Cobalt-Catalyzed Kumada Coupling Forming Sterically Encumbered C–C Bonds

• Published in: Organometallics 2022-07, Vol.41 (14), p.1769-1776
• Main Authors: Killion, Jack A., Darrow, William T., Brennan, Marshall R., Leahy, Clare A., Fout, Alison R.
• Format: Article
• Language: English
• ISSN: 0276-7333; 1520-6041
• DOI: 10.1021/acs.organomet.1c00513

A Co­(acac)3/PN precatalyst was developed and optimized for catalytic Kumada coupling of aryl Grignard reagents to sterically encumbered alkyl halides. The substrate scope demonstrates excellent yields for primary alkyl chlorides and bromides, including good performance using neopentyl chloride and neophyl chloride. Secondary alkyl halides were also successfully arylated in good yields, and the presence of β-hydrogen atoms in a substrate did not inhibit product formation. An intermolecular functional group tolerance screen was conducted which indicates that ester and amide functionality are well tolerated by the reaction conditions. Electrophiles containing ester, pyridine, and nitrile functionality were all coupled with 2-mesitylmagnesium bromide in good yields, supporting tolerance screen results. The intermolecular screen also showed that functional groups which are typically reactive with Grignard reagents such as alcohols and terminal alkynes were not well-tolerated by the reaction.