Redox Approaches to Carbene Generation in Catalytic Cyclopropanation Reactions

Abstract

Transition metal-catalyzed carbene transfer reactions have a century-old history in organic chemistry and are a primary method for the synthesis of cyclopropanes. Much of the work in this field has focused on the use of diazo compounds and related precursors, which can transfer a carbene fragment to a catalyst with concomitant loss of a stable byproduct. Despite the utility of this approach, there are persistent limitations in the scope of viable carbenes, most notably those lacking stabilizing substituents. By coupling carbene transfer chemistry with two-electron redox cycles, it is possible to expand the available starting materials that can be used as carbene precursors. In this Minireview, we discuss emerging catalytic reductive cyclopropanation reactions using either gem-dihaloalkanes or carbonyl compounds. This strategy is inspired by classic stoichiometric transformations, such as the Simmons–Smith cyclopropanation and the Clemmensen reduction, but instead entails the formation of a catalytically generated transition metal carbene or carbenoid. We also present recent efforts to generate carbenes directly from methylene (CR2H2) groups via a formal 1,1-dehydrogenation. These reactions are currently restricted to substrates containing electron-withdrawing substituents, which serve to facilitate deprotonation and subsequent oxidation of the anion.