Application Of Suzuki-Miyaura Coupling Reaction In The Synthesis Of Fine Chemicals

The Suzuki-Miyaura cross-coupling of boronic acids with organic halides is one of the most widely applied methods in modern synthetic organic chemistry.It has emerged as an important synthetic method that tolerates a wide range of functional groups and substrates providing efficient access to structurally diverse biaryl motifs.But the Suzuki-Miyaura cross-coupling reaction still suffers a major limitation in that it relies upon the direct use of boronic acids.Progress has been made to circumvent this limitation of the Suzuki-Miyaura cross-coupling reaction with the advent of the one-pot borylation/Suzuki-Miyaura cross-coupling reaction.The reaction is that organic borate ester and aryl halides or its analogues as raw material,firstly synthesize aryl boronic ester through C-B coupling reaction,and then obtain biaryl compounds through Suzuki-Miyaura cross-coupling reaction with the second kind of aryl halides or its analogues.The development of the reaction plays an important role in green chemistry.Palladium-catalyzed coupling reactions have become one of the central tools for the synthesis of biologically active compounds.Several palladium-catalyzed coupling reactions have been implemented into the industrial manufacture of pharmaceuticals and fine chemicals.Pesticide boscalid as new amide fungicide was developed by BASF Corporation in Germany.Boscalid has sterilization broad spectrum,high efficiency,low toxicity,no cross resistance to other bactericide on the market.However,boscalid did not apply for a patent in China,BASF Corporation obtained administrative protection of boscalid in 7.5 years,and the administrative protection has expired at the end of 2012.Therefore,the development of domestic industrial production line of boscalid is imperative.4'-chloro-2-nitro biphenyl is the key intermediates.of boscalid,so the synthesis of 4'-chloro-2-vitro biphenyl has very important significance.Therefore,we developed a new phosphine ligand for palladium catalyzed the one-pot of borylation/Suzuki-Miyaura coupling reaction.In addition,the synthesis process of key intermediates of boscalid 4'-chloro-2-nitro biphenyl was researched.The main details are as follows:[1]A novel ligand(2-(anthracen-9-yl)-1H-inden-3-yl)dicyclohexylphosphine was synthesized,which has a high activity and is stable in air.It can effectively catalyze the one-pot borylation/Suzuki-Miyaura coupling reaction combining with the Pd(dba)2,obtaining symmetrical and asymmetric biaryls compounds.[2]The synthesis process of key intermediates of boscalid 4'-chloro-2-nitro biphenyl was optimized,which obtained the yield of 94%under our optimal conditions.At the same time,in 100 gram scale,we study the technology of multiple batches,laid the foundation for the industrial manufacture of 4'-chloro-2-nitro biphenyl.