Nature Chemistry ( IF 21.8 ) Pub Date : 2018-04-30 , DOI: 10.1038/s41557-018-0020-0 Joseph R. Clark , Kaibo Feng , Anasheh Sookezian , M. Christina White
Reactions that directly install nitrogen into C–H bonds of complex molecules are significant because of their potential to change the chemical and biological properties of a given compound. Although selective intramolecular C–H amination reactions are known, achieving high levels of reactivity while maintaining excellent site selectivity and functional-group tolerance remains a challenge for intermolecular C–H amination. Here, we report a manganese perchlorophthalocyanine catalyst [MnIII(ClPc)] for intermolecular benzylic C–H amination of bioactive molecules and natural products that proceeds with unprecedented levels of reactivity and site selectivity. In the presence of a Brønsted or Lewis acid, the [MnIII(ClPc)]-catalysed C–H amination demonstrates unique tolerance for tertiary amine, pyridine and benzimidazole functionalities. Mechanistic studies suggest that C–H amination likely proceeds through an electrophilic metallonitrene intermediate via a stepwise pathway where C–H cleavage is the rate-determining step of the reaction. Collectively, these mechanistic features contrast with previous base–metal-catalysed C–H aminations and provide new opportunities for tunable selectivities.
中文翻译:
锰催化的苄基C(sp 3)–H胺化用于后期功能化
将氮直接安装到复杂分子的C - H键中的反应非常重要,因为它们具有改变给定化合物的化学和生物学特性的潜力。尽管选择性分子内C - H氨基化反应是已知的,但在保持出色的位点选择性和官能团耐受性的同时实现高水平的反应性仍然是分子间C - H氨基化的挑战。在这里,我们报道了一种用于生物活性分子和天然产物的分子间苄基C – H胺化反应的锰全氯酞菁催化剂[MnIII(ClPc)] ,其反应活性和位点选择性达到前所未有的水平。在布朗斯台德酸或路易斯酸的存在下,[MnIII(ClPc)]催化的C–氨基化显示出对叔胺,吡啶和苯并咪唑官能团的独特耐受性。机理研究表明,C - H氨基化反应可能通过逐步的途径通过亲电金属茂中间体进行,其中C - H裂解是反应的速率决定步骤。总的来说,这些机械特性与以前的贱金属催化的C - H胺形成对比,并为可调的选择性提供了新的机会。