A Convenient Asymmetric Synthesis of the Unnatural Amino Acid 2,6-Dimethyl-L-tyrosine

Abstract
The title compound was prepared in high optical purity by a five-step synthesis from 3,5-dimethylphenol on a kilogram scale. The key steps were a modified palladium-catalyzed coupling of an aryl iodide with methyl 2-acetamidoacrylate and hydrogenation of the resulting sterically hindered dehydroamino acid 4 using [Rh(1,5-COD)- (R,R-DIPAMP)]BF4 as catalyst.