Oxone®-Mediated Direct α-Hydroxylation of β-Dicarbonyl Compounds: Racemic Synthesis of Harzialactone A

Abstract

An environmentally benign method is described for the α-hydroxylation of malonates and cyclic analogues in aqueous medium at room temperature under mild conditions, based on the in situ generation of dimethyldioxirane through the combination of acetone and Oxone ® . This procedure was found to be substrate-dependent and was successfully performed to provide α-hydroxylated γ-lactones. To demonstrate the synthetic potential of this mild α-hydroxylation, two different concise routes were developed to synthesize harzialactone A in the racemic form with a moderate (3:1) diastereomeric ratio.Scheme 5. Two strategies for the racemic synthesis of harzialactone A (4a) starting with epoxide 2a.

Stereocontrolled Synthesis of Harzialactone A and Its Three Stereoisomers by Use of Standardized Polyketide Building Blocks

“…Due to the biological properties, Harzialactone A (and its stereoisomers and derivatives) became an interesting target compound for synthetic endeavors. Numerous groups reported synthetic approaches toward racemic product mixtures or enantioenriched material, starting from readily available carbohydrates and enantiomerically pure epoxides, or by using asymmetric catalysis or kinetic resolution …”