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

Abstract

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.

Synthesis of allo- and epi-Inositol via the NHC-Catalyzed Carbocyclization of Carbohydrate-Derived Dialdehydes

“…It is likely that the reactive conformations match the conformations determined by NMR as the alternative conformers have either three or four unfavorable axial benzyloxy groups. Furthermore, the alternative conformers would still have one axial 3-benzyloxy substituent and an axial 2-hydroxy substituent that would direct hydride to the opposite face to that observed . According to the model developed by Cieplak to explain reduction of cyclohexanones, the antibonding orbital (σ ‡ *) of the incipient nucleophile is more stabilized by the C2–H axial bond than the C2–C3 bond, and so, the axial hydride approach is preferred.…”

Boron Reagents in Process Chemistry: Excellent Tools for Selective Reductions

“…We did not include reactions utilizing boronic acids or esters in Suzuki−Miyaura C−C coupling reactions since these topics have been recently reviewed hydroborations, and boranes in asymmetric synthesis have appeared recently but are not specifically at a particular scale. A number of processes cannot be discussed in detail due to their proprietary nature.…”