On the origins of regioselectivity in the orthoester Claisen rearrangement of bisallylic alcohols

Abstract

When used as a strategy for selective carbon–carbon bond formation, the Johnson–Claisen rearrangement has proven extremely useful in the synthesis of complex natural products. Our attempts to prepare terminal diene esters as part of a modular strategy for the synthesis of Actinofuranone B has led us to investigate this reaction process further, especially in relation to the desymmetrization of bisallylic alcohols. In the present work, we revisit mechanistic studies that suggest that this type of rearrangement is best described as a [3,3] sigmatropic shift and subsequently present the results of our computational study of the Johnson–Claisen [3,3] sigmatropic rearrangement. Herein, evidence is presented to support our hypothesis that electronic considerations in the transition states of this reaction type oft dominate the product selectivities observed for this class of [3,3] sigmatropic rearrangements.