Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
University of Chinese Academy of Sciences, Beijing, 100049, China.
Nat Commun. 2017 Oct 27;8(1):1169. doi: 10.1038/s41467-017-01262-4.
Selectivity control of varied C-H bonds in a complex molecule is a long-standing goal and still a great challenge in C-H activation field. Most often, such selectivity is achieved by the innate reactivity of different C-H bonds. In this context, the classic Mannich reaction of acetophenone derivatives and imines is ascribed to the more reactive C(sp)-H bonds α to the carbonyl, with the much less reactive aromatic C(sp)-H bonds remaining intact. Herein we report an aromatic C(sp)-H addition of ketones to imines enabled by manganese catalysis, which totally reverses the innate reactivity of C-H bonds α to the carbonyl and those on the aromatic ring. Diverse products of ortho-C-H aminoalkylated ketones, cyclized exo-olefinic isoindolines, and three-component methylated isoindolines can be successfully accessed under mild reaction conditions, which significantly expands the synthetic utilities of ketones as simple bulk chemicals.
在复杂分子中选择性控制不同的 C-H 键是 C-H 活化领域中长期存在的目标，也是一个巨大的挑战。通常，这种选择性是通过不同 C-H 键的固有反应性来实现的。在这种情况下，苯乙酮衍生物和亚胺的经典曼尼希反应归因于羰基α位的更活泼的 C(sp)-H 键，而反应性差得多的芳族 C(sp)-H 键保持完整。本文报道了锰催化的酮与亚胺的芳香 C(sp)-H 加成反应，该反应完全反转了羰基α位以及芳环上 C-H 键的固有反应性。在温和的反应条件下，可以成功获得邻位-C-H 氨烷基化酮、环化的外向烯烃异吲哚啉和三组分甲基化异吲哚啉等多种产物，这显著扩展了酮作为简单大宗化学品的合成用途。
