Multimetallic Pd- and Ni-catalyzed C(sp2)–P cross-coupling under aqueous micellar conditions

Abstract

Organophosphorus compounds containing hydrolytically and metabolically stable C(sp³)– and C(sp²)–P bonds are widely used as reagents, ligands, pesticides, herbicides, flame retardants, surface modifiers, and antiviral and anticancer drugs. These applications rely on efficient C(sp³)– and C(sp²)–P bond-forming reactions. However, currently available C(sp²)–P cross-coupling protocols require high catalyst loadings and temperatures, as well as environmentally unsustainable and harmful organic solvents (e.g., N,N-dimethylformamide, DMF). Herein, we disclose a conceptually novel strategy for performing multimetallic Pd/Ni- and dual-ligand Pd-catalyzed C(sp²)–P cross-coupling reactions in aqueous micelles under mild and environmentally friendly conditions. Micellar catalysis in water enables C(sp²)–P cross-coupling while avoiding environmentally unsustainable organic solvents, thereby reducing organic waste generation. Such micellar C(sp²)–P cross-coupling reactions tolerate various functional groups and provide access to structurally diverse (hetero)aryl (thio)phosphonates, phosphinates and phosphine oxides using inexpensive commercial materials and catalysts. Moreover, C(sp²)–P cross-coupling reactions of medically relevant substrates and drugs under late-stage functionalization settings and multistep one-pot processes highlight the potential applications of this experimental paradigm.