NHC-Catalyzed Single-Electron Oxidation and Alkylation of Imines: Alkene Difunctionalization and Dehydrogenative Coupling

The development of a catalytic activation model enables
the innovation
of synthetic methods toward functional molecules. Recently, radical
NHC catalysis has attracted considerable attention and has achieved
numerous successes. It unlocks the potential to activate inert substrates
and access valuable ketones that are beyond the reach of conventional
methods. However, this strategy has so far been limited to the activation
of carbonyl compounds for ketone synthesis. In contrast, the radical
activation of imines under NHC catalysis for facile synthesis remains
an unmet challenge. Herein, we report the NHC-catalyzed single-electron
oxidation and alkylation of imines. Various agents, including Togni
reagent, α-iododifluoroacetate, phenyl(difluoroiodomethyl)sulfone,
perfluoroalkyl iodide, and peroxyester, proved to be effective single-electron
oxidants. This versatility enabled the development of both alkene
difunctionalization and a dehydrogenative coupling reaction. Preliminary
mechanistic studies supported the proposed reaction pathway. The utility
of this method is demonstrated through the late-stage functionalization
of pesticide-related molecules and the divergent transformation of
the products.

催化活化模型的发展推动了功能分子合成方法的革新。近年来，自由基氮杂环卡宾（NHC）催化受到广泛关注并取得诸多突破，其能够活化惰性底物，获取传统方法难以企及的高价值酮类化合物。然而目前该策略仅局限于活化羰基化合物以合成酮类，与之相对，NHC催化下亚胺的自由基活化用于便捷合成的策略仍属未解决的难题。本文报道了NHC催化的亚胺单电子氧化与烷基化反应，包括托吉试剂（Togni reagent）、α-碘二氟乙酸酯、苯基(二氟碘甲基)砜、全氟烷基碘及过氧酸酯在内的多种试剂均被证实为高效单电子氧化剂。该反应的普适性使得烯烃双官能化与脱氢偶联反应两种合成路径均可实现，初步机理研究验证了所提出的反应路径。通过农药相关分子的后期官能化以及产物的发散转化，证实了该方法的应用价值。