ORIGINS OF STEREOSELECTIVITY IN CHIRAL BORON ENOLATE ALDOL REACTIONS - A COMPUTATIONAL STUDY USING TRANSITION-STATE MODELING

A molecular mechanics model of the boron enolate aldol transition state is used to analyse the stereoselectivity of various synthetically interesting reactions. The model reproduces the sense and degree of stereoselectivity for several examples in Scheme 1, including reactions involving chiral ketones, as in 1 (substrate control) and chiral ligands on boron, as in 2 (reagent control). The origins of the stereoselectivity in the aldol reactions of Z enol diisopinocampheyl borinates are analysed in detail. It is concluded that the relative orientation of the ligands with respect to the chair transition structure core, as well as the relative orientation and restrained rotation of one ligand relative to the other, are important for determining the reaction selectivity. For chiral ketone cases, a general model 59 can be devised by inspection of the preferred transition structures viewed as the Newman projections (31, 38 and 44). This model has the hydrogen on the stereogenic centre of the enol borinate directed towards the boron ligand (i.e. the dihedral angle C = C-C*-H is in the range 133-173-degrees), the large group opposite to the incoming aldehyde, and the small group pointing towards the forming C-C bond of the chair transition structure. As shown by the work described here, our force field model of the boron aldol transition state is useful in understanding the origins of the stereoselectivity over a wide range of substrates. The alsol force field model, therefore, may also have predictive value in new situations.