Incorporation of germanium into amines via deoxygenative germylation of aromatic amides with hydrogermanes

Abstract

The development of novel strategies for the efficient incorporation of germanium into widespread molecular structures, especially for the synthesis of potentially bioactive molecules, is of interest to researchers. In this context, carbene-mediated insertion reactions of Ge−H bonds are appealing strategies for the construction of C−Ge bonds. However, the utilization of α-aminocarbene intermediates generated from readily available precursors in Ge–H bond insertion remains a longstanding challenge, although it would be a straightforward method for the synthesis of biologically important α-germylamines. Herein, we present a practical and general protocol for the synthesis of α-germylamines via Mg/SmI 2 -mediated deoxygenative cross-coupling of amides with hydrogermanes. The process is proposed to proceed via reductive deoxygenation of amides to an α-aminocarbene intermediate, which can undergo a Ge–H bond insertion process. This method allows for the incorporation of germanium structures into several drug-molecule-derived amides, offering a promising approach to altering their pharmacological profiles. • Insertion of germanium is achieved with an α-aminocarbene intermediate • Synthesis of α-germyl amines under mild conditions is shown • Deoxygenative functionalization of inert amides is facilitated via the α-aminocarbene The development of novel strategies for the incorporation of germanium into bioactive molecules is of great significance. Here, Wang et al. develop a deoxygenative cross-coupling of amides with germanes via α-aminocarbene intermediates, leading to a suite of functionally and structurally diverse α-germyl amines.