Quaternary Carbon Center Formation Via Dual Iron Salen and Photoredox Catalysis

Abstract

Medicinal chemists seek new strategies for forming bonds between sp3-hybridized carbon atoms, as this is correlated to increased structural complexity, target specificity, and ultimate clinical success of pharmaceutical molecules. However, the leading transition metal catalysis methodologies result in the synthesis of a disproportionate number of flat, sp2-rich aromatic structures, presenting a mismatch to the goal of increasing molecular three-dimensionality. Recently, the MacMillan group has circumvented this problem through a dual iron porphyrin catalysis and photocatalysis method of C(sp3)–C(sp3) cross-coupling. Herein is described an advance in the field of iron metallaphotoredox catalysis, in which an iron salen complex is discovered that is more synthetically accessible and structurally modular compared to the original porphyrin ligand system but exhibits similar cross-coupling behavior. Through a series of synthetic, experimental, and computational studies, an optimal iron salen complex and set of reaction conditions have been developed to promote catalytic C–C bond formation. The iron salen system also holds great promise for enabling enantioselective catalysis, as development of chiral salen catalysts are well precedented and straightforward due to the modularity of the salen ligand.