Intramolecular O,N-Acyl Transfer via Cyclic Intermediates of Nine and Twelve Members. Models for Extensions of the Amine Capture Strategy for Peptide Synthesis

Article abstract of DOI:10.1021/jo00316a003

Rate constants are reported for intramolecular O,N-acyl-transfer reactions of 2-amino-N-benzyl-N-<2-(acyloxy)-4-nitrobenzyl>acetamides,2-amino-N-benzyl-N-(4-acetoxy-5-xanthyl)methylene>acetamide, ethyl N-(2-acetoxybenzyl)-2-aminoacetate, methyl N-<(8-acetoxy-1-naphthyl)methylene>-2-aminoacetate and their alanine and valine analogues in acetonitrile, Me2SO, and other solvents.Synthesis of these substrates is described, and a novel two-step synthesis is reported of 4-hydroxy-5-formylxanthene from 2,3-diacetoxybenzaldehyde and 2-(isopropoxymethylene)cyclohexanon in 29percent yield.Facile intramolecular acyl transfer via cyclic intermediates of 9 and 12 members is described, and steric and solvent effects on rates of acyl transfer are reported for these processes and compared with those for other intra- and intermolecular acyl-transfer reactions.The significance of these results for amide formation by amine capture is discussed.