5H-Oxazol-4-ones as Building Blocks for Asymmetric Synthesis of α-Hydroxycarboxylic Acid Derivatives

Abstract

5H-Alkyl-2-phenyl-oxazol-4-ones, a little-known heterocyclic ring system, are readily available via a microwave-assisted, sodium fluoride catalyst cyclization of mono-alpha-haloimides, which in turn are accessed by N-acylation of benzamides with alpha-bromo acid halides. Terminally substituted allyl systems serve as excellent substrates for Mo-catalyzed asymmetric allylic alkylation. The resultant products are formed with excellent ees involving a catalyst derived from N,N'-bis-picolinamide of trans-1,2-diaminocyclohexane and cycloheptatriene molybdenum tris(carbonyl). In addition to benzenoid, nonbenzenoid aromatic and vinyl substituents on the allyl carbonate moiety provide good to excellent regio- and diastereoselectivity as well as excellent enantioselectivity. Substituents on the heterocycle include methyl, n-butyl, allyl, isobutyl, isopropyl, and cyclohexyl. The presence of a double bond in the product allows them to be further modified via the chemistry of the double-bond, including metathesis. The products are hydrolyzed under basic conditions to provide alpha-hydroxyamides.