Catalytic Dehydrative Peptide Synthesis with gem-Diboronic Acids

Alkane- gem -diboronic acids have emerged as versatile organoboron catalysts for dehydrative amidation of α-amino acids. A phenol-substituted multiboron catalyst with a B–C–B structure outperformed simple arylboronic acids in the condensation of α-amino acids with suppressed epimerization of electrophiles. gem -diboronic acid catalysis were compatible with various O, N, and S -functionalized α-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.