TBAF-Mediated [3+1] Cycloaddition of Difluorocarbene to Access <i>gem</i>-Difluorinated 1,2-Diazetidine Analogues as Potent Anticancer Agents
Yuyin Mao, Na Li, Jie Liu, Zhong‐Xing Jiang, Zhigang Yang
Abstract
The facile synthesis of gem -difluorinated 1,2-diazetidines was achieved by metal-free [3+1] annulation between C, N -cyclic azomethine imines with difluorocarbene. A library of 30 compounds benefiting from the TBAF-mediated cyclization process could be directly assembled in moderate to good yield under mild conditions. A plausible mechanism involving the difluorocarbene pathway was proposed based on carbene trapping and control experiments. Many compounds exhibited dramatic antiproliferative activity in 4T1, A549, and HeLa tumor cell lines.
Topics & Concepts
DifluorocarbeneChemistryCarbeneCycloadditionHeLaAnnulationCombinatorial chemistryYield (engineering)StereochemistryMedicinal chemistryCatalysisOrganic chemistryIn vitroMaterials scienceBiochemistryMetallurgyFluorine in Organic ChemistrySynthesis and Catalytic ReactionsCyclopropane Reaction Mechanisms