Synthesis of the C1-C15 fragment of apicularen a through a regioselective electron-transfer-initiated cyclization reaction

In this paper we report the preparation of the benzyltetrahydropyran fragment of the vacuolar ATPase inhibitor apicularen A through an oxidative cyclization protocol. In this reaction regioselective cleavage of one homobenzylic ether in the presence of another homobenzylic ether is achieved by selectively weakening one carbon-carbon sigma-bond through substitution. This work demonstrates that oxidative fragmentation reactions can be used to generate stable cations selectively, even in the presence of other readily oxidized groups, provided that bond cleavage is sufficiently rapid following oxidation.