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Chiral gem-difluoroalkyl reagents: gem-difluoroalkyl propargylic borons and gem-difluoroalkyl α-allenols† † Electronic supplementary information (ESI) available. CCDC 2246187. For ESI and crystallographic data in CIF or other electronic format see DOI: https://doi.org/10.1039/d3sc03266c

ABSTRACT: Chiral fluorinated reagents provide new opportunities for the discovery of drugs and functional materials because the introduction of a fluorinated group significantly alters a molecule's physicochemical properties. Chiral gem-difluoroalkyl fragments (R–CF2–C*) are key motifs in many drugs. However, the scarcity of synthetic methods and types of chiral gem-difluoroalkyl reagents limits the applications of these compounds. Herein, we report two types of chiral gem-difluoroalkyl reagents chiral gem-difluoroalkyl propargylic borons and gem-difluoroalkyl α-allenols and their synthesis by means of methods involving rhodium-catalyzed enantioselective B–H bond insertion reactions of carbenes and Lewis acid-promoted allenylation reactions. The mild, operationally simple method features a broad substrate scope and good functional group tolerance. These two types of reagents contain easily transformable boron and alkynyl or allenyl moieties and thus might facilitate rapid modular construction of chiral molecules containing chiral gem-difluoroalkyl fragments and might provide new opportunities for the discovery of chiral gem-difluoroalkyl drugs and other functional molecules. Two types of chiral gem-difluoroalkyl reagents, chiral gem-difluoroalkyl propargylic borons and gem-difluoroalkyl α-allenols were developed by means of Rh-catalyzed enantioselective B–H bond insertion and Lewis acid-promoted allenylation.

SUBMITTER: Zou H

PROVIDER: S-EPMC10466307 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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