Asymmetric [2+1] cycloaddition of difluoroalkyl-substituted carbenes with alkenes under rhodium catalysis: Synthesis of chiral difluoroalkyl-substituted cyclopropanes

Xinyu Zhang; Yongquan Ning; Chunqi Tian; Giuseppe Zanoni; Xihe Bi

doi:10.1016/j.isci.2022.105896

Asymmetric [2+1] cycloaddition of difluoroalkyl-substituted carbenes with alkenes under rhodium catalysis: Synthesis of chiral difluoroalkyl-substituted cyclopropanes

iScience. 2023 Feb 15;26(3):105896. doi: 10.1016/j.isci.2022.105896. eCollection 2023 Mar 17.

Authors

Xinyu Zhang¹, Yongquan Ning¹, Chunqi Tian¹, Giuseppe Zanoni², Xihe Bi^{1

3}

Affiliations

¹ Department of Chemistry, Northeast Normal University, Changchun 130024, China.
² Department of ChemistryUniversity of Pavia, Viale Taramelli 12, 27100 Pavia, Italy.
³ State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China.

Abstract

Herein, we report a novel strategy for the synthesis of chiral difluoroalkyl-substituted cyclopropanes through enantioselective [2 + 1] cyclopropanation of alkenes and difluoroalkyl-substituted carbenes under rhodium catalysis, wherein the newly designed α, α-difluoro-β-carbonyl ketone N-triftosylhydrazones are used as the difluoroalkyl-substituted carbenes precursors. This approach represents the first asymmetric cyclopropanation of alkenes with difluoroalkyl carbenes, featuring high yield, high enantioselectivity, and broad substrate scope. Gram-scale synthesis and further interconversion of diverse functional groups demonstrate the usefulness of this protocol in the preparation of diverse functionalized chiral difluoroalkyl-substituted cyclopropanes.

Keywords: Catalysis; Organic compound; Organic synthesis.