(-)-3-Chloro-1-phenyl-1-propanol

3.36 g (40.0 mmol) of HCOOK as the hydrogen source, 2.609 mg (4.0 μmol) of Cp*IrCl[(S, S)-MsDPEN] as the catalyst, and 1.349 g (8.0 mmol) of β-chloropropiophenone were introduced in a 20 mL Schlenk tube, and the mixture was subjected to argon substitution. 2 mL of water and 2 ml of toluene were added and the resulting mixture was maintained at 50° C. for 24 hr while stirring. The organic phase was washed three times with 3 mL of water, and the toluene was distilled off under reduced pressure to give an optically-active alcohol. GC analysis of the reactant confirmed that 3-chloro-1-phenylpropane-1-ol with optical purity of 85percent ee was produced in 94percent yield.Cat-6 (1.78 mmol, 575 mg) prepared in Preparation 2.6 was dissolved in 25 mL of THF, BH3-DMS (12.5 mmol, 1.18 mL) was added, and the mixture was stirred for about 7 minutes. To the reaction mixture was added dropwise a solution of 3-chloropropiophenone (17.8 mmol, 3.0 g) dissolved in 6 ml of THF dropwise over 10 minutes. After reacting at room temperature for 2 hours, the reaction was terminated by the addition of methanol. Example 1.1.(S) -3-chloro-1-phenyl-propanol (yield: 94percent, 91percent ee).The above compound was recrystallized from the nucleic acid to obtain (S) -3-chloro-1-phenyl-propanol (84percent recovery) with 99percent ee.Cat-1 (1.78 mmol, 575 mg) prepared in Preparation 1.1 was dissolved in 25 mL of THF, BH3-DMS (12.5 mmol, 1.18 mL) was added, and the mixture was stirred for about 7 minutes. A solution of 3-chloropropiophenone (17.8 mmol, 3.0 g) in 6 mL of THF was added dropwise to the reaction mixture dropwise over 10 minutes. After reacting at room temperature for 2 hours, the reaction was terminated by the addition of methanol. After removal of the solvent, ethyl acetate and water were added to separate the organic layer. Ethyl acetate was added to the separated aqueous layer to further extract it. The organic layers were combined, dried over Na2SO4, and filtered. The obtained filtrate was concentrated and purified by column chromatography (hexane: ethyl acetate = 3: 1) to obtain (S) -3-chloro-1-phenylpropan-1-ol (yield: 94percent & Lt; / RTI & gt; The above compound was recrystallized in a nucleic acid to obtain (S) -3-chloro-1-phenylpropan-1-ol (84percent recovery) at 99percent ee.To a stirred solution of (R)-(+)-2-methyl-CBS-oxazaborolidine (29 mg, 0.107 mmol) in anhydrous toluene (3 mL) was added N, N-diethylaniline borane (0.63 mL, 3.558 mmol) at room temperature. 3-Chloropropiophenone (2) (0.3 g, 1.779 mmol) in anhydrous toluene (3 mL) was slowly added with the aid of a syringe pump over 5 h under NFollowing a procedure recently reported by Wu and Li, 25Cu(OAc)2·H2O (119.8 mg, 0.6 mmol) and (S)-P-Phos (151.4 mg, 0.2mmol) were weighed under air and dissolved in toluene (66 mL). The reaction mixture was stirred at r.t. for 20 min, then a solution of phenylsilane(3 mL, 24 mmol) in toluene (32 mL) was added. The mixturewas cooled to –20 °C and a solution of 3-chloro-1-propiophenone(13) (3.4 g, 20 mmol) in toluene (32 mL) was added under vigorous stirring. The flask was stoppered and the reaction mixture was stirred for 24 h at the above temperature. Upon completion, the mixture was treated with 10percent HCl (130 mL) and the organic product was extracted with Et2O (3 × 150 mL). The combined organic layers were washed with H2O, dried over MgSO4, filtered and concentrated in vacuo. Purification by column chromatography on silica gel (hexane/EtOAc, 10:1)afforded alcohol (S)-23 (2.5 g, 73percent) as a white solid.The ee value was determined by chiral HPLC analysis with a Chiralcel IB column (eluent: hexane/2-propanol = 98:2; flow rate: 1 mL/min;detection: 254 nm), tR (R) = 16.2 min (areapercent 97), tR (S) = 18.1 min (areapercent3). Spectral data matched those previously reported for 23. Theoptical rotation matched literature data.32 [α]D27.4 –23 (c 1.0, CHCl3).General procedure: Erlenmeyer flasks (300 ml), each containing 100 ml of the medium consisting of 3 g glucose and 1 g aminobac dissolved in water, were inoculated with a suspension of microorganisms and then incubated for 3–7 days at 25 C on a rotary shaker (190 rpm). After full growth of the culture 20 mg of a substrate dissolved in 1 ml of acetone was added. After 1, 3, 6, 9, 12 h and 1, 3, 6, 9 days of incubation under the above conditions, portions of 5 ml of the transformation mixture were taken out and extracted with CHClCat-5 (0.05 mmol, 20 mg) prepared in Preparation Example 2.5 was dissolved in 1 ml of THF, BH3-DMS (0.42 mmol, 0.04 ml) was added, and the mixture was stirred for about 7 minutes. A solution of 3-chloropropiophenone (0.6 mmol, 100 mg) in 0.45 ml of THF was added dropwise to the reaction mixture. After reacting at room temperature for 2 hours, the reaction was terminated by the addition of methanol. (R) -3-chloro-1-phenylpropanol (yield: 75percent, 73percent ee) was obtained in the same manner as in Example 1.1.6.127 mg (8.0 μmol) of Cp*Ir(OTf)[(S, S)-MsDPEN] and 1.249 g (8.0 mmol) of β-chloropropiophenone were introduced in an autoclave, and the mixture was subjected to argon substitution. 3.3 mL of methanol was introduced and deaeration was performed, then hydrogen gas was introduced at 10 atm and the resulting mixture was maintained at 60° C. for 24 hr while stirring. The solvent was distilled off under reduced pressure to give a crude product. GC analysis of the reactant confirmed that 3-chloro-1-phenylpropane-1-ol with optical purity of 77percent ee was produced in 12percent yield. Comparison with Example E-1 demonstrated the superiority of the asymmetric reduction using a potassium formate solution as the hydrogen source.General procedure: To a solution of 1 (0.005–0.01 mmol, 0.5–1 mol percent) in dry THF(3 mL) at room temperature, a solution of BH3SMe2 (10 M, 100 lL, 1 mmol) in THF (2 mL) was added dropwise at a rate of3.2 mL per hour using a syringe pump. At the same time a solutionof ketone (1 mmol) in THF (2 mL) was also added to the reactionflask at a rate of 3 mL per hour. After the addition of both reagents, the reaction mixture was stirred for 20 min, quenched by the additionof MeOH (1 mL) at room temperature, and stirred for 30 min. Subsequently, the solvents were evaporated under vacuum and theproduct was isolated by column chromatography using hexane/EtOAc (4:1) as the eluent.General procedure: A flask was charged with azolium salt L12 (0.02 mmol, 9.1 mg), Ag2O (0.01 mmol, 2.4 mg) and CH2Cl2(1 mL). After stirring the resulting mixture at room temperature for 2 h in the dark, CH2Cl2 was removed in vacuo. Then, a THF (1 mL) solution of [IrCl(cod)]2(0.01 mmol, 6.9 mg) was added to the reaction vessel. The resulting mixture was stirred at room temperature for an additional 4 h in the dark, filtered through a membrane filter, and evaporated to dry-ness in vacuo. Subsequently, to the resulting flask containing yellow solid of the unpurified IrCl(cod)(NHC) complex, a solution of AgBF4(0.025 mmol, 4.9 mg) in CPME (2 mL) was added, and then stirred at room temperature for 1 h. Finally, propiophenone (0.5 mmol, 66 mg) and (EtO)2MeSiH (2.25 mmol, 294 mg) were added to the resulting CPME solution (see Appendix A. Supplementary data fordetails). After stirring at room temperature for 20 h under open-air conditions, K2CO3(2 mg) and MeOH (2 mL) were added. Then, the resulting mixture was stirred at room temperature for 2 h. Afterevaporation of the solvents, the residue obtained was purified bycolumn chromatography on silica gel (Et2O/n-hexane = 3:7) to give(S)-1-phenyl-1-propanol (61 mg, 91percent isolated yield). The ee was measured by chiral GLC.General procedure: In a typical procedure, isopropenyl acetate (1.5 equiv.) was added to a 4 mL-vial containing BSLPL-1c-D (3 mg), substrate (0.3 mmol), and anhydrous toluene (0.5 M). The resulting solution was then shaken at 25 °C until the reaction reached 46–50percent conversion. After being diluted with methylene chloride, the reaction mixture was filtered through a celite pad, concentrated, and then analyzed by HPLC to determine the enantiomeric excesses of remaining substrate and acetylated product. The enantioselectivity (E) was then calculated using the equation: E = ln[1−c(1+eeGeneral procedure: Fresh plates of each yeast strain were streaked from the frozen stock in PDA. A single colony was used to inoculate 100mL of YM Broth. The culture was incubated at 28°C and 150rpm for 48h and the cells were collected by centrifugation at 4000rpm and 4°C for 15min. The pellet was washed three times with 50mL physiological serum. Afterward, 2g of yeast cells (wet weight) were suspended in 20mL of 10percent dextrose solution and 30mg of the appropriate substrate were added. The culture was incubated at 28°C and 150rpm in an orbital shaker ZHICHENG ZHWY-211B for 48h.General procedure: Erlenmeyer flasks (300 ml), each containing 100 ml of the mediumconsisting of 3 g glucose and 1 g aminobac dissolved in water, were inoculated with a suspension of microorganisms and then incubated for 3–7 days at 25 C on a rotary shaker (190 rpm). After full growth of the culture 20 mg of a substrate dissolved in 1 ml of acetone was added. After 1, 3, 6, 9, 12 h and 1, 3, 6, 9 days of incubation under the above conditions, portions of 5 ml of the transformation mixture were taken out and extracted with CHClGeneral procedure: Erlenmeyer flasks (300 ml), each containing 100 ml of the mediumconsisting of 3 g glucose and 1 g aminobac dissolved in water, were inoculated with a suspension of microorganisms and then incubated for 3–7 days at 25 C on a rotary shaker (190 rpm). After full growth of the culture 20 mg of a substrate dissolved in 1 ml of acetone was added. After 1, 3, 6, 9, 12 h and 1, 3, 6, 9 days of incubation under the above conditions, portions of 5 ml of the transformation mixture were taken out and extracted with CHClGeneral procedure: Erlenmeyer flasks (300 ml), each containing 100 ml of the mediumconsisting of 3 g glucose and 1 g aminobac dissolved in water, were inoculated with a suspension of microorganisms and then incubated for 3–7 days at 25 C on a rotary shaker (190 rpm). After full growth of the culture 20 mg of a substrate dissolved in 1 ml of acetone was added. After 1, 3, 6, 9, 12 h and 1, 3, 6, 9 days of incubation under the above conditions, portions of 5 ml of the transformation mixture were taken out and extracted with CHClGeneral procedure: Erlenmeyer flasks (300 ml), each containing 100 ml of the mediumconsisting of 3 g glucose and 1 g aminobac dissolved in water, were inoculated with a suspension of microorganisms and then incubated for 3–7 days at 25 C on a rotary shaker (190 rpm). After full growth of the culture 20 mg of a substrate dissolved in 1 ml of acetone was added. After 1, 3, 6, 9, 12 h and 1, 3, 6, 9 days of incubation under the above conditions, portions of 5 ml of the transformation mixture were taken out and extracted with CHClGeneral procedure: Erlenmeyer flasks (300 ml), each containing 100 ml of the mediumconsisting of 3 g glucose and 1 g aminobac dissolved in water, were inoculated with a suspension of microorganisms and then incubated for 3–7 days at 25 C on a rotary shaker (190 rpm). After full growth of the culture 20 mg of a substrate dissolved in 1 ml of acetone was added. After 1, 3, 6, 9, 12 h and 1, 3, 6, 9 days of incubation under the above conditions, portions of 5 ml of the transformation mixture were taken out and extracted with CHClGeneral procedure: Erlenmeyer flasks (300 ml), each containing 100 ml of the mediumconsisting of 3 g glucose and 1 g aminobac dissolved in water, were inoculated with a suspension of microorganisms and then incubated for 3–7 days at 25 C on a rotary shaker (190 rpm). After full growth of the culture 20 mg of a substrate dissolved in 1 ml of acetone was added. After 1, 3, 6, 9, 12 h and 1, 3, 6, 9 days of incubation under the above conditions, portions of 5 ml of the transformation mixture were taken out and extracted with CHClGeneral procedure: Erlenmeyer flasks (300 ml), each containing 100 ml of the mediumconsisting of 3 g glucose and 1 g aminobac dissolved in water, were inoculated with a suspension of microorganisms and then incubated for 3–7 days at 25 C on a rotary shaker (190 rpm). After full growth of the culture 20 mg of a substrate dissolved in 1 ml of acetone was added. After 1, 3, 6, 9, 12 h and 1, 3, 6, 9 days of incubation under the above conditions, portions of 5 ml of the transformation mixture were taken out and extracted with CHClGeneral procedure: Erlenmeyer flasks (300 ml), each containing 100 ml of the mediumconsisting of 3 g glucose and 1 g aminobac dissolved in water, were inoculated with a suspension of microorganisms and then incubated for 3–7 days at 25 C on a rotary shaker (190 rpm). After full growth of the culture 20 mg of a substrate dissolved in 1 ml of acetone was added. After 1, 3, 6, 9, 12 h and 1, 3, 6, 9 days of incubation under the above conditions, portions of 5 ml of the transformation mixture were taken out and extracted with CHCl

Molecular Weight:170.63
XLogP3:2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:3
Exact Mass:170.0498427
Monoisotopic Mass:170.0498427
Topological Polar Surface Area:20.2
Heavy Atom Count:11
Complexity:99.7
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes