Iyer Karthik, Kavthe Rahul, Hu Yuting, Lipshutz Bruce H
Department of Chemistry and Biochemistry, University of California, Santa Barbara, California 93106, United States.
ACS Sustain Chem Eng. 2024 Jan 22;12(5):1997-2008. doi: 10.1021/acssuschemeng.3c06527. eCollection 2024 Feb 5.
A general protocol employing heterogeneous catalysis has been developed that enables ppm of Pd-catalyzed C-N cross-coupling reactions under aqueous micellar catalysis. A new nanoparticle catalyst containing specifically ligated Pd, in combination with nanoreactors composed of the designer surfactant Savie, a biodegradable amphiphile, catalyzes C-N bond formations in recyclable water. A variety of coupling partners, ranging from highly functionalized pharmaceutically relevant APIs to educts from the Merck Informer Library, readily participate under these environmentally responsible, sustainable reaction conditions. Other key features associated with this report include the low levels of residual Pd found in the products, the recyclability of the aqueous reaction medium, the use of ocean water as an alternative source of reaction medium, options for the use of pseudohalides as alternative reaction partners, and associated low factors. In addition, an unprecedented 5-step, one-pot sequence is presented, featuring several of the most widely used transformations in the pharmaceutical industry, suggesting potential industrial applications.
已开发出一种采用多相催化的通用方案，该方案能够在水性胶束催化下实现百万分之几的钯催化C-N交叉偶联反应。一种含有特定连接钯的新型纳米颗粒催化剂，与由可生物降解的两亲性设计表面活性剂Savie组成的纳米反应器相结合，可在可循环利用的水中催化C-N键的形成。从高度功能化的与药物相关的活性药物成分到默克信息库中的反应物等各种偶联伙伴，在这些对环境负责的可持续反应条件下都能轻松参与反应。与本报告相关的其他关键特性包括产物中残留钯含量低、水性反应介质可循环利用、使用海水作为反应介质的替代来源、使用拟卤化物作为替代反应伙伴的选择以及相关的低系数等。此外，还展示了一个前所未有的五步一锅法序列，其具有制药行业中一些最广泛使用的转化反应，暗示了潜在的工业应用。
