Radical thioesterification via nickel-catalysed sensitized electron transfer

Abstract

Multi-catalytic reaction modes have attracted widespread attention in synthetic chemistry. The merger of nickel catalysis with photoredox catalysis has offered a powerful platform for synthesis of molecules with attractive properties. Nonetheless, the conceptual development of nickel-catalysed, sensitized electron transfer is of pivotal relevance, but is still greatly limited. Here we describe the development of a radical cross-thioesterification process by nickel-catalysed sensitized electron transfer. The strategy can produce diverse methyl thioesters, which are not only found in natural products, materials and pharmaceuticals but also are widespread precursors in synthetic chemistry and biological processes. This catalytic mode features high chemoselectivity, good functional group tolerance and excellent scalability. Perhaps more important was the finding that various drugs and amino acids were successfully functionalized in this system. Experimental studies, nanosecond transient spectroscopic analysis, and density functional theory calculations reveal that the merger of photocatalytic electron transfer, energy transfer and nickel catalysis plays an essential role in this radical thioesterification reaction.

Energy transfer photocatalysis: exciting modes of reactivity

“…113 A combined study from Temps, Qi, and our group efficiently merges photoredox catalysis, energy transfer catalysis, and nickel catalysis for carboxylic acid functionalization. 181 Such multi-process combinations could be invaluable in harnessing the intrinsic properties of different catalytic manifolds. Most importantly, conceptual cross-connections of the basic principles of EnT-catalyzed processes are evident, and have significantly contributed to the overall development of the area.…”

Direct conversion of carboxylic acids to free thiols via radical relay acridine photocatalysis enabled by N–O bond cleavage

“… 9 Therefore, a mild transformation of the carboxylic moiety to free thiol would be a valuable tool for drug design and late-stage modification of bioactive compounds. At the recent surge of visible light driven chemistry, 10 multiple preparative methods based on photoinduced radical decarboxylation have been developed. 11 Radicals generated in these protocols were successfully used for carbon–carbon and carbon–heteroatom bond formation.…”

KF-catalyzed direct thiomethylation of carboxylic acids with DMSO to access methyl thioesters

“…10 Glorius and co-workers reported an Ir/Ni-catalyzed radical thioesterification using dimethyl disulfide (DMDS) as the methylthio source (Scheme 1b). 11 Despite significant progress, the requirements of transition metal complexes, special precursors and excessive bases still represent major shortcomings, especially towards the limited choice of “SMe” synthons.…”