Enantioselective Cu-Catalyzed Nucleophilic Addition of Fluorinated Reagents: C-C Bond Formation for the Synthesis of Chiral Vicinal Difluorides

Huaxin Lin; Wei Jiao; Zhiwei Chen; Jian Han; Dongmei Fang; Min Wang; Jian Liao

doi:10.1021/acs.orglett.2c00518

Enantioselective Cu-Catalyzed Nucleophilic Addition of Fluorinated Reagents: C-C Bond Formation for the Synthesis of Chiral Vicinal Difluorides

Org Lett. 2022 Mar 25;24(11):2197-2202. doi: 10.1021/acs.orglett.2c00518. Epub 2022 Mar 14.

Authors

Huaxin Lin^{1

2}, Wei Jiao^{1

2}, Zhiwei Chen^{1

2}, Jian Han³, Dongmei Fang¹, Min Wang^{1

2}, Jian Liao^{1

2

3}

Affiliations

¹ Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China.
² University of Chinese Academy of Sciences, Beijing 100049, China.
³ College of Chemical Engineering, Sichuan University, Chengdu 610065, China.

PMID: 35285236
DOI: 10.1021/acs.orglett.2c00518

Abstract

Herein we described the first enantioselective Cu/sulfoxide phosphine (SOP) complex catalyzed nucleophilic addition of fluorinated enolates to gem-difluoroalkenes. The enantioenriched vicinal difluorides, containing a chiral tertiary fluoride and a fluoroalkene, were successfully afforded via C-C bond formation in good yields (up to 94% yield), high Z/E-selectivity (5:1 → 50:1 for Z-isomer), and excellent enantioselectivities (up to 98.5:1.5 er). Utility of this approach was demonstrated by modification of complex biologically active compounds.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carboxylic Acids*
Catalysis
Indicators and Reagents
Molecular Structure
Stereoisomerism

Substances

Carboxylic Acids
Indicators and Reagents