This proposal describes a continuing investigation of transition metal- promoted higher-order cycloaddition chemistry. Application of group 6 (Cr, Mo, W) metal-mediated [6pi+4pi] and [6pi+2pi] cycloadditions to highly convergent syntheses of the antitumor germacranolides, melanpolidin and cis,cis- 15-desoxy-artemisiifolin as well as the important neurotoxin, anatoxin-a is planned. A strategy employing a tandem alkylation- cheletropic extrusion protocol starting from readily available dihydrothiepin-1,1-dioxide be investigated for the construction of the biologically active eicosanoid, lipoxin A. Considerable emphasis will be placed on developing several approaches to effecting higher-order cycloaddition with a high degree of asymmetric induction. In this context, the preparation of optically pure complexes via diastereoselective complexation and the identification of candidate chiral metal catalysts will be of primary importance. Several novel cycloaddition reactions have been identified and will be studied in more detail during the upcoming grant period. Of particular importance are tandem metal-promoted cycloaddition-CO insertion reactions that could afford rapid access to carbocyclic rings varying in size from 8 to 11 members and a divinyl cyclopropane based cycloaddition protocol that could be employed to make medium sized ring systems. An interesting entry into the AB rings of the very significant anti-cancer diterpene, taxol using this chemistry will also be examined. Throughout this study, heavy emphasis will be placed on extending the scope of the transition metal-mediated cycloadditions and, where applicable, natural product syntheses employing these reactions will be pursued. However, the major focus remains on methodology development at this stage of the investigation and only total syntheses that highlight a certain attribute of the cycloaddition reactions will be attempted.