Ring-opening Reactions of Cyclopropanated Heterobicyclic Alkenes

dc.contributor.advisorTam, William
dc.contributor.authorCarlson, Emily
dc.date.accessioned2016-08-29T13:54:00Z
dc.date.available2017-08-23T05:00:22Z
dc.date.copyright2016-08
dc.date.created2016-08-23
dc.date.issued2016-08-29
dc.degree.departmentDepartment of Chemistryen_US
dc.degree.grantorUniversity of Guelphen_US
dc.degree.nameDoctor of Philosophyen_US
dc.degree.programmeChemistryen_US
dc.description.abstractSynthetic organic chemistry centers around the development of useful reaction sequences. The primary objectives are to improve chemical transformations by making them more efficient and economical, to derive novel compounds and make them widely accessible, and to provide the scientific community with a better understanding of chemical behaviour so that new processes can be applied in the manufacture of similar structures, often with medicinal value. This thesis describes the construction of various novel heterotricyclo[3.2.1.02,4]octanes, and their subsequent ring-opening reactions to afford uniquely functionalized and structurally appealing organic frameworks. The first part of this work concerns the preparation of some common heterobicyclic alkenes and their derivatization by palladium-catalyzed diazocyclopropanation. This produced over 40 novel cyclopropanes with satisfactory yields (64-98%) and complete exo stereoselectivity. A higher equivalency of diazomethane was required to drive the reaction to completion for substrates bearing bulky substituents near the cyclopropanation site. Later portions of this work address transition metal or acid-catalyzed ring-opening reactions of the cyclopropanated heterobicycloalkenes, focusing on 7-oxa and 7-azabenzonorbornadienes. These studies have been subdivided into three types, each providing a unique class of product(s). Type 1 ring-openings led to the formation of cis-1,2-dihydro-2-methylnaphthalenols or polycyclic γ-lactams with facile incorporation of alkyl or aryl nucleophiles from organocuprates. Aromatization could be utilized to convert the dihydronaphthalenols to 2-methylnaphthalenes. Type 2 ring-openings proceeded with thermal acid-catalyzed conditions using alcohol or carboxylic acid nucleophiles, producing 2-(XCH2)naphthalenes (X=RO, RCO2). The reaction rate was found to increase with the acidity of the reaction medium. Type 3 ring-openings were discovered in conjunction with type 2-ring opening studies when bridgehead-substituted cyclopropanated oxabenzonorbornadienes underwent expansion to benzo-fused seven-membered rings. A greater proportion of type 3 product relative to type 2 product was obtained at lower reaction temperatures. Mechanisms for each transformation were supported by intramolecular reactions of cyclopropanated azabenzonorbornadienes under type 1 ring-opening conditions, or by tethered nucleophile-bearing substrates under type 2 and type 3 ring-opening conditions. Thus, several more novel polycyclic lactams, lactones and cyclic ethers were born. As the substrates of this investigation are still largely unexplored, future work in this area is promising.en_US
dc.description.sponsorshipNatural Sciences and Engineering Research Council of Canada
dc.identifier.urihttp://hdl.handle.net/10214/9901
dc.language.isoenen_US
dc.publisherUniversity of Guelphen_US
dc.rights.licenseAll items in the Atrium are protected by copyright with all rights reserved unless otherwise indicated.
dc.subjectcyclopropanationen_US
dc.subjectstrainen_US
dc.subjectheterocycleen_US
dc.subjectring-openingen_US
dc.subjecttransition metalen_US
dc.subjectacid-catalysisen_US
dc.subjectregioselectiveen_US
dc.subjectstereoselectiveen_US
dc.subjectsynthesisen_US
dc.subjectnatural producten_US
dc.subjectcopperen_US
dc.subjectpalladiumen_US
dc.subjectbridged ring systemen_US
dc.subjectalkeneen_US
dc.titleRing-opening Reactions of Cyclopropanated Heterobicyclic Alkenesen_US
dc.typeThesisen_US

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