Stereospecific syn-dichlorination of allylic amines enabled by identification of a superior stereo-directing group.

Abstract

Alteration of a well-established reaction mechanism for access to different molecular structures is an inherently intriguing research subject. In that context, syn-stereospecific alkene dihalogenation draws attention as a long-standing problem in synthetic organic chemistry. The simplest approach would be the incorporation of an additional stereo-inverting step within the traditional anti-dihalogenation process. Surprisingly, this seemingly trivial idea turned out challenging, and no suitable stereo-directing group was known before our work. Herein, we describe a highly efficient syn-dichlorination of N-protected allylic amines through the anchimeric assistant phenomenon that has been inapplicable to alkene dihalogenation. Upon rational identification of a superior stereo-director, 1,8-naphthalimide, our practical reaction conditions with mild and convenient dichlorinating reagents can accommodate the formerly unemployable aryl alkenes in excellent yields (>95%) and stereospecificity (>50:1). DFT calculation suggests a concerted internal trapping mechanism without a discrete carbocationic species, which accounts for the conservation of the stereochemical integrity.