Catalytic Dehydrative Peptide Synthesis with gem-Diboronic Acids

Alkane-gem-diboronic acids have emerged as versatile organoboron catalysts for dehydrative amidation of alpha-amino acids. A phenol-substituted multiboron catalyst with a B-C-B structure outperformed simple arylboronic acids in the condensation of alpha-amino acids with suppressed epimerization of electrophiles. gem-diboronic acid catalysis were compatible with various O, N, and S-functionalized alpha-amino acids bearing N-protecting groups including common carbamates used in peptide synthesis (Boc, Cbz, Fmoc). N-trifluoroacetyl protection enabled an unprecedented catalytic dehydrative peptide synthesis at room temperature. Preliminary mechanistic studies revealed carboxylate-binding nature of gem-diboronic acids, orthogonal to the activation of carboxylic acids by arylboronic acids. The distinctive reactivity of the gem-diboronic acids would open prospects for mild catalytic peptide condensation.