Current research in our laboratory falls into four broad areas. Our main goal is the design and invention of new strategies for the synthesis of carbocyclic and heterocyclic compounds. In this area an important objective is the development of methods that can be applied to highly substituted systems that are difficult to construct using existing methodology. The application of the methods we develop as key steps in the total synthesis of natural products is another important component of our program. These studies serve to test and further refine our new reactions in the context of more complicated systems. The synthesis of molecules with unusual electronic properties constitutes another goal in our lab. Past research in this area has included the development of new methods for the synthesis of azulenes and oligoazulenes and novel polycyclic aromatic and heteroaromatic systems. Finally, the development of methods for environmentally benign synthesis (“Green Chemistry”) is another aim of our program. Past research in this area has included investigations of the utility of supercritical carbon dioxide as a reaction medium for organic synthesis.

Pericyclic reactions serve as the primary vehicle we exploit in this research, with most of our efforts focused on the design of convergent annulation strategies based on cascades of pericyclic reactions. Our aim is to invent mechanistically novel transformations that will provide practical new synthetic routes to important carbocyclic and heterocyclic compounds. A common theme uniting the several components of our program is the development of unconventional approaches to important rings systems based on the application of highly unsaturated conjugated molecules as synthetic building blocks. We have pioneered the development of new synthetic methodology based on cycloadditions of unusual species such as vinylketenes, conjugated enynes, iminoacetonitriles, vinylallenes, and allenylimines. A number of the transformations we have studied proceed via highly strained molecules such as cyclobutenones, cyclic alkynes, and cyclic allenes.

Much of our research is concerned with the development of new cycloaddition and annulation strategies for the synthesis of very highly substituted aromatic and heteroaromatic compounds. Classical approaches to these systems generally are based on readily available benzene derivatives and rely heavily on electrophilic substitution, metalation, and transition-metal catalyzed coupling reactions to elaborate more highly substituted derivatives. Our program has focused on the design and invention of benzannulation strategies, in which the aromatic system is assembled from two or more non-aromatic precursors in a single step, with all (or most) substituents already in place. Benzannulation strategies enjoy significant advantages over classical linear substitution strategies, especially when applied to the preparation of highly substituted target molecules. For example, benzannulation routes frequently avoid the regiochemical ambiguities associated with aromatic substitution reactions and provide access to substitution patterns that cannot be obtained via the more conventional routes. Most significantly, the intrinsic convergent nature of benzannulation strategies facilitates the efficient assembly of highly substituted aromatics that would require long, multistep routes using classical substitution methodology.

An important feature of our program is the focus on the synthesis of highly substituted ring systems. While existing synthetic methodology often includes numerous routes to the same classes of compounds, these approaches frequently are not applicable to the efficient construction of the highly substituted and functionalized systems available by our methodology. For example, a number of useful strategies are available for the synthesis of indoles substituted on the five-membered ring, the majority of which involve the elaboration of the five-membered heterocycle from a simple aniline, o-halo aniline, or other 2-substituted aniline derivative. Few of these methods provide efficient and regiocontrolled access to indoles that are highly substituted on the benzenoid ring. Thus, the goal of our research in this particular area is the development of strategies applicable to the construction of indoles bearing multiple substituents on the six-membered ring.