The incorporation of trifluoromethyl groups into organic molecules represents a powerful strategy for modulating their physical,chemical,and biological properties.Although the 2H-pyran scaffold is a privileged structu...The incorporation of trifluoromethyl groups into organic molecules represents a powerful strategy for modulating their physical,chemical,and biological properties.Although the 2H-pyran scaffold is a privileged structure in bioactive compounds,practical methods for constructing trifluoromethylated 2H-pyrans remain limited.Herein,we report a palladium-catalyzed cascade reaction between trifluoroacetylsilanes and 1,3-enynes that efficiently produces diverse 6-CF_(3)-2H-pyrans in good yields.This transformation demonstrates broad substrate scope,excellent functional group tolerance,and high regio-and chemoselectivity.Computational studies reveal a reaction mechanism involving palladium-catalyzed C-Si insertion into the alkyne moiety,followed by oxa-6π-electrocyclization of the in situ generated trifluoromethylated oxatrienes.The synthetic utility of this methodology is further demonstrated through gram-scale synthesis and versatile downstream transformations.展开更多
基金National Key R&D Program of China(grant no.2022YFA1506100)National Natural Science Foundation of China(grant nos.22471201,22531010,and 22503064)Fundamental Research Funds for the Central Universities(grant no.2042025kf0052)for financial support.The theoretical calculations were performed on the supercomputing system in the Supercomputing Center of Wuhan University.
文摘The incorporation of trifluoromethyl groups into organic molecules represents a powerful strategy for modulating their physical,chemical,and biological properties.Although the 2H-pyran scaffold is a privileged structure in bioactive compounds,practical methods for constructing trifluoromethylated 2H-pyrans remain limited.Herein,we report a palladium-catalyzed cascade reaction between trifluoroacetylsilanes and 1,3-enynes that efficiently produces diverse 6-CF_(3)-2H-pyrans in good yields.This transformation demonstrates broad substrate scope,excellent functional group tolerance,and high regio-and chemoselectivity.Computational studies reveal a reaction mechanism involving palladium-catalyzed C-Si insertion into the alkyne moiety,followed by oxa-6π-electrocyclization of the in situ generated trifluoromethylated oxatrienes.The synthetic utility of this methodology is further demonstrated through gram-scale synthesis and versatile downstream transformations.
