A variety of urethane-protected α-amino acid N-carboxyanhydrides (UNCAs) were synthesized in high yields via the rapid dual activation of both an α-NCA and alkyl chloroformate by combination of two amines in a micro-flow reactor.

Smaller cyclic peptides containing non‐proteinogenic amino acids have garnered much attention for use as drugs, but their chemical synthesis is extremely challenging. In this study, a rapid (60.5 min) synthesis of 7‐ and 14‐membered cyclic peptides containing N‐methyl‐ and β‐amino acids was achieved by only switching the concentrations (0.20 M or 0.01 M) of the substrates. The developed approach required neither expensive transition‐metals nor expensive coupling agents. As far as we could ascertain, this is the first report of the synthesis of smaller (≤16‐membered) cyclic N‐methylated peptides via dimerization‐cyclization strategy.