Aldol Condensations of Ketones Using Chiral Boron Reagents

Abstract

Chiral boron triflate reagents, easily prepared from (+)- or (-)-α-pinene, may be used for enantioselective aldol condensation reactions of prochiral ketones with aldehydes. The stereochemical outcome of this method when applied to chiral ethylketones depends on enolisation stereoselectivity (E/Z isomer ratio), the influence of the chiral centre(s) in the ketone (double asymmetric induction), and the enantiomeric purity of the ketone (resolution effects). In many cases, the synthesis of syn-α-methyl-β-hydroxyketones in high enantiomeric purity can be carried out with high levels of diastereoselectivity. A theoretical study of the boron mediated aldol condensation has been performed using ab initio calculations to generate an empirical force field (MM2) for the intermediate enol borinates, leading to new insights into the factors controlling the π-face selectivity of these and other chiral enolates. Applications of this new methodology to the short and efficient synthesis of polypropionate subunits of several polyketide antibiotics will be outlined.