Methyl-substituted oxazaborolidines

Problems with the preparation and stability of oxazaborolidine (6) led to the development of a series of B-substituted ox-azaborolidines derived from diphenylprolinol. The B-methyl substituted oxazaborolidine (9a) was first prepared (eq 5) by reaction of diphenylprolinol (1) with methylboronic acid under dehydrating conditions (toluene at 23 °C in the presence of 4 X molecular sieves or toluene at reflux using a Dean-Stark trap) followed by vacuum distillation (0.1 mmHg, 170°C). Based on NMR evidence, the product (mp 74-87 °C) was reported to be a mixture of monomer and dimer. The corresponding B-butyloxazaborolidine (9c), prepared in a similar manner from n-butylboronic acid, was also reported to be a mixture of monomer and dimer. Subsequent investigations demonstrated that the reported dimers were in fact the intermediate (8) and the more stable disproportionation product (10) (eq 6). Furthermore, the presence of (8) or (10) was demonstrated to be deleterious to the enantioselectivity of the catalyst. ... 

Enantioselective Reduction ofa,P-Ynones. Oxazaborolidine ligands 1 are among the most effective catalysts for the enantioselective reduction of ketones to secondary alcohols. Substitution of the methyl or butyl group on boron by a trimethylsilylmethyl group led to a much improved catalyst for the catecholborane mediated reduction of a, 3-ynones. For example, the enantioselectiv-ities for the reduction of an a, 3-ynone was improved from 60% to 98.5% when the nature of the R group was modified (eq 1). ... 

The structure of enantiopure 1,3,2-oxazaborolidine was first characterized by Corey [22]. The oxazaborolidine is prepared from an amino alcohol and borane or substituted boronic acids (Scheme 1) [23,24,25]. B-Methyl derivatives of oxazaborolidine were prepared by the reaction of an amino alcohol with trimeth-ylboroxine [26,27]. 

One of the most effective oxazaborolidines is derived from (S)-a,a-diphenyl(2-pyrrolidi-ne)methanol. The pyrrolidine may be prepared by treatment of methyl (2.S )-1 -benzyloxycar-bonylpyrrolidine-2-carboxylate14 or 1,2-pyrrolidinedicarboxylic anhydride with phenylmagnc-sium chloride1 The latter method has been used with a variety of substituted Grignard reagents. 

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