Formation of α-Hydroxy-β-diketones through Hydroxylation of Isoxazolium Salts: Stereoselective Approach to Angular cis-Diols in Poly cyclic Systems

摘要

Among the natural products of the type-II polyketide biosynthesis, highly oxidized polycyclic structures, such as auxarthrol B (1) and tetracenomycin C (2), are attractive for their biological relevance as well as for synthetic challenges (Scheme 1). In our continuing synthetic studies on the exploitation of isoxazole-based intermediates like A, we have addressed the issue of installing the "angular cis-diols" that are characteristic of these compounds. We envisioned that, if viable, the oxidation of isoxazoles to α-hydroxy-β-dicarbonyl structures would be ideally suited for this purpose. However, in contrast to the well-known reductive N—O bond fission and hydrolysis that made isoxazoles useful synthetic equivalents to β-dicarbonyl compounds, the projected oxidation is unprecedented due to the resistance of this heterocycle toward various transformations. Judging from the inherent reactivities, however, we expected that the corresponding isoxazolium salt would provide a potential solution by allowing elaborations including oxidation.