Johnston Brandon, Loh Daniel M, Nocera Daniel G
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
Angew Chem Int Ed Engl. 2023 Dec 4;62(49):e202312128. doi: 10.1002/anie.202312128. Epub 2023 Nov 7.
Electrochemical approaches to form C(sp )-C(sp ) bonds have focused on coupling C(sp ) electrophiles that form stabilized carbon-centered radicals upon reduction or oxidation. Whereas alkyl bromides are desirable C(sp ) coupling partners owing to their availability and cost-effectiveness, their tendency to undergo radical-radical homocoupling makes them challenging substrates for electroreductive cross-coupling. Herein, we disclose a metal-free regioselective cross-coupling of 1,4-dicyanobenzene, a useful precursor to aromatic nitriles, and alkyl bromides. Alkyl bromide reduction is mediated directly by 1,4-dicyanobenzene radical anions, leading to negligible homocoupling and high cross-selectivity to form 1,4-alkyl cyanobenzenes. The cross-coupling scheme is compatible with oxidatively sensitive and acidic functional groups such as amines and alcohols, which have proven difficult to incorporate in alternative electrochemical approaches using carboxylic acids as C(sp ) precursors.
形成C(sp³)-C(sp²)键的电化学方法主要集中于偶联那些在还原或氧化时能形成稳定碳中心自由基的C(sp³)亲电试剂。尽管烷基溴因其可得性和成本效益而成为理想的C(sp³)偶联伙伴，但其发生自由基-自由基均偶联的倾向使其成为电还原交叉偶联的挑战性底物。在此，我们报道了一种无金属的区域选择性交叉偶联反应，该反应涉及1,4-二氰基苯（一种有用的芳腈前体）与烷基溴。烷基溴的还原直接由1,4-二氰基苯自由基阴离子介导，导致均偶联可忽略不计，并具有高交叉选择性以形成1,4-烷基氰基苯。该交叉偶联方案与氧化敏感和酸性官能团（如胺和醇）兼容，而在使用羧酸作为C(sp³)前体的其他电化学方法中，已证明难以引入这些官能团。
