Synlett 2017; 28(15): 1929-1933
DOI: 10.1055/s-0036-1588480
cluster
© Georg Thieme Verlag Stuttgart · New York

Product Selectivity in KAHA Ligations: Ester vs. Amide Formation with Cyclic Hydroxylamines

Florian Rohrbachera, Simon Baldaufa, Thomas G. Wucherpfenniga, Jeffrey W. Bode*a, b
  • aLaboratorium für Organische Chemie, Department of Chemistry and Applied Biosciences, ETH Zürich, 8093 Zürich, Switzerland   Email: bode@org.chem.ethz.ch
  • bInstitute of Transformative Bio-Molecules (WPI–ITbM), Nagoya University, Chikusa, Nagoya 464-8602, Japan
This work was supported by the Swiss National Science Foundation (150073, 169451)
Further Information

Publication History

Received: 30 April 2017

Accepted after revision: 04 June 2017

Publication Date:
19 July 2017 (eFirst)

Published as part of the Cluster Recent Advances in Protein and Peptide Synthesis

Abstract

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.

Supporting Information