Oxygen Bridge Activation by an Electron-Donating Group at the Bridgehead Carbon

Oxygen Bridge Activation by an Electron-Donating Group at the Bridgehead Carbon 

The cleavage of the ether bond in an oxabicydic compound bearing an oxygen substituent at the bridgehead (i. e. a bicyclic ketal or hemiketal) can be readily accomplished by solvolysis under acidic or basic conditions. 

The oxabicydic compounds required for this sequence can be assembled using 2-oxygenated furans. Gravel and Brisse synthesized the oxabicydic substrate 150 by the Diels-Alder reaction between 2-acetoxyfuran and chloromethyl maleic anhydride [150]. Ring-opening was induced by treatment with metha-nolic hydrogen chloride to give hydroxycyclohexanone 151, Eq. 102. 

Recendy, the first total synthesis of taxodone was accomplished via this strategy [152]. Cycloadduct 153, readily available from the Diels-Alder reaction of siloxyfuran 152 and methyl acrylate, was treated with acid to induce ring opening and dehydration to afford phenol 154, Eq. 103. 

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