Organometallic chemistry has become a cornerstone of modern organic synthesis. In particular, transition metal-promoted pericyclic reactions figure prominently in many complexity-creating synthetic transformations, their appeal lying in the fact that by using appropriate metal promoters, sluggish or even Woodward-Hoffmann-forbidden processes can be achieved efficiently.
Compared to that of metal-promoted cycloadditions, the synthetic potential of metal-promoted sigmatropic rearrangements has been largely untapped. We are using computational quantum chemistry to predict mechanisms and selectivities for such reactions and our predictions will then be tested experimentally.
Initially, we have focused on the following question: can we find an organometallic group that will promote efficient and stereoselective [1,3]-alkyl shifts? Metal-free [1,3] shifts generally require high temperatures and tend to produce mixtures of products resulting from biradical intermediates. Our goal is to overcome these shortcomings by stabilizing the transition states and/or high energy intermediates involved in thermal [1,3]-alkyl shifts by metal complexation. We are surveying various transition metals and ligands, in pursuit of an organometallic group that will promote this type of reaction in an efficient, general, and stereocontrolled manner.
In collaboration with Janis Louie at the University of Utah, we are examining nickel-promoted [1,3]-alkyl shifts of vinylcyclopropanes. The Louie group has shown that nickel/N-heterocyclic carbene complexes can catalyze these reactions at relatively low temperatures. We are examing the mechanisms of these processes computationally (an example of a computed reaction pathway is shown above) with the ultimate goal of designing even more efficient and stereoselective catalyst systems.
We are also exploring palladium-promoted [3,3]-shifts of 1,5-hexadienes (Cope rearrangements; see below). We've discovered that although the Pd(II) catalyzed [3,3] shift can proceed through a stepwise associative pathway (if appropriately substituted with a cation-stabilizing group), a simple change in substitution position or nature (e.g. an aptly placed electron withdrawing group) makes a concerted pathway energetically favorable. Since the Pd(II) promoted Cope rearrangement, much like its metal-free counterpart, changes mechanism based upon the nature and position of appended substituents, both can be described as "chameleonic".