Computer-assisted design of chiral boron enolates: The role of ate complexes in determining aldol stereoselectivity.

Abstract

Transition-state modelling for the aldol reaction of chiral Z and E enol borinates ( 1 and 2, Scheme 1) bearing mixed ligands (L 1 = Ipc, L 2 = 9) predicted higher enantioselectivities than those calculated and experimentally tested with C 2 symmetric systems (L 1 = L 2 = Ipc, L 1 = L 2 = 9). Reagent 8 was prepared and used to generate E enol borinates 24, which reacted with aldehydes to give the anti aldol products 25–28 with substantially lower enantiomeric excesses than predicted. This unexpected suggested that ate complex formation may be an important factor in controlling the selectivity of the boron-mediated aldol reaction. In particular, the presence of two different ligands on boron makes it a prostereogenic centre, and two diastereomeric ate complexes ( 29 and 30) can be formed on aldehyde complexation. These ate complexes are calculated to display different re: si face selectivities. The experimental results are similar to the ones predicted if the aldol reaction proceeds via the less selective ate complex 29.