Asymmetric Borane Reduction of Prochiral Ketone Using Chiral Bis(.ALPHA.,.ALPHA.-diphenyl-2-pyrrolidinemethanol) Carbonate.

Abstract

Several asymmetric borane reductions of prochiral ketones using a chiral oxazaborolidine catalyst prepared from a chiral b-amino alcohol have been reported. [1][2][3][4][5][6] Especially, the use of the oxazaborolidine, MeCBS or HCBS, prepared from chiral a,a-diphenyl-2-pyrrolidinemethanol (DPP) for the asymmetric borane reduction of various ketones showed high enantioselectivities ( Fig. 1). HCBS could be synthesized from DPP and a reducing reagent such as the borane-dimethyl sulfide complex (BH 3 · Me 2 S) or the borane-tetrahydrofuran complex. However, the synthesis of HCBS requires a long reaction time in tetrahydrofuran (THF).3) Masui and Shioiri reported the asymmetric reduction by BH 3 · Me 2 S using a catalyst easily generated in situ from chiral DPP and trimethyl borate. 7) We have also reported the efficient catalyst prepared from aluminum triethoxide 8) and DPP for asymmetric borane reduction. However, the additive, trimethyl borate or aluminum triethoxide, is necessary to prepare the catalysts in these methods. Mathre et al. tried to prepare a borane complex of HCBS in toluene by the same procedure used to prepare a borane complex of MeCBS (Fig. 1), but they obtained only a dimer complex.5) Salunkhe and Burkhardt reported that the complex generated from the chiral DPP and borane in toluene included the dimer complex.6) Efforts to use the dimer complex as a catalyst resulted in a low enantioselectivity for the reduction of acetophenone.In this paper, we report the asymmetric borane reduction of a prochiral ketone using a catalyst generated in situ from DPP and BH 3 · Me 2 S in various solvents. We also report that the carbonate of DPP is useful for the reduction.In our previous report, 8) we described that the asymmetric reduction of acetophenone using (S)-DPP and BH 3 · Me 2 S in THF required a long reaction time (1.5 h) after the addition of the ketone and gave (1R)-1-phenylethanol with 94.7% ee. During the reaction, immediately after BH 3 · Me 2 S was added to a solution of (S)-DPP in THF, the addition of the ketone to the solution was started. We thought that if the mixture of (S)-DPP and BH 3 · Me 2 S was stirred to prepare a catalyst for a sufficient time before the addition of the ketone, the reaction time would be shorter and the optical purity of the alcohol would be higher.First we examined the asymmetric borane reduction of acetophenone using a catalyst generated in situ from DPP and BH 3 · Me 2 S in various solvents. A catalyst solution was generated from (S)-DPP (0.5 mmol) and BH 3 · Me 2 S (5 mmol) in each solvent (5 ml) by stirring at room temperature for 1 h. A solution of acetophenone (5 mmol) in each solvent (10 ml) was then added dropwise to the catalyst solution via a syringe pump at room temperature over 1 h. The reaction solution was stirred until the acetophenone disappeared based on TLC. The resulting solution was quenched with 1 mol/l HCl. The usual workup provided (1R)-1-phenylethanol. These results are shown in Table 1. The reaction in THF, ether, or hexane gave (1R)-1-pheny...

Practical Enantioselective Reduction of Ketones Using Oxazaborolidine Catalysts Generated In Situ from Chiral Lactam Alcohols

“…The 11 B NMR (CDCl 3 ) spectrum indicated the presence of the oxazaborolidine complex with borane (+17.7 ppm and −13.2 ppm) and free oxazaborolidine (+27.2 ppm) [ 14 ]. These chemical shifts were mostly consistent with those of the oxazaborolidine 1a generated in situ from ( S )-diphenylpyrrolidinemethanol and borane [ 10 ] under the same conditions.…”

“…We considered that the chiral lactam alcohol 2 [ 13 ], ( S )-5-(diphenylhydroxymethyl)pyrrolidin-2-one, could be rapidly reduced with borane to the corresponding imine, which would be further reduced by the neighboring alkoxyborane to form the oxazaborolidine 1a ( Scheme 2 ). This was inferred from the report that the racemic amino alcohol 1 could be prepared from the racemic lactam alcohol 2 through its reduction with borane [ 10 ].…”

“…On the other hand, Quallich et al reported that the reaction of 1 with excess borane-dimethyl sulfide complex (BH 3 -Me 2 S) formed the oxazaborolidine 1a in THF at room temperature for 8–10 h ( Scheme 1 ) [ 9 ]. Later, Yanagi et al also reported that the catalyst 1a was generated from 1 and BH 3 -Me 2 S in THF, ether, and hexane at room temperature for 1 h [ 10 ]. Although the B-Me oxazaborolidine 1b formed by the reaction of 1 with methylboronic acid has been developed as an air- and moisture- stable catalyst that catalyzes the borane reduction of ketones with an excellent enantioselectivity [ 11 ], there is the requirement of complete removal of water to avoid undesired effects [ 12 ].…”

Chiral HPLC separation and absolute configuration assignment of a series of new triazole compounds

“…( S )‐α,α‐Diphenyl‐2‐pyrrolidinemethanol hydrochloride [( S )‐DDP . HCl] was synthesized according to the reported procedure 42 (Scheme 1). mp 246°C; Anal.…”

Asymmetric Reductions Involving Borohydrides: A Practical Asymmetric Reduction of Ketones Mediated by (l)-TarB−NO2: A Chiral Lewis Acid

“…Use of CBS and other oxazaborolidine catalysts in industrial processes is well documented. − Pfizer's development of the antidepressant Zoloft involved the exploration of several asymmetric synthetic methods, including a reduction using an oxazaborolidine catalyst. However, it is not cost efficient at an industrial scale so the current synthesis involves resolution of the racemate …”