Stereocontrolled Oxygenation of Camphor Derivatives as a Prelude to the Complete β-Ring Functionalization of Potential Precursors to Taxol and Structural Analogs Thereof

Article abstract of DOI:10.1021/jo00109a020

The possibility of realizing the predominant exo α-hydroxylation of camphor-related ketones is described.Both the direct oxidation of enolate anions with 1-phenyl-N-(phenylsulfonyl)oxaziridine or exposure of the derived silyl enol ethers to dimethyl dioxirane are conducive to exo attack.Following conversion to MOM derivatives, the acidity of the α-carbonyl proton is reduced sufficiently to allow direct condensation of these hindered ketones with cyclohexenyllithium reagents.The subsequent anionic oxy-Cope rearrangement of the resulting exo carbinols results in direct conversion to tricyclic products that feature the characteristic C-2,C-9,C-10 B-ring oxygenation pattern resident in taxol.Further, the stereogenic centers are introduced in their proper absolute configuration.The steric demands of the <3,3> sigmatropic shift are discussed and the stereochemical features conducive to the minimization of steric compression subjected to experimental verification.