Role of the heteroatom on stereoselectivity in the complex metal hydride reduction of six-membered cyclic ketones

The role of the heteroatom on the stereochemistry and the relative rate for the complex metal hydride reduction of heteracyclohexanones and methoxy substituted cyclohexanones is explained by the difference in the nonbonding two electron stabilization between the incipient sigma* bond and the anti periplanar allylic sigma(i) bonds which were perturbed by the through space and/or through bond interaction with the remote heteroatom. A significant directive effect of the 2 axial hydroxyl group appears in the reduction of cyclohexanone with representative complex metal hydrides, while the 3 axial hydroxyl group exhibits a steric hindrance. The distance between the carbonyl carbon and the hydroxyl group which interacts with the hydride reagent is mainly responsible for such a difference. The key point of the extremely high directive effect appeared in the Na[B(OAc)(3)H] reduction for both 2 and 3 axial hydroxycyclohexanone is the formation of Na[B(OAc)(2)(OR)H], which is far more reactive than the parent hydride, by exchanging the acetate ion with the alkoxide.