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

An environmentally benign method is described for the alpha-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 Oxon (R). This procedure was found to be substrate-dependent and was successfully performed to provide alpha-hydroxylated gamma-lactones. To demonstrate the synthetic potential of this mild alpha-hydroxylation, two different concise mutes were developed to synthesize harzialactone A in the racemic form with a moderate (3:1) diastereomeric ratio.