Laboratoire Hétérochimie Fondamentale et Appliquée, CNRS UMR 5069, Université Toulouse 3 - Paul Sabatier, 118 route de Narbonne, 31062 Toulouse Cedex 09, France.
Institut de Chimie de Toulouse, CNRS UAR 2599, 118 Route de Narbonne, Toulouse 31062 Cedex 09, France.
Org Biomol Chem. 2021 Dec 22;20(1):219-227. doi: 10.1039/d1ob02118d.
Herein we report the synthesis of imidazo[1,5-]pyridine heterocycles a Cu(II)-mediated functionalization of α'-C(sp)-H bonds of pyridinylaldimines and subsequent cyclization. This strategy exploits the inherent directing ability of heteroleptic aldimine and pyridine groups in the substrate yielding the C-H functionalization of α'-methylene groups in a regioselective fashion over distant methyl or methylene groups in β or γ positions. The observed correlation between the nature of the anionic ligands (halide carboxylate) bonded to copper and the chemoselectivity of the C(sp)-H activation process points to a concerted metalation-deprotonation pathway prior to cyclization to furnish the corresponding imidazo[1,5-]pyridine derivative. This copper-mediated C(sp)-H bond functionalization reaction works for a variety of substrates incorporating linear alkyl chains (from 3 to 12 carbon atoms), and good functional group tolerance (aryl, ether and ester groups). Cu-Catalyzed C(sp)-H cyanation on the imidazole ring can then take place selectively under oxidative conditions.
本文报道了一种通过铜(II)介导的吡啶亚胺的α'-C(sp)-H 键功能化和随后的环化反应来合成咪唑并[1,5-a]吡啶杂环的方法。该策略利用了底物中杂配亚胺和吡啶基团的固有导向能力，以区域选择性方式实现了α'-亚甲基上的 C-H 功能化，而β或γ位上的较远的甲基或亚甲基则不受影响。观察到与铜键合的阴离子配体（卤化物和羧酸盐）的性质与 C(sp)-H 活化过程的化学选择性之间存在相关性，这表明在环化之前存在协同的金属化-去质子化途径，从而得到相应的咪唑并[1,5-a]吡啶衍生物。这种铜介导的 C(sp)-H 键功能化反应适用于多种包含直链烷基链（3 到 12 个碳原子）的底物，并且具有良好的官能团耐受性（芳基、醚和酯基）。然后，在氧化条件下，可以选择性地进行咪唑环上的 Cu 催化 C(sp)-H 氰化反应。
