Reaction scope and mechanistic insights of nickel-catalyzed migratory Suzuki\u2013Miyaura cross-coupling

Yi Deng,Ruopeng Bai,Yixin Luo,Long Peng,Yu Lan,Binzhi Zhao,Hailiang Pang,Yuqiang Li,Wang Wang,Yangyang Li,Guoyin Yin

doi:10.1038/s41467-019-14016-1

Yi Deng, Ruopeng Bai + Show 9 more

Open Access

https://doi.org/10.1038/s41467-019-14016-1

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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.

Highlights

Cross-coupling reactions have developed into powerful approaches for carbon–carbon bond formation
The migratory Suzuki–Miyaura cross-coupling of alkyl electrophiles has only been demonstrated by Sigman with palladium catalysis, wherein only allylic products and 1,2-palladium migration could be efficiently achieved (Fig. 1c)[36,37]
A deuterium-labeled isopropyl bromide (6b-D6) was examined under the standard conditions, the deborylation product (8b) was isolated in 47% yield with 31% Dincorporation (Fig. 4f)[56,57]. These results suggest that the hydrogen atom of the deborylation product is partly from the alkyl electrophile, which agrees with the proposed catalytic cycle (Fig. 4e) and reveals that the aryl group of the alkyl electrophile plays the role of promoting the carbon–carbon bond formation at benzylic position

Summary

Introduction

Cross-coupling reactions have developed into powerful approaches for carbon–carbon bond formation. 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. Transition metal-catalyzed cross-coupling reactions have developed into powerful approaches for carbon–carbon bond formation, and have revolutionized synthetic strategies in medicinal chemistry and material science[1,2,3,4,5]. Chain-walking highlights great opportunities in bond formation at new positions, the exploration of transformations involving chain-walking have stimulated considerable interest in the synthetic community recently[17,18] In this context, the concept of migratory cross-coupling has been initially described by the Baudoin group in palladium-catalyzed C–H bond functionalization reactions (Fig. 1a)[19,20,21]. The especially useful, unactivated alkyl chlorides[38,39,40] have not been successfully employed in a migratory coupling event to date

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