Palladium-Catalyzed Desulfitative Cross-Coupling Of Sodium Arylsulfinates

Asymmetric biphenyl compound is a versatile chemical intermediates, widely used in many drugs, dyes, conductor, biologically active natural products and functional materials. Therefore, the formation of CAt-CAt is a hot research field of organic synthesis.In the past century, the transition-metal-catalyzed cross-coupling reaction has been extensively investigated. The traditional Suzuki coupling reaction is widely used, continuously improved, and brought a series of development. Nevertheless, the organometallic reagent is expensive, unstable and poisonous. Moreover, the operating conditions are cumbersome and it limits its application. Therefore, exploring a new reagent instead of the organometallic reagent, to participate in the reaction under mild conditions, has always pursue the goal of chemists.In this paper, we explore the reaction of o-cyano bromobenzene with sodium phenylsulfinate as the model reaction, and investigate ligands, solvents, and additives about the reaction. We use the Pd(OAc)2as catalyst to explore the coupling reaction between aryl bromide (Ar-Br) and sodium arylsulfinate (Ar-SO2Na). Finally, the optimal conditions is2mol%Pd(OAc)2as a catalyst,4mol%XPhos as the ligand, and toluene as the solvent,120℃for40h. Based on this, we test a wide range of aryl bromides and sodium arylsulfinates to evaluate the group tolerance obtaining a series of biphenyl compounds. The reaction conditions are also efficient to the less active aryl chlorides (Ar-Cl) and the substrates can mostly be transformed to obtain a high yield. The system has a better tolerance and is not sensitive to water. The operation is simple and easy.On the basis of this reaction, we further investigate the coupling reaction of the aryl triflates (Ar-OTf) with sodium arylsulfinates by the C-O activation. By optimizing ligand, solvent, temperature, reaction time, oxidant and other conditions, we have identified2mol%Pd(OAc)2as the catalyst,4mol%Xphos for ligand, toluene as the solvent,120℃reaction of24h as the optimal conditions. Under this condition, we perform a functional group tolerance of the experiment. The electron-withdrawing group is more conducive to the smooth progress of the reaction. Cyano and aldehyde group of the aryl triflate (Ar-OTf) can be obtained a near equivalent product, and electron-donating groups has a moderate reaction yield. The steric effect is not obvious in this reaction. For the sodium arylsulfinate (Ar-SO2Na), the electron donating group is more conducive to the smooth progress, such as methyl, methoxy, trifluoromethyl and chloro group. The reaction obtained the target product in a high yield efficiently.