Advances in the Synthesis of Cyclopropylamines

Abstract

Cyclopropylamines are an important subclass of substituted cyclopropanes that combine the unique electronic and steric properties of cyclopropanes with the presence of a donor nitrogen atom. In addition to their presence in a diverse array of biologically active compounds, cyclopropylamines are utilized as important synthetic intermediates, particularly in ring-opening or cycloaddition reactions. Consequently, the synthesis of these compounds has constituted a significant research topic, as evidenced by the abundant published synthetic methods. In addition to the widely used Curtius rearrangement, classical cyclopropanation methods have been adapted to integrate a nitrogen function (Simmons–Smith reaction, metal-catalyzed reaction of diazo compounds on olefins, Michael-initiated ring-closure reactions) with significant advances in enantioselective synthesis. More recently, specific methods have been developed for the preparation of the aminocyclopropane moiety (Kulinkovich reactions applied to amides and nitriles, addition to cyclopropenes, metal-catalyzed reactions involving C–H functionalization, ...). The topic of this review is to present the different methods for the preparation of cyclopropylamine derivatives, with the aim of covering the methodological advances as best as possible, highlighting their scope, their stereochemical aspects and future trends.