Nickel-catalyzed Reductive Coupling Reaction Of 2-chloropyrimidine Derivatives

In recent years,transition metal-catalyzed cross-coupling reactions have become an effective reaction for the construction of C-C bonds.In particular,nickel(Ni)-catalyzed reductive cross-coupling reactions have become a hot topic in organic chemistry research,with the advantages of low reduction potential,rapid oxidative addition,mild reaction conditions,and avoidance of pre-preparation and pretreatment of metal reagents.Organosilicon compounds are widely used in materials science,medicinal chemistry and organic synthesis.Transition metal-catalyzed cross-coupling reactions involving chlorosilanes are commonly used methods for constructing C-Si bonds.These methods make the preparation of organosilanes have better functional group tolerance,more complex structure and milder conditions.The structure of 3,4-dihydropyrimidin-2-ones(DHPMs)is widely present in many drug active molecular skeletons and is a dominant structural unit in drug synthesis.The 2-chloro-4-alkyl-6-arylpyrimidine-5-carboxylate and 4-alkyl-6-aryl-2-(p-toluenesulfonyloxy)pyrimidine-5-carboxylate prepared from DHPMs are stable and easy to prepare electrophiles.The main contents and results of this paper are as follows:Firstly,transition metal-catalyzed C-C coupling and C-Si coupling reactions are briefly reviewed.Then,using 2-chloro-4-alkyl-6-arylpyrimidine-5-carboxylate and dimethylvinylchlorosilane as substrates,nickel trifluoromethanesulfonate as catalyst,2,9-dimethyl-4,7-biphenyl-1,10-phenanthroline as ligand,manganese as reducing agent,a series of 2-(dimethyl(vinyl)silyl)-4-alkyl-6-arylpyrimidine-5-carboxylate compounds were synthesized by nickel-catalyzed electrophilic cross-coupling of heteroaryl compounds with chlorosilane for the first time.Finally,using 2-chloro-4-alkyl-6-arylpyrimidine-5-carboxylic acid esters and alkyl bromides as electrophiles,diethylene glycol dimethyl ether nickel bromide as catalyst,terpyridine derivatives as ligands,and zinc as reducing agent,the C-C coupling of 2-chloro-4-alkyl-6-arylpyrimidine-5-carboxylic acid esters with alkyl bromides was realized at room temperature,and a series of C-2-substituted pyrimidines were prepared.