Nanoparticles as Heterogeneous Catalysts for ppm Pd-Catalyzed Aminations in Water

Abstract

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 E 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.