Developing Functionalized Peroxide Precursors for the Synthesis of Cyclic and Spirocyclic Ethers

There is increasing interest in the development of methods for the synthesis of oxetanes and spirocyclic oxetanes, a class of molecules of interest to chemists as they synthesize libraries of possible drug target scaffolds with tunable physiochemical and biological properties.1,2 Although most ethers are prepared through reaction of nucleophilic oxygen with electrophilic carbon, this work explores new reagents and routes for the synthesis of spirocyclic oxetanes based upon an application of umpolung or polarity reversal involving attack of nucleophilic carbon on the electrophilic oxygen of a peroxide (Scheme 1). In this work, a 2-carbon peroxide synthon for reverse etherification has been developed and tested with several nucleophilic substrate. Advisor: Patrick H. Dussaul