| The design and the development of a rhodium(I)-catalyzed intramolecular [6+2] cycloaddition of 2-vinylcyclobutanone with alkenes to form eight-membered rings is described. The scope and generality of this cycloaddition is investigated with respect to solvent effects, catalyst type, tether atoms (C-, N-, and O-linked systems), substitution of the alkene, and the utility of an allene.; Preliminary investigation into the intermolecular [6+2] cycloadditions led to the discovery of a metal-catalyzed C-C bond activation in an allenylcyclobutyl ether moiety. The efficiency of this catalytic process is demonstrated through the first examples of a transition metal-catalyzed [6+1] cycloaddition of allenylcyclobutyl ethers with CO, a new approach to seven-membered rings.; In contrast, the analogous rhodium-catalyzed cycloaddition of less strained allenyl ethers with CO led to the discovery of a novel rhodium(I)-catalyzed carbonylative rearrangement reaction to form a variety of lactones. Of mechanistic significance is the selective activation of a C-O bond over a C-C bond in these unstrained systems. Preliminary results are also described.; Another focus in the Wender group involves the synthesis of structurally novel polycyclic natural products with unique biological activity. Report herein is a concise and flexible macrolactonization approach towards the synthesis of gnidimacrin. The synthesis of the ABC tricyclic core of gnidimacrin is achieved in 20 sequential steps from commercially available acrolein (24 overall steps). Key reactions include a room temperature oxidopyrylium [5+2] cycloaddition to construct the BC ring system, a 1,2-addition reaction to introduce the side-chain of gnidimacrin, and a complex "ligandless" palladium-catalyzed reductive enyne cyclization to furnish the ABC core structure.; From the ABC ring system, the appendage of the alkyl side-chain of gnidimacrin is successfully achieved. Additionally, utilizing a high yielding oxo-bridge cleavage and a stereoselective opening of an alpha epoxide, the synthesis of a macrolactone precursor is reported in 34 steps from commercially available starting material. |
