The Merger of Benzophenone HAT Photocatalysis and Silyl Radical-Induced XAT Enables Both Nickel-Catalyzed Cross-Electrophile Coupling and 1,2-Dicarbofunctionalization of Olefins

Abstract

A strategy for both cross-electrophile coupling and 1,2-dicarbofunctionalization of olefins has been developed. Carbon-centered radicals are generated from alkyl bromides by merging benzophenone hydrogen atom transfer (HAT) photocatalysis and silyl radical-induced halogen atom transfer (XAT) and are subsequently intercepted by a nickel catalyst to forge the targeted C(sp 3 )–C(sp 2 ) and C(sp 3 )–C(sp 3 ) bonds. The mild protocol is fast and scalable using flow technology, displays broad functional group tolerance, and is amenable to a wide variety of medicinally relevant moieties. Mechanistic investigations reveal that the ketone catalyst, upon photoexcitation, is responsible for the direct activation of the silicon-based XAT reagent (HAT-mediated XAT) that furnishes the targeted alkyl radical and is ultimately involved in the turnover of the nickel catalytic cycle.

Photocatalytic Deoxygenative Alkylation of C(sp3)−H Bonds Using Sulfonylhydrazones

“…[21][22][23][24] Notably, these N-sulfonyl hydrazones can be exploited as a suitable electrophilic site for both polar and radical addition to yield, upon dinitrogen and sulfinate extrusion, the targeted C(sp 3 )-C(sp 3 ) bonds. [25][26][27][28][29][30][31][32] To realize a metalfree protocol, we anticipated that a photocatalytic Hydrogen Atom Transfer (HAT) strategy would be appealing to activate aliphatic C-H bonds, [33][34][35][36][37][38][39][40][41][42][43][44][45] thus generating from cheap commodity chemicals the required nucleophilic radicals which can subsequently add to the polarity-matched N-sulfonyl hydrazone. Herein, we describe the realization of such a photocatalytic deoxygenative alkylation of N-sulfonyl hydrazones using diarylketones as the photocatalyst (Figure 1b).…”

Photoredox Csp3−Csp2 Reductive Cross‐Couplings of Cereblon Ligands for PROTAC Linker Exploration in Batch and Flow

“…In 2016, the group of MacMillan reported the first nickel‐photoredox C sp 3 −C sp 2 coupling, operating via a silyl radical [16] . Since then, this reactivity has been further explored and built on by numerous research groups, introducing developments such as: chloride C sp 3 coupling partners, [17] amine‐based halogen atom transfer (XAT) reagents [18] and related olefin 1,2‐dicarbofunctionalization [19] …”

Photocatalytic Alkylation of C(sp3)−H Bonds Using Sulfonylhydrazones**

“…[21][22][23][24] Notably, these N-sulfonyl hydrazones can be exploited as a suitable electrophilic site for both polar and radical addition to yield, upon dinitrogen and sulfinate extrusion, the targeted C(sp 3 )À C(sp 3 ) bonds. [25][26][27][28][29][30][31][32] To realize a metal-free protocol, we anticipated that a photocatalytic hydrogen atom transfer (HAT) strategy would be appealing to activate aliphatic CÀ H bonds, [33][34][35][36][37][38][39][40][41][42][43][44][45] thus generating from cheap commodity chemicals the required nucleophilic radicals which can subsequently add to the polarity-matched N-sulfonylhydrazone. Herein, we describe the realization of such a photocatalytic denitrogenative alkylation of N-sulfonyl hydrazones using diarylketones as the photocatalyst (Figure 1B).…”