Nickel-catalyzed reductive coupling of homoenolates and their higher homologues with unactivated alkyl bromides

Tingzhi Lin,¹ Yuanyun Gu,¹ Pengcheng Qian,¹ Haixing Guan,¹ Patrick J Walsh²* and Jianyou Mao,¹*

¹Technical Institute of Fluorochemistry (TIF), Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Nanjing Tech University, 30 South Puzhu Road, Nanjing 211816 (P.R. China)

²Roy and Diana Vagelos Laboratories, Penn/Merck Laboratory for High-Throughput Experimentation, University of Pennsylvania, Department of Chemistry, 231 South 34th Street, Philadelphia, Pennsylvania 19104, USA.

Abstract: The catalytic generation of homoenolates and their higher homologues has been a long-standing challenge. Like the generation of transition metal enolates, which have been used to great affect in synthesis and medicinal chemistries, homoenolates and their higher homologues have much potential, albeit largely unrealized. Herein, a nickel-catalyzed generation of homoenolates, and their higher homologues, via decarbonylation of readily available cyclic anhydrides has been developed. The utility of nickel-bound homoenolates and their higher homologues is demonstrated by cross-coupling with unactivated alkyl bromides, generating a

diverse array of aliphatic acids. A broad range of functional groups is tolerated. Preliminary mechanistic studies demonstrate that: (1) oxidative addition of anhydrides by the catalyst is faster than oxidative addition of alkyl bromides; (2) nickel bound metallocycles are involved in this transformation and (3) the catalyst undergoes a single electron transfer (SET) process with the alkyl bromide.

Nature communications. 2020, 11, 5638 (2020年影响因子: 12.121).

论文链接：https://www.nature.com/articles/s41467-020-19194-x