Synthesis of Trans-2-Substituted-Cyclopropylamines from α-Chloroaldehydes

Cyclopropylamines are prevalent motifs in pharmaceuticals and agrochemicals. Herein, we report the synthesis of trans-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 product. We have also observed that cis/trans-isomerization of the cyclopropylamine can occur in the presence of zinc halide salts and that this process can be turned off by the addition of a polar aprotic co-solvent to the reaction.