Palladium-catalyzed N-(2-pyridyl)sulfonyl-directed C(sp(3))-H gamma-arylation of amino acid derivatives

The direct Pd-catalyzed gamma-arylation of amino acid esters bearing a removable N-(2-pyridyl)sulfonyl directing group is described. A variety of N-(2-pyridyl)sulfonamide amino acid derivatives, including alpha-quaternary amino acid and beta-amino acid substrates, react with iodoarenes in the presence of Pd(OAc)(2) to provide gamma-arylated products in synthetically useful yields. An unprecedented remote C(sp(3))-H arylation of dipeptides is presented, illustrating the compatibility of the method with the presence of the peptidic bond. The process occurs without racemization at the C alpha center and the auxiliary controlling group can be easily installed and removed in the amino acid backbone. A bimetallic Pd-II gamma-metalated complex has been isolated and characterized showing the key role exerted by the (2-pyridyl)sulfonyl unit.