 19,p. 1994 - 1997
[28]Letters in drug design and discovery,2017,vol. 14,p. 528 - 539
[29]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 3726 - 3732
[30]Organic and Biomolecular Chemistry,2017,vol. 15,p. 8134 - 8139
[31]Advanced Synthesis and Catalysis,2018,vol. 360,p. 1628 - 1633
[32]Tetrahedron Letters,2018,vol. 59,p. 3214 - 3219
[33]Chemical Communications,2018,vol. 54,p. 12182 - 12185
[34]Tetrahedron Letters,2018,vol. 59,p. 3955 - 3957
[35]European Journal of Organic Chemistry,2019,vol. 2019,p. 2520 - 2527
[36]Medicinal Chemistry Research,2019,vol. 28,p. 1461 - 1470
[37]Journal of Natural Products,2019
[38]Journal of the American Chemical Society,2020,vol. 142,p. 9982 - 9992

3
[ 1443-80-7 ]
4-(1-hydroxyethyl)benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With methanol; sodium tetrahydridoborate In tetrahydrofuran at 0 - 20℃; for 0.666667h;	39.1 Step 1: 4-(1 -hydroxyethyl)benzonitrile4-Acetylbenzonitrile (2.0 g; 13.8 mmol) was disolved in THF (10 mL) and MeOH (10 ml_).Sodium borohydride (782 mg; 20.7 mmol) was added portionwise at 0°C and the reaction was let stirred at RT for 40min. Solvents were removed under vaccuum, EtOAC was added, and the organic phases were washed with H20, dried over MgS04, filtered and concentrated affording the title compound as a colorless oil (2.3 g, quantitative). HPLC (Method A) Rt 4.31 min (Purity: 99.2%).
100%	With methanol; sodium tetrahydridoborate at 0 - 25℃; for 5h; Inert atmosphere;	7-2 [Step 7-2] Synthesis of 4- (1-hydroxyethyl) benzonitrile (Compound 16) 4-cyanoacetophenone (compound 15, manufactured by Tokyo Chemical Industry Co., Ltd.) (0.29 g, 2.0 mmol) was dissolved in methanol (10 mL)Sodium borohydride (0.11 g, 3.0 mmol) was added at 0 ° C., and the mixture was stirred at room temperature (25 ° C.) for 5 hours under an argon gas atmosphere.After completion of the reaction,The reaction solution was concentrated under reduced pressure,Add water,Extraction was carried out twice with dichloromethane.The combined dichloromethane layer was dried over anhydrous sodium sulfate, concentrated under reduced pressure,Compound 16 (0.30 g, 2.0 mmol, quantitative) was obtained.
99%	With C₁₅H₁₃MnN₃O₃⁽¹⁺⁾*Br^(1-); potassium-t-butoxide; isopropanol at 70℃; for 24h; Schlenk technique; Inert atmosphere; chemoselective reaction;

99%	Stage #1: 4-cyanophenyl methyl ketone With bis-[N,N′-bis(2,6-(di-isopropyl)phenyl)imidazol-2-ylidene]-(1H-1,2,4-triazol-1-yl)}copper(I) In tetrahydrofuran at 55℃; for 3h; Stage #2: With sodium hydroxide In methanol; water monomer at 25℃; for 1.5h;
99%	With formic acid; C₁₈H₂₄ClIrN₃ In water monomer at 80℃; for 4h; Schlenk technique; Inert atmosphere; chemoselective reaction;
99%	Stage #1: 4-cyanophenyl methyl ketone With C₄₈H₆₂ErN₇O₂Si₂; 4,4,5,5-tetramethyl-1,3,2-dioxaborolane In toluene at 23℃; for 1.5h; Inert atmosphere; Stage #2: With mesoporous silica In methanol at 60℃; for 3h; Inert atmosphere;
99%	With isopropanol; potassium hydroxide at 80℃; for 16h; Schlenk technique;
98%	With C₁₂H₁₉ClCoN₅⁽¹⁺⁾*Cl^(1-); sodium tertiary butoxide In isopropanol at 85℃; for 24h; Inert atmosphere;
98%	Stage #1: 4-cyanophenyl methyl ketone With [(N,N'-bis(diisopropylphosphino)-2,6-diaminopyridine)Mn(CO)₂H] In 1,2-dimethoxyethane at 110℃; for 18h; Inert atmosphere; Sealed tube; Stage #2: With sodium hydroxide at 25℃; for 18h; Inert atmosphere; chemoselective reaction;	General procedure for hydrosilylation reactions General procedure: Inside an Ar-flushed glovebox, an 8 cm3 microwave vial was charged with complex (0.01-0.03 mol%), carbonyl substrate (0.35 mmol), 2 cm3 solvent, and silane (0.035-0.1 mmol) in this order. A stirring bar was added, and the vial was sealed. The closed vial was removed from the glovebox and stirred for 18 h at the indicated temperature in a heated aluminum block. The vial was allowed to reach room temperature and the reaction was quenched by exposure to air. In case of screening reactions, fluorobenzene (0.35 mmol) was added and the reaction mixture was analyzed by 19F{1H} NMR. Isolation of the product To the reaction mixture 2 cm3 of a 20 wt% NaOH-solution were added and the solution was stirred for 18 h at room temperature. The phases were separated, and the aqueous phase was three times extracted with 2 cm3 diethyl ether. The combined organic phases were filtrated over a pad of silica, dried over Na2SO4 and the solvent was removed. Spectroscopic data of all isolated products are in line with the literature [11, 42-49].
97%	With diisobutylaluminum borohydride In tetrahydrofuran at 0℃; for 4h; Inert atmosphere;
96%	Stage #1: 4-cyanophenyl methyl ketone With C₂₅H₃₅N₂NiO; phenylsilane In [D₃]acetonitrile at 100℃; for 2h; Inert atmosphere; Stage #2: With toluene-4-sulfonic acid In methanol; [D₃]acetonitrile for 12h; Inert atmosphere;
95%	With isopropanol; sodium hydroxide at 60℃; for 5h; Inert atmosphere;
95%	With Cp*Ir(6,6'-dionato-2,2'-bipyridine)(H₂O); isopropanol In water monomer at 82℃; for 6h; Inert atmosphere; Schlenk technique; chemoselective reaction;
95%	Stage #1: 4-cyanophenyl methyl ketone With C₃₆H₃₆FeN₆ at 20℃; for 3h; Inert atmosphere; Glovebox; Stage #2: With water monomer; sodium hydroxide for 1.5h;
95%	With Cp*Ir(6,6'-dionato-2,2'-bipyridine)(H₂O); isopropanol at 82℃; for 6h; Inert atmosphere; Green chemistry;	12 4-(1-Hydroxyethyl)benzonitrile The 4 - cyano-acetophenone (145 mg, 1.0 mmol), cat. [Ir] (1.1 mg, 0 . 002 mmol, 0.2 μM %) and isopropyl alcohol (5 ml) are added to the 25 ml Kjeldahl tube, N2Protection, 82 °C reaction 6 h. Cooling to room temperature, rotary evaporation to remove the solvent, then through the column chromatography (developing solvent: petroleum ether/ethyl acetate) to obtain the pure target compound, yield: 95%
95%	With [Cp*Ir(2,2'-bpyO)(OH)][Na]; hydrogen In water monomer at 30℃; for 12h; Green chemistry;	4.1. General procedure for catalytic hydrogenation of ketones,aldehydes or unsaturated aldehydes General procedure: To an oven-dried 5 mL round-bottom flask were added ketonesor aldehydes or unsaturated aldehydes (1 mmol), cat. 6 (5.5 mg,1 mol %) and H2O (1 mL). Next, vacuum was applied to the flask followedby filling with H2 gas and keeping the flask attached to a balloonfilled with H2 gas. The mixture was heated at 30 °C for 12 h.After completion of the reaction, the mixture was extracted withethyl acetate (5 mL x 3). Then, the ethyl acetate layers were combined, dried with anhydrous sodium sulfate, filtered, and concentratedby evaporation under reduced pressure. The alcohols wereisolated and purified by filtering a hexanes/ethyl acetate (8:1)solution of the crude product through a pad of silica gel. Thenthe solvent was removed under reduced pressure to afford the correspondingproducts. The purity of alcohol products was assessedusing 1H NMR spectroscopy.
95%	With [Cp*Ir(2,2'-bpyO)(OH)][Na]; hydrogen In water monomer at 30℃; for 12h;	16 The method was: 4-Acetylbenzonitrile (145 mg, 1.0 mmol), metal ruthenium complex [Cp*Ir(2,2'-bpyO)(OH)][Na](4.6 mg, 0.01 mmol, 1 mol%) and water (1 mL) are added to 25 ml round bottom flasks, and the air in the round bottom flask is replaced with hydrogen. The pressure of hydrogen gas in the system during the entire process of the reaction was 1 standard atmospheric pressure, and the reaction mixture was reacted at 30 °C, the hydrogen atmosphere was 12 h. After the reaction is completed, the solvent is removed by rotary evaporation, and then the pure target compound is obtained by column chromatography (eluent: petroleum ether / ethyl acetate = 8:1), yield: 95%.
94%	With chloro-trimethyl-silane; calcium hydride; anhydrous zinc chloride In tetrahydrofuran at 40℃;
94%	With manganese(I) pentacarbonyl bromide; potassium-t-butoxide; Ethane-1,2-diamine In isopropanol at 80℃; for 3h;	2.1. Representative procedure for transfer hydrogenation reaction ofacetophenone General procedure: To a solution of acetophenone (58 μL, 0.5 mmol) in 2-propanol (0.5 mL) was added a stock solution of manganese pentacarbonyl bromide (0.5 mL, 0.005 mol·L-1; 2.7 mg, 0.010 mmol, in 2 mL 2-propanol)followed, in this order, by a stock solution of ethylenediamine (0.5 mL,0.005 mol·L-1; 1.0 μL, 0.0125 mmol, in 2.5 mL 2-propanol) and tBuOK (0.5 mL, 0.010 mol·L-1; 2.4 mg, 0.020 mmol, in 2 mL 2-propanol). The reaction mixture was stirred for 3 h at 80 °C in an oil bath. The solution was then filtered through a small pad of silica (2 cm in a Pasteur pip-ette). The silica was washed with ethyl acetate. The filtrate was evaporated and the conversion was determined by 1H NMR. The crude residue was then puried by column chromatography (SiO 2 , mixture of petroleum ether/ethyl acetate or dietyl ether as eluent. Enantiomeric excesses were determined by GC analyses performedon GC-2014 (Shimadzu) 2010 apparatus equipped with Supelco beta-DEX 120 column (30 m × 0.25 mm). The determination of the absoluteconguration was done by comparison with (S)-alcohol obtained bykinetic resolution of racemic alcohols with Novozym 435 (CandidaAntarctica Lipase B) and by comparison of the retention times with the literature [32-34].
93%	Stage #1: 4-cyanophenyl methyl ketone With n-butyllithium; 1-(2-hydroxyethyl)-3-methyl-1H-imidazol-3-ium trifluoromethanesulfonate; ferrous acetate In tetrahydrofuran at 65℃; for 1h; Inert atmosphere; Stage #2: With water monomer; sodium hydroxide In tetrahydrofuran; methanol at 20℃; for 2h; Inert atmosphere;
93%	With potassium diisobutyl-t-butoxy aluminum hydride In tetrahydrofuran at 0℃; for 1h; Inert atmosphere; chemoselective reaction;	4.5 Chemoselective reduction of dicarbonyl compounds with PDBBA (Table3) General procedure: A dry and argon-flushed flask, equipped with a magnetic stirring bar and a septum, was charged with dicarbonyl compound (1.0 mmol) and 10 mL THF. After cooling to 0°C, PDBBA (1.3 mmol) was added dropwise and stirred for 1h at same temperature. The reaction was stopped by the aqueous 1N HCl (10mL) and extracted with diethyl ether (2×10mL). The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. Purification of the residue by column chromatography on silica gel afforded the desired product.
93%	With hydrogen; anhydrous silver perchlorate; 1,1,1,3,3,3-hexamethyldisilazane potassium In toluene at 25℃; for 17h; Glovebox; chemoselective reaction;
93%	With methanol; [Cp*Ir(2,2'-bpyO)(OH)][Na] at 66℃; for 12h; Inert atmosphere; Schlenk technique;
91%	With formic acid; C₂₅H₂₆ClIrN₂; anhydrous sodium formate In water monomer at 80℃; for 12h; Inert atmosphere;
91%	With (2-aminomethylpyridine); manganese(I) pentacarbonyl bromide; potassium-t-butoxide; hydrogen In tetrahydrofuran at 120℃; for 20h; Autoclave; chemoselective reaction;	4.3. Representative procedure for the catalytic hydrogenation reactions General procedure: A 4 ml glass vial was sequentially charged with solid [Mn(CO)5Br](0.015 0.030 mmol), the substrate (0.5 mmol), 2-picolylamine(0.015 0.030 mmol), and a magnetic stirring bar. The reaction componentswere then dissolved in THF (2 ml) or 1,4-dioxane (2 ml)whereupon the resulting yellow solution was then gently stirred(200 rpm) for a period of 5 min. Whilst stirring, the glass vial was sealed with the septum cap. Hereafter, solid t-BuOK (0.015 0.030 mmol) was added to the reaction mixture upon which the reaction vessel was again sealed with a septum cap which was then penetrated with a needle.Notably, the base addition was carried out without stirring. After that,the glass vial was placed in a drilled aluminum liner which was promptly transferred into the 300 ml autoclave. Once tightly sealed, the latter was purged five times with H2 (20 bar per cycle) before being pressurized to the desired value. The autoclave was then placed on a pre-heated stirring plate and heated up to the required reaction temperature. On completion of the hydrogenation reaction, the autoclave was allowed to reach room temperature. Afterwards, the remaining gas was slowlyreleased upon which the reaction mixture was degassed through brieflystirring on air. Finally, n-dodecane (12 mg) or n-hexadecane (20 mg)were added and an aliquot of 30 μl was taken from the solution, mixedwith acetone (1 ml) whereupon the resulting solution was analyzed byGC.
91%	With KB₃H₈ In water monomer for 3h; Reflux; Green chemistry;
90%	Stage #1: 4-cyanophenyl methyl ketone With phenylsilane; potassium-t-butoxide In toluene at 20℃; for 0.5h; Inert atmosphere; Stage #2: With water monomer; sodium hydroxide In toluene at 0 - 20℃; chemoselective reaction;
90%	Stage #1: 4-cyanophenyl methyl ketone With N,N,N-tributylbutan-1-aminium fluoride; HSiPh₃ In tetrahydrofuran at 20℃; for 6h; Stage #2: With water monomer; sodium hydroxide In tetrahydrofuran for 0.166667h; chemoselective reaction;
90%	Stage #1: 4-cyanophenyl methyl ketone With 1-Methylpyrrolidine; 2-chloro-5-fluorophenylboronic acid; phenylsilane at 20℃; for 16h; Inert atmosphere; Stage #2: With sodium hydroxide In water monomer at 20℃; for 2h; chemoselective reaction;
89%	With (Cp-NHC)Fe(CO)(OH); diphenylsilane In toluene for 1h;
89%	With potassium hydroxide In tetrahydrofuran at 20℃; for 48h; Inert atmosphere; Schlenk technique; Glovebox; chemoselective reaction;
89%	With water monomer; 1,8-diazabicyclo[5.4.0]undec-7-ene; 4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl-4',4',5',5'-tetramethyl-1,3,2-dioxaborolane at 60℃; for 10h; Sealed tube; chemoselective reaction;
89%	With palladium diacetate; glacial acetic acid; 4,4,5,5-tetramethyl-1,3,2-dioxaborolane In dichloromethane at 25℃; for 12h; Schlenk technique; Inert atmosphere;	69 Replace the gas environment in the Shrek tube with a nitrogen environment, add 4-acetylbenzonitrile 0.25 mmol, palladium acetate 0.025 mmol, methylene chloride 0.5 mL, and add pinacol borane 0.55 mmol and acetic acid 0.275 mmol under stirring. The reaction was carried out at room temperature for 12 hours. The reaction solution obtained after the completion of the reaction was subjected to column chromatography, and the target product obtained in 89% yield was a colorless liquid.
89%	With palladium diacetate; glacial acetic acid; 4,4,5,5-tetramethyl-1,3,2-dioxaborolane In dichloromethane at 25℃; for 12h; Sealed tube; Inert atmosphere; chemoselective reaction;
88%	With lithium isopropoxide; 1,2-(diphenylphosphino)ethane In isopropanol at 100℃; for 1h; Inert atmosphere; Schlenk technique;
87%	With lithium isopropoxide In isopropanol at 180℃; for 0.333333h; microwave irradiation;
83%	Stage #1: 4-cyanophenyl methyl ketone With 2-phenyl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-2-ium chloride; diphenylsilane; sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; Stage #2: With N,N,N-tributylbutan-1-aminium fluoride In tetrahydrofuran; N,N-dimethyl-formamide for 0.5h; chemoselective reaction;
83%	With sodium tetrahydridoborate In methanol at 0 - 18℃; for 2h;
82%	With 2,2'-bi(1,3,6,2-dioxazaborocane); water monomer In tetrahydrofuran at 20℃; for 18h; Inert atmosphere; Sealed tube;
81%	With [2,2]bipyridinyl; sodium hypophosphite monohydrate; di-μ-chlorobis-[(η⁶-p-cymene)chlororuthenium(II)] In water monomer; toluene at 80℃; for 24h; Inert atmosphere; Sealed tube; chemoselective reaction;
81%	With cis-[(H)(SePh)Fe(PMe₃)₄]; sodium tertiary butoxide In isopropanol at 80℃; for 24h;
78%	Stage #1: 4-cyanophenyl methyl ketone With phenylsilane; N,N,N-tributylbutan-1-aminium fluoride In tetrahydrofuran; toluene at 20℃; for 2h; Inert atmosphere; Schlenk technique; Stage #2: With hydrogenchloride In tetrahydrofuran; methanol; toluene for 1.5h; Inert atmosphere; Schlenk technique;
78%	With C₉H₈BrMnN₂O₃; potassium-t-butoxide In isopropanol at 30℃; for 72h; Inert atmosphere; Schlenk technique; Glovebox;
77%	With lithium aluminium hydride on silica gel In diethyl ether at 20℃; for 2h;
76%	With sodium tetrahydridoborate In methanol at 20℃;
74%	With diphenylsilane; [L₂CoBr](PF₆) In acetonitrile for 24h; Glovebox; Reflux;
71%	With C₁₇H₁₃BrMnN₃O₃; sodium isopropanolate; isopropanol at 90℃; for 2h; Inert atmosphere; Sealed tube;
68%	With C₁₃H₈BrMnN₂O₅; potassium-t-butoxide In isopropanol at 80℃; for 24h; Inert atmosphere; Sealed tube;
59%	With C₁₂A₇ electride In 1,4-dioxane; water monomer at 100℃; for 9h;	16 Into an eggplant type flask 10 mL in volume were put 10 mg of a ketone compound having R and R1 groups of No. 1 as a raw material (compound 1) shown in Table 3, 196 mg of a C12A7 electride, and 5 mL of a solvent (water: dioxane = 1:4). In the state that the flask was open to the atmosphere, the active components were caused to react at a reaction temperature shown in Table 3 for a reaction time shown therein while the solution was stirred. Thus, a reaction solution was prepared. Next, the reaction solution was transferred to an eggplant type flask 50 mL in volume, and hydrochloric acid (1 N, 7 mL) was added thereto. Thereafter, thereto was added ethyl acetate (20 mL) and then the product was extracted. This extracting process was repeated 3 times, and then the product was washed with sodium bicarbonate solution and sodium chloride solution. Thereto was added magnesium sulfate to adsorb water, thereby removing water. Next, magnesium sulfate was filtrated off, and the solvent was distilled off. The resultant was purified by column chromatography (silica gel) to yield a compound having a purity of more than 98%. The identification of the compound was attained through the H1 nuclear magnetic resonance spectrum thereof. The product (compound 2) is shown in Table 4. The compound was a secondary alcohol represented by the formula of RR1HC-OH in Table 4. The yield of the purified secondary alcohol was 59%.
45%	With methanol; bis[dichlorido(η⁵-1,2,3,4,5-pentamethyl-cyclopentadienyl)iridium(III)]; 6,6′-dihydroxy-2,2′-bipyridine; potassium hydroxide at 60℃; for 24h; Inert atmosphere;
41%	With stannous trifluoromethanesulfonate In toluene at 120℃; for 7h;
35%	With trimethylamine-N-oxide; triscarbonyl-(2,4-bis(trimethylsilyl)bicyclo[3.3.0]nona-1,4-dien-3-one)iron; hydrogen In water monomer at 100℃; for 14h; Autoclave; Inert atmosphere;
27%	With Mn(CO)<SUB>3</SUB>Br(k<SUP>2</SUP>P,N-Ph<SUB>2</SUB>PN(H)Py); hydrogen; 1,1,1,3,3,3-hexamethyldisilazane potassium In toluene at 50℃; for 20h; Glovebox; Autoclave; Inert atmosphere;
	With triethylsilane; perchloric acid In acetonitrile at 24.9℃; kinetic isotope effect;
	With perchloric acid In acetonitrile at 57.9℃;
	With tris isopropylate aluminium; isopropanol
	With tris isopropylate aluminium; isopropanol; toluene
	With perchloric acid In acetonitrile at 331℃;
	With triethylsilane; perchloric acid In acetonitrile at 24.9℃;
	With sodium tetrahydridoborate In methanol for 18h; Ambient temperature;
	With sodium hydroxide; PMHS; N,N,N-tributylbutan-1-aminium fluoride 1.) THF, room t., 2.) THF; Yield given. Multistep reaction;
	With sodium tetrahydridoborate In ethanol at 20℃;
	With sodium tetrahydridoborate; Orthoboric acid for 0.0833333h;
	With isopropanol; lithium tert-butylate at 180℃; for 0.333333h;
	With sodium tetrahydridoborate In methanol for 3h;	391,391a,391b.1 Preparation of Examples 391 , 391a, and 391b; Step V.; To 4-acetylcyanobenzene (2.0 g, 13.8 mmol) in MeOH (55 mL) was added NaBH4 (0.52 g, 13.0 mmol) in one portion. The reaction was stirred for 3 h, allowing the cold bath to warm. The reaction mixture was concentrated in vacuo. Water was added and the mixture was extracted with ether. The combined organic layers were washed with water and brine, dried (MgSO4), filtered, and concentrated in vacuo to provide the corresponding alcohol (2.0 g, 13.6 mmol).
	With Candida tenuis AKR₂B₅ xylose reductase [E_.⁽¹⁾C₁₁₁₇₅]; water monomer; NADH In ethanol at 25℃; aq. phosphate buffer; Enzymatic reaction;
98 %Chromat.	With anhydrous sodium carbonate; isopropanol at 82℃; for 8h; Inert atmosphere;
98 %Spectr.	With [((CH₃)5C₅)2Ir₂(H)(C₆H₄C(CH₃)NO)(C₆H₄C(CH₃)NOH)]; isopropanol at 50℃; for 15h; Inert atmosphere;
	With C₅₅H₄₁ClN₂O₃P₂Ru; isopropanol; potassium hydroxide In 1,3-dimethylbenzene at 20 - 82℃; for 4h; Inert atmosphere;	Typical procedure for transfer hydrogenation of ketones General procedure: In an oven-dried round bottom flask, were placed ketone (2.4 mmol), catalyst (3 mol), base (12 mol), internal standard (m-xylene, 30 L, 0.24 mmol) and i-PrOH (5 mL) at room temperature. The reaction mixture was heated at 82 °C for the required reaction time under an atmosphere of nitrogen. Aliquots (0.2 mL) were taken at fixed time and the catalyst removed as precipitate from the reaction mixture by the addition of diethyl ether. The organic layer was neutralized with 1 N HCl, washed with water and dried over anhydrous Na2SO4. The combined organic layer passed through a short path of silica gel and then subjected to GCMS analysis. The conversions obtained are related to the residual unreacted ketone and are averages of two runs in the case of all catalytic reactions.
	With [RuCl(PPh₃)₂(3-phenylindenyl)]; 1,1,1,3,3,3-hexamethyldisilazane potassium; isopropanol at 89℃; for 14h; Glovebox;
	With (Cp*RhTsDPEN)⁺CF₃SO₃^-; tetrabutylammonium bromide; anhydrous sodium formate In water monomer at 20℃; Inert atmosphere; Schlenk technique; Sonication;
	With CpRu(PiPr₃)(CH₃CN)2PF₆; potassium-t-butoxide In isopropanol at 20℃; for 0.5h;
	With C₃₃H₂₇ClN₃O₂PRu; isopropanol; potassium hydroxide at 82℃; for 4h; Inert atmosphere;	2.8 Typical procedure for transfer hydrogenation of ketones General procedure: The ketone (2.5 mmol), catalyst (5 μmol), base (20 μmol) and i-PrOH (5 mL) were placed in an oven-dried round bottom flask at room temperature. The reaction mixture was heated under reflux for the required reaction time under an atmosphere of nitrogen. The reaction was then cooled to room temperature and the catalyst precipitated from the reaction mixture by the addition of diethyl ether. The organic layer was neutralized with 1N HCl, washed with water and dried over anhydrous Na2SO4. The combined organic layer was passed through a short path of silica gel and then subjected to GC-MS analysis. The conversions obtained are related to the residual unreacted ketone and are averages of two runs in the case of all catalytic reactions.
	With C₅₄H₅₂Cl₄N₅O₆P₃Ru₂; isopropanol; potassium hydroxide for 2h; Inert atmosphere; Reflux;
	Stage #1: 4-cyanophenyl methyl ketone With cyclopentadienyl iron(II) dicarbonyl dimer; diethoxymethylane at 100℃; for 24h; Stage #2: With water monomer; sodium hydroxide In methanol
	With sodium tetrahydridoborate In ethanol
89 %Chromat.	With (4-NHCpr)Triaz(NHP<SUP>i</SUP>Pr<SUB>2</SUB>)<SUB>2</SUB>Mn(CO)<SUB>2</SUB>Br; potassium-t-butoxide; hydrogen In toluene at 80℃; for 4h; Inert atmosphere; Autoclave;
	With sodium tetrahydridoborate
	With [(N,N′-bis(diisopropylphosphino)-2,6-diaminopyridine)Mn(CO)₃][Br]; potassium-t-butoxide; hydrogen In toluene at 130℃; for 22h; Glovebox; Autoclave;	2.2. Typical catalytic hydrogenation General procedure: In a glove box, an autoclave was charged with the desired ketone (0.5 mmol), toluene (2 mL), Mn complex 1 (14 mg, 5 mol%) followed by t-BuOK (5.6 mg, 10 mol%), in this order. The autoclave is then closed and charged with H2 (50 bar).
95 %Chromat.	With sodium tetrahydridoborate; cobalt sulphate heptahydrate In ethanol; water monomer at 0 - 21℃; for 0.05h;
	Multi-step reaction with 2 steps 1: C₁₉H₄₄FeOP₄Se / tetrahydrofuran / 24 h / 60 °C 2: water monomer; sodium hydroxide / methanol / 24 h / 60 °C
	With sodium tetrahydridoborate
	Stage #1: 4-cyanophenyl methyl ketone With sodium tetrahydridoborate In tetrahydrofuran; methanol at 0 - 20℃; for 0.5h; Stage #2: With hydrogenchloride In water monomer	13.A 4-Acetylbenzonitrile (3 g, 20.67 mmol) was dissolved in THF (5 mL) and MeOH (5 mL) and cooled to 0° C. NaBH4 (0.782 g, 20.67 mmol) was added slowly. The reaction aged at rt for 30 min and was concentrated. 2M aq HCl was added and the solution was extracted with EtOAc. The organic layer was washed with water, dried with Na2SO4, filtered and concentrated to provide the product.
	Multi-step reaction with 2 steps 1: C₄₅H₆₉FeN₈PSi₂ / tetrahydrofuran / 6 h / 20 °C / Inert atmosphere; Schlenk technique 2: mesoporous silica / ethyl acetate; Petroleum ether
95 %Chromat.	With C₂₂H₂₅BrN₄Ni; sodium tertiary butoxide In isopropanol at 80℃; for 48h; Inert atmosphere;
	With sodium tetrahydridoborate In methanol at 20℃; for 0.5h;	General procedure for reduction of ketones and subsequentphosphorylation To an ice-cold solution of an alkyl aryl ketone (1 equiv) in MeOHwas added NaBH4 (ca. 1.5 equiv) portionwise. The mixture wasstirred at rt for 30e60 min and diluted with saturated NH4Cl. Theresulting mixture was extracted with EtOAc repeatedly. The com-bined extracts were washed with brine, dried over MgSO4, andconcentrated under reduced pressure. The alcohol thus obtainedwas passed through a short column of silica gel (hexane/EtOAc).To an ice-cold solution of a benzylic alcohol (1 equiv) in CH2Cl2 were added N-methylimidazole (1.2e2 equiv) and diethyl ordiphenyl chlorophosphate (1.1e1.5 equiv). The solution was stirredat rt and diluted with saturated NaHCO3 with vigorous stirring. Theresulting mixture was extracted with EtOAc several times. Thecombined extracts were washed with brine, dried over MgSO4, andconcentrated under reduced pressure. The residual oil was puriedby chromatography on silica gel (hexane/EtOAc) to give thephosphate.
	With methanol; sodium tetrahydridoborate at 0 - 20℃; for 3h; Inert atmosphere;
	Multi-step reaction with 2 steps 1: lithium triethylhydroborate / tetrahydrofuran / 0.17 h / 20 °C 2: sodium hydroxide / tetrahydrofuran; diethyl ether; water monomer / 0.5 h / 20 °C
19 %Chromat.	With C₁₈H₂₁BrMnN₃O₃; potassium-t-butoxide; isopropanol at 40℃; for 24h;
	With sodium tetrahydridoborate; water monomer In tetrahydrofuran; methanol at 20℃; for 2h;
	Multi-step reaction with 2 steps 1: potassium fluoride / N,N-dimethyl-formamide / 0.25 h / 20 °C 2: sodium hydroxide / diethyl ether; water monomer / 0.5 h / 20 °C
	Multi-step reaction with 2 steps 1: C₈₄H₁₀₈Cl₂N₁₀Pd₂ / 12 h / 60 °C 2: mesoporous silica; methanol / 6 h / 60 °C
	Multi-step reaction with 2 steps 1: C₁₆H₁₁BrMnN₃O₃ / tetrahydrofuran / 3 h / 100 °C / Inert atmosphere; Sealed tube 2: sodium hydroxide; water monomer / tetrahydrofuran; methanol / 20 °C
	Multi-step reaction with 2 steps 1: methyl[3-phenyl-5-([2-(phenylthio-S)ethyl]amino-N}methyl)-1H-pyrazol-1-yl]zinc; methanol / toluene / 0.5 h / 60 °C / Inert atmosphere; Sealed tube 2: potassium hydroxide / methanol; toluene / 0.33 h / 20 °C
	With ammonia; hydrogen In water monomer; isopropanol at 110℃; for 24h; Autoclave;
	Multi-step reaction with 2 steps 1: C₈₄H₁₁₀N₁₀Zn₂ / neat (no solvent) / 6 h / 20 °C / Sealed tube; Inert atmosphere; Schlenk technique; Glovebox 2: mesoporous silica / methanol / 6 h / 60 °C / Inert atmosphere; Schlenk technique; Glovebox
	Multi-step reaction with 2 steps 1: C₈₄H₁₁₀N₁₀Zn₂ / neat (no solvent) / 12 h / 20 °C / Sealed tube; Inert atmosphere; Schlenk technique; Glovebox 2: sodium hydroxide / water monomer; methanol / 6 h / 60 °C / Inert atmosphere; Schlenk technique; Glovebox
	With potassium-t-butoxide; C₁₉H₂₅BrNNiOP; isopropanol at 100℃; for 10h; Inert atmosphere; Glovebox; Schlenk technique;
	With sodium tetrahydridoborate; ethanol at 20℃; for 16h; Inert atmosphere;
28 %Spectr.	With formic acid; (RuCl<SUB>2</SUB>(p-cymene))<SUB>2</SUB>(dppf); tetrabutylammonium bromide; triethylamine at 60℃; for 16h; chemoselective reaction;	4.1 General procedure for the catalytic TH of carbonyl compounds and imines General procedure: The selected substrate (0.2-1.0mmol, 1 eq), [RuCl2(p-cymene)}2-μ-dppf] (6) (0.002-0.01mmol, 0,01-0,05 eq, 2.3-58.3mg), NEt3 (1.4-8.6mmol, 0.2-1.2mL) and CPME (0.5-1.5mL) were transferred into a 4mL vial. The mixture was heated at the selected temperature (40-80°C) under stirring for ca. 15min and finally the DES-5 (0.45-1.7mL) was added. After the addition of the DES, the vial was put into the oil bath and the Teflon cap pierced with a needle to help the emission of the CO2 produced. The reaction was then leaved to react at the selected temperature from 2 to 24h, depending on the substrate. The reaction mixture was worked taken up with water (1.5mL) and extracted with diethyl ether (4×1.5mL), then the combined organic layers washed with brine (1.5mL). The organic phase was then separated, dried over Na2SO4 and filtered. The solvent was removed and the crude was analysed by 1H and, when pure products were afforded, by 13C NMR spectroscopy.

Reference： [1]Current Patent Assignee: MERCK KGAA - WO2012/4287, 2012, A1 Location in patent: Page/Page column 116
[2]Current Patent Assignee: SUMITOMO CHEMICAL COMPANY LIMITED; GENERAL ELECTRIC CO; KYOTO UNIVERSITY; Sumitomo Chemical (w/o Dongwoo Fine-Chem) - JP2015/110563, 2015, A Location in patent: Paragraph 0016; 0078; 0080
[3]Perez, Marc; Elangovan, Saravanakumar; Spannenberg, Anke; Junge, Kathrin; Beller, Matthias [ChemSusChem, 2017, vol. 10, # 1, p. 83 - 86]
[4]Trose, Michael; Lazreg, Faïma; Chang, Tao; Nahra, Fady; Cordes, David B.; Slawin, Alexandra M. Z.; Cazin, Catherine S. J. [ACS Catalysis, 2017, vol. 7, # 1, p. 238 - 242]
[5]Liu, Ji-Tian; Yang, Shiyi; Tang, Weiping; Yang, Zhanhui; Xu, Jiaxi [Green Chemistry, 2018, vol. 20, # 9, p. 2118 - 2124]
[6]Huang, Zeming; Wang, Shaowu; Zhu, Xiancui; Yuan, Qingbing; Wei, Yun; Zhou, Shuangliu; Mu, Xiaolong [Inorganic Chemistry, 2018, vol. 57, # 24, p. 15069 - 15078]
[7]Blanco, Matías; Cembellín, Sara; Agnoli, Stefano; Alemán, José [ChemCatChem, 2021, vol. 13, # 24, p. 5156 - 5165]
[8]Ibrahim, Jessica Juweriah; Reddy, C. Bal; Fang, Xiaolong; Yang, Yong [European Journal of Organic Chemistry, 2020, vol. 2020, # 28, p. 4429 - 4432]
[9]Weber, Stefan; Iebed, Dina; Glatz, Mathias; Kirchner, Karl [Monatshefte fur Chemie, 2021, vol. 152, # 6, p. 635 - 639]
[10]Amberchan, Gabriella; Snelling, Rachel A.; Moya, Enrique; Landi, Madison; Lutz, Kyle; Gatihi, Roxanne; Singaram, Bakthan [Journal of Organic Chemistry, 2021, vol. 86, # 9, p. 6207 - 6227]
[11]Postigo, Lorena; Royo, Beatriz [Advanced Synthesis and Catalysis, 2012, vol. 354, # 14-15, p. 2613 - 2618]
[12]Salam, Noor; Kundu, Sudipta K.; Roy, Anupam Singha; Mondal, Paramita; Ghosh, Kajari; Bhaumik, Asim; Islam [Dalton Transactions, 2014, vol. 43, # 19, p. 7057 - 7068]
[13]Wang, Rongzhou; Tang, Yawen; Xu, Meng; Meng, Chong; Li, Feng [Journal of Organic Chemistry, 2018, vol. 83, # 4, p. 2274 - 2281]
[14]Liang, Qiuming; Liu, Nina Jiabao; Song, Datong [Dalton Transactions, 2018, vol. 47, # 29, p. 9889 - 9896]
[15]Current Patent Assignee: NANJING UNIVERSITY OF SCIENCE AND TECHNOLOGY - CN109384645, 2019, A Location in patent: Paragraph 0080; 0081; 0082; 0083
[16]Wang, Rongzhou; Yue, Yuancheng; Qi, Jipeng; Liu, Shiyuan; Song, Ao; Zhuo, Shuping; Xing, Ling-Bao [Journal of Catalysis, 2021, vol. 399, p. 1 - 7]
[17]Current Patent Assignee: SHANGHAI XIANGSHI CHEMICAL - CN113105305, 2021, A Location in patent: Paragraph 0035-0036
[18]Tsuhako, Akiko; He, Jing-Qian; Mihara, Mariko; Saino, Naoko; Okamoto, Sentaro [Tetrahedron Letters, 2007, vol. 48, # 52, p. 9120 - 9123]
[19]Wang, Ding; Bruneau-Voisine, Antoine; Sortais, Jean-Baptiste [Catalysis Communications, 2018, vol. 105, p. 31 - 36]
[20]Buitrago, Elina; Tinnis, Fredrik; Adolfsson, Hans [Advanced Synthesis and Catalysis, 2012, vol. 354, # 1, p. 217 - 222]
[21]Kim, Joo Yeon; Shin, Won Kyu; Jaladi, Ashok Kumar; An, Duk Keun [Tetrahedron, 2018, vol. 74, # 31, p. 4236 - 4241]
[22]Wang, Shengdong; Huang, Haiyun; Tsareva, Svetlana; Bruneau, Christian; Fischmeister, Cédric [Advanced Synthesis and Catalysis, 2019, vol. 361, # 4, p. 786 - 790]
[23]Han, Xingyou; Li, Feng; Liu, Peng; Wang, Rongzhou; Xu, Jing [Journal of Organic Chemistry, 2020, vol. 85, # 4, p. 2242 - 2249]
[24]Wei, Yawen; Xue, Dong; Lei, Qian; Wang, Chao; Xiao, Jianliang [Green Chemistry, 2013, vol. 15, # 3, p. 629 - 634]
[25]Topf, Christoph; Vielhaber, Thomas [Applied Catalysis A: General, 2021, vol. 623]
[26]Li, Xinying; Mi, Tongge; Guo, Wenjing; Ruan, Zhongrui; Guo, Yu; Ma, Yan-Na; Chen, Xuenian [Chemical Communications, 2021, vol. 57, # 95, p. 12776 - 12779]
[27]Location in patent: experimental part Addis, Daniele; Zhou, Shaolin; Das, Shoubhik; Junge, Kathrin; Kosslick, Hendrik; Harloff, Joerg; Lund, Henrik; Schulz, Axel; Beller, Matthias [Chemistry - An Asian Journal, 2010, vol. 5, # 11, p. 2341 - 2345]
[28]Mamillapalli, N. Chary; Sekar, Govindasamy [RSC Advances, 2014, vol. 4, # 105, p. 61077 - 61085]
[29]Chardon, Aurélien; Rouden, Jacques; Blanchet, Jérôme [European Journal of Organic Chemistry, 2019, vol. 2019, # 5, p. 995 - 998]
[30]Lopes, Rita; Cardoso, Joao M.S.; Postigo, Lorena; Royo, Beatriz [Catalysis Letters, 2013, vol. 143, # 10, p. 1061 - 1066]
[31]Revunova, Kseniya; Nikonov, Georgii I. [Chemistry - A European Journal, 2014, vol. 20, # 3, p. 839 - 845]
[32]Xuan, Qingqing; Zhao, Cong; Song, Qiuling [Organic and Biomolecular Chemistry, 2017, vol. 15, # 24, p. 5140 - 5144]
[33]Current Patent Assignee: ZHENGZHOU UNIVERSITY - CN111099986, 2020, A Location in patent: Paragraph 0034; 0317-0320
[34]Wang, Yong; Cao, Xinyi; Zhao, Leyao; Pi, Chao; Ji, Jingfei; Cui, Xiuling; Wu, Yangjie [Advanced Synthesis and Catalysis, 2020, vol. 362, # 19, p. 4119 - 4129]
[35]Alshakova, Iryna D.; Dudding, Travis; Foy, Hayden C.; Nikonov, Georgii I. [Chemistry - A European Journal, 2019]
[36]Ekstroem, Jesper; Wettergren, Jenny; Adolfsson, Hans [Advanced Synthesis and Catalysis, 2007, vol. 349, # 10, p. 1609 - 1613]
[37]Zhao, Qiwu; Curran, Dennis P.; Malacria, Max; Fensterbank, Louis; Goddard, Jean-Philippe; Lacôte, Emmanuel [Synlett, 2012, # 3, p. 433 - 437]
[38]Mambwe, Dickson; Kumar, Malkeet; Ferger, Richard; Taylor, Dale; Njoroge, Mathew; Coertzen, Dina; Reader, Janette; Van Der Watt, Mariëtte; Birkholtz, Lyn-Marie; Chibale, Kelly [ACS Medicinal Chemistry Letters, 2021, vol. 12, # 8, p. 1333 - 1341]
[39]Flinker, Mathias; Yin, Hongfei; Juhl, René W.; Eikeland, Espen Z.; Overgaard, Jacob; Nielsen, Dennis U.; Skrydstrup, Troels [Angewandte Chemie - International Edition, 2017, vol. 56, # 50, p. 15910 - 15915][Angew. Chem., 2017, vol. 56, # 50, p. 15910 - 15915,6]
[40]Guyon, Carole; Metay, Estelle; Duguet, Nicolas; Lemaire, Marc [European Journal of Organic Chemistry, 2013, # 24, p. 5439 - 5444]
[41]Wang, Yangyang; Du, Zhengyin; Zheng, Tingting; Sun, Hongjian; Li, Xiaoyan [Catalysis Communications, 2019, vol. 124, p. 32 - 35]
[42]Bornschein, Christoph; Werkmeister, Svenja; Junge, Kathrin; Beller, Matthias [New Journal of Chemistry, 2013, vol. 37, # 7, p. 2061 - 2065]
[43]Bruneau-Voisine, Antoine; Wang, Ding; Dorcet, Vincent; Roisnel, Thierry; Darcel, Christophe; Sortais, Jean-Baptiste [Organic Letters, 2017, vol. 19, # 13, p. 3656 - 3659]
[44]Kamitori, Yasuhiro; Hojo, Masaru; Masuda, Ryoichi; Inoue, Tatsuro; Izumi, Tatsuo [Tetrahedron Letters, 1983, vol. 24, # 25, p. 2575 - 2576]
[45]Ciszek, Benjamin; Fleischer, Ivana [Chemistry - A European Journal, 2018, vol. 24, # 47, p. 12259 - 12263]
[46]Schiltz, Pauline; Casaretto, Nicolas; Auffrant, Audrey; Gosmini, Corinne [Chemistry - A European Journal, 2022, vol. 28, # 32]
[47]Ganguli, Kasturi; Shee, Sujan; Panja, Dibyajyoti; Kundu, Sabuj [Dalton Transactions, 2019, vol. 48, # 21, p. 7358 - 7366]
[48]Dubey, Abhishek; Rahaman, S. M. Wahidur; Fayzullin, Robert R.; Khusnutdinova, Julia R. [ChemCatChem, 2019, vol. 11, # 16, p. 3844 - 3852]
[49]Current Patent Assignee: JAPAN SCIENCE AND TECHNOLOGY AGENCY - EP2067761, 2009, A1 Location in patent: Page/Page column 12-13
[50]Garg, Nidhi; Paira, Soumen; Sundararaju, Basker [ChemCatChem, 2020, vol. 12, # 13, p. 3472 - 3476]
[51]Nayal, Onkar S.; Thakur, Maheshwar S.; Bhatt, Vinod; Kumar, Manoranjan; Kumar, Neeraj; Singh, Bikram; Sharma, Upendra [Chemical Communications, 2016, vol. 52, # 62, p. 9648 - 9651]
[52]Merel, Delphine S.; Elie, Margaux; Lohier, Jean-Francois; Gaillard, Sylvain; Renaud, Jean-Luc [ChemCatChem, 2013, vol. 5, # 10, p. 2939 - 2945]
[53]Wei, Duo; Bruneau-Voisine, Antoine; Chauvin, Téo; Dorcet, Vincent; Roisnel, Thierry; Valyaev, Dmitry A.; Lugan, Noël; Sortais, Jean-Baptiste [Advanced Synthesis and Catalysis, 2018, vol. 360, # 4, p. 676 - 681]
[54]Fukuzumi, Shunichi; Fujita, Morifumi [Chemistry Letters, 1991, p. 2059 - 2062]
[55]Fukuzumi, Shunichi; Chiba, Makoto; Tanaka, Toshio [Chemistry Letters, 1989, p. 31 - 34]
[56]Mowry; Renoll; Huber [Journal of the American Chemical Society, 1946, vol. 68, p. 1105,1107]
[57]Marvel; Overberger [Journal of the American Chemical Society, 1945, vol. 67, p. 2250]
[58]Fukuzumi, Shunichi; Chiba, Makoto; Tanaka, Toshio [Chemistry Letters, 1989, p. 31 - 34]
[59]Fukuzumi, Shunichi; Fujita, Morifumi [Chemistry Letters, 1991, p. 2059 - 2062]
[60]Vries, Erik F. J. de; Brussee, Johannes; Gen, Arne van der [Journal of Organic Chemistry, 1994, vol. 59, # 23, p. 7133 - 7137]
[61]Drew, Mark D.; Lawrence, Nicholas J.; Fontaine, David; Sehkri, Lakhdar; Bowles, Stephen A.; Watson, William [Synlett, 1997, vol. 1997, # 8, p. 989 - 991]
[62]Martin-Matute, Belen; Edin, Michaela; Bogar, Krisztian; Kaynak, F. Betuel; Baeckvall, Jan-E. [Journal of the American Chemical Society, 2005, vol. 127, # 24, p. 8817 - 8825]
[63]Cho, Byung Tae; Kang, Sang Kyu; Kim, Min Sung; Ryu, Soo Ryeon; An, Duk Keun [Tetrahedron, 2006, vol. 62, # 34, p. 8164 - 8168]
[64]Location in patent: experimental part Sedelmeier, Joerg; Ley, Steven V.; Baxendale, Ian R. [Green Chemistry, 2009, vol. 11, # 5, p. 683 - 685]
[65]Current Patent Assignee: MERCK & CO INC - WO2006/60461, 2006, A1 Location in patent: Page/Page column 198-199
[66]Location in patent: experimental part Vogl, Michael; Kratzer, Regina; Nidetzky, Bernd; Brecker, Lothar [Organic and Biomolecular Chemistry, 2011, vol. 9, # 16, p. 5863 - 5870]
[67]Location in patent: scheme or table Bogar, Krisztian; Krumlinde, Patrik; Bacsik, Zoltan; Hedin, Niklas; Baeckvall, Jan-E. [European Journal of Organic Chemistry, 2011, # 23, p. 4409 - 4414]
[68]Location in patent: experimental part Watanabe, Megumi; Kashiwame, Yohei; Kuwata, Shigeki; Ikariya, Takao [European Journal of Inorganic Chemistry, 2012, # 3, p. 504 - 511]
[69]Prabhu, Rupesh Narayana; Ramesh, Rengan [Journal of Organometallic Chemistry, 2012, vol. 718, p. 43 - 51,9]
[70]Manzini, Simone; Blanco, Cesar A. Urbina; Nolan, Steven P. [Advanced Synthesis and Catalysis, 2012, vol. 354, # 16, p. 3036 - 3044]
[71]Xu, Yulong; Cheng, Tanyu; Long, Jie; Liu, Ketang; Qian, Qingqian; Gao, Fei; Liu, Guohua; Li, Hexing [Advanced Synthesis and Catalysis, 2012, vol. 354, # 17, p. 3250 - 3258]
[72]Lee, Sun-Hwa; Nikonov, Georgii I. [ChemCatChem, 2015, vol. 7, # 1, p. 107 - 113]
[73]Suganthy, Pandimuni Kalpaga; Prabhu, Rupesh Narayana; Sridevi, Venugopal Shanmugham [Polyhedron, 2015, vol. 88, p. 57 - 62]
[74]irali, Digdem Erdener; Uyar, Zafer; Koyuncu, Ismail; Haciolu, Nurcihan [Applied Organometallic Chemistry, 2015, vol. 29, # 8, p. 536 - 542]
[75]Jung, Thais Cordeiro; Argouarch, Gilles; Van De Weghe, Pierre [Catalysis Communications, 2016, vol. 78, p. 52 - 54]
[76]Aimar, Mario L.; BordN, Daniela L.; Formica, Stella M.; Cantero, Juan J.; Vazquez, Ana M.; Velasco, Manuel I.; Rossi, Laura I. [Biocatalysis and Biotransformation, 2014, vol. 32, # 5-6, p. 348 - 357]
[77]Kallmeier, Fabian; Irrgang, Torsten; Dietel, Thomas; Kempe, Rhett [Angewandte Chemie - International Edition, 2016, vol. 55, # 39, p. 11806 - 11809][Angew. Chem., 2016, vol. 128, # 39, p. 11984 - 11988,5]
[78]Olivo, Giorgio; Giosia, Simone; Barbieri, Alessia; Lanzalunga, Osvaldo; Di Stefano, Stefano [Organic and Biomolecular Chemistry, 2016, vol. 14, # 45, p. 10630 - 10635]
[79]Bruneau-Voisine, Antoine; Wang, Ding; Roisnel, Thierry; Darcel, Christophe; Sortais, Jean-Baptiste [Catalysis Communications, 2017, vol. 92, p. 1 - 4]
[80]Lundevall, Frida Johanne; Elumalai, Vijayaragavan; Drageset, Audun; Totland, Christian; Bjørsvik, Hans-René [European Journal of Organic Chemistry, 2018, vol. 2018, # 26, p. 3416 - 3425]
[81]Wang, Yangyang; Ren, Shishuai; Zhang, Wenbo; Xue, Benjing; Qi, Xinghao; Sun, Hongjian; Li, Xiaoyan; Fuhr, Olaf; Fenske, Dieter [Catalysis Communications, 2018, vol. 115, p. 1 - 5]
[82]Current Patent Assignee: Schlesinger; Brown - US2683721, 1952, A
[83]Current Patent Assignee: MERCK & CO INC - US2009/239876, 2009, A1 Location in patent: Page/Page column 48
[84]Qi, Xinghao; Zheng, Tingting; Zhou, Junhao; Dong, Yanhong; Zuo, Xia; Li, Xiaoyan; Sun, Hongjian; Fuhr, Olaf; Fenske, Dieter [Organometallics, 2019, vol. 38, # 2, p. 268 - 277]
[85]Wang, Zijing; Li, Xiaoyan; Xie, Shangqing; Zheng, Tingting; Sun, Hongjian [Applied Organometallic Chemistry, 2019, vol. 33, # 6]
[86]Shinohara, Riku; Kawashima, Hidehisa; Ogawa, Narihito; Kobayashi, Yuichi [Tetrahedron, 2019, vol. 75, # 18, p. 2717 - 2725]
[87]Pan, Yingying; Gong, Yuxin; Song, Yanhong; Tong, Weiqi; Gong, Hegui [Organic and Biomolecular Chemistry, 2019, vol. 17, # 17, p. 4230 - 4233]
[88]Kuciński, Krzysztof; Hreczycho, Grzegorz [Green Chemistry, 2019, vol. 21, # 8, p. 1912 - 1915]
[89]van Putten, Robbert; Benschop, Joeri; de Munck, Vincent J.; Weber, Manuela; Müller, Christian; Filonenko, Georgy A.; Pidko, Evgeny A. [ChemCatChem, 2019, vol. 11, # 21, p. 5232 - 5235]
[90]Falconnet, Alban; Magre, Marc; Maity, Bholanath; Cavallo, Luigi; Rueping, Magnus [Angewandte Chemie - International Edition, 2019, vol. 58, # 49, p. 17567 - 17571][Angew. Chem., 2019, vol. 131, # 49, p. 17731 - 17735,5]
[91]Kuciński, Krzysztof; Hreczycho, Grzegorz [European Journal of Organic Chemistry, 2020, vol. 2020, # 5, p. 552 - 555]
[92]Sarkar, Nabin; Mahato, Mamata; Nembenna, Sharanappa [European Journal of Inorganic Chemistry, 2020, vol. 2020, # 23, p. 2295 - 2301]
[93]Ganguli, Kasturi; Mandal, Adarsha; Sarkar, Bidisha; Kundu, Sabuj [Tetrahedron, 2020, vol. 76, # 37]
[94]Alshakova, Iryna D.; Nikonov, Georgii I. [Synthesis, 2019, vol. 51, # 17, p. 3305 - 3312]
[95]Formenti, Dario; Mocci, Rita; Atia, Hanan; Dastgir, Sarim; Anwar, Muhammad; Bachmann, Stephan; Scalone, Michelangelo; Junge, Kathrin; Beller, Matthias [Chemistry - A European Journal, 2020, vol. 26, # 67, p. 15589 - 15595]
[96]Sahoo, Rajata Kumar; Mahato, Mamata; Jana, Achintya; Nembenna, Sharanappa [Journal of Organic Chemistry, 2020, vol. 85, # 17, p. 11200 - 11210]
[97]Sahoo, Rajata Kumar; Mahato, Mamata; Jana, Achintya; Nembenna, Sharanappa [Journal of Organic Chemistry, 2020, vol. 85, # 17, p. 11200 - 11210]
[98]Öztopçu, Özgür; Hayrapetyan, Davit; Khalimon, Andrey Y.; Lyssenko, Konstantin A.; Segizbayev, Medet; Shakhman, Dinmukhamed [Dalton Transactions, 2020, vol. 49, # 34, p. 11950 - 11957]
[99]Titze, Marvin; Heitkämper, Juliane; Junge, Thorsten; Kästner, Johannes; Peters, René [Angewandte Chemie - International Edition, 2021, vol. 60, # 10, p. 5544 - 5553][Angew. Chem., 2021, vol. 133, # 10, p. 5604 - 5613,10]
[100]Cavallo, Marzia; Arnodo, Davide; Mannu, Alberto; Blangetti, Marco; Prandi, Cristina; Baratta, Walter; Baldino, Salvatore [Tetrahedron, 2021, vol. 83]

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Yield	Reaction Conditions	Operation in experiment
100%	With diethylamino-sulfur trifluoride In dichloromethane at 50℃; for 20h;	152 4-( 1 , 1 -difluoroethyl)benzonitrile Diethylaminosulfur trifluoride (2 ml, 15.1 mmol) was added to 4- acetylbenzonitrile (300 mg, 2.07 mmol) in dichloromethane (4 ml) at room temperature. The mixture was heated gradually to 50 °C over 2 hours. After 18 hours of stirring at this temperature the mixture was added dropwise onto ice over 10 minutes, water was added and the mixture extracted with dichloromethane (3x3 ml). The combined organic phases were dried using a phase separator and concentrated to oil. The crude material was purified by column chromatography using silicon dioxide gel, eluting with 3-50% ethyl acetate in petroleum ether to afford the title compound as oil (355 mg, quantitative).
68.6%	With (bis-(2-methoxyethyl)amino)sulfur trufluoride for 24h;	IX-10 The starting 4-(l,l-difluoroethyl)benzonitrile for Preparation IX-10 is obtained as follows: Add bis-(2-methoxyethyl)aminosulfur trifluoride (30.516 g, 137.931 mmol) to4-acetylbenzonitrile (10.000 g, 68.966 mmol) and stir under a nitrogen atmosphere in a Teflon flask for 24 hr. Dilute with dichloromethane, followed by excess satd NaHCO3 to quench. Extract with EtOAc, dry (MgSθ4) and evaporate. Chromatograph on silica gel, eluting with hexane and EtOAc (gradient of 3- 30%), to afford 4-(l,l-difluoroethyl)- benzonitrile. Yield: 68.6%.
	With F₆Mo; boron trifluoride In dichloromethane at -20 - 20℃;

With (bis-(2-methoxyethyl)amino)sulfur trufluoride In ethanol; dichloromethane at 20 - 65℃; for 24h; Inert atmosphere; Schlenk technique;

Reference： [1]Current Patent Assignee: ACADIA PHARMACEUTICALS INC - WO2019/40107, 2019, A1 Location in patent: Paragraph 00717-00718
[2]Current Patent Assignee: ELI LILLY & CO - WO2008/103185, 2008, A2 Location in patent: Page/Page column 25
[3]Mathey,F.; Bensoam,J. [Tetrahedron, 1975, vol. 31, p. 391 - 401]
[4]Bo, Zhi-Yu; Chen, Lin; Gao, Tian-Yu; Jing, Ke; Lan, Yu; Liu, Shi-Han; Luo, Shu-Ping; Yan, Si-Shun; Yu, Bo; Yu, Da-Gang [Chem, 2021, vol. 7, # 11, p. 3099 - 3113]

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[ 1443-80-7 ]
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[ 127087-66-5 ]