Current methods to access aryl/alkyl thiol-substituted bicyclo[1.1.1]pentane(BCP)derivatives(valuable bioisosteres for thiophenols/thioethers)remain underdeveloped.Herein,we report a photocatalytic multicomponent reac...Current methods to access aryl/alkyl thiol-substituted bicyclo[1.1.1]pentane(BCP)derivatives(valuable bioisosteres for thiophenols/thioethers)remain underdeveloped.Herein,we report a photocatalytic multicomponent reaction via consecutive photoinduced electron transfer(ConPET)to enable simultaneous Csp3-C and Csp3-Y(Y=S,Se,Te)bond formation on[1.1.1]pentanes.This strategy delivers diverse alkyl halides(Cl,Br,I;primary,secondary,tertiary).Late-stage derivatization of drug molecules(e.g.,aspirin,methylprednisolone)and oxidations to sulfoxides/sulfones demonstrate synthetic versatility.Mechanistic studies support a radical relay pathway initiated by ConPET-mediated alkyl radical generation.The method establishes a robust platform for constructing chalcogen-rich BCP bioisosteres,addressing a critical gap in medicinal chemistry and offering significant potential for drug discovery.展开更多
基金the Natural Science Foundation of Zhejiang Province(No.LMS25B060007)the Key Research&Development Project of Science Technology Department of Zhejiang Province(No.2024C01203)for financial support.
文摘Current methods to access aryl/alkyl thiol-substituted bicyclo[1.1.1]pentane(BCP)derivatives(valuable bioisosteres for thiophenols/thioethers)remain underdeveloped.Herein,we report a photocatalytic multicomponent reaction via consecutive photoinduced electron transfer(ConPET)to enable simultaneous Csp3-C and Csp3-Y(Y=S,Se,Te)bond formation on[1.1.1]pentanes.This strategy delivers diverse alkyl halides(Cl,Br,I;primary,secondary,tertiary).Late-stage derivatization of drug molecules(e.g.,aspirin,methylprednisolone)and oxidations to sulfoxides/sulfones demonstrate synthetic versatility.Mechanistic studies support a radical relay pathway initiated by ConPET-mediated alkyl radical generation.The method establishes a robust platform for constructing chalcogen-rich BCP bioisosteres,addressing a critical gap in medicinal chemistry and offering significant potential for drug discovery.
