Synthesis of 1- and 1,2-Substituted Cyclopropylamines from Ketone Homoenolates

Abstract

Ketone homoenolates are intermediates with both nucleophilic and electrophilic properties. While there are several reports on their use as nucleophiles, there are few reports on their potential as electrophiles. Herein, we report the use of ketone zinc/ copper homoenolates as electrophiles in the synthesis of 1-and 1,2substituted cyclopropylamines. We found that CuCN•2LiCl is essential to produce a more reactive homoenolate intermediate. We also report a facile telescoped sequence from β-substituted enones toward 1,2-disubstituted cyclopropylamines.

Synthesis of Cyclopropylamines through an Electro-Induced Hofmann Rearrangement

“…25 An efficient synthesis of -substituted cyclopropyl amines from ketones homoenolates was also recently reported (Scheme 2h). 26 Hence, as part of our ongoing research program dedicated to electrosynthesis 27 and cyclopropane chemistry, 28 we planned to develop a versatile access to cyclopropylamines through an electro-induced Hofmann rearrangement of the readily available 1-substituted cyclopropyl amides (Scheme 2i). Indeed, in light of the importance of cyclopropyl amine, as versatile scaffold, the constant demand of novel method to build up cyclopropyl amine led us to investigate this electrochemical approach.…”

“…25 An efficient synthesis of α-substituted cyclopropylamines from ketones homoenolates was also recently reported (Scheme 2h ). 26…”