Over the past decade, our lab has built a program in nickel-catalyzed C(sp3)–C cross-coupling. Given nickel’s proclivity to both accept and generate reactive radical species, we questioned whether carbon-centered radicals generated by visible light photoredox catalysis could be intercepted by nickel to effect cross coupling. Our group, alongside the MacMillan and Molander groups, first demonstrated that the merger of nickel and photoredox catalysis is possible and can enable otherwise challenging bond-forming reactions. Ni/photoredox catalysis has since emerged as a versatile platform for the development of a broad array of C–C and C¬–heteroatom bond-forming methodologies.

An ongoing program of research in the Doyle laboratory is to develop mild and selective C(sp3)–H cross-coupling reactions using Ni/photoredox catalysis.

Direct cross coupling with C(sp3)–H bonds presents a significant challenge in organic synthesis, typically requiring directing groups, a large excess of the C–H partner, or forcing reaction conditions. We have reported examples of selective cross coupling of the α-amino C(sp3)–H bonds of acyclic and cyclic anilines with aryl halides and anhydrides using a nickel-photoredox dual catalyst system. More recently, we have pursued C(sp3)–H cross coupling of ethers and unactivated alkanes enabled by photocatalysis at nickel. In particular, photolysis of Ni(III) aryl and acyl chloride intermediates leads to elimination of a chlorine radical that can mediate substrate activation via HAT. Using this strategy, our lab has reported etherification, formylation, and methylation reactions of (hetero)aryl chlorides, in addition to esterification of strong and entirely unactivated C(sp3)–H bonds.

Ni/photoredox catalysis has been demonstrated by our group and others to be a powerful platform for conducting challenging cross-coupling reactions under mild conditions. Characteristic of these reactions is excitation of a visible-light-absorbing photoredox catalyst. However, catalytic Ni species can also absorb visible light, and several reports have demonstrated the importance of excited Ni species in Ni/photoredox reactions. We therefore sought to elucidate the photophysics and photochemistry of Ni complexes that are commonly proposed intermediates in these reactions. In collaboration with the Scholes and Castellano groups, we have investigated the photophysics and photochemistry of bipyridine-ligated Ni(II) oxidative addition complexes. Our studies demonstrated that visible light excitation generates a relatively long-lived 3d-d state that can undergo Ni–aryl bond homolysis event to generate Ni(I) species. These studies provide a mechanistic basis for developing light-promoted Ni-catalyzed reactions that do not require an exogenous photocatalyst.

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