Palladium-catalyzed N-(2-pyridyl)sulfonyl-directed C(sp3)–H γ-arylation of amino acid derivatives

Abstract

The direct Pd-catalyzed γ-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 α-quaternary amino acid and β-amino acid substrates, react with iodoarenes in the presence of Pd(OAc)₂ to provide γ-arylated products in synthetically useful yields. An unprecedented remote C(sp³)–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 Cα center and the auxiliary controlling group can be easily installed and removed in the amino acid backbone. A bimetallic Pd^II γ-metalated complex has been isolated and characterized showing the key role exerted by the (2-pyridyl)sulfonyl unit.