| The continued progress of organic synthesis depends heavily on the design and development of new strategies and strategic reactions that allow for the synthesis of complex, and therefore information rich, targets in a step-economical, if not ideal, fashion from readily available starting materials. Serial and multi-component cycloadditions provide a powerful means to achieve this goal.; Based on the chemoselectivity of the transition metal-catalyzed intermolecular [5+2] cycloaddition of vinylcyclopropanes for reaction with alkynes over alkenes, a serial [5+2]/[4+2] cycloaddition strategy was envisioned. This multi-component process affords complex polycyclic products with the formation of two new rings and up to four new stereocenters from three simple, readily available components. Significantly, higher yields are observed for a one-stage addition serial procedure than for the analogous two-stage addition procedure.; The capture of intermediates of transition metal-catalyzed [ m+n] cycloadditions with one or more additional components is an attractive strategy to produce new multi-component [ m+n+o...(+x)] cycloadditions. Based on capture of intermediates of a [5+2] cycloaddition, a fundamentally new [5+2+1] cycloaddition of vinylcyclopropanes, alkynes, and CO has been developed. This three-component cycloaddition proceeds in good to excellent yields and with high or complete regioselectivity to give cyclooctendione products, as well as bicyclo[3.3.0]octenone products that result from a serial in situ transannular closure process.; The capture of intermediates of the transition metal-catalyzed [4+2] cycloaddition of dienynes has led to the first example of a transition metal-catalyzed [4+2+1] cycloaddition, as well as a novel variation of the Pauson-Khand reaction. The dienyl Pauson-Khand reaction produces alkenylcyclopentenones in good to excellent yields and excellent diastereoselectivities. Significantly, control studies indicate that the diene facilitates the [2+2+1] cycloaddition relative to the analogous reactions with simple alkenes.; During studies of the [5+2+1] cycloaddition, a fundamentally new [5+1+2+1] cycloaddition was identified. This four-component process affords hydroxyindanone products in good yields from vinylcyclopropanes, alkynes, and two equivalents of CO. A variety of terminal alkyl- and aryl- alkynes and substituted vinylcyclopropanes are effective in the reaction, leading to predictably substituted indanone derivatives. The reaction can also be carried out bidirectionally, with the formation of ten carbon-carbon bonds from seven components in a single operation. |
