Influence of steric parameters on the synthesis of tetramates from α-amino-β-alkoxy-esters and Ph 3PCCO

• Published in: Tetrahedron Vol. 68; no. 2; pp. 697 - 704
• Main Authors: Loke, Inga, Park, Natja, Kempf, Karl, Jagusch, Carsten, Schobert, Rainer, Laschat, Sabine
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 2012
• Subjects: Amino acids; Phosphorus ylides; Tetramic acids; Wittig olefination; Tetramic acids; Wittig olefination; Amino acids; Phosphorus ylides
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2011.10.099

α-Aminoesters react with Ph 3PCCO 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 2 R/3 R-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. [Display omitted]