Pd-Catalyzed Dimethylation of Tyrosine-Derived Picolinamide for Synthesis of (S)-N-Boc-2,6-dimethyltyrosine and Its Analogues.

A short and efficient synthesis of (S)-N-Boc-2,6-dimethyltyrosine utilizing palladium-catalyzed directed C-H functionalization is described. This represents the first general method for the ortho-dimethylation of tyrosine derivatives and offers a practical approach for preparing this synthetically important building block. Notably, throughout the reaction sequence no racemization occurs at the susceptible α-chiral centers.