Catalytic Chemical Amide Synthesis at Room Temperature: One More Step Toward Peptide Synthesis
An uncommon use of a boronic acid: as catalyst to prepare amides.
It is a tribute to the importance of amides in nature that there are some many protocols and reagents described for the synthesis of these compounds… and that we are still looking for more. Even the most modern methods have limitations. Racemization is one of them, but lately is the use of expensive reagents in stoichiometric quantities. The goal is to find a cheap reagent that act as catalyst for the formation of amides under mild conditions, without racemization.
This work by Blanchet et al. (Universite? de Caen Basse-Normandie, France) is another step in the right direction. Following some hints in the literature (a quote by Newton would come in handy here) they have synthesized and assayed a dozen boronic acids. Their best candidate is the 2-(thiophen-2-ylmethyl)phenyl)boronic acid, which they used in a fairly simple protocol. Just solve the components in dichloromethane with 5 Å molecular sieves at room temperature and stirring for several hours. The yields obtained are not bad, but for some substrates some heating is required. When used to couple more challenging substrates they switch to other solvents, DCE and toluene, but with the usual troublemakers, a-aminoacids, they have to switch to fluorobenzene. In those conditions, the racemization is almost neglected, specially when compared with previous results in literature.
J. Org. Chem. 2015, Article ASAP.