Influence of steric parameters on the synthesis of tetramates from I+/--amino- beta -alkoxy-esters and Ph sub(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: 14.01.2012
• Subjects: Amides; Benzoic acid; Esters; Formations; Residues; Synthesis (chemistry); Tetrahedrons
• ISSN: 0040-4020
• DOI: 10.1016/j.tet.2011.10.099

alpha -Aminoesters react with Ph sub(3PCCO in a domino addition-Wittig cyclization sequence affording enantiomerically pure tetramates. In the case of beta -oxo functionalized alpha -aminoesters, e.g., esters of serine, threonine or beta -hydroxyornithine the yields of this reaction depend heavily on the bulkiness of the beta -OR group and on the configuration of beta -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.)