Reductive Alkylation of Alkenyl Acetates with Alkyl Bromides by Nickel Catalysis

• Published in: Angewandte Chemie International Edition 2022-01, Vol.61 (4), p.e202114556-n/a
• Main Authors: He, Rong‐De, Bai, Yunfei, Han, Guan‐Yu, Zhao, Zhen‐Zhen, Pang, Xiaobo, Pan, Xiaobo, Liu, Xue‐Yuan, Shu, Xing‐Zhong
• Format: Article
• Language: English
• Subjects: Acetates; Acetic acid; Alkenes; Alkenylation; Alkylation; Biological activity; Bromides; Catalysis; Coupling (molecular); Cross-coupling; Nickel; Reagents; Reductive alkylation
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202114556

Catalytic alkylation of stable alkenyl C−O electrophiles is synthetically appealing, but studies to date have typically focused on the reactions with alkyl Grignard reagents. We report herein a cross‐electrophile reaction of alkenyl acetates with alkyl bromides. This work has enabled a new method for the synthesis of aliphatic alkenes from alkenyl acetates to be established that can be used to add more structural complexity and molecular diversity with enhanced functionality tolerance. The method allows for a gram‐scale reaction and modification of biologically active molecules, and it affords access to useful building blocks. Preliminary mechanistic studies reveal that the NiI species plays an essential role for the success of the coupling of these two reactivity‐mismatched electrophiles. A new C−C bond‐forming reaction between alkenyl acetates and alkyl bromides was achieved by reductive nickel catalysis. This method offers very mild reaction conditions for facile and precise synthesis of structurally versatile aliphatic alkenes using readily available and stable alkenyl reagents. It allows for a gram‐scale reaction and modification of biologically active molecules, and it affords access to useful building blocks.