Abstract：
The 2,2-difluoroethyl group is an important lipophilic hydrogen bond donor in medicinal chemistry, but its incorporation into small molecules is often challenging. Herein, we demonstrate electrophilic 2,2-difluoroethylation of thiol, amine and alcohol nucleophiles with a hypervalent iodine reagent, (2,2-difluoro-ethyl)(aryl)iodonium triflate, via a proposed ligand coupling mechanism. This transformation offers a complementary strategy to existing 2,2-difluoroethylation methods and allows access to a wide range of 2,2-difluoroethylated nucleophiles, including the drugs Captopril, Normorphine and Mefloquine.
摘要：
2,2-二氟乙基是药物化学中重要的亲脂性氢键供体,但它与小分子的结合往往是具有挑战性的。在这里，我们证明了硫醇的亲电子2,2-二氟乙基化，胺和醇亲核试剂与高价碘试剂，(2,2-二氟乙基)(芳基)三氟甲磺酸碘鎓，通过提出的配体偶联机制。这种转变为现有的2,2-二氟乙基化方法提供了补充策略，并允许获得广泛的2,2-二氟乙基化亲核试剂，包括药物卡托普利,去甲吗啡和甲氯喹.
