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

• Published in: Chemistry : a European journal 2011-06, Vol.17 (27), p.7480-7491
• Main Authors: Lechel, Tilman, Gerhard, Markus, Trawny, Daniel, Brusilowskij, Boris, Schefzig, Luise, Zimmer, Reinhold, Rabe, Jürgen P., Lentz, Dieter, Schalley, Christoph A., Reissig, Hans-Ulrich
• Format: Article
• Language: English
• Subjects: allenes; Amides - chemistry; cross-coupling; Crystallography, X-Ray; heterocycles; Ketones - chemical synthesis; Ketones - chemistry; Models, Molecular; Molecular Structure; monolayers; Oxazoles - chemical synthesis; Oxazoles - chemistry; scanning probe microscopy; self-assembly; Stereoisomerism
• 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 β‐alkoxy‐β‐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. Simple, flexible, versatile: The scope and limitations of a new synthesis of 5‐acetyloxazoles based on a three‐component approach to β‐alkoxy‐β‐ketoenamides are discussed (see scheme). The functional groups allow many transformations into a variety of new, interesting oxazole derivatives. The self‐assembly of a star‐shaped product with three oxazole ligands on highly oriented pyrolytic graphite (HOPG) was studied by scanning tunneling microscopy (STM).