CARBONAZIDATE-INITIATED CASCADE REACTIONS: SYNTHESIS OF BRIDGED AZACYCLES, PROPELLANES AND -OXO-N-VINYLIMIDATES VIA HUISGEN CYCLIZATION/CARBENE CASCADE REACTIONS AND ACYL OXAZOLINONES VIA AN OXIDATIVE NITRENE/ALKYNE CASCADE REACTION

dc.contributor.advisorMay, Jeremy A.
dc.contributor.committeeMemberGilbertson, Scott R.
dc.contributor.committeeMemberTeets, Thomas S.
dc.contributor.committeeMemberWu, Judy I-Chia
dc.contributor.committeeMemberBall, Zachary T.
dc.creatorWang, Qinxuan
dc.creator.orcid0000-0003-2000-4386
dc.date.accessioned2022-06-29T23:51:55Z
dc.date.createdMay 2021
dc.date.issued2021-05
dc.date.submittedMay 2021
dc.date.updated2022-06-29T23:51:56Z
dc.description.abstractThis dissertation covers four projects utilizing carbonazidate-initiated cascade reactions. Both the first and second projects are based on Huisgen cyclization/carbene alkyne cascades. By using this method of initiation, bridged azacycles, propellanes, or -oxo-N-vinylimidates could be selectively synthesized. The third project arises from an alternate mechanistic path. Starting with nitrene generation, followed by cyclization and oxidation, acyl oxazolinones were successfully formed. The last project focuses on an experimental mechanistic study, which provided evidence to support proposed intermediates found by the collaborative computational study. A Huisgen cyclization/carbene alkyne cascade reaction terminating in C–H bond insertion to form functionalized bridged azacycles is presented in Chapter 2. Accessible nitrene precursors were assessed, and carbonazidates were found to be the only effective initiators. Substrates with different ring sizes as well as different aryl and heteroaryl groups were also explored. Examples incorporating stereocenters on the initiator tether demonstrated diasteroselectivity in the formation of the bridged ring and two new stereocenters. Additionally, propellanes can be obtained from the bridged azacycles in an acid-promoted rearrangement. Alternatively, via Huisgen cyclization/carbene cascade, -oxo-N-vinylimidates could be directly obtained by intermolecular trapping of esters (Chapter 3). Mechanistic control experiments suggested that a reversible dipole formation by ester addition to the carbene and nitrogen attack on the ester carbonyl was irreversibly followed by stereoselective decarboxylative elimination to give the Z-vinyl imidate product. The potential reactivity of the cross-conjugated enone, imidate, and enamine functional groups in the cascade product offers novel synthetic pathways to functionalized oxazoles. High polarity aprotic solvents as well as Cu(II) catalysts can facilitate nitrene generation from carbonazidates, which allow an oxidative nitrene/alkyne cascade reaction to form 4-acyl-oxazolinone (Chapter 4). Computational investigations revealed several novel potential intermediates for these Huisgen cyclization/carbene alkyne cascade reactions like triplet carbenes, a vinylidene, and a Si–N cyclobutene containing enamine. Combining computational and experimental mechanistic studies revealed novel intermediates and plausible reaction pathways were validated (Chapter 5).
dc.description.departmentChemistry, Department of
dc.format.digitalOriginborn digital
dc.format.mimetypeapplication/pdf
dc.identifier.citationPortions of this document appear in: Wang, Qinxuan, and Jeremy A. May. "Synthesis of bridged azacycles and propellanes via nitrene/alkyne cascades." Organic letters 22, no. 8 (2020): 3039-3044; and in: Wang, Qinxuan, and Jeremy A. May. "Formation of β-Oxo-N-vinylimidates via Intermolecular Ester Incorporation in Huisgen Cyclization/Carbene Cascade Reactions." Organic Letters 22, no. 24 (2020): 9579-9584.
dc.identifier.urihttps://hdl.handle.net/10657/10211
dc.language.isoeng
dc.rightsThe author of this work is the copyright owner. UH Libraries and the Texas Digital Library have their permission to store and provide access to this work. UH Libraries has secured permission to reproduce any and all previously published materials contained in the work. Further transmission, reproduction, or presentation of this work is prohibited except with permission of the author(s).
dc.subjectcarbene
dc.subjectnitrene
dc.subjectcascade
dc.subjectbridged polycycles
dc.subjectimidates
dc.titleCARBONAZIDATE-INITIATED CASCADE REACTIONS: SYNTHESIS OF BRIDGED AZACYCLES, PROPELLANES AND -OXO-N-VINYLIMIDATES VIA HUISGEN CYCLIZATION/CARBENE CASCADE REACTIONS AND ACYL OXAZOLINONES VIA AN OXIDATIVE NITRENE/ALKYNE CASCADE REACTION
dc.type.dcmiText
dc.type.genreThesis
local.embargo.lift2023-05-01
local.embargo.terms2023-05-01
thesis.degree.collegeCollege of Natural Sciences and Mathematics
thesis.degree.departmentChemistry, Department of
thesis.degree.disciplineChemistry
thesis.degree.grantorUniversity of Houston
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy

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