Total syntheses of (+)- and (-)-peribysin E

A convergent, stereocontrolled route to either antipode of the cell adhesion inhibitor, peribysin E, has been achieved from carvone. Highlights of the synthesis include a Diels-Alder reaction to generate a cis-decalin framework, followed by semipinacol-type ring contraction to secure the stereochemistry of the C7 quaternary center. Potential mechanistic pathways for the critical ring contraction were studied through deuterium incorporation studies. In addition, an optimized olefin isomerization/Saegusa oxidation protocol is described for the conversion of [4+2] cycloadducts of 2-(trialkylsilyloxy)-1,3-dienes to 1,6(2H,7H)-naphthalenediones, having stereochemical arrangements not accessible via conventional Robinson annulation protocols. Finally, the ability to independently prepare either enantiomer of peribysin E from the corresponding antipode of carvone led to a reassignment of the absolute configuration of peribysin E.