Marchese Austin D, Mirabi Bijan, Johnson Colton E, Lautens Mark
Department of Chemistry, Davenport Chemical Laboratories, University of Toronto, Toronto, Ontario, Canada.
Nat Chem. 2022 Apr;14(4):398-406. doi: 10.1038/s41557-022-00898-0. Epub 2022 Mar 17.
A widely appreciated principle is that all reactions are fundamentally reversible. Observing reversible transition metal-catalysed reactions, particularly those that include the cleavage of C-C bonds, is more challenging. The development of palladium- and nickel-catalysed carboiodination reactions afforded access to the cis and trans diastereomers of the iodo-dihydroisoquinolone products. Using these substrates, an extensive study investigating the reversibility of C-C bond formation using a simple palladium catalyst was undertaken. Herein we report a comprehensive investigation of reversible C-C bond formation using palladium catalysis employing diastereomeric neopentyl iodides as the starting point. It was shown that both diastereomers could be converted to a common product under identical catalytic conditions. A combination of experimental and computational studies were used to probe the operative mechanism. A variety of concepts key to understanding the process of reversible C-C bond formations were investigated, including the effect of electronic and steric parameters on the C-C bond-cleavage step.
一个广为人知的原则是，所有反应从根本上来说都是可逆的。观察可逆的过渡金属催化反应，尤其是那些涉及碳-碳键断裂的反应，更具挑战性。钯和镍催化的碳碘化反应的发展，使得能够获得碘代二氢异喹啉酮产物的顺式和反式非对映异构体。使用这些底物，开展了一项广泛的研究，以研究使用简单钯催化剂时碳-碳键形成的可逆性。在此，我们报告一项以非对映异构新戊基碘化物为起点，使用钯催化对可逆碳-碳键形成进行的全面研究。结果表明，在相同的催化条件下，两种非对映异构体都可以转化为一种共同产物。结合实验和计算研究来探究反应机理。研究了各种对于理解可逆碳-碳键形成过程至关重要的概念，包括电子和空间参数对碳-碳键断裂步骤的影响。
