Palladium-Catalyzed Suzuki Reaction Of Arylboron Compounds In Aqueous Media

The Suzuki reaction has been recognized as a powerful tool for the construction of carbon-carbon bond, and has been extensively used to synthesize pharmaceuticals, natural products and advanced functional materials. Arylboronic acids are the most frequently utilized nucleophilic reagents in the Suzuki reaction due to their nontoxic, air- and water-stable properties, and good functional group tolerance. In recent years, potassium organotrifluoroborates and N-methyliminodiacetic acid boronates as new organoboron reagents have received great attention. These nucleophilic reagents can be stored indefinitely without any special precaution, and nearly not undergo homo-coupling or protodeboronation under the Suzuki reaction conditions. Thus, the development of simple, efficient and green Suzuki catalytic system for new organoboron reagents has been attracted great research interests.Water is an attractive solvent for chemical reactions for reasons of low cost, readily availability and non-toxicity. Although many aqueous Suzuki reaction systems have been reported, most of them employed surfactants and/or ligands. In this study, several aqueous Suzuki reaction systems have been developed for the cross-couplings of aryl halides and arylboronic acids, potassium aryltrifluoroborates, or aryl N-methyliminodiacetic acid (MIDA) boronate. The main contents are as follows:(1) A palladium-catalyzed ligand-free Suzuki reaction system for potassium aryltrifluoroborates in aqueous ethanol has been developed. Using Pd(OAc)2 as catalyst, various aryl bromides or heteroaryl halides were efficiently coupled with potassium aryltrifluoroborates. A series of unsymmetrical teraryls were prepared in good yields by one-pot Suzuki reaction using potassium bromo-phenyltrifluoroborates as starting reagent.(2) A room temperature and palladium-catalyzed ligand-free Suzuki reaction catalytic system in water has been developed. Using Pd(OAc)2 as catalyst and Et3N as base, various aryl bromides and arylboronic acids were coupled smoothly at room temperature. Moreover, a series of fluorinated liquid-crystalline compounds have been successfully prepared in this system with the highest yield up to 94%.(3) A palladium-catalyzed ligand-free Suzuki reaction system for potassium aryltrifluoroborates in water has been developed. This catalytic system, using Pd(OAc)2 as catalyst, (i-Pr)2NH as base, could realize the Suzuki cross-couplings between aryl/heteroaryl halides and potassium aryltrifluoroborates with high efficiency. Moreover, the cross-coupling reactions were performed well on gram-scale, and the products could be purified by simple recrystallization with a small amount of organic solvent.(4) A palladium-catalyzed ligand-free system for the Suzuki reaction of aryl MIDA boronate in water has been developed. In the presences of Pd(OAc)2 and (i-Pr)2NH, this system was efficient for the Suzuki cross-coupling reaction between heteroaryl halides and aryl MIDA boronate under air at 100℃ with the highest yield up to 96%.(5) A palladium/amine complex Pd(OAc)2[(i-Pr)2NH]2 has been prepared and demonstrated high catalytic efficiency for the Suzuki reaction between hetero/aryl halides and different arylboron, including arylboronic acids, potassium aryltrifluoroborotes and aryl N-methyliminodiacetic acid boronates.