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

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. [ABSTRACT FROM AUTHOR]