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

Abstract

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.

Up-Scale Synthesis of p-(CH2═CH)C6H4CH2CH2CH2Cl and p-ClC6H4SiR3 by CuCN-Catalyzed Coupling Reactions of Grignard Reagents with Organic Halides

“…On the other hand, Grignard reagents do not react with organic halide electrophiles, typically requiring a catalyst for the coupling reactions with them. Various transition-metal-based catalysts have been developed, − and Cu complexes among those are the oldest and most frequently employed catalyst. − Chlorosilane compounds are known to be good counterpart electrophiles, but they are also unreactive in some cases, especially when either chlorosilanes or Grignard reagents are sterically encumbered (vide infra). , …”

Palladium-catalyzed C–H dimethylamination of 1-chloromethyl naphthalenes with N,N-dimethylformamide as the dimethyl amino source

“…The result is similar to the reported one obtained using N , N -dimethyl-2-(diphenylphosphino)aniline as the ligand. 15 Control experiments were conducted to gain insights into the mechanism of this type of direct aromatic C–H bond dimethylamination reaction. According to the results of the optimization, H 2 O was beneficial for the transformation.…”