Synthesis of 5-Acetyloxazoles and 1,2-Diketones from [beta]-Alkoxy-[beta]-ketoenamides and Their Subsequent Transformations

• Published in: Chemistry : a European journal 2011-06, Vol.17 (27), p.7480
• Main Authors: Lechel, Tilman, Gerhard, Markus, Trawny, Daniel, Brusilowskij, Boris, Schefzig, Luise, Zimmer, Reinhold, Rabe, Jurgen P, Lentz, Dieter, Schalley, Christoph A, Reissig, Hans-Ulrich
• Format: Article
• Language: English
• Subjects: Chemistry
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201100382

Lithiated alkoxyallenes, nitriles, and carboxylic acids have been employed as precursors in a three-component reaction leading to highly substituted [beta]-alkoxy-[beta]-ketoenamides. Upon treatment with trifluoroacetic acid, these enamides could be easily cyclized to 5-acetyloxazole derivatives. The synthesis is very flexible with respect to the substitution pattern at C-2 and C-4 of the oxazole core. A mechanistic suggestion for the oxazole formation is presented on the basis of 18O-labeled compounds and their mass spectrometric analysis. In several cases, 1,2-diketones are formed as side products or even as major components. The acetyl moiety at C-5 of the oxazole derivatives can efficiently be converted into alkenyl or alkynyl moieties, which allows a multitude of subsequent reactions. Condensation reactions of the acetyl group provided the expected oxime or hydrazone. By applying a Fischer reaction, the phenylhydrazone could be transferred into an indole, which emphasizes the potential of 5-acetyloxazoles for the preparation of highly substituted (poly)heterocyclic systems. The alkynyl group at C-2 is prone to addition reactions, providing an enamine with interesting photophysical properties. Sonogashira couplings were performed with 5-alkynyl-substituted oxazoles, furnishing the expected aryl-substituted products. This alkynyl unit was employed for the preparation of a new, star-shaped trisoxazole derivative. The ability of this multivalent compound to form self-assembled monolayers between the basal plane of highly oriented pyrolytic graphite and 1-phenyloctane was demonstrated by scanning tunneling microscopy (STM). The star-shaped compound seems to prefer the C3-symmetric arrangement in this two-dimensional crystal. Two 1,2-diketones were smoothly converted into functionalized quinoxaline derivatives.