Nickel-Catalyzed, Enantioselective Hydrofluoromethylation of Olefins: Access to Chiral α-Fluoromethylated Amides and Esters

Yiming Du; Shuxin Chen; Hexiang Cao; Yichen Zhang; Hongtao Lei; Guoqin Xia; Huicai Huang; Zhaodong Li

doi:10.1021/acs.orglett.3c00357

Nickel-Catalyzed, Enantioselective Hydrofluoromethylation of Olefins: Access to Chiral α-Fluoromethylated Amides and Esters

Org Lett. 2023 Apr 7;25(13):2218-2222. doi: 10.1021/acs.orglett.3c00357. Epub 2023 Mar 24.

Authors

Yiming Du¹, Shuxin Chen¹, Hexiang Cao¹, Yichen Zhang¹, Hongtao Lei², Guoqin Xia³, Huicai Huang⁴, Zhaodong Li^{1

5}

Affiliations

¹ College of Materials and Energy, South China Agricultural University, 510642 Guangzhou, China.
² Guangdong Provincial Key Laboratory of Food Quality and Safety/National-Local Joint Engineering Research Center for Machining and Safety of Livestock and Poultry Products, South China Agricultural University, Guangzhou 510642, China; Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China.
³ Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan Tsuihang New District, Zhongshan, Guangdong 528400, China.
⁴ Key Laboratory of Chinese Medicinal Resource from Lingnan, Ministry of Education, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, P. R. China.
⁵ Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. China.

PMID: 36961340
DOI: 10.1021/acs.orglett.3c00357

Abstract

We herein report the nickel-catalyzed enantioselective hydrofluoromethylation of enamides and enol esters with CH₂FI as the fluoromethyl source to enable the diversity-oriented synthesis (DOS) of chiral α-fluoromethylated amides as well as esters with features of wide functional group compatibility as well as excellent enantioselectivity. The synthetic value of this protocol was demonstrated by transformations of the resulted α-fluoromethylated amides to different scaffolds including amine, oxazoline, thiazoline, and α-fluoromethylated tetrahydroquinoline.