The construction of ring compounds occupies an important position in synthetic organic chemistry. Under the Organic and Macromolecular Chemistry Program, this project is studying a novel reaction which very efficiently constructs six-membered rings containing an important functional group. This methodology will be employed to synthesize a series of natually occurring compounds. The participation of alpha, beta-unsaturated isocyanates in ?4+2! cycloaddition-like reactions with a variety of dienophilic partners including: enamines, vinyl ethers, silyl enol ethers, and benzynes is under study. The basic validity of the proposition has been established with the successful cycloaddition of several functionalized cyclohexenyl isocyanates and certain enamines, enolates and benzyne. The fundamental methodology is expanded to include the construction of a number of potentially useful functionalized octahydrophenanthridine species. In addition, further exploitation of the chemistry for the elaboration of several examples of the amaryllidaceae alkaloids is planned. The fundamental strategy exploits the potential for construction of the phenanthridine nucleus of the alkaloids in essentially one operation using appropriately functionalized vinyl isocyanates in ?4+2! cycloaddition type reactions. The strategy will also be used to construct several pyridone containing fungal metabolites.
