Controllable Defluorinative Cyclization for Divergent Synthesis of Pyrrolo[2,3-d]pyrimidines and Fluorinated...

This study successfully developed a novel controllable defluorinative cyclization strategy for β-CF₃-1,3-enynes, achieving the divergent synthesis of pyrrolo[2,3-d]pyrimidines and fluorinated pyrimidines. The reaction between β-CF₃-1,3-enynes and amidine hydrochlorides at a 1:2 molar ratio triggered selective [3+3]/[4+1] defluorinative cyclization, which efficiently constructed the pyrrolo[2,3-d]pyrimidine framework. Notably, this work first reported that the process achieved cleavage/annulation of triple C-F bonds in the CF₃ group of β-CF₃-1,3-enynes in a single step. In contrast, at a 1:1 molar ratio, fluorinated pyrimidine derivatives were generated through [3+3] defluorinative cyclization. Moreover, the synthetic utility was demonstrated through postfunctionalization of both pyrrolo[2,3-d]pyrimidine and fluorinated pyrimidine, highlighting their potential as versatile building blocks in medicinal chemistry.