Influence of steric parameters on the synthesis of tetramates from α-amino-β-alkoxy-esters and Ph3PCCO

α-Aminoesters react with Ph3PCCO in a domino addition-Wittig cyclization sequence affording enantiomerically pure tetramates. In the case of β-oxo functionalized α-aminoesters, e.g., esters of serine, threonine or β-hydroxyornithine the yields of this reaction depend heavily on the bulkiness of the β-OR group and on the configuration of β-carbon atom C-3. Smaller residues and 2R/3R-configured aminoesters give better yields. The alkoxycarbonyl group of the ester moiety and the residue on the N-atom are less important. These findings can be accounted for by assuming an early puckered transition state for the intramolecular ring-closing Wittig reaction. The addition of sub-stoichiometric amounts of benzoic acid or N-hydroxysuccinimide (for acid-sensitive compounds) is advantageous in some cases as it accelerates the formation of the intermediate amide ylides.