Cobalt-catalyzed Kumada coupling and the development of a CC ligand and metalation to cobalt

Inspired by work in our group using low-coordinate Co(I) complexes for amination of aryl halides, 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 successfully arylated in good yields as well, and the presence of β-hydrogens 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. A series of bidentate CC ligands were developed featuring an anionic Caryl and N¬-heterocyclic carbene (NHC) coordination to provide an electron rich, strong field ligand environment and promote novel reactivity by first-row transition metals. These ligands were treated with various cobalt sources to attempt to coordinate the NHC and affect CarylBr activation to produce the desired bidentate complexes. However, four coordinate cobalt(II) complexes binding at the NHC of two ligands and two halides were preferentially formed, limiting the applicability of this ligand.