MacLean Ian, Blanco Laura, Echávarri Elena, Collado Alba, Marzo Leyre, Alemán José
Organic Chemistry Department (Módulo 1), Universidad Autónoma de Madrid, C/ Francisco Tomás y Valiente 7, Madrid, 28049, Spain.
Inorganic Chemistry Department (Módulo 7), Universidad Autónoma de Madrid, Madrid, 28049, Spain.
Chemistry. 2025 Jul 22;31(41):e202501779. doi: 10.1002/chem.202501779. Epub 2025 Jul 2.
The 1,4-keto carboxylate scaffold is present in the structure of many biologically relevant compounds. To date, there are only a branch of methods to prepare them, using either transition metal catalysts, or noncommercially available and sensitive starting materials. Herein, we describe a sustainable electrochemical methodology starting from commercially available and highly stable 1,3-diketones and alkenes to prepare 1,4-keto aryl and alkyl carboxylates in a highly efficient manner, without the need of an external catalyst or harsh reaction conditions. This electrochemical oxidative radical polar crossover transformation presents a broad scope, is compatible with many functional groups, and can even be applied in flow chemistry. In addition, the key stabilization of the intermediate carbocation by anchimeric assistance allows a high diastereo- and regio-control of the reaction. Moreover, the utility of these 1,4-keto carboxylates was demonstrated in several derivatizations and applications in the late-stage functionalization of bioactive compounds.
1,4-酮羧酸盐骨架存在于许多具有生物学相关性的化合物结构中。迄今为止,制备它们的方法只有一小类,要么使用过渡金属催化剂,要么使用非市售且敏感的起始原料。在此,我们描述了一种可持续的电化学方法,该方法从市售且高度稳定的1,3-二酮和烯烃出发,以高效的方式制备1,4-酮芳基和烷基羧酸盐,无需外部催化剂或苛刻的反应条件。这种电化学氧化自由基极性交叉转化适用范围广,与许多官能团兼容,甚至可应用于流动化学。此外,通过邻基参与对中间体碳正离子的关键稳定作用实现了反应的高非对映和区域控制。此外,这些1,4-酮羧酸盐在生物活性化合物后期功能化的几种衍生化和应用中得到了验证。