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Stereoselective α,α′-Annelation Reactions of 1,3-Dioxan-5-ones

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posted on 05.11.2010, 00:00 by Tyrone C. Casey, Julie Carlisle, Patrizia Tisselli, Louise Male, Neil Spencer, Richard S. Grainger
Pyrrolidine enamines derived from three 1,3-dioxan-5-ones undergo α,α′-annelation reactions with methyl α-(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.