The application of tandem O-H insertion/ring-closing metathesis to the synthesis of unsaturated cyclic ethers. Approaches to rogioloxepane and isolaurepinnacin

The utilization of rhodium-mediated insertion reactions and ring-closing metathesis (RCM) in a tandem process has been examined as a synthetically useful route to the preparation of unsaturated cyclic ethers. The strategy employed involves the formation of a rhodium-mediated carbenoid through the catalytic decomposition of various alpha-diazoesters in the presence of olefinic-substituted alcohols. The first transformation of the tandem process provides an alpha-alkoxy ester possessing two tethered olefins (C=C) poised for a subsequent ring-closing metathesis reaction, affording an unsaturated cyclic ether.;The marine metabolites rogioloxepane and isolaurepinnacin were chosen as synthetic targets for the application of this methodology due in part to their structural core of an oxepene, a seven-membered unsaturated cyclic ether. The oxepene core can be constructed via the tandem process. The target molecules can be completed through elaboration of the alkyl side chains at C2 and C6 to differentiate and delineate the natural product syntheses. Variations in the structural composition of the alpha-diazoester and the olefinic alcohol would also allow for the preparation and study of structural analogs of the natural product.;A similar methodology was applied to a synthesis of (+/-)-pironetin, a substituted dihydropyranone possessing six chiral centers, which is a potential immunosuppressant and antitumor agent. Alternatively, interesting bicyclic compounds resulted from a competing ylide reaction followed by a subsequent 1,3-dipolar cycloaddition with a tethered olefin.