Zheng Yan-Long, Xie Pei-Pei, Daneshfar Omid, Houk Kendall N, Hong Xin, Newman Stephen G
Centre for Catalysis Research and Innovation, Department of Chemistry and Biomolecular Sciences, University of Ottawa, 10 Marie-Curie, Ottawa, Ontario, K1N 6N5, Canada.
Department of Chemistry, Zhejiang University, Hangzhou, 310027, China.
Angew Chem Int Ed Engl. 2021 Jun 7;60(24):13476-13483. doi: 10.1002/anie.202103327. Epub 2021 May 6.
The direct conversion of alkyl esters to ketones has been hindered by the sluggish reactivity of the starting materials and the susceptibility of the product towards subsequent nucleophilic attack. We have now achieved a cross-coupling approach to this transformation using nickel, a bulky N-heterocyclic carbene ligand, and alkyl organoboron coupling partners. 65 alkyl ketones bearing diverse functional groups and heterocyclic scaffolds have been synthesized with this method. Catalyst-controlled chemoselectivity is observed for C(acyl)-O bond activation of multi-functional substrates bearing other bonds prone to cleavage by Ni, including aryl ether, aryl fluoride, and N-Ph amide functional groups. Density functional theory calculations provide mechanistic support for a Ni /Ni catalytic cycle and demonstrate how stabilizing non-covalent interactions between the bulky catalyst and substrate are critical for the reaction's success.
起始原料的低反应活性以及产物对后续亲核攻击的敏感性阻碍了烷基酯向酮的直接转化。我们现在已经实现了一种交叉偶联方法来进行这种转化，该方法使用镍、一种大位阻的N-杂环卡宾配体以及烷基有机硼偶联试剂。用这种方法已经合成了65种带有不同官能团和杂环骨架的烷基酮。对于带有其他易于被镍裂解的键的多功能底物的C(酰基)-O键活化，观察到了催化剂控制的化学选择性，这些键包括芳基醚、芳基氟和N-苯基酰胺官能团。密度泛函理论计算为镍/镍催化循环提供了机理支持，并证明了大位阻催化剂与底物之间稳定的非共价相互作用对反应成功的关键作用。
