Product Selectivity in KAHA Ligations: Ester vs. Amide Formation with Cyclic HydroxylaminesThis work was supported by the Swiss National Science Foundation (150073, 169451)
Received: 30 April 2017
Accepted after revision: 04 June 2017
19 July 2017 (eFirst)
Published as part of the Cluster Recent Advances in Protein and Peptide Synthesis
Cyclic hydroxylamines form esters instead of the expected amides as major product upon reaction with α-ketoacids. In this report, we document a systematic investigation into the effect of the hydroxylamine structure and the solvent mixture on the product ratio of amides vs. ester in the KAHA ligation. We show that the ratio is almost exclusively determined by the structure of the hydroxylamine, with only minor contributions from the reaction solvent or the structure of the α-ketoacid.