Asymmetric Total Synthesis and Structure Confirmation of (+)-(3E)-Isolaurefucin Methyl Ether

An asymmetric total synthesis and structure confirmation of (+)-(3E)-isolaurefucin methyl ether (2a) was accomplished. Our synthesis features two complementary routes to construct the alpha,alpha'-trans-2,8-dioxabicyclo[5.2.1]decane skeleton of the natural product from alpha,alpha'-trans-gamma,delta-unsaturated oxocene alcohol 7, namely, an intramolecular epoxide opening route and a novel methoxyetherification route based on organoseleniummediated oxonium ion formation/fragmentation. A computational analysis was performed to model the observed different fragmentation behaviors of the respective oxonium ions 8 and 8' derived from alpha,alpha'-trans- and alpha,alpha'-cis-gamma,delta-unsaturated oxocene alcohols 7 and 7' during the organoselenium-mediated oxonium ion formation/fragmentation. Regarding the possibility of the natural product being an artifact, the reactivity of chlorofucin surrogate 16 and neoprelaurefucin surrogate 16' during methanolysis was compared, the results were in good agreement with calculations.