5-Endo-Dig Cyclization of a Carbon-Centered Radical and Utility of Cyclopentene Bromosulfone Product

The Baldwin rules provide a robust guideline for predicting the favorability of ring closure of reactive intermediates based upon stereoelectronic considerations. Our group was intrigued by the lack of examples of 5-endo-dig cyclizations with carbon-centered radicals, particularly because these reactions were suggested to be favorable according to the Baldwin rules and to our previous computational investigations using density functional analysis. We therefore set out to fill the gap in the arsenal of radical C-C bond forming processes by using computational data to design a new radical process. The first part of this thesis describes our studies aimed at the discovery of the first efficient 5-endo-dig cyclization of a carbon-centered radical. This is followed by experimental design and synthesis of substrates and finally reaction conditions which yield products through this novel mode of cyclization. The second part of this thesis explores the synthetic utility of the cyclized cyclopentene bromosulfone products. First, background information for the preparation and utility of vinyl sulfones is provided. This is followed by our results for derivatization of the bromide functional group of our cyclopentene bromosulfone products. Proper design of substrates and reaction conditions has allowed the 5-endo-dig radical cyclizations to finally become an experimental reality after more than forty years since the original prediction. The cyclized products which are enriched with functionality have been transformed into a variety of other products, emphasizing the importance of this discovery.