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.

中文翻译：

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通过高价碘策略进行杂原子亲核试剂的 2,2-二氟乙基化


2,2-二氟乙基是药物化学中重要的亲脂性氢键供体，但将其掺入小分子中通常具有挑战性。在此，我们证明了硫醇、胺和醇亲核试剂与高价碘试剂（2,2-二氟乙基）（芳基）三氟甲磺酸碘通过拟议的配体偶联机制发生亲电2,2二氟乙基化。这种转化为现有的 2,2-二氟乙基化方法提供了补充策略，并允许获得多种 2,2-二氟乙基化亲核试剂，包括药物卡托普利、去甲吗啡和甲氟喹。