N-Methylcaprolactam as a Dipolar Aprotic Solvent for Iron-Catalyzed Cross-Coupling Reactions: Matching Efficiency with Safer Reaction Media

Although iron-catalysis provides a powerful alternative to the more conventional palladium and nickel in the cross-coupling arena, the major limitation is the necessity for carcinogenic N-methylpyrrolidone as a co-solvent in the vast majority of catalytic reactions. Herein, we introduce N-methylcaprolactam as an efficient, non-toxic and practical dipolar aprotic solvent for iron-catalyzed C(sp(2))-C(sp(3)) alkylative cross-coupling of aryl chlorides and tosylates. The utility of this method is reflected by its wide substrate scope, high yields and capacity to cross-couple challenging alkyl organometallics prone to b-hydride elimination and homocoupling. Considering the broad utility of iron-catalyzed cross-coupling, we envision that N-methylcaprolactam will find wide application as a substitute for carcinogenic NMP.