Synthesis of <i>trans</i> -2-Substituted Cyclopropylamines from α-Chloroaldehydes

Abstract

Cyclopropylamines are prevalent in pharmaceuticals and agrochemicals. Herein, we report the synthesis of <i>trans</i>-2-substituted cyclopropylamines in high diastereoselectivity from readily available α-chloroaldehydes. The reaction proceeds via trapping of an electrophilic zinc homoenolate with an amine followed by ring closure to generate the cyclopropylamine. We have also observed that cyclopropylamine <i>cis</i>/<i>trans-</i>isomerization occurs in the presence of zinc halide salts and that this process can be turned off by the addition of a polar aprotic cosolvent.