The general goal of this proposal is to develop new cycloaddition technologies for preparing five-membered rings. The types of simple feedstocks such as alkenes, alkynes, and dienes that are so powerful in Diels Alder reactions and other widely used cycloaddition methods typically cannot directly combine to allow assembly of odd-numbered rings. This proposal aims to develop several solutions to this existing limitation of currently available transformations. The first goal involves developing a new strategy that allows two simple even-numbered pi-systems to combine in a catalytic cycloaddition to generate a five-membered ring product while the starting materials undergo a net two-electron reduction. Secondly, simple cyclopropyl ketones and imines will be used in ring-opening cycloadditions that install a three-carbon unit from the cyclopropane into a five-membered ring product. Finally, two new reactions will be developed that involve cycloaddition of two simple two-atom pi-systems with a one carbon unit or one-silicon unit to prepare carbocyclic or silacyclic five-membered rings. In addition to new cycloaddition approaches, the proposal will also develop a novel reductive coupling procedure of alkynes and electron deficient alkenes in order to address challenges and limitations of currently available conjugate addition procedures.
With this award, the Organic and Macromolecular Chemistry Program is renewing support for the work of Professor John Montgomery, of the Department of Chemistry at the University of Michigan. While powerful methods have been developed for the synthesis of molecules containing six-membered rings, general approaches for the synthesis of five-membered rings have lagged behind. Professor Montgomery and his students are discovering fundamentally new cycloaddition processes affording access to these smaller-sized rings, which are ubiquitous in compounds displaying biological or pharmacological activity, as well as in numerous compounds of interest in a variety of other disciplines, including materials science and molecular electronics. Professor Montgomery will also be involved in a study of the feasibility of a major multi-institution program designed to attract and mentor students from under-represented groups.
