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dc.contributor.advisorWengryniuk, Sarah E.
dc.creatorMikhael, Myriam
dc.date.accessioned2021-08-23T18:20:37Z
dc.date.available2021-08-23T18:20:37Z
dc.date.issued2021
dc.identifier.urihttp://hdl.handle.net/20.500.12613/6903
dc.description.abstractThe development of new strategies and associated reagents that enable previously inaccessible synthetic disconnections is largely attributing to the remarkable progress in exploring new chemical space for drug discovery and innovative complex molecule syntheses. In the Wengryniuk laboratory, we are devoted to discovering new synthetic methodologies that are based on umpolung or reverse polarity, strategies, enabled by Nitrogen-ligated (bis)cationic hypervalent iodine reagents (N-HVIs). I(III) N-HVIs represent an attractive new class of oxidant as they are environmentally benign, highly tunable, and have shown ability in enabling distinguished modes of reactivity. This dissertation focuses on demonstrating the synthetic utility of these N-HVI reagents towards C–O bond formation via a reverse polarity approach.In Chapter 1, a summary of the reactivity and characteristics of hypervalent iodine reagents is provided. Chapter 2 describes a mild and metal-free strategy for alcohol oxidation mediated by I(III) N-HVI reagents. This method demonstrates the first method for chemoselective oxidation of equatorial over axial alcohols and was the first in situ synthesis and application of N-HVIs for a simple one-pot procedure. Chapter 3 discusses a novel strategy for a dual C–H functionalization to access functionalized chroman scaffolds via an umpolung oxygen activation cyclization cascade. Computational studies in collaboration with Prof. Dean Tantillo (UC-Davis) along with experimental probes in our laboratory, support the formation of an umpoled oxygen intermediate as well as competitive direct and spirocyclization pathways for the key C–O bond forming event. The utility of the developed method is demonstrated through a downstream derivatization of the iodonium salt moiety to access C–H, C–X, and C–C substitution via established Pd-catalyzed cross couplings. Total synthesis of (±)-conicol natural product was performed in 8 steps and 23% overall yield, further demonstrating the synthetic utility of the developed method. Key synthetic steps include a smooth construction of the chroman core via N-HVI mediated C–H etherification of a pendant alcohol followed by a late-stage double bond installation. Overall, this dissertation summarizes the current state of research enabled by N-HVI reagents, with a focus on their utility in reverse polarity heteroatom activation strategies, and it serves as a practical guide for future development in the field.
dc.format.extent547 pages
dc.language.isoeng
dc.publisherTemple University. Libraries
dc.relation.ispartofTheses and Dissertations
dc.rightsIN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available.
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/
dc.subjectOrganic chemistry
dc.subjectChemoselective oxidation
dc.subjectDual C-H functionalization
dc.subjectHypervalent iodine
dc.subjectOxidation
dc.subjectOxygen electrophilic activation
dc.subjectUmpolung strategies
dc.titleNOVEL UMPOLUNG STRATEGIES FOR C−O BOND FORMATION WITH HYPERVALENT IODINE REAGENTS
dc.typeText
dc.type.genreThesis/Dissertation
dc.contributor.committeememberDobereiner, Graham
dc.contributor.committeememberWang, Rongsheng
dc.contributor.committeememberWatson, Mary P.
dc.description.departmentChemistry
dc.relation.doihttp://dx.doi.org/10.34944/dspace/6885
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.description.degreePh.D.
dc.identifier.proqst14647
dc.creator.orcid0000-0003-4895-6119
dc.date.updated2021-08-21T10:09:54Z
dc.embargo.lift12/01/2021
dc.identifier.filenameMikhael_temple_0225E_14647.pdf


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