Mechanochemical Production of Biphenyls from Nitrogen-Containing Organic Compounds: Amides, Anilines, and Sulfonamides

Abstract

The presence of C(sp2)–NH2 in pharmaceutical building blocks provokes a pressing demand for the discovery and development of deaminative functionalization of the C(sp2)–NH2 moeity to enable new routes for late-stage functionalization of complex molecules. In this work, we disclose a mechanochemical deaminative arylation of C(sp2)–NH2 by in situ conversion of C(sp2)–NH2 to reactive pyridinium salts via selective condensation of C(sp2)–NH2 with pyrylium tetrafluoroborate. Deaminative coupling of anilines, amides, and sulfonamide represents a key development for the selective functionalization process, enabling production of precursor biphenyl compounds with the potential to develop biologically active molecules.