13287-12-2Relevant academic research and scientific papers
N-Methylcaprolactam as a Dipolar Aprotic Solvent for Iron-Catalyzed Cross-Coupling Reactions: Matching Efficiency with Safer Reaction Media
Bisz, Elwira,Podchorodecka, Pamela,Szostak, Michal
, p. 1196 - 1199 (2019)
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(sp2)?C(sp3) 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.
N -Butylpyrrolidone (NBP) as a non-toxic substitute for NMP in iron-catalyzed C(sp2)-C(sp3) cross-coupling of aryl chlorides
Bisz, Elwira,Koston, Martina,Szostak, Michal
supporting information, p. 7515 - 7521 (2021/10/12)
Although iron catalyzed cross-coupling reactions show extraordinary promise in reducing the environmental impact of more toxic and scarce transition metals, one of the main challenges is the use of reprotoxic NMP (NMP = N-methylpyrrolidone) as the key ligand to iron in the most successful protocols in this reactivity platform. Herein, we report that non-toxic and sustainable N-butylpyrrolidone (NBP) serves as a highly effective substitute for NMP in iron-catalyzed C(sp2)-C(sp3) cross-coupling of aryl chlorides with alkyl Grignard reagents. This challenging alkylation proceeds with organometallics bearing β-hydrogens with efficiency superseding or matching that of NMP with ample scope and broad functional group tolerance. Appealing applications are demonstrated in the cross-coupling in the presence of sensitive functional groups and the synthesis of several pharmaceutical intermediates, including a dual NK1/serotonin inhibitor, a fibrinolysis inhibitor and an antifungal agent. Considering that the iron/NMP system has emerged as one of the most powerful iron cross-coupling technologies available in both academic and industrial research, we anticipate that this method will be of broad interest.
