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CAS No. : | 16523-54-9 | MDL No. : | MFCD00014294 |
Formula : | C12H22ClP | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | AKJFBIZAEPTXIL-UHFFFAOYSA-N |
M.W : | 232.73 | Pubchem ID : | 2734135 |
Synonyms : |
|
Signal Word: | Danger | Class: | 8 |
Precautionary Statements: | P264-P280-P301+P330+P331-P303+P361+P353-P304+P340+P310-P305+P351+P338+P310-P363-P405-P501 | UN#: | 3265 |
Hazard Statements: | H314 | Packing Group: | Ⅱ |
GHS Pictogram: |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | Stage #1: With n-butyllithium In tetrahydrofuran at 0℃; for 1 h; Inert atmosphere Stage #2: at 0℃; for 1 h; Inert atmosphere |
Under the protection of nitrogen, 200 ml of THF and 31g of 2, 4, 6-tri-isopropyl-bromobenzene was added to 1L three-mouth bottle. The temperature was cooled down to 0 °C, and 46 ml of 2.5M n-butyl lithiumwas added dropwise. The reaction was continued for 1 hour after the addition. At 0 °C, 24.6g O-dibromobenzene was added dropwise. The reaction was continued for 1 hour after the addition. At0 °C, 42 ml of 2.5M n-butyl lithiumwas added dropwise to the reaction liquid.After the addition, the reaction was continued for 1 hour. 26.7g of dicyclohexyl phosphine was added dropwise, and the temperature was naturally warmed to react at room temperature for 2 hours. 200 ml saturated ammonium chloride aqueous solution was added dropwsie to the reaction liquid under the ice bath to quench the reaction. After phase separation, the organic phase was precipitated, and methanol was added for crystallization. Byfiltering, 44.5g white product of 2’-dicyclohexyl phosphino-2, 4, 6-tri-isopropyl biphenyl was obtained, with a yield of 89percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | Stage #1: at 0℃; for 1 h; Stage #2: at 20℃; for 2 h; |
At 0 °C,42 ml of 2.5M n-butyl lithium was added dropwise to the reaction liquid. After the addition, the reaction was continued for 1 hour.26.7g of dicyclohexyl phosphine was added dropwise, and the temperature was naturally warmed to react at room temperature for 2 hours. 200 ml saturated ammonium chloride aqueous solution was added dropwsie to the reaction liquid under the ice bathto quench the reaction.After phase separation, the organic phase was precipitated,and methanol was added for crystallization. Byfiltering,45g white product of 2’-dicyclohexyl phosphino-2, 4, 6-tri-isopropyl biphenyl was obtained, with a yield of 90percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
36% | Stage #1: With n-butyllithium In tetrahydrofuran at 0 - 20℃; for 3.5 h; Stage #2: at 0℃; for 0.5 h; |
To a solution of 1,3-dimethoxybenzene (2 ml, 15.30 mmol) in anhydrous THF (35 ml) at 0° C., nBuLi (6.2 ml, 15.50 mmol) is added to the dropping funnel for 5 min. The reaction medium is stirred at room temperature for 3.5 h, then 2-bromochlorobenzene (1.6 ml, 13.70 mmol) is added by syringe, dropwise, at 0° C., for 30 min. After 15 min of stirring, the reaction medium is cooled to -78° C. and nBuLi (6.20 ml, 15.50 mmol) is added to the dropping funnel dropwise for 5 min. After 30 min, chlorodicyclohexylphosphine (3.03 ml, 13.70 mmol) is added. The reaction medium is maintained at -78° C. for 1 h, under rapid stirring (mechanical stirring). After returning to room temperature, the precipitate obtained is filtered on a fritted disc containing silica topped with a layer of cellulose acetate, with 600 ml ethyl acetate. The solvents are evaporated with a rotary evaporator, and the orange oil obtained is recrystallized in acetone to obtain S-Phos ligand in the form of white crystals with a yield of 36percent (1.22 g, 2.97 mmol). MP: 163-165° C. (Lit. MP 162.0-162.5° C.); TLC: (AcOEt/cyclohexane 10/90). Rf=0.65; 1H-NMR (CDCl3): δ=0.99-1.26 (m, 10H, H(Cy)), 1.60-1.77 (m, 12H, H(Cy)), 3.67 (s, 6H, Me), 6.58 (d, 2H, J=8.2 Hz, H3' and H5'), 7.15-7.18 (m, 1H, H(Ar)), 7.18-7.42 (m, 3H, H(Ar)), 7.57 (d, 1H, J=7.4 Hz, H(Ar)) ppm; 13C-NMR (CDCl3): δ=26.5, 27.3, 27.4, 27.6, 29.0, 29.1, 29.8, 30.1, 33.8, 34.0 (C(Cy)), 55.3 (Cb), 103.1 (Ca), 126.2, 128.2, 128.8 (C3', C4', C5'), 130.9, 131.00, 132.4, 135.8 (C3, C4, C5, C6), 135.8, 136.1, 142.7, 143.1, 157.4 (C2', C6') ppm; IR (KBr): υ=3000, 2923, 2851, 1588, 1471, 1442, 1428, 1108 cm-1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; Inert atmosphere Stage #2: at -78 - 20℃; Inert atmosphere |
EXAMPLE TWO: General Procedure for the Synthesis of Compounds 1 through 5; An oven-dried 25 mL round bottom flask, which was equipped with a magnetic stir bar and charged with 2-iodo-2',4',6'-triisopropyl-3,6-dimethoxybiphenyl (1 g, 2.15 mmol), was evacuated and backfilled with argon (this process was repeated a total of 3 times).THF (10 mL) was added via syringe and the reaction was cooled to -78 0C and n-BuLi (2.5 M in Hexane, 940 μL, 2.36 mmol) was added dropwise over a 10 min period. The solution was stirred for 30 min and then the ClPR2 (2.26 mmol) was added dropwise over a 10 min period. The reaction was stirred for 1 h at -78 0C and then warmed slowly to room temperature and stirred for an additional 1.5 h. The solution was filtered through a plug of Celite layered on a plug of silica (eluting with EtOAc) and then concentrated on a rotary evaporator to give a white solid. The crude material was recrystallized from acetone <n="117"/>(ligands 2 through 5 were recrystallized from MeOH) to yield white crystals of the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With water In tetrahydrofuran at 20℃; for 2h; Inert atmosphere; | 10 Reference Example 10 Under argon atmosphere, chlorodicyclohexylphosphine (2.2 mL, 10 mmol) was dissolved into tetrahydrofuran (50 mL), and water (5.0 mL) was added and [the mixture] was stirred at room temperature for 2 hours. After a solvent(s) was removed by concentration, chloroform (20 mL) was poured into the reactant mixture, and a chloroform layer was separated. This operation was repeated twice. After organic layers were dried with sodium sulfate, these were concentrated under reduced pressure, and a white solid of dicyclohexylphosphine oxide (yield amount: 2.04 g, yield: 95%). 1H-NMR (400 MHz, CDCl3), δ (ppm): 6.31 (d, JPH=433.5 Hz, 1H), 2.01˜1.65 (m, 12H), 1.57˜1.19 (m, 10H). 31P-NMR (162 MHz, CDCl3), δ (ppm): 49.4 (s). |
86% | With water In tetrahydrofuran at 20℃; for 5h; | |
With water Ambient temperature; |
Multi-step reaction with 2 steps 1: (i) nBuLi, benzene, hexane, (ii) /BRN= 956672/ 2: H2O / CHCl3 | ||
With hydrogenchloride In water at 0 - 20℃; for 24h; | Synthesis of the α-aminoalkylphosphine oxides General procedure: The synthesis of α-aminoalkylphosphine oxides startedwith the preparation of diaryl or dialkyl phosphine oxidesobtained via the oxidation of diaryl or dialkylchlorophosphines with 1 M HClaq (0 °C → r.t., 24 h).The resulting crude phosphine oxide (1 eq.) was dissolvedin toluene, and a tritylimine (1 eq.) was added. The reactionwas performed under reflux for 8 h. The volatilecomponents were removed under vacuum, and the tritylprotecting group was removed with TFA (2 h, r.t.) for thearyl derivatives or HCl (10 eq.) in MeOH (30 min, reflux)for the alkyl derivatives. The crude products were used inthe next steps of peptidyl derivative preparation. The synthesisof the α-aminoalkylphosphine oxides is outlined inFig. 9a. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | Stage #1: diphenyl sulphone With n-butyllithium In tetrahydrofuran at -78℃; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran at -78 - 20℃; Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | Stage #1: phenylacetylene With n-butyllithium In tetrahydrofuran; hexane at 0℃; for 0.5h; Inert atmosphere; Schlenk technique; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran; hexane at 0 - 20℃; for 1h; Inert atmosphere; Schlenk technique; | |
93% | Stage #1: phenylacetylene With n-butyllithium In tetrahydrofuran; hexane at 0℃; for 0.5h; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran; hexane at 20℃; for 1h; | |
75% | With n-butyllithium In Dimethyl ether at -78 - 20℃; for 14h; |
Stage #1: phenylacetylene With n-butyllithium In tetrahydrofuran at -78 - 0℃; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran at -78 - 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | Stage #1: 1,5-diphenyl-1H-1,2,3-triazole With lithium diisopropyl amide In tetrahydrofuran at 0℃; for 1.5h; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran at 0 - 20℃; | |
93% | Stage #1: 1,5-diphenyl-1H-1,2,3-triazole With lithium diisopropyl amide In tetrahydrofuran at 0℃; for 1.5h; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran at 0 - 20℃; for 4h; | 1; 4 Example 1.; Synthesis of Clickphosphines (L1a, L1b and L1c).[0024] Clickphosphines L1a, L1b and L1c were prepared by reacting an phenyl azide with a phenyl alkyne Mg halide such as phenyl alkyne MgCl or phenyl alkyne MgBr and then with a substituted chlorophophine. The reaction scheme is illustrated below:[0025] Following the first two steps reported by Sharpless et al. [Krasinski, A.; Fokin,V. V.; Sharpless, K. B. Org. Lett. 2004, 6, 1237], 1,5-diphenyltriazole was obtained in good yield by quenching, in situ, formed 4-bromomagnesium triazole intermediate with NH4CI. Treatment of the 1,5-diphenyltriazole with LDA (lithium di-isopropyl amide) followed by addition of chlorophosphine form a phosphine ligand having structure L1. Triazole phosphine compounds or phosphine ligands L1a, L1b and L1c were obtained in high yields. It is worthy of note that the synthesis could be shortened into a one pot operation with comparable crude yield of the desired product by directly quenching the intermediate 4 with chlorophosphine. The isolation of the 1,5-diphenyltriazole prior to adding the phosphino EPO substituents is sorely due to the ease of purification of the final phosphine ligands, i.e. L1b and L1c.; Example 4Preparation of Phosphine Ligand ( L1b) (Dicyclohexylphosphanyl-1,5-diphenyl- 1H-[1,2,3]triazole).[0028] To a solution of 1,5-diphenyltriazole (0.500g, 2.26 mmol) in THF (20 mL) at 0°C was added LDA (2.26 mmol), which was prepared from diisopropylamine (0.317 mL, 2.26 mmol) and n-BuLi (2.26 mmol) at 0°C. The reaction mixture was stirred at 0°C for 1.5 hours followed by addition of P(Cy)2Cl (0.500 mL, 2.26 mmol). The resulting mixture was slowly warmed to room temperature and stirred for 4 hours. TLC showed the reaction was essentially complete. The organic solution was washed with brine (10 mL), dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel under nitrogen (hexane:ether, 80:20) to obtain L1b as a white solid (0.88 g, 93%). 1H NMR (CD2Cl2, 360 MHz) δ 7.41-7.23 (m, 10H), 2.28-2.21 (m, 2H),1.87-1.67 (m, 10H), 1.38-1.09 (m, 10H); 13C NMR (CDCl3, 90 MHz) δ 144.7 (d, J = 34.8 Hz), 141.2 (d, J = 24.6 Hz), 137.2, 130.9 (d, J = 2.9 Hz), 129.4, 129.3, 129.1, 128.6, 128.0, 125.3, 33.5 (d, J = 8.4 Hz), 30.8 (d, J = 16.3 Hz), 29.8 (d, J = 7.5 Hz), 27.5 (d, J = 18.5 Hz), 27.4 (d, J = 1.6 Hz), 26.8; 31P NMR (CD2Cl2, 145 Hz) δ -27.76; HRMS (ESI+) calculated for C26H33N3P (MH+) 418.2419, found 418.2412 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | Stage #1: 2<SUP>,</SUP>,6-dibromo-2-methoxy-1,1<SUP>,</SUP>-biphenyl With n-butyllithium In tetrahydrofuran; hexane at -75℃; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran; hexane | |
79% | Stage #1: 2<SUP>,</SUP>,6-dibromo-2-methoxy-1,1<SUP>,</SUP>-biphenyl With n-butyllithium In tetrahydrofuran; hexane at -75℃; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran; hexane at -75 - 25℃; Further stages.; | |
79% | Stage #1: 2<SUP>,</SUP>,6-dibromo-2-methoxy-1,1<SUP>,</SUP>-biphenyl With n-butyllithium In tetrahydrofuran; hexanes at -75℃; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran; hexanes | 8 Example 8: (2'-Bromo-6-methoxy-l,l'-biphenyl-2-yl)dicyclohexylphosphine (Vila;R1 = Me and R2 = cyclohexyl); At -75 °C, n-butyllithium (0.10 mol) in hexanes (63 mL) was added to a solution of com- pound Via (34 g, 0.10 mol) in tetrahydrofuran (0.50 L). After the addition was completed,the mixture was treated with a 2.0 M solution of chlorodicyclohexylphosphine (22 mL,24 g, 0.10 mol) in tetrahydrofuran (0.10 L). The mixture was allowed to reach 25 °C andtreated with a saturated aqueous solution of ammonium chloride (0.20 L). The mixture wasextracted with ethyl acetate (3x0.10 L), and the combined organic layers were dried oversodium sulfate. Evaporation of the solvents and crystallization form a 9 :1 mixture (v/v)hexanes / ethyl acetate (50 mL) afforded 36 g (79%) colorless needles;m.p. 100 to 102°C;'H NMR (CDC13,400 MHz): 8 = 7.61 (d, /= 7.8 Hz, 1 H), 7.38 (t, J= 7.9 Hz, 1 H),7.33 (t, J= 7.3 Hz, 1 H), 7.21 (dt, J= 7.9,1.5 Hz, 2 H), 7.14 (dd, J= 7.6,1.8 Hz, 1 H),6.96 (d, J= 8.2 Hz, 1 H), 3.72 (s, 3 H), 1.7 (m, 12 H), 1.2 (m, 10 H);31P-NMR (CDC13,162 MHz): 8 - -13.8 (s);C25H32BrOP (459.41): calcd. (%) C 65.36, H 7.02; found C 65.52, H 7.07. |
79% | Stage #1: 2<SUP>,</SUP>,6-dibromo-2-methoxy-1,1<SUP>,</SUP>-biphenyl With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1h; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran; hexane; toluene at -78℃; for 1h; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | Stage #1: 2<SUP>,</SUP>,6-dibromo-2-methoxy-1,1<SUP>,</SUP>-biphenyl With n-butyllithium In tetrahydrofuran; hexane at -75℃; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran; hexane | |
74% | Stage #1: 2<SUP>,</SUP>,6-dibromo-2-methoxy-1,1<SUP>,</SUP>-biphenyl With n-butyllithium In tetrahydrofuran; hexane at -75℃; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran; hexane at -75 - 25℃; Further stages.; | |
74% | Stage #1: 2<SUP>,</SUP>,6-dibromo-2-methoxy-1,1<SUP>,</SUP>-biphenyl With n-butyllithium In tetrahydrofuran; hexane at -75℃; for 0.25h; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran; hexane; toluene at -75 - 25℃; Further stages.; |
74% | Stage #1: 2<SUP>,</SUP>,6-dibromo-2-methoxy-1,1<SUP>,</SUP>-biphenyl With n-butyllithium In tetrahydrofuran; hexanes at -75℃; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran; hexanes | 7 Example 7: 2',6-Bis(dicyclohexylphosphinyl)-2-methoxy-l,l'-biphenyl (Ib; R1 = Me,R2 = R3 = cyclohexyl); At -75 °C, n-butyllithium (0.10 mol) in hexanes (63 mL) was added to a solution of com- pound Vila (17 g, 50 mmol) in tetrahydrofuran (0.25 L). After the addition was completed,the mixture was treated with a 2.0 M solution of chlorodicyclohexylphosphine(22 mL, 24 g, 0.10 mol) in tetrahydrofaran (50 mL). The mixture was allowed to reach25 °C and treated with a saturated aqueous solution of ammonium chloride (0.10 L). Themixture was extracted with ethyl acetate (3^50 mL), and the combined organic layers weredried over sodium sulfate. The diphosphine 43 g (74%) was obtained after evaporation ofthe solvents and crystallization form methanol (0.10 L) as colorless cubes;m.p. 220 to 221 °C (decomposition);.H-NMR (CDC13,400 MHz): 8 = 7.56 (m sym., 1 H), 7.4 (m, 3 H), 7.16 (d, J= 7.5 Hz,1 H), 7.08 (m sym., 1 H), 6.88 (d, J= 7.8 Hz, 1 H), 3.66 (s, 3 H), 1.7 (m, 24 H), 1.2 (m,20 H);31P-NMR (CDC13,162 MHz): 8 = -9.9 (d, /= 12.1 Hz), -11.5 (d, /= 12.2 Hz);C37H54OP2 (576.79): calculated (%) C 77.05, H 9.44; found C 77.17, H 9.14. |
74% | Stage #1: 2<SUP>,</SUP>,6-dibromo-2-methoxy-1,1<SUP>,</SUP>-biphenyl With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1h; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran; hexane at -78℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With triethylamine In toluene at 20℃; for 6h; | 1 R, R-1, 2-Bis (dicyclohexylphosphinamino) cyclohexane (R, R-DCYPPACH): A solution of chlorodicyclohexylphosphine (4.07 g, 17.5 mmol) in toluene (20 ml) was added dropwise to a solution of R,R-1, 2-cyclohexyldiamine (1.0 g, 8.75 mmol) and triethylamine (2.0 g, 19.4 mmol) in toluene (20 ml) and the resulting suspension stirred for 6 hours at room temperature. It was then evaporated to dryness, the solids washed with ethanol (2 x 10 ml) (in order to remove triethylammonium chloride) and hexanes (3 x 5 ml) and dried under vacuum. Yield = 3.86 g, 87%. 1H NMR: 0.95-2. 38 ppm (m) ; 3lP {lH} NMR: 51.3 ppm (s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
420 mg (54%) | In tetrahydrofuran; hexane; | EXAMPLE 23 Synthesis of 2-Dicyclohexylphosphino-2'-methoxy-1,1'-biphenyl A solution of 1 (535 mg, 2.03 mmol) in THF (20 mL) was cooled to -78 C. under argon, then n-BuLi (1.6 M in hexane, 1.35 mL, 2.16 mmol) was added dropwise. After 2.5 h at -78 C., a solution of chlorodicyclohexylphosphine (570 mg, 2.45 mmol) in THF (3 mL) was added over 10 min. The reaction mixture was then allowed to warm to room temperature overnight, then quenched with saturated aqueous NaHCO3 and concentrated in vacuo. The resulting aqueous suspension was extracted with ether (2*50 mL), and the combined ethereal layers were dried (Na2SO4), filtered and concentrated in vacuo. The resulting crude solid was recrystallized from ethanol to afford 420 mg (54%) of a white solid. |
420 mg (54%) | In tetrahydrofuran; hexane; | Example 23 Synthesis of 2-Dicyclohexylphosphino-2'-methoxy-1,1'-biphenyl A solution of 1 (535 mg, 2.03 mmol) in THF (20 mL) was cooled to -78 C. under argon, then n-BuLi (1.6 M in hexane, 1.35 mL, 2.16 mmol) was added dropwise. After 2.5 h at -78 C., a solution of chlorodicyclohexylphosphine (570 mg, 2.45 mmol) in THF (3 mL) was added over 10 min. The reaction mixture was then allowed to warm to room temperature overnight, then quenched with saturated aqueous NaHCO3 and concentrated in vacuo. The resulting aqueous suspension was extracted with ether (2*50 mL), and the combined ethereal layers were dried (Na2SO4), filtered and concentrated in vacuo. The resulting crude solid was recrystallized from ethanol to afford 420 mg (54%) of a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | Stage #1: (RC,SFc,SP)-1-[2-(1-dimethylaminoethyl)ferrocen-1-yl]phenylphosphino-1'-bromoferrocene With sec.-butyllithium In tert-butyl methyl ether; cyclohexane at 0℃; for 1h; Stage #2: chlorodicyclohexylphosphane In tert-butyl methyl ether; cyclohexane at 0 - 20℃; for 2h; | 100 Example 100; Preparation of (RC,SFC,SP)-1 -[2-(1 -dimethylaminoethyl)ferrocen-1 -yl]phenylphosphino-1 '-dicyclohexylphosphinoferrocene (100) of the formula; To a solution of 629 mg (1 mmol) of compound L in 5 ml of tert-butyl methyl ether (TBME) are added dropwise, whereby the temperature is below 0°C, 0.85 ml (1.1 mmol) of sec-butyllithium (s-BuLi) (1.3 M in cyclohexane). At a temperature of 00C, the mixture is stirred further for 1 hour and then 0.24 ml (1.1 mmol) of chlor- odicyclohexylphosphine is added. The temperature is allowed to rise to room temperature, the mixture is stirred further for 2 hours and then the reaction mixture is admixed with 5 ml of a saturated aqueous NaHCO3 solution. The organic phase is removed and dried over sodium sulphate, and the solvent is distilled off under reduced pressure on a rotary evaporator. After chromatographic purification (silica gel 60; eluent = 85:10:5 heptane/ethyl acetate/triethylamine) and recrystallization in methanol, the compound 100 is obtained as orange crystals and as a pure diastereomer in a yield of 95%. 31P NMR (121.5 MHz, CDCI3): δ -35.4 (s), -6.5 (s). |
95% | Stage #1: (RC,SFc,SP)-1-[2-(1-dimethylaminoethyl)ferrocen-1-yl]phenylphosphino-1'-bromoferrocene With n-butyllithium In hexane; tert-butyl methyl ether at -5 - 0℃; Stage #2: chlorodicyclohexylphosphane In hexane; tert-butyl methyl ether at 0 - 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | 120 ml (0.3 mol) of n-BuLi (2.5 M in hexane) are added dropwise at a temperature of <-30C to a solution of 103 g (0.3 mol) of 1 ,1 '-<strong>[1293-65-8]dibromoferrocene</strong> in 300 ml of THF. The mixture is stirred further at this temperature for 1.5 hours. The mixture is then cooled to -500C, and 66.2 ml (0.3 mol) of dicyclohexylphosphine chloride are slowly added dropwise at such a rate that the temperature does not rise above -45C. After stirring for a further 10 minutes, the temperature is allowed to rise to room temperature and the mixture is stirred for another one hour. After adding 150 ml of water, the reaction mixture is extracted by shaking with hexane. The organic phases are dried over sodium sulphate, and the solvent is distilled off under reduced pressure on a rotary evaporator. The residue is crystallized in ethanol. The product 13 is obtained with a yield of 84% (yellow solid). 1H NMR (300 MHz, C6D6): delta 1.20-2.11 (m, 22H), 3.97 (m, 2H), 4.23 (m, 2H), 4.26 (m, 2H), 4.41 (m, 2H). 31P NMR (121.5 MHz, C6D6): delta -8.3 (s). | |
84% | To a solution of 103 g (0.3 mol) of 1 ,1 '-<strong>[1293-65-8]dibromoferrocene</strong> in 300 ml of THF are added dropwise, at a temperature of < -300C, 120 ml (0.3 mol) of n-BuLi (2.5 M in hexane). <n="34"/>The mixture is stirred at this temperature for a further 1.5 hour. The mixture is then cooled to -500C, and 66.2 ml (0.3 mol) of dicyclohexylphosphine chloride are added dropwise sufficiently slowly that the temperature does not rise above -45C. After stirring for a further 10 minutes, the temperature is allowed to rise to room temperature and the mixture is stirred for another hour. After 150 ml of water have been added, the reaction mixture is extracted by shaking with hexane. The organic phases are dried over sodium sulphate and the solvent is distilled off under reduced pressure on a rotary evaporator. The residue is crystallized in ethanol. The product A2 is obtained with a yield of 84% (yellow solid).31P NMR (121.5 MHz, C6D6): delta -8.3 (s); 1H NMR (300 MHz, C6D6): delta 4.41 (m, 2H), 4.26 (m, 2H), 4.23 (m, 2H), 3.97 (m, 2H), 1.20-2.11 (m, 22H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | Stage #1: N-methyl-2-(2'-bromophenyl)-1H-indole With n-butyllithium In tetrahydrofuran at -78℃; for 0.5h; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran at -78 - 20℃; Further stages.; | |
88% | Stage #1: N-methyl-2-(2'-bromophenyl)-1H-indole With n-butyllithium In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran at -78 - 20℃; Inert atmosphere; | |
88% | Stage #1: N-methyl-2-(2'-bromophenyl)-1H-indole With n-butyllithium In tetrahydrofuran at -78 - 20℃; Inert atmosphere; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran at -78 - 20℃; Inert atmosphere; |
With n-butyllithium In tetrahydrofuran at -78℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | Stage #1: N-methyl-2-phenyl-3-bromo-1H-indole With n-butyllithium In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran at -78 - 20℃; Inert atmosphere; | |
71% | Stage #1: N-methyl-2-phenyl-3-bromo-1H-indole With n-butyllithium In tetrahydrofuran at -78℃; for 0.5h; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran at -78 - 20℃; Further stages.; | |
71% | Stage #1: N-methyl-2-phenyl-3-bromo-1H-indole With n-butyllithium In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran at -78 - 20℃; Inert atmosphere; |
71% | Stage #1: N-methyl-2-phenyl-3-bromo-1H-indole With n-butyllithium In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran at 20℃; Inert atmosphere; | 1 Example 1: Synthesis of 3- (dicyclohexylphosphino) -1-methyl-2-phenyl-1H-indole In a 50 ml two-necked flask, 0.855 g of 3-bromo-1-methyl-2-phenyl-1H-indole (3.0 mmol) was weighed out. After 3 cycles of vacuum nitrogen round-trip exchange, 20 ml of freshly distilled tetrahydrofuran was added under nitrogen, stirring evenly. After the mixture was cooled to -78 ° C, n-butyllithium (3.3 mmol) was slowly added and reacted for 0.5 hour. The mixed solution of 0.66 ml of dicyclohexylphosphine chloride (3.3 mmol) and 5 ml of freshly distilled tetrahydrofuran was then slowly added. The reaction is left at room temperature for 18-24 hours. After all solutions have been removed under reduced pressure, they are washed three times with cold methanol, The pure product was obtained as a white powder, 0.85 g of 3- (dicyclohexylphosphino) -1-methyl-2-phenyl-1H-indole in 71% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | EXAMPLE TWO: General Procedure for the Synthesis of Compounds 1 through 5; An oven-dried 25 mL round bottom flask, which was equipped with a magnetic stir bar and charged with 2-iodo-2',4',6'-triisopropyl-3,6-dimethoxybiphenyl (1 g, 2.15 mmol), was evacuated and backfilled with argon (this process was repeated a total of 3 times).THF (10 mL) was added via syringe and the reaction was cooled to -78 0C and n-BuLi (2.5 M in Hexane, 940 muL, 2.36 mmol) was added dropwise over a 10 min period. The solution was stirred for 30 min and then the ClPR2 (2.26 mmol) was added dropwise over a 10 min period. The reaction was stirred for 1 h at -78 0C and then warmed slowly to room temperature and stirred for an additional 1.5 h. The solution was filtered through a plug of Celite layered on a plug of silica (eluting with EtOAc) and then concentrated on a rotary evaporator to give a white solid. The crude material was recrystallized from acetone <n="117"/>(ligands 2 through 5 were recrystallized from MeOH) to yield white crystals of the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
28% | EXAMPLE TEN: Synthesis of Ligand 7; An oven-dried three-neck 250 mL round bottom flask, which was equipped with a magnetic stir bar and charged with magnesium shavings (559 mg, 24.3 mmol), was fitted with a reflux condenser, addition funnel, and glass stopper. The flask was purged with argon and then THF (15 mL) and 2,4,6-triisopropylbromobenzene (2.83 g, 10 mmol) were added via syringe. The reaction mixture was heated to reflux and 1 ,2-dibromethane (40 uL) was added via syringe. The reaction was allowed to stir at reflux for 1 h and then the addition funnel, which was charged with l,2-dibromo-3,4,5,6-tetramethylbenzene (2.92 g, 10 mmol) in 40 mL of THF, was opened and the solution was added over a 1 h period. The mixture was stirred for 5 h at reflux and then cooled to room temperature where CuCl (1.0 g, 10 mmol) was added quickly to the reaction mixture. Next, ClPCy2 (2.65 mL, 10 mmol) was then added in a dropwise fashion and the reaction mixture was heated to 75 0C for 60 h. The reaction mixture was then cooled to room temperature, diluted with EtOAc, washed 3 times with 30% NH4OH, dried over MgSO4, and concentrated under reduced pressure. The crude material was recrystallized from benzene to yield the product as a white solid (1.507 g, 28% yield). 1H NMR (300 MHz, CDCl3) δ: 7.36 (s, 5H), 7.15 (s, 2H), 2.99 (septet, J= 7.0 Hz, IH), 2.44 (s, 3H), 2.35-2.14 (m, HH), 1.98 (s, 2H), 1.80-1.44 (m, 14H), 1.39-1.04 (m, 22H), 0.91 (d, J= 6.5 Hz, 6H) ppm. 13C NMR (75 MHz, CDCl3) δ: 150.9, 145.8, 145.4, 144.6, 140.0, 138.5, 135.8, 135.6, 135.5, 135.5, 128.6, 124.3, 40.2, 39.9, 35.4, <n="123"/>35.2, 34.5, 30.7, 29.5, 27.8, 27.7, 27.4, 27.2, 25.9, 25.0, 24.6, 21.2, 20.8, 17.7, 17.3 ppm (Observed complexity is due to P-C splitting). 31P NMR (121 MHz, CDCl3) δ: 16.33 ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | Stage #1: 1,3-Dimethoxybenzene With n-butyllithium In tetrahydrofuran at 20℃; for 5h; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran at 20℃; for 12h; | |
96% | Stage #1: 1,3-Dimethoxybenzene With n-butyllithium In tetrahydrofuran; hexanes at 0 - 20℃; for 5.17h; Inert atmosphere; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran at 0 - 20℃; for 12.17h; Inert atmosphere; | 11 EXAMPLE ELEVEN: Synthesis of Ligand 9; To a 0 0C solution of 1,3-dimethoxybenzene (2.0 mL, 15.3 mmol) in THF (35 mL) was added n-BuLi (6.20 mL, 2.5 M in hexanes, 15.5 mmol) via syringe over a 10 min period. The mixture was then allowed to warm to room temperature and stirred for 5 h. The mixture was re-cooled to 0 0C and ClPCy2 (3.07 mL, 13.9 mmol) was added via syringe over a 10 min period. The reaction mixture was allowed to warm to room temperature where it was stirred for 12 h. The solution was then filtered through a plug of silica, eluting with EtOAc, and concentrated under reduced pressure to yield the product as a white solid (4.89 g, 96% yield). 1H NMR (300 MHz, CDCl3) δ: 7.21 (t, J= 8.0 Hz, IH), 6.46 (d, J= 8.0 Hz, 2H), 3.74 (s, 6H), 2.26 (m, 2H), 1.86 (m, 2H), 1.70 (m, 2H), 1.56 (m, 4H), 1.42-0.89 (m, 12H) ppm. 13C NMR (75 MHz, CDCl3) δ: 164.5, 164.4, 131.1, 111.6, 111.2, 104.1, 55.8, 34.3, 34.1, 32.5, 32.2, 30.5, 30.4, 27.6, 27.5, 27.5, 27.3, 26.7 ppm (Observed complexity is due to P-C splitting). 31P NMR (121 MHz, CDCl3) δ: -11.8 ppm. IR (neat, cm"1): 2921, 2847, 1581, 1463, 1428, 1242, 1103, 777. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | Stage #1: 2-(N-methylamino)pyridine With potassium hydride In toluene at -40 - 20℃; Stage #2: chlorodicyclohexylphosphane In toluene at -30 - 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With n-butyllithium In tetrahydrofuran; hexane at -78 - 20℃; for 3.5h; Inert atmosphere; | |
72% | Stage #1: N,N-diisopropyl benzamide With n-butyllithium In tetrahydrofuran; hexane at -78℃; Inert atmosphere; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran; hexane at -78 - 20℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | Stage #1: benzenesulfonic acid With n-butyllithium In tetrahydrofuran; hexane at 0 - 20℃; for 2.5h; Inert atmosphere; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran; hexane at -78 - 20℃; for 24h; | Synthesis of Compound 1a (a) Synthesis of Compound 1a n-Butyllithium (manufactured by Kanto Chemical Co., Inc., 1.65 M hexane solution, 5.1 ml, 8.4 mmol) was added to a tetrahydrofuran (THF) solution (20 ml) of benzenesulfonic acid (manufactured by Tokyo Chemical Industry Co., Ltd., 0.66 g, 4.2 mmol) at 0° C. under argon atmosphere and the mixture was stirred for 2.5 hours at room temperature. After cooling the reaction container to -78° C., chlorodicyclohexylphosphine (manufactured by Sigma-Aldrich, 0.89 mg, 3.8 mmol) was added thereto at -78° C. and stirred for 24 hours at room temperature. After ceasing the reaction with trifluoroacetic acid (manufactured by Tokyo Chemical Industry Co., Ltd., 0.50 M THF solution, 8.4 ml, 4.2 mmol), the precipitate formed was collected by filtration and dried under reduced pressure to obtain 2-(dicyclohexylphosphino)benzenesulfonic acid (compound 1a). The yield was 0.66 g (85%). 1H-NMR(400 MHz, CDCl3):δ 0.98-0.27 (m, 4H), 1.30-1.58 (m, 6H), 1.62-1.78 (m, 4H), 1.88 (br s, 4H), 2.28 (br s, 2H), 3.33 (br s, 2H), 5.19 (br d, 1JPH=370 Hz, 1H), 7.48-7.58 (m, 2H), 7.80 (br s, 1H), 8.27 (br s, 1H); 13C-NMR(101 MHz,CDCl3):δ 25.0 (s), 25.6-26.2 (m), 28.8 (br), 30.3 (br), 34.6 (br d, 1JPC=40 Hz), 113.4 (br d, 1JPC=87 Hz), 128.8 (d, JPC=9 Hz), 130.1 (d, JPC=9 Hz), 135.4 (br), 137.1 (br), 150.5 (br); 31P-NMR(162MHz, CDCl3):δ 52.8 (d, 1JPH=370 Hz) (90%), 20.8 (d, 1JPH=530 Hz) (10%); Anal. calcd for C18H27O3PS, C, 60.99; H, 7.68. found: C, 60.90; H, 7.55. |
65% | Stage #1: benzenesulfonic acid With n-butyllithium In tetrahydrofuran; hexane at 0 - 20℃; Inert atmosphere; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran; hexane at -78 - 20℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
25% | [0288] Synthesis of 2-(dicyclohexylphosphino)-iV^V-dimethylaniline (L3).[0289] To a glass vial containing <strong>[698-00-0]2-bromo-N,N-dimethylaniline</strong> (288 uL, 2.0 mmol) in 3 mL Et20 (pre-cooled to -35 C), was added n-BuLi (759 2.2 mmol). After 30 minutes at -35 C and an additional 15 minutes at room temperature, the resulting yellow precipitate was isolated by removing the solvent by using a pipette, followed by washing of the remaining solid with cold hexanes (3 x 2 mL), after which the volatile materials were removed in vacuo. The resulting solid was dissolved in 6 mL Et20 and ClPCy2 (440 uL, 2.0 mmol) was added dropwise. The mixture was stirred magnetically at room temperature for 48 h. The solvent and volatile materials were then removed in vacuo. The resulting mixture was dissolved in CH2C12 and washed with 10 mL of saturated NaHC03 and 10 mL of water. The organic layer was extracted, dried in vacuo and passed through a plug of silica as a pentane solution.Removal of the solvent in vacuo yielded the product as a white solid (0.162 g, 0.51 mmol, 25% yield). 1H NMR (CDC13): delta 7.35 (d of t, J = 7.6, 1.9 Hz, 1H), 7.28 (m, 1H), 7.13 (d of d of d, 7 = 8.0, 4.3, 1.2, 1H), 7.05 (d of t, 7 = 7.4, 1.3, 1H), 2.72 (s, 6H), 1.90-1.74 (m, 12H), 1.30-0.99 (m, 10H). 13C{ 1H} NMR (CDC13): delta 160.8, 133.8 (d, J = 2.7 Hz), 132.0, 129.8, 123.6, 120.2 (d, J = 2.9 Hz), 46.4 (d, J = 5.0 Hz), 34.2 (d, J = 14.3), 30.8 (d, J = 16.6 Hz), 29.6 (d, J = 8.9 Hz), 27.8 (d, / = 11.6 Hz), 27.7 (d, J = 7.6 Hz), 27.0.31P{ } NMR (CDC13): delta -12.7. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | Stage #1: 4-bromo-1,1'-biphenyl With n-butyllithium In diethyl ether; hexane at -20℃; for 2h; Inert atmosphere; Stage #2: chlorodicyclohexylphosphane In diethyl ether; hexane at 20℃; for 6h; Cooling; | 14 Reference Example 14 Under argon atmosphere, 4-bromobiphenyl (513 mg, 2.2 mmol) was dissolved into diethyl ether (5.0 mL), and [the obtainment] was cooled down to -20° C. Into this solution, n-butyllithium in a 2.67M hexane solution (0.85 mL, 2.3 mmol) was delivered by drops, and after stirring for 2 hours, chlorodicyclohexylphosphine (0.44 mL, 2.0 mmol) was added, and [the mixture] was heated to room temperature and stirred for 6 hours. The reactant mixture was concentrated under reduced pressure and a white solid of 4-biphenyl (dicyclohexyl) phosphine was obtained by refining the obtained crude product by silica gel column chromatography (eluent: hexane/ethyl acetate) (yield amount: 592 mg, yield: 85%). 1H-NMR (400 MHz, CDCl3), δ (ppm): 7.72 (m, 1H), 7.657.59 (m, 2H), 7.597.49 (m, 3H), 7.487.32 (m, 3H), 2.121.54 (m, 12H), 1.410.96 (m, 10H). 31P-NMR (162 MHz, CDCl3), δ (ppm): 2.19 (s). |
70% | Stage #1: 4-bromo-1,1'-biphenyl With magnesium In tetrahydrofuran for 1h; Reflux; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With triethylamine In dichloromethane at 0 - 20℃; Inert atmosphere; | 4.2.2. (2R)-2-[Benzyl{(2-((dicyclohexylphosphanyl)oxy)ethyl)}amino]butyldicyclohexylphosphinite, (2) Chlorodicyclohexylphosphine (216 mg, 0.90 mmol) was added to a stirred solution (2R)-2-[benzyl(2-hyroxyethyl)amino]butan-1-ol (100 mg, 0.45 mmol) and triethylamine (92 mg, 0.90 mmol) in CH2Cl2 (40 mL) at 0 °C with vigorous stirring. The mixture was stirred at room temperature for 48 h, and the solvent was removedunder reduced pressure. After addition of dry toluene, the white precipitate (triethylammonium chloride) was filtered off under argon and dried in vacuo to produce a white viscous oily compound 2 (Yield: 273 mg, 99%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88.3% | (Setting-Up and Reaction) To a 200 mL four-necked round-bottomed flask, a three-way stopcock, a Teflon-coated magnetic stirring bar, a 20 mL dropping funnel, and a thermometer were attached, and the inside was purged with nitrogen. To this flask, <strong>[902518-11-0]N-(2-bromophenyl)carbazole</strong> (7) (8.8 g, 27.3 mmol, 1.0 eq.) obtained in the first step and anhydrous tetrahydrofuran (hereinafter, abbreviated as THF) (54.6 mL) were sequentially added, and the obtained reactant solution was cooled to -70C by use of a dry ice/acetone bath. Subsequently, a n-butyllithium (hereinafter, abbreviated as n-BuLi)/n-hexane solution (1.60 mol/L, 17. 9 mL, 28. 6 mmol, 1.05 eq.) was placed in the dropping funnel, and added dropwise over 15 minutes, while the reactant solution was being stirred, and the inside temperature was being kept at -50C or below. Then, the dropping funnel was rinsed with anhydrous n-hexane (1 mL) . The obtained cream-colored suspension was stirred at -70C for 1 hour. Then, an anhydrous THF (14 mL) solution of chlorodicyclohexylphosphine (hereinafter, abbreviated as Cy2PCl) (7.0 g, 30.1 mmol, 1.1 eq.) was placed in the dropping funnel, and added dropwise over 15 minutes, while the suspension was being stirred, and the inside temperature was being kept at -50 C or below (the suspension was dissolved rapidly). After completion of the dropwise addition, the dry ice/acetone bath was taken out, and the temperature of the reaction solution was raised to room temperature over 30 minutes, followed by stirring for further 30 minutes. (Post Treatment and Purification) After the reaction solution had been concentrated under reduced pressure, toluene and an aqueous solution of sodium hydrogen carbonate (2.3 g, approximately 1 eq.) were added to the residue. The mixture was transferred to a separating funnel, shaken and allowed to stand, and the layers were separated (Aqueous Layer 1: pH=9). Then, the organic layer was further washed with water (Aqueous Layer 2: pH=7). The solvent was distilled off from the organic layer under reduced pressure, and toluene and silica gel (0.7 g) were added to the obtained light brown residue. The mixture was stirred at room temperature for 10 minutes and filtered by use of diatomaceous earth, and the residue was washed with toluene. The filtrate was concentrated, until crystals were precipitated. Then, methanol was added, and the obtained white suspension was filtered. The product obtained by the filtration was washed with methanol, and then dried under reduced pressure to give 10.6 g of title compound (2-1) as a colorless powder. Isolated Yield: 88.3%. 1H NMR (300 MHz, CDCl3): delta=8.12 (d, J=7.5 Hz, 2H), 7.76 (dt, J=1.5, 4.8 Hz, 1H), 7.57-7.47 (m, 2H), 7.38-7.28 (m, 3H), 7.23 (dt, J=0.9, 6.9 Hz, 2H), 7.02 (d, J=8.1 Hz, 2H), 1.85-1.38 (m, 12H), 1.22-0.90 (m, 10H). 31P NMR (121 MHz, CDCl3): delta=-14.5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
36% | To a solution of 1,3-dimethoxybenzene (2 ml, 15.30 mmol) in anhydrous THF (35 ml) at 0 C., nBuLi (6.2 ml, 15.50 mmol) is added to the dropping funnel for 5 min. The reaction medium is stirred at room temperature for 3.5 h, then 2-bromochlorobenzene (1.6 ml, 13.70 mmol) is added by syringe, dropwise, at 0 C., for 30 min. After 15 min of stirring, the reaction medium is cooled to -78 C. and nBuLi (6.20 ml, 15.50 mmol) is added to the dropping funnel dropwise for 5 min. After 30 min, chlorodicyclohexylphosphine (3.03 ml, 13.70 mmol) is added. The reaction medium is maintained at -78 C. for 1 h, under rapid stirring (mechanical stirring). After returning to room temperature, the precipitate obtained is filtered on a fritted disc containing silica topped with a layer of cellulose acetate, with 600 ml ethyl acetate. The solvents are evaporated with a rotary evaporator, and the orange oil obtained is recrystallized in acetone to obtain S-Phos ligand in the form of white crystals with a yield of 36% (1.22 g, 2.97 mmol). MP: 163-165 C. (Lit. MP 162.0-162.5 C.); TLC: (AcOEt/cyclohexane 10/90). Rf=0.65; 1H-NMR (CDCl3): delta=0.99-1.26 (m, 10H, H(Cy)), 1.60-1.77 (m, 12H, H(Cy)), 3.67 (s, 6H, Me), 6.58 (d, 2H, J=8.2 Hz, H3' and H5'), 7.15-7.18 (m, 1H, H(Ar)), 7.18-7.42 (m, 3H, H(Ar)), 7.57 (d, 1H, J=7.4 Hz, H(Ar)) ppm; 13C-NMR (CDCl3): delta=26.5, 27.3, 27.4, 27.6, 29.0, 29.1, 29.8, 30.1, 33.8, 34.0 (C(Cy)), 55.3 (Cb), 103.1 (Ca), 126.2, 128.2, 128.8 (C3', C4', C5'), 130.9, 131.00, 132.4, 135.8 (C3, C4, C5, C6), 135.8, 136.1, 142.7, 143.1, 157.4 (C2', C6') ppm; IR (KBr): upsilon=3000, 2923, 2851, 1588, 1471, 1442, 1428, 1108 cm-1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | Stage #1: 1-(4-methoxyphenyl)-1H-imidazole With n-butyllithium In tetrahydrofuran; hexane at -30℃; for 0.5h; Inert atmosphere; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran; hexane at -30 - 50℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | Stage #1: 1-(2-bromophenyl)-1H-pyrrole With n-butyllithium; N,N,N,N,-tetramethylethylenediamine In hexane at -78℃; for 0.25h; Inert atmosphere; Schlenk technique; Reflux; Stage #2: chlorodicyclohexylphosphane In hexane for 3.5h; Inert atmosphere; Schlenk technique; Reflux; | |
62% | Stage #1: 1-(2-bromophenyl)-1H-pyrrole With n-butyllithium In tetrahydrofuran at -78 - 20℃; for 0.5h; Inert atmosphere; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran at -78 - 20℃; for 9h; Inert atmosphere; | 1-(2-(Dicyclohexylphosphino)phenyl)-1H-pyrrole (L5) To a stirred solution of 1-(2-bromophenyl)-1H-pyrrole (1k) (222mg, 1mmol) in THF (4mL) under argon atmosphere was added n-BuLi (0.6mL, 1mmol, 1.6M in THF) drop wise at -78°C. The mixture was slowly warmed to rt and then stirred for further 1/2 h at rt. After the mixture was cooled to -78°C, chloro dicyclohexylphosphine (0.2mL, 1mmol) was added and stirring was continued for 9h. It was then quenched with saturated NH4Cl solution at 0°C and extracted with diethyl ether (2×25mL). The combined organic layer was washed with water and brine and dried over anhydrous Na2SO4. Evaporation of the solvent under reduced pressure gave the crude product. Purification by flash column chromatography (Silica gel 230-400 mesh, 0.5% ethyl acetate/petroleum ether) afforded ligand (L5) as a white solid (210mg, 62%). Rf (petroleum ether) 0.24; mp 90°C-92°C; 1H NMR (CDCl3, 500.1MHz, ppm). δ 7.63-7.62 (m, 1H, Ar-H), 7.42-7.40 (m, 2H, Ar-H), 7.34-7.28 (m, 1H, Ar-H), 6.84 (s, 2H, -CH of pyrrole), 6.33 (t, J=2Hz, 2H, -CH of pyrrole), 1.87-1.54 (m, 11H, Cy-H), 1.33-1.08 (m, 11H, Cy-H). 13C NMR (CDCl3, 125.8MHz, ppm). δ 147.9, 147.7, 134.1, 133.9, 133.6, 129.3, 127.5, 127.2, 123.4, 108.4, 34.4, 34.3, 30.5, 30.4, 29.3, 29.2, 27.5, 27.4, 27.3, 27.2, 26.7, 26.5; 31P NMR (CDCl3, 202.44MHz, ppm). δ-14.08 (s); HRMS (ESI) m/z calculated for C22H31NP [M+H]+ 340.2194, found 340.2186; Anal. calcd for C22H30NP C, 77.84; H, 8.91; N, 4.13; found C, 77.08; H. 8.91; N, 4.03. |
62% | Stage #1: 1-(2-bromophenyl)-1H-pyrrole With n-butyllithium In tetrahydrofuran at -78 - 20℃; for 0.5h; Inert atmosphere; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran at -78℃; for 9h; Inert atmosphere; | 1-(2-(Dicyclohexylphosphino)phenyl)-1H-pyrrole (L5) To a stirred solution of 1-(2-bromophenyl)-1H-pyrrole (1k) (222 mg, 1 mmol) in THF (4mL) under argon atmosphere was added n-BuLi (0.6 mL, 1 mmol, 1.6 M in THF) drop wise at -78 °C. The mixture was slowly warmed to rt and then stirred for further 1/2 h at rt. After the mixture was cooled to -78 °C, chloro dicyclohexylphosphine (0.2 mL, 1 mmol) was added and stirring was continued for 9 h. It was then quenched with saturated NH4Cl solution at 0 °C and extracted with diethyl ether (2×25 mL). The combined organic layer was washed with water and brine and dried over anhydrous Na2SO4. Evaporation of the solvent under reduced pressure gave the crude product. Purification by flash column chromatography (Silica gel 230-400 mesh, 0.5% ethyl acetate/petroleum ether) afforded ligand (L5) as a white solid (210 mg, 62 %). Rf (petroleum ether) 0.24; mp 90 °C- 92 °C; 1H NMR (CDCl3, 500.1 MHz, ppm). δ 7.63-7.62 (m, 1H, Ar-H), 7.42-7.40 (m, 2H, Ar-H), 7.34-7.28 (m, 1H, Ar-H), 6.84 (s, 2H, -CH of pyrrole), 6.33 (t, J=2Hz, 2H, -CH of pyrrole), 1.87-1.54 (m, 11H, Cy-H), 1.33-1.08 (m, 11H, Cy-H). 13C NMR (CDCl3, 125.8 MHz, ppm). δ 147.9, 147.7, 134.1, 133.9, 133.6, 129.3, 127.5, 127.2, 123.4, 108.4, 34.4, 34.3, 30.5, 30.4, 29.3, 29.2, 27.5, 27.4, 27.3, 27.2, 26.7, 26.5; 31P NMR (CDCl3, 202.44 MHz, ppm). δ-14.08 (s); HRMS (ESI) m/z calculated for C22H31NP [M+H]+ 340.2194, found 340.2186; Anal. calcd for C22H30NP C, 77.84; H, 8.91; N, 4.13; found C, 77.08; H. 8.91; N, 4.03. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95.5% | Stage #1: 1-chloro-3-(3-methylimidazolidin-1-yl)propan-2-ol chloride With n-butyllithium In hexane; dichloromethane at -78 - 20℃; for 1.5h; Inert atmosphere; Schlenk technique; Stage #2: chlorodicyclohexylphosphane In hexane; dichloromethane at -78 - 20℃; for 4h; Inert atmosphere; Schlenk technique; | 3.3.3 Synthesis of [(Cy2PO)-C7H14N2Cl]Cl (3) A dry and degassed CH2Cl2 (20 ml) solution of 1-chloro-3-(3-methylimidazolidin-1-yl)propan-2-ol chloride (1) (0.100 g, 0.47 mmol) under an argon atmosphere was cooled to -78°C in an acetone and dry ice bath. To the cooled solution was added dropwise a hexane solution of n-BuLi (0.293 ml, 0.47 mmol). After the addition, the mixture was stirred at -78°C for 1 h and then for an additional 30 min at room temperature. The reaction solution was cooled to -78° C again and a solution of dicyclohexylchlorophosphine (0.112 g, 0.47 mmol) in CH2Cl2 (10 ml) was added dropwise to the reaction medium. Stirring was continued for a further 1 h at -78° C, then the cooling bath was removed and the mixture was stirred for 3 h at room temperature. Precipitated lithium chloride was removed by filtration under argon and then the volatiles were evaporated in vacuo to leave a viscous oil of the phosphinite ligand, 3. Yield 0.183 g, 95.5 %; 1H NMR (400.1 MHz, CDCl3, ppm) δ: 10.48 (s, 1H, -(CH3)NCHN-), 7.64, 7.45 (2xs, 2H, -NCHCHN-), 4.84 (m, 1H, NCH2, (a)), 4.53 (m, 1H, NCH2, (b)), 4.16 (br, 1H, -CHOP), 4.10 (s, 3H, NCH3), 3.83 (m, 1H, -CH2Cl, (a)), 3.68 (m, 1H, -CH2Cl, (b)), 1.00-1.95 (m, 22H, protons of P(C6H11)2; 13C NMR (100.6 MHz, CDCl3, ppm) δ: 26.20, 26.27, 26.64, 26.85, 26.98, 27.21 (CH2 of P(C6H11)2), 36.77 (NCH3), 37.20 (d, 1J=15.1Hz, CH of P(C6H11)2), 44.05 (-CH2Cl), 52.34 (NCH2), 77.32 (d, 2J=22.7Hz, -CHOP), 123.05, 123.43 (-NCHCHN-), 138.67 (-(CH3)NCHN-); assignment was based on the 1H-13C HETCOR, DEPT and 1H-1H COSY spectra; 31P-{1H} NMR (162.0 MHz, CDCl3, ppm) δ: 148.76 (s, OPCy2); IR, (KBr, cm-1) ν: 2923, 2850 (aliphatic C-H), 1446 (P-Cy), 1059 (O-P); Anal. Calc. for C19H36N2OCl2P (410.39 g/mol): C, 55.61; H, 8.84; N, 6.83. Found: C, 55.56; H, 8.71; N, 6.70 %. |
95.5% | Stage #1: 1-chloro-3-(3-methylimidazolidin-1-yl)propan-2-ol chloride With n-butyllithium In hexane; dichloromethane at -78 - 20℃; for 1.5h; Inert atmosphere; Stage #2: chlorodicyclohexylphosphane In hexane; dichloromethane at -78 - 20℃; for 2h; Inert atmosphere; | |
95.5% | Stage #1: 1-chloro-3-(3-methylimidazolidin-1-yl)propan-2-ol chloride With n-butyllithium In hexane; dichloromethane; acetone at -78 - 20℃; for 1.5h; Inert atmosphere; Stage #2: chlorodicyclohexylphosphane In hexane; dichloromethane; acetone at -78 - 20℃; for 2h; Inert atmosphere; |
94.8% | Stage #1: 1-chloro-3-(3-methylimidazolidin-1-yl)propan-2-ol chloride With n-butyllithium In dichloromethane at -78 - 20℃; for 1.5h; Inert atmosphere; Schlenk technique; Stage #2: chlorodicyclohexylphosphane In dichloromethane at -78 - 20℃; for 2h; Inert atmosphere; Schlenk technique; | General procedure for the synthesis of phosphinites (1 and 2) General procedure: A dry and degassed CH2Cl2 (20 ml) solution of 1-(3-chloro- 2-hydroxypropyl)-3-methylimidazolium chloride under argon atmosphere (0.100 g, 0.474 mmol) was cooled to - 78 °C in acetone and dry ice bath. To the cooled solution, was added dropwise a hexane solution of n-BuLi (0.296 ml, 0.474 mmol). After the addition, the mixture was stirred at - 78 °C for 1 h and for an additional 30 min at room temperature. The reaction solution was cooled to - 78 °C again, and a solution of chlorodiphenylphosphine for 1 or chlorodicyclohexylphosphine for 2 (0.474 mmol) in CH2Cl2 (10 ml) was added dropwise to the reaction medium. Stirring was maintained for further 1 h at - 78 °C. Then, the cooling bath was removed and the mixture was stirred for another 1 h at room temperature. Precipitated lithium chloride was removed by filtration under argon, and then, the volatiles were evaporated in vacuo to leave viscous oily phosphinite ligand 1 or 2. The experimental details were in given in a reference by Aydemir et al. (2014). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | Stage #1: 1-(2-bromophenyl)-3,5-dimethyl-1H-pyrazole With n-butyllithium In tetrahydrofuran at -78 - 20℃; for 0.5h; Inert atmosphere; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran at -78 - 20℃; for 8h; Inert atmosphere; | 1-(2-(Dicyclohexylphosphino)phenyl)-3,5-dimethyl-1H-pyrazole (L1) To a stirred solution of 1-(2-bromophenyl)-3,5-dimethyl-1H-pyrazole (1d) (1.04g, 4mmol) in THF (15mL) under argon atmosphere was added n-BuLi (2.5mL, 4mmol, 1.6M in THF) dropwise at-78°C. The mixture was slowly warmed to rt and then stirred for a further 1/2 h at rt. After the mixture cooled to -78°C, chloro dicyclohexylphosphine (0.9mL, 4mmol) was added dropwise. The mixture was then warmed to rt and stirred for further 8h. It was then quenched with saturated NH4Cl solution at 0°C and extracted with diethyl ether (2×35mL). The combined organic layer was washed with water and brine and dried with anhydrous Na2SO4. Evaporation of the solvent under reduced pressure gave the crude product. Purification by flash column chromatography (silica gel 230-400 mesh, 2% ethyl acetate/petroleum ether) afforded ligand (L1) as a white solid (1.10g, 72%); Rf (10% ethyl acetate/petroleum ether) 0.56; mp 77°C-79°C; 1H NMR (CDCl3, 500.1MHz, ppm) δ 7.57 (d, J=5Hz, 1H, Ar-H), 7.44-7.40 (m, 2H, Ar-H), 7.30-7.29 (m, 1H, Ar-H), 5.96 (s, 1H, -CH of Pyrazole), 2.27 (s, 3H, -CH3), 2.08 (s, 3H, -CH3), 1.85-1.55 (m, 12H, Cy-H), 1.25-1.02 (m, 10H, Cy-H);13C NMR (CDCl3, 125.8MHz, ppm) δ 147.7, 146.0, 145.8, 140.5, 136.1, 135.9, 133.2, 129.5, 128.8, 128.3, 104.9, 33.8, 30.2, 30.0, 29.8, 29.7, 27.4, 27.4, 26.5, 13.7, 12.2, 12.1, 12.0; 31P NMR (CDCl3, 202.44MHz, ppm) δ-11.57 (s); HRMS(ESI) m/z calculated for C23H34N2P [M+H]+ 369.2460, found 369.2454; Anal. calcd for C23H33N2P C, 74.97; H, 9.03; N,7.60; found C, 74.67; H. 9.17; N, 7.50. |
72% | Stage #1: 1-(2-bromophenyl)-3,5-dimethyl-1H-pyrazole With n-butyllithium In tetrahydrofuran at -78 - 20℃; for 0.5h; Inert atmosphere; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran at -78 - 20℃; for 8h; Inert atmosphere; | 1-(2-(Dicyclohexylphosphino)phenyl)-3,5-dimethyl-1H-pyrazole (L1) To a stirred solution of 1-(2-bromophenyl)-3,5-dimethyl-1H-pyrazole (1d) (1.04 g, 4 mmol) in THF (15 mL) under argon atmosphere was added n-BuLi (2.5 mL, 4 mmol, 1.6 M in THF) dropwise at -78 °C. The mixture was slowly warmed to rt and then stirred for a further 1/2 h at rt. After the mixture cooled to -78 °C, chloro dicyclohexylphosphine (0.9 mL, 4 mmol) was added dropwise. The mixture was then warmed to rt and stirred for further 8 h. It was then quenched with saturated NH4Cl solution at 0 °C and extracted with diethyl ether (2×35 mL). The combined organic layer was washed with water and brine and dried with anhydrous Na2SO4. Evaporation of the solvent under reduced pressure gave the crude product. Purification by flash column chromatography (silica gel 230-400 mesh, 2% ethyl acetate/petroleum ether) afforded ligand (L1) as a white solid (1.10 g, 72 %); Rf (10% ethyl acetate/petroleum ether) 0.56; mp 77 °C - 79 °C; 1H NMR (CDCl3, 500.1 MHz, ppm) δ 7.57 (d, J=5Hz, 1H, Ar-H), 7.44-7.40 (m, 2H, Ar-H), 7.30-7.29 (m, 1H, Ar-H), 5.96 (s, 1H, -CH of Pyrazole), 2.27 (s, 3H, -CH3), 2.08 (s, 3H, -CH3), 1.85-1.55 (m, 12H, Cy-H), 1.25-1.02 (m, 10H, Cy-H);13C NMR (CDCl3, 125.8 MHz, ppm) δ 147.7, 146.0, 145.8, 140.5, 136.1, 135.9, 133.2, 129.5, 128.8, 128.3, 104.9, 33.8, 30.2, 30.0, 29.8, 29.7, 27.4, 27.4, 26.5, 13.7, 12.2, 12.1, 12.0; 31P NMR (CDCl3, 202.44 MHz, ppm) δ-11.57 (s); HRMS(ESI) m/z calculated for C23H34N2P [M+H]+ 369.2460, found 369.2454; Anal. calcd for C23H33N2P C, 74.97; H, 9.03; N,7.60; found C, 74.67; H. 9.17; N, 7.50 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.69 g | Stage #1: 2.3-dihydrobenzofuran With n-butyllithium In diethyl ether; hexane at 23℃; for 20h; Inert atmosphere; Stage #2: chlorodicyclohexylphosphane In diethyl ether at -40 - 23℃; Inert atmosphere; | 3 AP Ex 3 : Dicvclohexyl(2.3-dihvdrobenzofuran-7-yl)phosphine [0034] Prepare AP Ex 3 as follows to yield aryllithium (1.79 g). Repeat AP Ex 1, but with changes, add dihydrobenzofuran (2.65 g) to a glass jar. Stir the contents of the glass jar for 20 hrs at 23 °C. [0035] Add the aryllithium (1.79 g) and diethyl ether (40 mL) to a second glass jar to dissolve the aryllithium. Place the contents of the second glass jar in a freezer at -40 °C for 10 minutes. Add a PTFE-coated stirbar to the contents of the second glass jar and add dicyclohexylchlorophosphine (2.6 mL, 1 1.9 mmol) while stirring. Stir the contents of the second glass jar overnight at 23 °C. Add 30 mL of water to the contents of the second glass jar to quench the reaction. Isolate the organic layer and rinse with 20 mL of water. Dry the organic layer over MgS04, filter, and place under vacuum to remove solvent. Add hot (-50 °C) MeOH to the contents of the second glass jar to suspend oil. Decant the hot MeOH from the oil. Add hot (-50 °C) MeOH again to the contents of the second glass jar to suspend the oil. Decant the hot MeOH from the oil and cool the contents of the second glass jar in a freezer at -40 °C to produce AP Ex 3 (0.69 g) in a solid form. [0036] Analyze AP Ex 3 by XH, 13C, and 31P NMR spectroscopy to confirm formation. XH NMR (400 MHz, CD2C12) δ 7.18 (m, 2H), 6.82 (t, J= 7.4 Hz, 1H), 4.52 (t, J- 8.8 Hz, 2H), 3.19 (t, J= 8.7 Hz, 2H), 2.11 (m, 2H), 1.55-1.95 (m, 10H), 0.95-1.4 (m, 10H); "C^H} NMR (101 MHz, CD2C12) peaks not identified δ 164.44, 164.37, 134.80, 134.62, 127.12, 125.97, 120.40, 120.34, 116.31, 116.09, 71.13, 33.34, 33.22, 31.35, 31.17, 30.30, 30.12, 30.04, 27.87, 27.74, 27.67, 27.12; ^P^H} NMR (162 MHz, CD2C12) δ-5.3 (s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | Stage #1: 1‐(2,4,6‐triisopropylphenylsulfonyl)‐1H‐benzo[d]imidazole With n-butyllithium In tetrahydrofuran; toluene at -78℃; for 0.25h; Inert atmosphere; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran; toluene at -78 - 20℃; Inert atmosphere; | 20 Synthesis of 2-(dicyclohexylphosphino)-1-(2,4,6-triisopropylphenylsulfonyl)-1H-benzo[d]imidazole (2o) 1-(2,4,6-triisopropylphenylsulfonyl)-1H-benzo[d]imidazole (1d) (1.92 g, 5.0 mmol) was dissolved in freshly distilled THF (20 mL) and toluene (40 mL, the reaction mixture THF/toluene= 1:2) at room temperature under nitrogen atmosphere. The solution was cooled to -78°C in dry ice/acetone bath. Titrated n-BuLi (5.5 mmol) was added dropwise by syringe. The reaction mixture was further stirred for 15 min at -78°C and chlorodicyclohexylphosphine (1.33 mL,6.0 mmol) was then added dropwise by syringe. The reaction was allowed to reach room temperature and stirred for overnight. MeOH (~10 mL) was added slowly to quench the reaction. Solvent was removed under reduced pressure. Ethyl acetate (~200 mL) and water (~100 mL) was added to the mixture and the aqueous phase was separated. The organic phase was further washed with brine (~50 mL x 3), and dried by Na2SO4 and concentrated. The concentrated mixture was applied to 1 x 1 inch silica pad and eluted with diethyl ether. After the solvent was removed under vacuum, the white crystals (2o) (1.81 g, 77%) were obtained after re-crystallization from ether/hexane. Melting point: 208.8-210.0°C; 1H NMR (400 MHz, CD2Cl2) δ 0.87-1.36 (m, 30H), 1.53-1.86 (m, 8H), 2.05-2.11 (m, 2H), 2.91-2.98 (m, 1H), 4.23-4.29 (m, 2H), 7.20 (s, 2H), 7.37-7.44 (m, 2H), 7.78 (d, J = 7.2Hz, 1H), 8.09 (d, J = 7.6 Hz, 1H); 13C NMR (100MHz, CD2Cl2) δ 26.7, 26.8, 26.9, 29.2, 29.3, 29.5, 29.6, 29.8, 34.3, 34.7, 34.8, 113.9, 120.1, 123.7, 123.8, 124.9, 133.8, 134.3, 142.8, 151.6, 155.0, 155.9, 156.3 (complex unresolved C-P splitting was observed); 31P NMR (202 MHz, CD2Cl2) δ -14.25; IR (cm-1) 3447.50, 3048.54, 2927.62, 2850.75, 1599.22, 1583.18, 1560.10, 1550.26, 1459.10, 1445.69, 1426.76, 1375.85, 1346.95, 1332.42, 1292.71, 1251.55, 1229.16, 1181.46, 1157.48, 1142.31, 1106.33, 1057.58, 1037.79, 1023.23, 1011.10, 938.35, 902.43, 881.00, 850.61, 844.69, 816.68, 765.34, 746.69, 671.77, 654.25, 646.00, 624.02, 607.44, 575.97, 557.33, 542.45, 523.35, 433.64, 418.76; MS (EI): m/z (relative intensity) 580 (M+, 0), 383 (100), 231 (23), 207 (19); HRMS: calcd. for C34H49N2O2SPH+: 581.3331, found 581.3306. |
77% | Stage #1: 1‐(2,4,6‐triisopropylphenylsulfonyl)‐1H‐benzo[d]imidazole With n-butyllithium In tetrahydrofuran; toluene at -78℃; for 0.25h; Inert atmosphere; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran; toluene at 20℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | Stage #1: 9-(2-bromophenyl)-3,6-di-tert-butyl-9H-carbazole With n-butyllithium In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran at -78 - 20℃; for 12h; Inert atmosphere; | |
82% | Stage #1: 9-(2-bromophenyl)-3,6-di-tert-butyl-9H-carbazole With n-butyllithium In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran at -78 - 20℃; for 12h; Inert atmosphere; | |
82% | Stage #1: 9-(2-bromophenyl)-3,6-di-tert-butyl-9H-carbazole With n-butyllithium In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran at 20℃; for 24h; | 1 In a 100 ml three-necked flask, 2.17 g of 9- (2-bromophenyl) -3,6-di-tert-butyl-9H-carbazole (5.0Mmol), then the three bottles with nitrogen drainage,In the case of nitrogen by adding 25 ml of fresh steam tetrahydrofuran,Stir evenly. The mixture was cooled to -78 ° C with n-butyllithium (5.5 mmol)Reaction for 0.5 hours. And slowly adding 1.32 ml of dicyclohexylphosphonium chloride (6.0 mmol).Slowly rose to room temperature for 24 hours. Decompress all the solution,Washed twice with cold methanol,To give 2.26 g of pure product 9- (2-dicyclohexylphosphonophenyl) -3,6-di-tert-butyl-9H-carbazole as a white powder. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | At 0 C,42 ml of 2.5M n-butyl lithium was added dropwise to the reaction liquid. After the addition, the reaction was continued for 1 hour.26.7g of dicyclohexyl phosphine was added dropwise, and the temperature was naturally warmed to react at room temperature for 2 hours. 200 ml saturated ammonium chloride aqueous solution was added dropwsie to the reaction liquid under the ice bathto quench the reaction.After phase separation, the organic phase was precipitated,and methanol was added for crystallization. Byfiltering,45g white product of 2?-dicyclohexyl phosphino-2, 4, 6-tri-isopropyl biphenyl was obtained, with a yield of 90%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | Stage #1: 6,6'-dimethyl-2,2'-bipyridine With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at 0 - 25℃; for 1h; Inert atmosphere; Stage #2: chlorodicyclohexylphosphane With borane-THF In tetrahydrofuran; hexane | A2.1 (1) Synthesis of Compound 6 A stirrer, 6,6′-bi-2-picoline (1850.0 mg, 10 mmol) and THF (60 mL) were placed in a 1,000-mL double neck flask that had been dried and substituted with argon gas, and the mixture was sufficiently stirred. Thereafter, while stirring, the flask was sufficiently cooled by being immersed in a refrigerant (icy water) at 0° C., thereby obtaining a 6,6′-bi-2-picoline-THF solution. THF (30 mL) and diisopropylamine (8.4 mL, 60 mmol) were placed in a 300-mL double neck flask that had been dried and substituted with argon gas, and the mixture was sufficiently stirred. Thereafter, while stirring, the flask was sufficiently cooled by being immersed in a refrigerant (icy water) at 0° C. A n-butyllithium-hexane solution (40-mL, 1.5-M hexane solution, 60 mmol) was gradually added dropwise to the solution, thereby causing a reaction. Subsequently, the stirring of the reaction solution continued for another 10 minutes while keeping the temperature of the reaction solution at 0° C., thereby obtaining a lithium diisopropylamide-THF solution. Subsequently, the lithium diisopropylamide-THF solution was added dropwise to the double neck flask containing the 6,6′-bi-2-picoline-THF solution using a cannular, thereby causing a reaction; as a result, a colorless and transparent reaction solution was changed to a bluish-purple solution. While thus adding the lithium diisopropylamide-THF solution dropwise, the temperature inside the flask was kept at 0° C. After the dropwise addition was completed, the flask was taken out of the refrigerant. While the stirring of the reaction solution continued, the solution was restored to room temperature (25° C.). After an hour, chlorodicyclohexylphosphine (4.4 mL, 20 mmol) was added dropwise to the reaction solution, and the stirring of the solution continued for another 2 and a half hours. Subsequently, a borane-THF solution (100-mL, 1.0-M THF solution, 100 mmol) was added, and the stirring continued overnight. Thereafter, the flask was sufficiently cooled by being immersed in a refrigerant (icy water) at 0° C. After cooling, water was added to the reaction solution, and the whole solution was concentrated by an evaporator. The obtained residue was transferred to a 1,000-mL separatory funnel, and 100 mL of distilled water, 50 mL of dichloromethane and a small amount of saturated saline were added. This mixture was subjected to separation and extraction four times in total, and the desired organic compound was extracted in the organic layer (dichloromethane layer). The resulting organic layer was dehydrated with sodium sulfate. A filtrate obtained by filtration was concentrated by an evaporator. After the concentration, a small amount of THF was added to the resulting residue to suspend the residue. White powder was obtained by filtration. The white powder was washed with THF several times, thereby obtaining 2,417.6 mg (4.0 mmol) of a 6,6′-bis dicyclohexyl phosphino methyl-2,2′-bipyridine borane complex (Compound 6) as a white powder at an isolation yield of 40%. The spectral data of Compound 6 is shown below. 1H NMR (600 MHz, CDCl3): δ 8.29 (d, 2H, J=8.3 Hz, C10H6N2), 7.75 (t, 2H, J=7.6 Hz, C10H6N2), 7.31 (d, 2H, J=7.6 Hz, C10H6N2), 3.31 (d, 4H, J=11.0 Hz, PCH2), 1.60-2.00 (m, 24H, C6H11), 1.11-1.50 (m, 20H, C6H). 13C NMR (151 MHz, CDCl3): δ 155.2, 154.5 (d, 2JPC=7.2 Hz), 137.2, 125.0, 118.7, 31.5 (d, 1JPC=30.3 Hz), 30.5 (d, 1JPC=27.5 Hz), 27.01, 26.94, 26.86, 26.75, 26.63, 25.97. 31P{1H} NMR (243 MHz, CDCl3): δ 28.6, HRMS (ESI, (M+H)+) Calcd for C36H60B2N2P2+: 605.4502. Found m/z=605.4502 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | Under the protection of nitrogen, 200 ml of THF and 31g of 2, 4, 6-tri-isopropyl-bromobenzene was added to 1L three-mouth bottle. The temperature was cooled down to 0 C, and 46 ml of 2.5M n-butyl lithiumwas added dropwise. The reaction was continued for 1 hour after the addition. At 0 C, 24.6g O-dibromobenzene was added dropwise. The reaction was continued for 1 hour after the addition. At0 C, 42 ml of 2.5M n-butyl lithiumwas added dropwise to the reaction liquid.After the addition, the reaction was continued for 1 hour. 26.7g of dicyclohexyl phosphine was added dropwise, and the temperature was naturally warmed to react at room temperature for 2 hours. 200 ml saturated ammonium chloride aqueous solution was added dropwsie to the reaction liquid under the ice bath to quench the reaction. After phase separation, the organic phase was precipitated, and methanol was added for crystallization. Byfiltering, 44.5g white product of 2?-dicyclohexyl phosphino-2, 4, 6-tri-isopropyl biphenyl was obtained, with a yield of 89%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | Stage #1: tetra(4-bromobiphenyl)silane With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1.5h; Schlenk technique; Inert atmosphere; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran; hexane at -78 - 20℃; Schlenk technique; Inert atmosphere; | Synthesis of Si(p-C6H4-p-C6H4PCy2)4 (3): General procedure: The synthesis of 3 was performed in analogy to the synthesis of 2 described above. Compound 3 was obtained as a white powder in a yield of 93%. 1H NMR (CDCl3, 500.1 MHz): δ = 7.75 (H2, d, 3J(H-H) = 8.1 Hz), 7.70 (H3, d 3J(H-H) = 8.3 Hz), 7.64 (H7, d, 3J(H-H) = 7.8 Hz), 7.56 (H6, dd, 3J(H-H) = 7.3 Hz, 3J(P-H) = 7.3 Hz), 1.98-1.66 (9, 10e, 11e, 13e, 12e, 14e, m), 1.43-0.91 (11a, 13a, 10a, 12a, 14a, m) ppm ((Fig. 3); 13CNMR (CDCl3, 125.8 MHz): δ 141.70 (C4, s), 140.91 (C5, s), 136.91 (C2,s), 135.18 (C7, d, 2J(P-C) 19.1 Hz), 134.02 (C8, d, 1J(P-C) 17.7 Hz),133.05 (C1, s), 126.54 (C3, s), 126.40 (C6, d, 3J(P-C) 7.4 Hz), 32.49(C9, d, 1J(P-C) 11.2 Hz), 30.01 (C10, d, 2J(P-C) 15.8 Hz), 28.82(C14, d, 2J(P-C) 7.0 Hz), 27.24 (C11, d, 3J(P-C) 12.6 Hz), 27.00(C13, d, 3J(P-C) 7.4 Hz), 26.39 (C12, s) ppm; 31P NMR (CDCl3,162.0 MHz) 1.92 ppm. mp 117 °C. ESI-MS+: [M+1] 1425.78 (96%)and [M+2] 1426.76 (100%) plus decomposition products, calculated1425.81 (92%), 1426.81 (100%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 2-bromo-1-(trimethylsilylethynyl)benzene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1h; Inert atmosphere; Schlenk technique; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran; hexane at -78 - 20℃; for 2h; Inert atmosphere; Schlenk technique; | General procedure for the synthesis of compound 1. General procedure: The starting ortho-bromophenylalkynes were synthesized by Sonogashira coupling. 1a, 1h-1n were synthesizedaccording to the literature procedures[1-3], other new compounds 1 were synthesized as similar procedures: To asolution of alkyne (8 mmol) in THF (25 mL) was added dropwise n-butyllithium in n-hexane (5.5 ml, 1.6 mol/L, 8.8mmol) at -78 oC over 15 minutes under N2 atmosphere. The reaction mixture was stirred for 45 minutes at -78 oC, thenR2PCl (8 mmol) was added, after that the mixture was slowly warmed to room temperature and stirred for another 2hours to give a pale yellow solution. After removal of the solvent under reduced pressure by the rotating instrument,the crude residue was chromatographed over silica gel to give pure products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | Stage #1: 1-([(1R,2R)-2-[(2-hydroxynaphthalen-1-yl)methylidene]amino}cyclohexyl]imino}methyl)-naphthalen-2-ol With triethylamine In dichloromethane for 0.166667h; Inert atmosphere; Schlenk technique; Stage #2: chlorodicyclohexylphosphane In dichloromethane at 20℃; Inert atmosphere; Schlenk technique; | 2.1.2.1. General procedure for the synthesis of bis(phosphinite) ligands(1-3) General procedure: The new chiral C2-symmetric bis(phosphinite) ligands were prepared according to the our recent publications [33]. To a solution of 1-([(1R,2R)-2-[(2-hydroxynaphthalen-1-yl)methylidene] amino}cyclohexyl]imino}methyl)-naphthalen-2-ol (1.5 mmol) in dry CH2Cl2 (20 mL) was added triethylamine (3.0 mmol) and the mixture was stirred for 10 min under argon atmosphere. To this solution was added dropwise Ph2PCl (3.0 mmol), (i-Pr)2PCl (3.0 mmol) or (Cy)2PCl (3.0 mmol). The mixture was then stirred at room temperature until the reactions were completed. A white precipitate of triethylamine hydrochloride was removed by filtration under argon and the remaining organic phase was evaporated under reduced pressure to produce a yellow oily product. The progress of these reactions was followed by 31P-{1H} NMR spectroscopy. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | 1) Under the protection of argon, add 1L of reaction solvent tetrahydrofuran and fluorobenzene (96g, 1mol) to the dry reactor,At -78C, 1.1L of 1M LDA tetrahydrofuran solution was added, and after reacting at this temperature for 2 hours, dicyclohexyl phosphine chloride (255 g, 1.1 mol) was added and the temperature was slowly raised to 15C for 10 hours.2) Add 1L of reaction solvent tetrahydrofuran into another dry reactor,Sequentially add 1,3,5-<strong>[717-74-8]triisopropylbenzene</strong> (205g, 1mol), potassium tert-butoxide (123g, 1.1mol), then add 0.44L of 2.5M n-butyllithium n-hexane solution at 0, and then heat to React at 30C for 4 hours, transfer the reaction system of step 1) to this reaction system, then heat to 60C for 12 hours, add water to quench the reaction, extract, dry, and recrystallize from methanol to obtain 2-dicyclohexylphosphine- 2',4',6'-triisopropylbiphenyl 442g, the yield is 93% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | Stage #1: chlorodicyclohexylphosphane With magnesium In tetrahydrofuran at -10 - 10℃; for 2h; Inert atmosphere; Stage #2: 2-bromo-3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl With bis(η3-allyl)nickel(II) In tetrahydrofuran at 80℃; for 12h; | 1 Example 1: Synthesis of 2-Dicyclohexylphosphine-3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl Under the protection of argon, 0.5L of tetrahydrofuran and magnesium metal (26g, 1.1mol) were added to the dry reactor, and then dicyclohexylphosphine chloride (232g, 1mol) was added at -10-10°C to react for 2 hours, then add nickel catalyst Ni(π-C3H5)2 (7g, 0.05mol) and 2-bromo-3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl (419g, 1mol), then the temperature was raised to 80°C and reacted for 12 hours, then 500mL of saturated ammonium chloride aqueous solution was added to quench the reaction, then the solvent was removed by liquid separation, the organic phase was concentrated to remove the solvent, and recrystallized from methanol 487 g of 2-dicyclohexylphosphine-3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl was obtained with a yield of 91%. |
90.3% | With n-butyllithium In hexane |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With n-butyllithium In tetrahydrofuran at 20℃; diastereoselective reaction; | |
89% | Stage #1: C22H27FeN With n-butyllithium In diethyl ether; hexane at 25℃; Schlenk technique; Inert atmosphere; Molecular sieve; Stage #2: chlorodicyclohexylphosphane In diethyl ether; hexane at 38℃; for 17h; Schlenk technique; Inert atmosphere; Reflux; | 10 Preparation In a 100mL Schlenk reaction flask, the product of Example 2 (1.8g, 5mmol) was replaced with nitrogen three times,Add 40 mL of dry molecular sieve ether, room temperature 25, drop 2.4M n-BuLi hexane solution (4.2mL, 10mmol) into the syringe pump within 1.5 hours, continue lithiation at room temperature 25 for 4-6 hours, Then the oil bath is heated to 38°C, and dicyclohexylchlorophosphine (1.74 g, 7.5 mmol) is added dropwise to the syringe pump within 1 hour, and the reaction is refluxed overnight for 16 hours. The TLC spot plate reaction was complete, and column chromatography using petroleum ether and ethyl acetate as solvents to obtain 2.48 g of an orange oily compound (refrigerated as a solid), with a yield of 89%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | Stage #1: 2-bromo-2’,4’,6’-triisopropyl-6-methyl-3-(3-pentyloxy)-1,1’-biphenyl With tert.-butyl lithium In tetrahydrofuran; pentane at -78℃; for 0.5h; Schlenk technique; Inert atmosphere; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran; pentane at -78 - 20℃; for 4h; Schlenk technique; Inert atmosphere; | |
90% | Stage #1: 2-bromo-2’,4’,6’-triisopropyl-6-methyl-3-(3-pentyloxy)-1,1’-biphenyl With tert.-butyl lithium In tetrahydrofuran at -78℃; for 0.5h; Schlenk technique; Inert atmosphere; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran at 20℃; for 4h; Inert atmosphere; Schlenk technique; | 26 Synthesis of 2-dicyclohexylphosphino-2', 4', 6'-triisopropyl-3- (3-pentyroxy) -6-methylbiphenyl (formula (1a-20) above) Under air, in a 20 mL Schlenk flask, stirrer, 2-bromo-2', 4', 6'-triisopropyl-6-methyl-3- (3-pentyroxy) biphenyl 229 mg (0. 50 mmol) was added and a flask was attached. The inside of the reaction vessel was replaced with argon, 2.0 mL of tetrahydrofuran was added, and the mixture was cooled to -78 ° C. with acetone / dry ice. 0.70 mL of 1.52 M tert-butyllithium pentane solution was slowly added dropwise, stirred at -78 ° C. for 30 minutes, and then 121 μL (0.55 mmol) of chlorodicyclohexylphosphine was slowly added. The reaction vessel was returned to room temperature, stirred for 4 hours, and then the solid was removed by filtration. The residue obtained by concentration was purified by recrystallization using hot acetone, and 2-dicyclohexylphosphino-2', 4', 6'-triisopropyl-3- (3-pentyroxy) -6-methylbiphenyl. Was obtained as a colorless solid in an amount of 258 mg (yield 90%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | Stage #1: 2-bromo-3-cyclohexyloxy-2’,4’,6’-triisopropyl-6-methyl-1,1’-biphenyl With tert.-butyl lithium In tetrahydrofuran at -78℃; for 0.5h; Schlenk technique; Inert atmosphere; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran at 80℃; for 96h; Schlenk technique; Inert atmosphere; | 27 Synthesis of 3-cyclohexyloxy-2-dicyclohexylphosphino-2', 4', 6'-triisopropyl-6-methylbiphenyl (compound represented by the above formula (1a-21)) Under air, in an 80 mL Schlenk flask, stirrer, 2.6 g (5.5 mmol) of 2-bromo-3-cyclohexyloxy-2', 4', 6'-triisopropyl-6-methylbiphenyl synthesized in Synthesis Example 2. ) Was added and the flask was attached. The inside of the reaction vessel was replaced with argon, 40 mL of tetrahydrofuran was added, and the mixture was cooled to -78 ° C. with acetone / dry ice. 6.8 mL of 1.61 M tert-butyllithium pentane solution was slowly added dropwise, stirred at -78 ° C. for 30 minutes, and then 1.7 mL (7.7 mmol) of chlorodicyclohexylphosphine was slowly added. The reaction vessel was heated to 80 ° C., stirred for 4 days, returned to room temperature, and the solid was removed by filtration. The residue obtained by concentration is purified by recrystallization using hot acetone, and 3-cyclohexyloxy-2-dicyclohexylphosphino-2', 4', 6'-triisopropyl-6-methylbiphenyl is a colorless solid. As a result, 2.5 g was obtained (yield 77%). |
65% | Stage #1: 2-bromo-3-cyclohexyloxy-2’,4’,6’-triisopropyl-6-methyl-1,1’-biphenyl With tert.-butyl lithium In tetrahydrofuran; pentane at -78℃; for 0.833333h; Schlenk technique; Inert atmosphere; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran; pentane at 80℃; for 48h; Schlenk technique; Inert atmosphere; |
Tags: 16523-54-9 synthesis path| 16523-54-9 SDS| 16523-54-9 COA| 16523-54-9 purity| 16523-54-9 application| 16523-54-9 NMR| 16523-54-9 COA| 16523-54-9 structure
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