Centre for Catalysis Research and Innovation, Department of Chemistry, University of Ottawa, 10 Marie Curie, Ottawa, Ontario K1N 6N5, Canada.
J Am Chem Soc. 2011 Apr 27;133(16):6449-57. doi: 10.1021/ja201143v. Epub 2011 Mar 31.
Directing groups that can act as internal oxidants have recently been shown to be beneficial in metal-catalyzed heterocycle syntheses that undergo C-H functionalization. Pursuant to the rhodium(III)-catalyzed redox-neutral isoquinolone synthesis that we recently reported, we present in this article the development of a more reactive internal oxidant/directing group that can promote the formation of a wide variety of isoquinolones at room temperature while employing low catalyst loadings (0.5 mol %). In contrast to previously reported oxidative rhodium(III)-catalyzed heterocycle syntheses, the new conditions allow for the first time the use of terminal alkynes. Also, it is shown that the use of alkenes, including ethylene, instead of alkynes leads to the room temperature formation of 3,4-dihydroisoquinolones. Mechanistic investigations of this new system point to a change in the turnover limiting step of the catalytic cycle relative to the previously reported conditions. Concerted metalation-deprotonation (CMD) is now proposed to be the turnover limiting step. In addition, DFT calculations conducted on this system agree with a stepwise C-N bond reductive elimination/N-O bond oxidative addition mechanism to afford the desired heterocycle. Concepts highlighted by the calculations were found to be consistent with experimental results.
最近的研究表明，在经历 C-H 官能化的金属催化杂环合成中，使用可以充当内部氧化剂的导向基团具有优势。在我们最近报道的铑（III）催化的氧化还原中性异喹啉合成的基础上，本文提出了开发一种更具反应性的内部氧化剂/导向基团的方法，该方法可以在室温下使用低催化剂负载量（0.5 mol%）促进各种异喹啉的形成。与之前报道的氧化铑（III）催化杂环合成相比，新条件首次允许使用末端炔烃。此外，研究表明，使用烯烃（包括乙烯）代替炔烃可以在室温下形成 3,4-二氢异喹啉。对该新体系的机理研究表明，相对于之前报道的条件，催化循环的周转限制步骤发生了变化。现在提出协同金属化-去质子化（CMD）是周转限制步骤。此外，对该体系进行的 DFT 计算表明，通过逐步的 C-N 键还原消除/N-O 键氧化加成机制来获得所需的杂环，这与实验结果一致。计算中突出的概念与实验结果一致。
