Nickel-Catalyzed Reductive Cross-Coupling of Heteroaryl Chlorides and Aryl Chlorides

Abstract

We report a nickel-catalyzed cross-electrophile coupling reaction of aryl chlorides and heteroaryl chlorides enabled by a synergistic combination consisting of halide effects and the addition of a magnesium salt. The reaction relies on the electronic difference between the aromatic and heteroaromatic coupling partners to afford the cross-coupled biaryl products using a single catalyst. A variety of heterocycles were amenable to the reaction, as well as a wide range of aryl chlorides, with electron-deficient aryl chlorides performing the best in the reaction. Preliminary mechanistic evidence demonstrates the MgCl2 is essential to the reaction by accelerating the reduction of Ni­(II), and that small quantities of iodide lead to improved yields.

Nickel-Catalyzed Chemo- and Regioselective Benzylarylation of Unactivated Alkenes with o-Bromobenzyl Chlorides

“…On the basis of our experimental results and previous reports, ,,− a plausible mechanism for the nickel-catalyzed reductive benzylarylation is illustrated in Scheme . Initially, a putative Ni(0) species I is generated from NiBr 2 under reductive conditions and was coordinated by the AQ auxiliary on pentenamide 1 .…”

Modular Access to Chiral α-(Hetero)aryl Amines via Ni/Photoredox-Catalyzed Enantioselective Cross-Coupling

“…Aryl chlorides, which are the most ubiquitous, less-toxic, and inexpensive aryl halide coupling partners, have not previously been employed in enantioselective metallaphotoredox catalysis. 65,66 Notably, our reaction is not highly sensitive to air and can be performed using lower catalyst loading with similar efficiency (entries 2 and 3). Ethyl acetate was also a suitable solvent (entry 4).…”

Chemodivergent Csp 3 ─F bond functionalization and cross-electrophile alkyl-alkyl coupling with alkyl fluorides

“…Corriu-Kumada, Suzuki, Stille, Negishi, and Hiyama couplings require prior conversion of one reaction partner into a Grignard, boronic acid, stannane, zinc, or silyl compound. To overcome this drawback, reductive and photoredox methods for bond construction with alkyl and aryl chlorides, bromides, iodides, carboxylates, sulfonates, or pseudohalides have been introduced (45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57). The prospect of direct alkyl halide cross-coupling is paradigm-shifting in the realm of organic synthesis because it is substantially more efficient and minimizes cost and waste production.…”