ORIGINS OF PI-FACE SELECTIVITY IN THE ALDOL REACTIONS OF CHIRAL E-ENOL BORINATES - A COMPUTATIONAL STUDY USING TRANSITION-STATE MODELING

A molecular mechanics transition state model is used to analyse the stereoselectivity of a series of aldol reactions of E-enol borinates of type 3 with aldehydes. The model reproduces the sense and degree of pi-face selectivity for the chiral E-enol borinates 8, 11, 13 and 14 in the Table. Enolates 8 and 10 preferentially attack the re-face of aldehydes, which is explained (Scheme 5) by the aldol addition proceeding through the preferred transition structure TS-A for both electronic and steric reasons. In contrast, enolates 11, 13 and 14 preferentially attack the si-face of aldehydes solely for steric reasons, which is explained by invoking the favoured transition structure TS-B derived from the modelling results. These two transition state models, TS-A and TS-B, which apply to E-enol borinates, differ substantially from the transition state model, TS-C, used for chiral Z-enol borinates with similar substituents. Our force field model of the boron aldol transition state is shown to be useful in understanding the origins of the pi-face selectivity over a wide range of substrates.