Investigation of the diastereoselectivity in the addition of organometallics to the α-keto esters of axially chiral 1,1′-binaphthalen-2-ol derivatives

Abstract

The inherent chiral induction abilities of axially chiral 2′-substituted 1,1′-binaphthalen-2-ols 2a-f as the chiral auxiliary for the addition of organometallics to their α-keto acid esters were examined as a function of the following reaction variables: size of the 2′-substituent, nature of the organometallic reagent, solvent, and temperature. In the addition of MeMgl to the phenylglyoxylates 3a-f of the alcohols 2a-f, the corresponding atrolactic acid esters 5a-f and 6a-f were obtained with up to 52% diastereoisomeric excess (d.e.). The preferred diastereoisomer depended on the size of the 2′-substituent, and thus could not solely be determined by the helicity of the 1,1′-binaphthalene framework. By using MeZnl as the nucleophile, the selectivity increased up to 84% d.e. with the same diastereofacial selectivity as that of MeMgl. On the other hand, the diastereofacial selection was reversed when MeTiCl3 was employed as the nucleophile, with low selectivity (14% d.e.).It is concluded that MeMgl or MeZnl, as a nucleophile of low Lewis acidity, adds to the keto ester moiety in the s-trans conformation, while the strong Lewis acid MeTiCl3 mainly adds to the s-cis conformer from the same direction as that of the Grignard addition, thus giving the opposite diastereoisomer.