Controlled Regioselective Anilide Formation from Aspartic and Glutamic Acid Anhydrides

The regioselectivity of the reaction of aniline with a series of N -protected aspartic and glutamic acid anhydrides was controlled through the choice of reaction solvent. In benzene, the formation of aspartic or glutamic acid α-anilides was favored, with α:(β or γ) regioselectivities as high as 100:0. On the other hand, in DMSO, the formation of either aspartic acid β-anilide or glutamic acid γ-anilide was favored, with α:(β or γ) regioselectivities as high as 0:100. This regioselectivity was not observed for alkylamines, amino acids, thiols, or alcohols. However, the high yields of the aniline reactions and the ability to specify their regioselectivities demonstrate the usefulness of our method for the formation of aspartic and glutamic acid anilide bonds.