Anodic oxidation of N-acyl and N-alkoxycarbonyl dipeptide esters as a key step for the formation of chiral heterocyclic synthetic building blocks

Abstract

The anodic oxidation of N-protected dipeptide esters using chloride as a redox catalyst can be performed regioselectively at the C-terminal amino acid. With methanol as solvent, glycine as the C-terminal, and L-valine or L-proline as N-terminal amino acid methoxylation at the glycine residue takes place. Deprotection of this product leads to the (3 S,6 RS)-6-methoxy-2,5-piperazinedione( 3) which can be applied as a chiral cationic glycine equivalent. The exchange of the methoxy group by C-nucleophiles takes place with high trans-diastereoselectivity under steric control by the substituent in 3-position. With branched amino acids at the C-terminus of the dipeptide ester the anodic oxidation in acetonitrile/methanol (95:5) as solvent with tetraethylammonium chloride as supporting electrolyte and redox catalyst leads to methyl imidazolidin-4-one-2-carboxylates. The cyclization takes place via the intermediate formation of the N-acylimino ester of the C-terminal amino acid.