Electrochemical Synthesis of Unnatural Amino Acids Embedding 5- and 6‑Membered Heteroaromatics

Using a commercially available potentiostat, the electrochemical
synthesis of unnatural amino acids bearing heteroaromatics on the
lateral chain has been accomplished. This strategy exploits the side-chain
decarboxylative arylation of aspartic/glutamic acid, a reaction that
becomes challenging with electron-rich coupling partners such as 5-
and 6-membered heteroaromatics. These rings are underrepresented in
unnatural amino acids, therefore allowing a wider exploration of the
chemical space, given the abundance of the aryl bromides employable
in this reaction.