A unified approach for divergent synthesis of contiguous stereodiads employing a small boronyl group.

Abstract

Acyclic contiguous stereocenters are frequently seen in biologically active natural and synthetic molecules. Although various synthetic methods have been reported, predictable and unified approaches to all possible stereoisomers are rare, particularly for those containing non-reactive hydrocarbon substituents. Herein, a β-boronyl group is employed as a readily accessible handle for predictable α-functionalization of enolates with either syn or anti selectivity depending on reaction conditions. Contiguous tertiary-tertiary and tertiary-quaternary stereocenters are thus accessed in generally good yields and diastereoselectivity. Based on experimental and computational studies, mechanism for syn selective alkylation is proposed, and Bpin (pinacolatoboronyl) behaves as a smaller group than most carbon-centered groups. The synthetic utility of this methodology is demonstrated by preparation of several key intermediates for bioactive molecules.