Dalian Institute of Chemical Physics, Chinese Academy of Sciences , Dalian 116023, China.
J Am Chem Soc. 2015 Feb 4;137(4):1623-31. doi: 10.1021/ja511796h. Epub 2015 Jan 21.
Rh(III)-catalyzed C-H activation assisted by an oxidizing directing group has evolved to a mild and redox-economic strategy for the construction of heterocycles. Despite the success, these coupling systems are currently limited to cleavage of an oxidizing N-O or N-N bond. Cleavage of an oxidizing C-N bond, which allows for complementary carbocycle synthesis, is unprecedented. In this article, α-ammonium acetophenones with an oxidizing C-N bond have been designed as substrates for Rh(III)-catalyzed C-H activation under redox-neutral conditions. The coupling with α-diazo esters afforded benzocyclopentanones, and the coupling with unactivated alkenes such as styrenes and aliphatic olefins gave ortho-olefinated acetophenoes. In both systems the reactions proceeded with a broad scope, high efficiency, and functional group tolerance. Moreover, efficient one-pot coupling of diazo esters has been realized starting from α-bromoacetophenones and triethylamine. The reaction mechanism for the coupling with diazo esters has been studied by a combination of experimental and theoretical methods. In particular, three distinct mechanistic pathways have been scrutinized by DFT studies, which revealed that the C-H activation occurs via a C-bound enolate-assisted concerted metalation-deprotonation mechanism and is rate-limiting. In subsequent C-C formation steps, the lowest energy pathway involves two rhodium carbene species as key intermediates.
铱（III）催化的 C-H 活化辅助氧化导向基团已经发展成为构建杂环的温和且氧化还原经济的策略。尽管取得了成功，但这些偶联系统目前仅限于氧化 N-O 或 N-N 键的断裂。氧化 C-N 键的断裂可以实现互补的碳环合成，这是前所未有的。在本文中，设计了具有氧化 C-N 键的α-氨甲基苯乙酮作为铱（III）催化在氧化还原中性条件下 C-H 活化的底物。与α-重氮酯的偶联得到了苯并环戊酮，与苯乙烯和脂肪族烯烃等未活化的烯烃的偶联得到了邻位烯丙基苯乙酮。在这两个体系中，反应具有广泛的范围、高效率和官能团耐受性。此外，还可以从α-溴代苯乙酮和三乙胺出发，实现高效一锅法偶联重氮酯。通过实验和理论方法的结合研究了与重氮酯偶联的反应机理。特别是，通过 DFT 研究仔细研究了三种不同的反应机理途径，揭示了 C-H 活化通过 C 键烯醇化物辅助的协同金属化-去质子化机制发生，这是限速步骤。在随后的 C-C 形成步骤中，最低能量途径涉及两种铱卡宾物种作为关键中间体。
