Concise Synthesis of Norrisolide

The marine natural product norrisolide has been synthesized in a convergent manner with a longest linear sequence of 14 steps. The hydrindane portion of the molecules is prepared through conjugate addition of a functionalized allyl group into cyclopentenone, followed by stereoselective trapping of the enolate generated from the resulting enol silyl ether with an allyl electrophile. Ring-closing metathesis then establishes the 65 ring system. Likewise, selective preparation of the side chain features an enantioselective cyclopropanation of furan-2-one, followed by rearrangement and hydrogenation. Coupling of the two major fragments through a Shapiro reaction, followed by reduction and olefination then completes the carbon framework of the natural product. The final steps of the synthesis involve adjustments to the oxidation state of the side chain. New strategies to generate both the hydrindane core and the oxidized side chain has allowed for the more concise and efficient preparation of the natural product.