Diphenyl-2-pyrrolidinemethanol

S)-Tetrahydro-l -methyl-3,3-diphenyl-1 H,3H-pyrrolo[1,2-c][1,3,2]oxazabo-role was prepared from (S)-proline in two steps according to the literature procedure4 and purified by bulb-to-bulb distillation (170°C, 0.2 mm). The enantiomeric purity of the intermediate, (S)-a,a-diphenyl-2-pyrrolidinemethanol, was determined to be 99% ee by chiral HPLC analysis of its corresponding N-p-toluenesulfonamide derivative (DIACEL Chiralcel OD column hexane/ethanol, 92/8 1.0 mLVmin Rt(S) 8.6 min Rt(R) 12.8 min). The checkers used the crystalline p-methyloxazaborolidineborane complex (1.84 g, 6.34 mmol) as the catalyst. 

The solid is recrystallized by dissolution in boiling hexane (20 mL) and cooling to 0°C to afford 1.37 g of (S)-a,cx-diphenyl-2-pyrrolidinemethanol. The mother liquor is then concentrated and recrystallized from hexane (10 mL) to afford an additional 0.13 g of material. The physical properties are as follows mp 75-76°C H... 

Borane-methyl sulfide complex Methyl sulfide, compd. with borane (1 1) (8) Borane, compd. with thiobis[methane] (1 1) (9) (13292-87-0) (S)-a,a-Diphenyl-2-pyrrolidinemethanol 2-Pyrrolidinemethanol, a,a-diphenyl-,... 

Addition of phenylmagnesium chloride to methyl pyroglutamate followed by reduction with borane to give racemic a,a-diphenyl-2-pyrrolidinemelhanol (3 steps, 51% yield from pyrroglutamic acid) that was then resolved as its O-acetylmandelate salt 10 give (R)- or (S)-a,a-diphenyl-2-pyrrolidinemethanol (2 steps, 3 recrystallizations, 30% yield from racemic a,a-diphenyl-2-pyrrolidinemethanol ref. 5f). 

Addition of (S)-proline ethyl ester to phenylmagnesium chloride to give (S)-a,a-diaryl-2-pyrrolidinemethanol (2 steps, 21% yield from (S)-proline) (a) Roussel-UCLAF French Patent FR M3638, 1965 Chem. Abstr. 1969, 70, 106375m An earlier report (26% yield) did not indicate the enantiomeric purity of the product (b) Kapfhammer, J. Matthes, A. Z physiol. Chem. 1933, 223, 43-52. In the submitters hands, addition of (S)-proline methyl ester hydrochloride to phenylmagnesium chloride, afforded (S)-a,a-diphenyl-2-pyrrolidinemethanol in 20% yield and 80% e.e. See also ref. 5d. 

Related Reagents. a,a-Diphenyl-2-pyrrolidinemethanol Ephedrine-borane Norephedrine-Borane Tetrahydro-l-me-thyl-3,3-diphenyl-l//,3//-pyrrolo[l,2-c][l,3,2]oxazaborole. 

Preparative Methods the reagent is easily prepared from trime-thylsilylmethylboronic acid and (5)-(—)-a,a-diphenyl-2-py-rrolidinemethano 1. - The other enantiomer is also readily available from (R)-(+)-a,a-diphenyl-2-pyrrolidinemethanol. 

Related Reagents. a,a-Diphenyl-2-pyrrolidinemethanol Norephedrine-Borane Tetrahydro- l-methyl-3,3-diphenyl- IH, 3H-pyrrolo[ 1,2-c] [ 1,3,2]oxazaborole. 

Enantioselective Ketone Reduction. After the pioneering work of Itsuno et al., Corey s group isolated the 1,3,2-oxazaborolidine derived from chiral a,a-diphenyl-2-pyrrolidinemethanol (2) and applied it (and also other related B-alkyl compounds) to the stereoselective reduction of ketones with borane-tetrahydrofuran, borane-dimethyl sulfide (BMS) or catecholborane.It was named the CBS method (after Corey, Bakshi, and Shibata). Since then, the CBS method has become a standard and has been extensively used, specially for aromatic and a,p-unsaturated ketones, not only in academic laboratories but also in industrial processes. ... 

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