Pan Huang, Huifang Ma, Lianmin Yang, Shuli Wang, Shuwei Zhang, Duo Zhang, Guodong Zhang
Bicyclo[3.1.1]heptane (BCHep) is a rigid three-dimensional bioisostere of meta-substituted benzene, yet functionalized derivatives remain scarce. We report a copper-promoted three-component difluoroalkylative alkynylation of [3.1.1]propellane with terminal alkynes and bromodifluoroacetates, enabling simultaneous installation of a gem-difluoro group and a versatile alkyne handle at the bridgehead. This one-step transformation provides modular access to difunctionalized BCHep scaffolds under mild conditions with broad functional group tolerance and offers opportunities for late-stage diversification of complex molecules.