Xiao Wei-Guo, Xuan Bin, Xiao Li-Jun, Zhou Qi-Lin
State Key Laboratory, Institute of Elemento-Organic Chemistry, College of Chemistry, Frontiers Science Center for New Organic Matter, Nankai University Tianjin 300071 China
Chem Sci. 2023 Jul 25;14(32):8644-8650. doi: 10.1039/d3sc03233g. eCollection 2023 Aug 16.
Molecules with an allylic amine motif provide access to important building blocks and versatile applications of biologically relevant chemical space. The need for diverse allylic amines requires the development of increasingly general and modular multicomponent reactions for allylic amine synthesis. Herein, we report an efficient catalytic multicomponent coupling reaction of simple alkenes, aldehydes, and amides by combining nickel catalysis and Lewis acid catalysis, thus providing a practical, environmentally friendly, and modular protocol to build architecturally complex and functionally diverse allylic amines in a single step. The method is remarkably simple, shows broad functional-group tolerance, and facilitates the synthesis of drug-like allylic amines that are not readily accessible by other methods. The utilization of accessible starting materials and inexpensive Ni(ii) salt as the alternative precatalyst offers a significant practical advantage. In addition, the practicality of the process was also demonstrated in an efficient, gram-scale preparation of the prostaglandin agonist.
具有烯丙基胺基序的分子为获取重要的结构单元以及生物相关化学空间的多种应用提供了途径。对多样化烯丙基胺的需求促使人们开发出越来越通用且模块化的多组分反应来合成烯丙基胺。在此，我们报道了一种通过结合镍催化和路易斯酸催化实现简单烯烃、醛和酰胺的高效催化多组分偶联反应，从而提供了一种实用、环境友好且模块化的方法，可一步构建结构复杂且功能多样的烯丙基胺。该方法非常简单，具有广泛的官能团耐受性，并且有助于合成其他方法难以获得的类药物烯丙基胺。使用易得的起始原料和廉价的Ni(ii)盐作为替代前催化剂具有显著的实际优势。此外，该方法的实用性还在前列腺素激动剂的高效克级制备中得到了证明。
