Behera Sourav, Fartade Dipak J, Mocci Rita, Matta Michela, De Luca Lidia, Porcheddu Andrea
Dipartimento di Scienze Chimiche e Geologiche, Università degli Studi di Cagliari, Cittadella Universitaria, Cagliari, 09042, Italy.
Dipartimento di Scienze Chimiche, Fisiche, Matematiche e Naturali, Università degli Studi di Sassari, Via Vienna 2, Sassari, 07100, Italy.
Angew Chem Int Ed Engl. 2025 Aug 4;64(32):e202508050. doi: 10.1002/anie.202508050. Epub 2025 Jun 23.
This study presents the first mechanochemical borrowing hydrogenation (BH) strategy, offering a direct and efficient route to N-alkylated amines and heterocycles. This solvent-free approach overcomes many challenges associated with conventional solution-based syntheses, such as toxic reagents, inert atmospheres, high temperatures, lengthy reaction times, excessive catalyst loadings, and the use of solvents. By applying this method under mechanochemical conditions and employing a readily available ruthenium-based catalyst, we achieved high conversions of a diverse set of primary amines and alcohols into N-alkylated amines. Furthermore, kinetic isotope effect (KIE) studies and Hammett analyses provided key insights into the underlying reaction mechanism. Ultimately, this protocol expands synthetic possibilities by facilitating the preparation of heterocycles.
本研究提出了首个机械化学借氢氢化（BH）策略，为制备N-烷基化胺和杂环化合物提供了一条直接且高效的途径。这种无溶剂方法克服了许多与传统溶液合成相关的挑战，例如有毒试剂、惰性气氛、高温、冗长的反应时间、过量的催化剂负载量以及溶剂的使用。通过在机械化学条件下应用该方法并使用一种易于获得的钌基催化剂，我们实现了将多种伯胺和醇高效转化为N-烷基化胺。此外，动力学同位素效应（KIE）研究和哈米特分析为潜在的反应机理提供了关键见解。最终，该方案通过促进杂环化合物的制备扩展了合成可能性。
