Xin Zhao, Wenjun Ye, Fangying Yuan, Fachang Yang, Jianbo Liu, Tinglei Zhang, Tingting Li, Shi-Chao Ren
The cross-dehydrogenative coupling of cyclic aldimines (C-H) and corresponding nucleophiles (X-H) provides one of the most straightforward synthetic methods for cyclic imidic acid derivatives. However, the method is currently limited to the cross-coupling of aldimines with amines to prepare amides. A robust and general synthetic method that enables the involvement of amines, alcohols, and even thiols as nucleophiles to divergently synthesize imidic acid derivatives is unknown. Herein, we disclose a carbene-catalyzed cross-dehydrogenative coupling between cyclic aldimines and amines, alcohols, and thiols, enabling efficient and divergent synthesis of cyclic imidic-acid-derived amidines, imidates, and imidothioates. The mild reaction conditions enable an excellent tolerance of various functional groups, allowing for the modification of complex natural products and pharmaceuticals. The practical utility of the current method is demonstrated by its successful application to the divergent synthesis of a wide range of substituted probenazole and dichlobentiazox (two marketed pesticide molecules).