Synthesis of an amidosulfonate-tagged biphenyl phosphine and its application in the Suzuki–Miyaura reaction affording biphenyl-substituted amino acids in water.

An amidosulfonate-tagged phosphinobiphenyl, viz triethylammonium 2-(dicyclohexylphosphino)-4′-{[(sulfonatomethyl)amino]carbonyl}biphenyl ( 3 ), was prepared in two steps from 2-(dicyclohexylphosphino)biphenyl-4′-carboxylic acid and fully characterized including the crystal structure determination. As a highly polar phosphine ligand, compound 3 was employed in the Pd-catalyzed Suzuki–Miyaura cross-coupling of N -Boc protected 4-bromo and 4-chlorophenylalanine with aromatic boronic acids to afford the corresponding biphenyls in aqueous N,N -dimethylformamide or pure water. The coupling was demonstrated to proceed very well and without the loss of the Boc protecting group when the bromo-substituted substrate is reacted in the presence of 1 mol.% of Pd/ 3 catalyst in water at 40 °C. Reactions with boronic acids bearing electron-withdrawing substituents and, mainly, those with the less reactive chlorophenylalanine substrate required slightly higher reaction temperature and more catalyst to achieve similar results. [ABSTRACT FROM AUTHOR]