Synthesis of trans-2-Substituted Cyclopropylamines from α‑Chloroaldehydes
journal contributionposted on 07.10.2019 by Michael S. West, L. Reginald Mills, Tyler R. McDonald, Jessica B. Lee, Deeba Ensan, Sophie A. L. Rousseaux
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Cyclopropylamines are prevalent 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. We have also observed that cyclopropylamine cis/trans-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.