Natural products (NP) and their metabolites isolated from diverse origins have been an extraordinary source of active pharmaceuticals, agrochemicals and other applications. Often, NP also serve as templates to obtain more potent and selective agents through structure-activity relationship (SAR) studies. A ubiquitous feature of NP and their metabolites is that they often contain fascinating fused-ring skeletons. Unfortunately, the vast majority of NP cannot be isolated in large quantities from their natural source. Consequently, the need to develop highly efficient synthetic methods that provide access to fused ring-skeletons with handles for further modification is necessary. Transition metal-catalyzed carbocyclization and cycloaddition reactions have proven to be among the most efficient methods for NP synthesis as well as constructing"natural product-like" (NPL) and"drug-like" (DL) skeletons.As part of ongoing studies by the Ojima lab into transition metal catalyzed carbocyclizations and higher-order cycloaddition reactions, the Rh(I)-catalyzed [2+2+2+1] cycloaddition of enediyne derivatives was investigated. The reaction of cyclohexene-diynes in the presence of [Rh(CO)2Cl]2 and CO (2 atm) gave novel 5-7-6-5 fused tetracyclic products while the reaction of cyclopentene-diynes under similar conditions gave the corresponding 5-7-5-5 fused tetracyclics in good to excellent yields. In addition to the expected products, the diene shifted regioisomers were obtained for all 1-silyl-substituted cycloalkenyl-diyne substrates investigated. Æ-Butyrolactones are prominent constituents in a diverse class of biologically active compounds. Thus, the Rh(I)-catalyzed [2+2+2+1] cycloaddition of 1-methyl-dodec-11-ene-8-oxo-1,6-diyneswhich afforded 5-7-5 tricyclic products with fused gamma-butyrolactones was also investigated. The reaction variables as well as the mechanism for the formation of these fused products are presented.