A Homolytic Substitution Approach for Directing Group-Free Nickel-Catalyzed Dialkylation of Unactivated Alkenes

Fei Cong; Jun Wei Ng; Ming Joo Koh

doi:10.1055/a-2352-4902

Synlett, Inhaltsverzeichnis

Synlett 2025; 36(03): 199-205
DOI: 10.1055/a-2352-4902

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A Homolytic Substitution Approach for Directing Group-Free Nickel-Catalyzed Dialkylation of Unactivated Alkenes

Fei Cong

^aDepartment of Chemistry, National University of Singapore, 4 Science Drive 2, Republic of Singapore, 117544

,

Jun Wei Ng

^aDepartment of Chemistry, National University of Singapore, 4 Science Drive 2, Republic of Singapore, 117544

,

Ming Joo Koh ∗

^aDepartment of Chemistry, National University of Singapore, 4 Science Drive 2, Republic of Singapore, 117544

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Abstract

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Abstract

The selective construction of two C(sp³)–C(sp³) bonds through trimolecular cross-coupling of unactivated alkenes remains one of the most difficult challenges in organic synthesis. Despite previous advances in metal-catalyzed coupling for the dicarbofunctionalization of alkenes, dialkylation is still problematic due to the instability of the requisite metal–alkyl intermediate, which undergoes facile β-hydride elimination or protodemetalation. Recently, our group was successful in developing a bimolecular homolytic substitution (S_H2) strategy that circumvents metal–alkyl side reactions and accomplishes the challenging cross-coupling of metal–alkyl intermediates with alkyl radicals in the absence of a directing auxiliary, permitting a highly regioselective dialkylation of unactivated alkenes.

1 Introduction

2 Nickel-Catalyzed Dicarbofunctionalization of Unactivated Alkenes

3 Nickel-Catalyzed Dialkylation of Unactivated Alkenes

4 Conclusions and Perspectives

Key words

nickel catalysis - dialkylation - unactivated alkenes - bimolecular homolytic substitution - radicals

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Referenzen

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20 During the course of preparing our manuscript, a paper on alkene dialkylation involving S_H2 mechanism appeared on ChemRxiv: Wang J. Z., Lyon W. L., MacMillan D. W. C.; Nature; 2024, 628: 104; also published as a preprint: ChemRxiv 2023, DOI: 10.26434/chemrxiv-2023-q4whd
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