Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA.
Nat Chem. 2018 Feb;10(2):165-169. doi: 10.1038/nchem.2871. Epub 2017 Nov 6.
Cyclic amines are ubiquitous core structures of bioactive natural products and pharmaceutical drugs. Although the site-selective abstraction of C-H bonds is an attractive strategy for preparing valuable functionalized amines from their readily available parent heterocycles, this approach has largely been limited to substrates that require protection of the amine nitrogen atom. In addition, most methods rely on transition metals and are incompatible with the presence of amine N-H bonds. Here we introduce a protecting-group-free approach for the α-functionalization of cyclic secondary amines. An operationally simple one-pot procedure generates products via a process that involves intermolecular hydride transfer to generate an imine intermediate that is subsequently captured by a nucleophile, such as an alkyl or aryl lithium compound. Reactions are regioselective and stereospecific and enable the rapid preparation of bioactive amines, as exemplified by the facile synthesis of anabasine and (-)-solenopsin A.
环胺是生物活性天然产物和药物中普遍存在的核心结构。尽管选择性地从其易得的母体杂环中提取 C-H 键是一种从有价值的功能化胺的制备方法，但这种方法主要限于需要保护胺氮原子的底物。此外，大多数方法依赖于过渡金属，并且与胺 N-H 键的存在不兼容。在这里，我们引入了一种无保护基团的方法，用于环状仲胺的α-官能化。一种操作简单的一锅法通过涉及氢化物向分子间转移生成亚胺中间体的过程来生成产物，然后亚胺中间体被亲核试剂捕获，如烷基或芳基锂化合物。反应具有区域选择性和立体特异性，能够快速制备生物活性胺，例如，易于合成的新斯卡灵和(-)-solenopsin A。
