RHODIUM CARBENOID INITIATED CASCADES FOR THE SYNTHESIS OF DIVERSE MEDIUM-SIZED HETEROCYCLES

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dc.contributor.advisorSharma, Indrajeet
dc.contributor.authorMassaro, Nicholas
dc.contributor.committeeMemberCrossley, Steven
dc.contributor.committeeMemberGlatzhofer, Daniel
dc.contributor.committeeMemberDuerfeldt, Adam
dc.contributor.committeeMemberBurgett, Anthony
dc.date.accessioned2019-07-23T20:05:26Z
dc.date.available2019-07-23T20:05:26Z
dc.date.issued2019
dc.date.manuscript2019-06-14
dc.description.abstractMedium-sized rings (8–12 membered) are a unique class of cyclic molecules. These structures are present within a plethora of relevant natural products often possessing enhanced pharmacokinetic properties due to their dynamic structures. However, these molecules are drastically underrepresented due to the challenges associated with their construction. For this reason, more efficient methods to synthesize medium-sized rings may increase their presence in future drug scaffolds. The research presented in this thesis provides a highly convergent strategy to access diverse medium-sized heterocycles. The strategy relies on ambiphilic rhodium vinylcarbenoid precursors and dual-purpose nucleophile/electrophile synthons, which allow for smaller ring construction followed by subsequent ring expansion. The initial ring annulation occurs via a heteroatom insertion into a highly electrophilic rhodium carbenoid, derived from diazo synthons, generating a reactive zwitterionic intermediate. This intermediate then undergoes an intramolecular aldol cyclization to provide an oxy-Cope capable synthon primed for ring expansion which, upon thermal treatment, yields the highly functionalized medium-sized ring. This approach has been applied to O–H and N–H nucleophiles. Furthermore, this zwitterionic portion of the cascade was further extended to tolerate carboxylic acids, different ring sizes and the use of earth abundant iron catalysts. In addition to the synthesis of medium-sized rings, these products proved to be versatile substrates for serendipitous ring contraction cascades, leading to relevant bioactive natural product cores, such as highly functionalized quinolines and cyclopentanes in a diastereoselective manner. As a final remark, many of the products produced have been submitted for high throughput screening which has allowed for the identification of hit molecules that are now being further studied in the Sharma Research Group.en_US
dc.identifier.urihttps://hdl.handle.net/11244/321044
dc.languageen_USen_US
dc.subjectCascadesen_US
dc.subjectMedium-sized Ringsen_US
dc.subjectRhodium Carbenoidsen_US
dc.subjectMethodologyen_US
dc.thesis.degreePh.D.en_US
dc.titleRHODIUM CARBENOID INITIATED CASCADES FOR THE SYNTHESIS OF DIVERSE MEDIUM-SIZED HETEROCYCLESen_US
ou.groupCollege of Arts and Sciences::Department of Chemistry and Biochemistryen_US
shareok.orcid0000-0002-6008-7676en_US

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