Unified Protocol for Cobalt-Catalyzed Oxidative Assembly of Two Aryl Metal Reagents Using Oxygen as an Oxidant.

The first cobalt-catalyzed oxidative cross-coupling reaction of two aryl metal reagents is described. An equivalent amount of two aryl Grignard or lithium reagents, after mediation by an equivalent amount of simple ClTi(OEt)3, was facilely assembled under the catalysis of 1 mol % of CoCl2/10 mol % of DMPU using oxygen. The cross-couplings between various aryl metal reagents, especially between two structurally similar aryl Grignard reagents, proceeded smoothly and selectively and, thus, provided a highly general and efficient method for the construction of biaryl compounds.

Iron catalyzed oxidative assembly of N-heteroaryl and aryl metal reagents using oxygen as an oxidant.

An equivalent amount of N-heteroaryl and aryl Grignard or lithium reagents, after mediation by an equivalent of titanate, was facilely coupled to furnish N-heteroaryl-aryl compounds under the catalysis of FeCl3/TMEDA at ambient temperature using oxygen as an oxidant. Most of the common N-heteroaryls were all good candidates, and thus provided a general, green and pratical protocol for the flexible construction of various N-heteroaryl-aryl structures.

Reductive couplings of 2-halopyridines without external ligand: phosphine-free nickel-catalyzed synthesis of symmetrical and unsymmetrical 2,2'-bipyridines.

An unexpectedly facile synthetic approach for symmetrical and unsymmetrical 2,2'-bipyridines through the Ni-catalyzed reductive couplings of 2-halopyridines was developed. The couplings were efficiently catalyzed by 5 mol % of NiCl2·6H2O without the use of external ligands. A variety of 2,2'-bipyridines including caerulomycin F have been efficiently synthesized.

Arylation, alkenylation, and alkylation of 2-halopyridine N-oxides with grignard reagents: a solution to the problem of C2/C6 regioselective functionalization of pyridine derivatives.

A facile arylation, alkenylation, and alkylation of functionalized 2-halopyridine N-oxides with various Grignard reagents was developed. It represented a highly efficient and selective C-H bond functionalization of pyridine derivatives in the presence of reactive C-Cl or C-Br bonds. Using Cl or Br as a blocking group, C2/C6 site-controllable functionalization of pyridine derivatives has been achieved. Various pyridine compounds can be prepared as illustrated in the total syntheses of Onychine, dielsine, and PARP-1 inhibitor GPI 16539.