Stereoselective α,α'-annelation reactions of 1,3-dioxan-5-ones

Pyrrolidine enamines derived from three 1,3-dioxan-5-ones undergo (alpha,alpha'-annelation reactions with methyl alpha-(bromomethyl)acrylate to produce bridged 2,4-dioxabicyclo[3.3.1]-nonane ring systems with complete stereocontrol. Stereochemical outcomes have been rationalized based on steric and stereoelectronic interactions in intermediate boat-like conformations of the 1,3-dioxane ring and subsequent kinetic protonation to set an axial ester group on the cyclohexanone ring. Base-mediated ester epimerization provides the stereochemical array found in the highly oxygenated cyclohexane ring of phyllaemblic acid and glochicoccins B and D.