Reaction scope and mechanistic insights of nickel-catalyzed migratory Suzuki–Miyaura cross-coupling

Abstract

Cross-coupling reactions have developed into powerful approaches for carbon–carbon bond formation. In this work, a Ni-catalyzed migratory Suzuki–Miyaura cross-coupling featuring high benzylic or allylic selectivity has been developed. With this method, unactivated alkyl electrophiles and aryl or vinyl boronic acids can be efficiently transferred to diarylalkane or allylbenzene derivatives under mild conditions. Importantly, unactivated alkyl chlorides can also be successfully used as the coupling partners. To demonstrate the applicability of this method, we showcase that this strategy can serve as a platform for the synthesis of terminal, partially deuterium-labeled molecules from readily accessible starting materials. Experimental studies suggest that migratory cross-coupling products are generated from Ni(0/II) catalytic cycle. Theoretical calculations indicate that the chain-walking occurs at a neutral nickel complex rather than a cationic one. In addition, the original-site cross-coupling products can be obtained by alternating the ligand, wherein the formation of the products has been rationalized by a radical chain process.

Migratory cross-coupling reactions are powerful tools to form bonds at predictable positions. Here the authors report a nickel-catalyzed migratory Suzuki–Miyaura cross-coupling of unactivated alkyl electrophiles with aryl and vinyl boron reagents and provide experimental and computational mechanistic evidence.