{"id":{"repo_id":"uwo","oai_identifier":"oai:uwo.scholaris.ca:20.500.14721/36278"},"canonical_url":"https://search.dev.ndltd.org/etd/uwo/oai:uwo.scholaris.ca:20.500.14721/36278","repository":{"repo_id":"uwo","name":"Western University","base_url":"https://uwo.scholaris.ca/server/oai/request"},"display":{"title":"Donor-Acceptor Cyclobutanes and Their Application for Heterocycle Synthesis and Progress Towards Biselide A","abstract":"The chemistry of cyclobutane-1,1-diester has been investigated with aldehydes and alkyne reaction partners independently of each other. Under Yb(OTf)3 catalysis donor-acceptor cyclobutanes undergo a formal [4+2] cycloaddition with aldehydes to generate tetrahydropyrans exclusively in a cis disposition. Activated aldehydes were generally well tolerated giving tetrahydropyrans in moderate to good yields (51 - 89%) whereas less reactive congeners gave lower yields (51 - 72%). All carbon reaction partners were used in BF3·OEt2 mediated conditions to afford an unexpected 2,3-dihydrooxepine product resulting from alkynyl addition and rearrangement. Aryl acetylenes were compatible with the reaction conditions and moderate yields were obtained (31 - 53%). When a silyl ether protected aryl acetylene was deployed the expected formal [4+2] cycloadduct is observed. The application of a water soluble Co(nmp)2 catalyst was used in the progress towards the polyketides natural product biselide A. Key reactions for the formation of a single diastereomer of an advanced stage intermediate included: Evans’ asymmetric aldol and a Prasad reduction to form a 1,3-syn diol exclusively which cyclized with Co(nmp)2 in high yield (93%). A tethering strategy will be used for the formation of the macrocyclic portion of the natural product.","abstract_html":"The chemistry of cyclobutane-1,1-diester has been investigated with aldehydes and alkyne reaction partners independently of each other. Under Yb(OTf)3 catalysis donor-acceptor cyclobutanes undergo a formal [4+2] cycloaddition with aldehydes to generate tetrahydropyrans exclusively in a cis disposition. Activated aldehydes were generally well tolerated giving tetrahydropyrans in moderate to good yields (51 - 89%) whereas less reactive congeners gave lower yields (51 - 72%). All carbon reaction partners were used in BF3·OEt2 mediated conditions to afford an unexpected 2,3-dihydrooxepine product resulting from alkynyl addition and rearrangement. Aryl acetylenes were compatible with the reaction conditions and moderate yields were obtained (31 - 53%). When a silyl ether protected aryl acetylene was deployed the expected formal [4+2] cycloadduct is observed. The application of a water soluble Co(nmp)2 catalyst was used in the progress towards the polyketides natural product biselide A. Key reactions for the formation of a single diastereomer of an advanced stage intermediate included: Evans’ asymmetric aldol and a Prasad reduction to form a 1,3-syn diol exclusively which cyclized with Co(nmp)2 in high yield (93%). A tethering strategy will be used for the formation of the macrocyclic portion of the natural product.","abstract_has_math":false,"creators":["Machin, Benjamin"],"institution":"The University of Western Ontario","degree_name":"Ph D","degree_level":null,"degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":[],"advisors":["Brian L. Pagenkopf"],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013-07-23","date_published":"2013-07-23","updated_at":"2026-07-27T21:56:09Z","subjects":["dipolar cycloaddition","donor-acceptor cyclobutanes","alkyne","aldehyde","tetrahydrofuran","biselide A"],"languages":["en_ca"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/20.500.14721/36278","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Brian L. 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In citing or referring to this thesis, use the DOI or handle from this page instead. Sample citation: Author name, \"Thesis title.\" (Year). Western University Open Repository. https://doi.org/10.71858/123456."]},{"key":"dc:description.abstract","label":"Abstract","values":["The chemistry of cyclobutane-1,1-diester has been investigated with aldehydes and alkyne reaction partners independently of each other. Under Yb(OTf)3 catalysis donor-acceptor cyclobutanes undergo a formal [4+2] cycloaddition with aldehydes to generate tetrahydropyrans exclusively in a cis disposition. Activated aldehydes were generally well tolerated giving tetrahydropyrans in moderate to good yields (51 - 89%) whereas less reactive congeners gave lower yields (51 - 72%). All carbon reaction partners were used in BF3·OEt2 mediated conditions to afford an unexpected 2,3-dihydrooxepine product resulting from alkynyl addition and rearrangement. Aryl acetylenes were compatible with the reaction conditions and moderate yields were obtained (31 - 53%). When a silyl ether protected aryl acetylene was deployed the expected formal [4+2] cycloadduct is observed. The application of a water soluble Co(nmp)2 catalyst was used in the progress towards the polyketides natural product biselide A. Key reactions for the formation of a single diastereomer of an advanced stage intermediate included: Evans’ asymmetric aldol and a Prasad reduction to form a 1,3-syn diol exclusively which cyclized with Co(nmp)2 in high yield (93%). A tethering strategy will be used for the formation of the macrocyclic portion of the natural product."]},{"key":"dc:title","label":"Title","values":["Donor-Acceptor Cyclobutanes and Their Application for Heterocycle Synthesis and Progress Towards Biselide A"]}]}],"canonical_facts":{"dc:contributor.advisor":["Brian L. Pagenkopf"],"dc:creator":["Machin, Benjamin"],"dc:date.accessioned":["2025-07-10T21:20:45Z"],"dc:date.available":["2025-07-10T21:20:45Z"],"dc:date.issued":["2013-07-23"],"dc:description":["The thesis cover page in the PDF document includes references to Western University’s previous institutional repository platform, known as Scholarship@Western, and links to that platform (beginning with ir.lib.uwo.ca). In citing or referring to this thesis, use the DOI or handle from this page instead. Sample citation: Author name, \"Thesis title.\" (Year). Western University Open Repository. https://doi.org/10.71858/123456."],"dc:description.abstract":["The chemistry of cyclobutane-1,1-diester has been investigated with aldehydes and alkyne reaction partners independently of each other. Under Yb(OTf)3 catalysis donor-acceptor cyclobutanes undergo a formal [4+2] cycloaddition with aldehydes to generate tetrahydropyrans exclusively in a cis disposition. Activated aldehydes were generally well tolerated giving tetrahydropyrans in moderate to good yields (51 - 89%) whereas less reactive congeners gave lower yields (51 - 72%). All carbon reaction partners were used in BF3·OEt2 mediated conditions to afford an unexpected 2,3-dihydrooxepine product resulting from alkynyl addition and rearrangement. Aryl acetylenes were compatible with the reaction conditions and moderate yields were obtained (31 - 53%). When a silyl ether protected aryl acetylene was deployed the expected formal [4+2] cycloadduct is observed. The application of a water soluble Co(nmp)2 catalyst was used in the progress towards the polyketides natural product biselide A. Key reactions for the formation of a single diastereomer of an advanced stage intermediate included: Evans’ asymmetric aldol and a Prasad reduction to form a 1,3-syn diol exclusively which cyclized with Co(nmp)2 in high yield (93%). A tethering strategy will be used for the formation of the macrocyclic portion of the natural product."],"dc:identifier.uri":["https://hdl.handle.net/20.500.14721/36278"],"dc:language.iso":["en_ca"],"dc:publisher":["The University of Western Ontario"],"dc:subject":["dipolar cycloaddition","donor-acceptor cyclobutanes","alkyne","aldehyde","tetrahydrofuran","biselide A"],"dc:title":["Donor-Acceptor Cyclobutanes and Their Application for Heterocycle Synthesis and Progress Towards Biselide A"],"dc:type":["thesis"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_name":["Ph D"]},"updated_at":"2026-07-27T21:56:09Z"}