Regio- and enantioselective umpolung gem-difluoroallylation of hydrazones via palladium catalysis enabled by N-heterocyclic carbene ligand

Nature Communications

Xiao-Long Wan¹  Chang-Hua Ding²  Fei-Fei Tong³  Xingang Zhang³  Xuebing Leng⁴  Da-Chang Bai⁴  Yang-Jie Jiang⁴  Shuai Huang⁴  Ying-Long Guo⁴  Gao-Peng Zhang⁴  Bo Zhang⁴  Xue-Long Hou⁵ 

[1] Department of Analytic Chemistry, Center for Excellence in Molecular Synthesis, SIOC, CAS, Shanghai, China;Department of Chemistry, Innovative Drug Research Center, Shanghai University, Shanghai, China;Key Laboratory of Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, SIOC, CAS, Shanghai, China;State Key Laboratory of Organometallic Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry (SIOC), Chinese Academy of Sciences (CAS), Shanghai, China;State Key Laboratory of Organometallic Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry (SIOC), Chinese Academy of Sciences (CAS), Shanghai, China;Shanghai-Hong Kong Joint Laboratory in Chemical Synthesis, SIOC, CAS, Shanghai, China;

DOI  :  10.1038/s41467-021-26667-0

来源: Springer

【 摘 要 】

The enantioselective construction of C–CF2R (R: alkyl or fluoroalkyl) bonds has attracted the attention of synthetic chemists because of the importance of chiral fluorinated compounds in life and materials sciences. Catalytic asymmetric fluoroalkylation has mainly been realized under organocatalysis and Lewis acid catalysis, with substrates limited to carbonyl compounds. Few examples using transition-metal catalysis exist, owing to side reactions including decomposition and isomerization of fluoroalkylating reagents. Herein we report umpolung asymmetric difluoroallylation of hydrazones with 3-bromo-3,3-difluoropropene (BDFP) under palladium catalysis. Difluoroallylation products having quaternary chiral carbon centers are afforded in good yields with high α/γ- and enantioselectivities. The usefulness of the reaction products is demonstrated and an inner-sphere mechanism of the reaction is proposed. The use of chiral N-heterocyclic carbene as ligand is the key for the selectivities as well as the productivity of the reaction.

【 授权许可】

CC BY