A major thrust of our research is the rational design of organocatalysts. Organocatalysis is a rapidly developing area of synthetic organic chemistry. Driven by a desire to develop catalysts that do not rely on transition metals, many highly stereoselective catalytic reactions have been developed over the last decade that utilize small organic molecules. Although a great deal of progress has been made in this field, there is still only limited information available regarding how these catalysts achieve such a high degree of reactivity and stereoselectivity.

We are using computational chemistry to unravel the mechanisms of organocatalyzed reactions and to provide structural information regarding the stereocontrolling transition states in these reactions. This information can then be used to devise new catalysts with improved reactivity and selectivity.

One particular target is N-oxide and N,N'-dioxide catalyzed allylation and propargylation reactions. Allylations and propargylations are key synthetic transformations leading to enantiopure allylic and propargylic alcohols. These, in turn, are key building blocks for a wide range of chiral products. We have developed alternative models of the origin of stereoselectivity in allylation and propargylation reactions catalyzed by the bipyridine N-oxides, and are currently designing novel N-oxide catalysts for asymmetric propargylation reactions. We are also pursuing computational studies of many other organocatalyzed reactions.