Synthesis of 2,6-Dimethyltyrosine-Like Amino Acids through Pinacolinamide-Enabled C-H Dimethylation of 4-Dibenzylamino Phenylalanine

The synthesis of a small library of NH-Boc- or NH-Fmoc-protected L-phenylalanines carrying methyl groups at positions 2 and 6 and diverse functionalitics at position 4 has been achieved. The approach, which took advantage of a Pd-catalyzed directed C-H dimethylation of picolinamide derivatives, allowed the electronic and steric properties of the resulting amino acid derivatives to be altered by appending a variety of electronwithdrawing, electron-donating, or bulky groups.

Automated summary

A small library of NH-Boc- or NH-Fmoc-protected L-phenylalanines carrying methyl groups at positions 2 and 6 and diverse functionalities at position 4 has been synthesized through a Pd-catalyzed directed C-H dimethylation. The electronic and steric properties of the resulting amino acid derivatives can be altered by appending a variety of electron-withdrawing, electron-donating, or bulky groups.