Zhou Xin-Yue, Liu Lu, Lyu Hairong, Wang Xiao-Chen
State Key Laboratory and Institute of Elemento-Organic Chemistry, Haihe Laboratory of Sustainable Chemical Transformations, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin, China.
Department of Chemistry, The Chinese University of Hong Kong, Hong Kong SAR, China.
Nat Chem. 2025 Jun 12. doi: 10.1038/s41557-025-01849-1.
The site-specific modification of amines has been a highly sought-after objective in organic synthesis. Despite the rapid advancement of carbon-hydrogen (C-H) bond functionalization methods, effective strategies for carbon-carbon (C-C) bond functionalization of amines remain elusive. Here we report a borane-catalysed method for the selective insertion of alkynes into alkyl C-C bonds of amines, resulting in the ring expansion of cyclic amines and chain elongation of acyclic amines. This approach begins with the cleavage of C-H bonds in amines, then transitioning to C-C bond functionalization upon reaction with alkynes. This method is effective with amines lacking an activating or leaving group and is suitable for late-stage functionalization of pharmaceuticals through C-C bond modification. Furthermore, by coupling this reaction with hydrolysis and hydrogenation steps, successive alkyne insertions are achieved, enabling modular and iterative alkyl growth of amines.
胺的位点特异性修饰一直是有机合成中备受追捧的目标。尽管碳-氢键（C-H）官能化方法发展迅速，但胺的碳-碳（C-C）键官能化的有效策略仍然难以捉摸。在此，我们报告了一种硼烷催化的方法，用于将炔烃选择性插入胺的烷基C-C键中，导致环状胺的环扩展和非环状胺的链延长。该方法始于胺中C-H键的裂解，然后在与炔烃反应时转变为C-C键官能化。该方法对于缺乏活化或离去基团的胺有效，并且适用于通过C-C键修饰对药物进行后期官能化。此外，通过将该反应与水解和氢化步骤相结合，实现了连续的炔烃插入，从而实现了胺的模块化和迭代烷基增长。
