Automated Alkylation of Heteroaromatic Thioethers with Organozinc Reagents for Library Synthesis

Abstract

In this study, we describe the implementation of an automated high-throughput workflow to efficiently functionalize medicinal-chemistry-relevant heteroaryl thioethers with diverse alkyl organozinc reagents in flow. The successful coupling observed with different aryl thioether substrates and organozinc reagents highlights the broad applicability of this platform for rapid library diversification. This platform greatly improves the speed and efficiency of modifying heteroaromatic thioethers featuring C(sp³) centers, thereby facilitating the discovery of novel bioactive compounds and positioning it as a valuable resource for medicinal chemistry projects.