New CF2H-Synthon Enables Asymmetric Radical Difluoroalkylation for Synthesis of Chiral Difluoromethylated Amines DOI Creative Commons
Xi‐Sheng Wang, Peng Liu, Yan He

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 29, 2024

Abstract The difluoromethyl group (CF₂H) is a crucial fluorinated moiety with distinctive biological properties, and the synthesis of chiral CF₂H-containing analogs has been recognized as powerful strategy in drug design screening. To date, most established method for accessing enantioenriched compounds involves enantioselective functionalization nucleophilic electrophilic CF₂H synthons. However, this approach limited by reaction scope, lower reactivity, reduced enantioselectivity. Leveraging unique fluorine effect, we designed synthesized novel radical synthon incorporating isoindolinone into alkyl halides asymmetric transformation. Here, report an efficient construction carbon stereocenters featuring via nickel-catalyzed Negishi cross-coupling. This demonstrates mild conditions, broad substrate excellent Given that optically pure difluoromethylated amines isoindolinones are key structural motifs bioactive compounds, offers practical solution drug-like molecules pharmaceutical research development.

Language: Английский

New CF2H-Synthon Enables Asymmetric Radical Difluoroalkylation for Synthesis of Chiral Difluoromethylated Amines DOI Creative Commons
Xi‐Sheng Wang, Peng Liu, Yan He

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 29, 2024

Abstract The difluoromethyl group (CF₂H) is a crucial fluorinated moiety with distinctive biological properties, and the synthesis of chiral CF₂H-containing analogs has been recognized as powerful strategy in drug design screening. To date, most established method for accessing enantioenriched compounds involves enantioselective functionalization nucleophilic electrophilic CF₂H synthons. However, this approach limited by reaction scope, lower reactivity, reduced enantioselectivity. Leveraging unique fluorine effect, we designed synthesized novel radical synthon incorporating isoindolinone into alkyl halides asymmetric transformation. Here, report an efficient construction carbon stereocenters featuring via nickel-catalyzed Negishi cross-coupling. This demonstrates mild conditions, broad substrate excellent Given that optically pure difluoromethylated amines isoindolinones are key structural motifs bioactive compounds, offers practical solution drug-like molecules pharmaceutical research development.

Language: Английский

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