COMPUTER-ASSISTED DESIGN OF CHIRAL BORON ENOLATES - THE ROLE OF ATE COMPLEXES IN DETERMINING ALDOL STEREOSELECTIVITY

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 man those calculated and experimentally tested with CI 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 result 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.