Synthesis of Pyrrolidine-2-ylidenes from Isoxazolines and Allenes

Abstract

A diastereoselective addition and rearrangement reaction has been developed for the synthesis of pyrrolidine-2-ylidenes from NH-isoxazolines and electron-deficient allenes. This method proceeds via the rearrangement of a proposed N-alkenylisoxazoline intermediate to generate densely functionalized pyrrolidine-2-ylidenes under simple catalyst-free conditions that tolerate ketone substituents and install relative stereochemistry at positions 3 and 4 of the heterocycle. Reaction optimization and the substrate scope are described in addition to studies evaluating the reactivity of the gem-dione and enaminone groups of the products.