Broadly Applicable Copper(I)-Catalyzed Alkyne Semihydrogenation and Hydrogenation of α,β-Unsaturated Amides Enabled by Bifunctional Iminopyridine Ligands

Abstract

A highly active bifunctional catalyst consisting of a copper(I)/N-heterocyclic carbene complex and a basic 2-iminopyridine subunit allows for copper hydride chemistry under low H2 pressure, achieving efficient catalysis reaching 1 bar (balloon pressure). The bifunctional catalyst tolerates a remarkable variety of functional groups in catalytic alkyne semihydrogenations. Furthermore, this catalyst design gives rise to a high reactivity that allows for the catalytic hydrogenation of α,β-unsaturated amides (a substrate class hitherto unreactive in copper hydride catalysis) at a low H2 pressure for the first time. In this manner, late-stage modification and isotope labeling of α,β-unsaturated amides, common subunits in biologically active compounds, can be realized through catalytic hydrogenation using a first-row transition metal catalyst based on abundant copper. Preliminary mechanistic experiments indicate that the bifunctional catalyst operates via an iminopyridine-mediated proximity effect. We hypothesize that the coordination of an alcohol as a proton source on the copper(I) complex facilitates the overall reactions through a rapid proto-decupration step.