{"id":{"repo_id":"maynooth","oai_identifier":"oai:mural.maynoothuniversity.ie:4771"},"canonical_url":"https://search.dev.ndltd.org/etd/maynooth/oai:mural.maynoothuniversity.ie:4771","repository":{"repo_id":"maynooth","name":"National University of Ireland - Maynooth","base_url":"http://mural.maynoothuniversity.ie/cgi/oai2"},"display":{"title":"Studies in Synthesis and Organocatalysis: (i) The Design and Synthesis of Novel Electron Deficient Dienes and their Application in the First Enamine Activated Organocatalytic 1,6-Conjugate Addition. (ii) The Development of a New Organocatalytic Methodology through the Combination of DNA-Based Catalysis and Organocatalysis","abstract":"A novel approach to substrate design led to the development of charge de-localized extended Michael acceptors. Using this methodology a family of both alkyl and aryl bis-phenylsulfonyl butadienes were synthesised and characterised. The first enamine activated organocatalytic 1,6- conjugate addition was performed on the sulfonyl acceptors, using aldehydic enamines, giving excellent yields and selectivities (up to 98% yield, uniformly 99% ee). The mechanism of this reaction was explored in detail. The products of these additions were fully characterised and were subsequently used as substrates for the conjugate addition of methyllithium (52% yield, 12 : 1 d.r.) and an organocatalysed inverse electron demand Diels-Alder reaction (DAINV) (76% yield, 3.1 : 1 : 1.5 d.r.). Combining the 1,6-addition and DAINV methodology let to the development of an enamine/iminium ion organocatalytic cascade reaction which delivered a product with 5 contiguous stereocenters (75% yield, 3.1 : 1 : 1.5 d.r.). We attempted to apply our 1,6-conjuagate addition methodology to the synthesis of Sildenafil analogues. Several steps of this challenging synthesis were completed. The step involving the oxidation of a homo-allylic alcohol remains to be solved. Interestingly a DMSO-based oxidation generated a sulfur ylide in high yield (90%), a possible explanation is provided. A second class of butadienes, bis-cyano butadienes, that are suitable substrates for 1,6-conjugate additions, were prepared and characterised. Addition of aldehydic enamines to these acceptors also yielded a regioselective 1,6-adduct in high yield and selectivity (up to 75% yield, up to 99% ee). An experimental investigation was performed into the synthesis of suitable trienes for 1,8-conugate additions. A 1,3-bis-phenylsulfonyl hexatriene was synthesised and characterised which did not undergo a selective 1,8-conjugate addition with aldehydic enamines. Upon heating, this triene was found to undergo an electrocyclisation reaction to give a biphenyl with a near zero twist angle. Synthesis of α,γ,ε-tris activated triene led to the isolation of a bis-phenylsulfonyl-cyano-arene and not the desired triene. A final experimental study was undertaken exploring the use of DNA and a suitable intercalating organocatalyst in asymmetric transformations. The design, synthesis and characterization of a novel achiral DNA-intercalating imidazolidinone was realized in high yield (40% yield over 4 steps). Several synthetic routes to the intercalating imidazolidinone were explored. The catalyst was found to still retain the ability to generate a reactive iminium ion and participate in a Diels-Alder reaction without DNA, albeit in reduced potency (24% yield). Future work will entail the application of the intercalating catalyst with salmon testes DNA.","abstract_html":"A novel approach to substrate design led to the development of charge de-localized extended Michael acceptors. Using this methodology a family of both alkyl and aryl bis-phenylsulfonyl butadienes were synthesised and characterised. The first enamine activated organocatalytic 1,6- conjugate addition was performed on the sulfonyl acceptors, using aldehydic enamines, giving excellent yields and selectivities (up to 98% yield, uniformly 99% ee). The mechanism of this reaction was explored in detail. The products of these additions were fully characterised and were subsequently used as substrates for the conjugate addition of methyllithium (52% yield, 12 : 1 d.r.) and an organocatalysed inverse electron demand Diels-Alder reaction (DAINV) (76% yield, 3.1 : 1 : 1.5 d.r.). Combining the 1,6-addition and DAINV methodology let to the development of an enamine/iminium ion organocatalytic cascade reaction which delivered a product with 5 contiguous stereocenters (75% yield, 3.1 : 1 : 1.5 d.r.). We attempted to apply our 1,6-conjuagate addition methodology to the synthesis of Sildenafil analogues. Several steps of this challenging synthesis were completed. The step involving the oxidation of a homo-allylic alcohol remains to be solved. Interestingly a DMSO-based oxidation generated a sulfur ylide in high yield (90%), a possible explanation is provided. A second class of butadienes, bis-cyano butadienes, that are suitable substrates for 1,6-conjugate additions, were prepared and characterised. Addition of aldehydic enamines to these acceptors also yielded a regioselective 1,6-adduct in high yield and selectivity (up to 75% yield, up to 99% ee). An experimental investigation was performed into the synthesis of suitable trienes for 1,8-conugate additions. A 1,3-bis-phenylsulfonyl hexatriene was synthesised and characterised which did not undergo a selective 1,8-conjugate addition with aldehydic enamines. Upon heating, this triene was found to undergo an electrocyclisation reaction to give a biphenyl with a near zero twist angle. Synthesis of α,γ,ε-tris activated triene led to the isolation of a bis-phenylsulfonyl-cyano-arene and not the desired triene. A final experimental study was undertaken exploring the use of DNA and a suitable intercalating organocatalyst in asymmetric transformations. The design, synthesis and characterization of a novel achiral DNA-intercalating imidazolidinone was realized in high yield (40% yield over 4 steps). Several synthetic routes to the intercalating imidazolidinone were explored. The catalyst was found to still retain the ability to generate a reactive iminium ion and participate in a Diels-Alder reaction without DNA, albeit in reduced potency (24% yield). Future work will entail the application of the intercalating catalyst with salmon testes DNA.","abstract_has_math":false,"creators":["Murphy, John J."],"institution":"National University of Ireland Maynooth","degree_name":"phd","degree_level":"doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2012,"date_issued":"2012-10","date_published":"2012-10","updated_at":"2026-07-24T03:02:41Z","subjects":["Chemistry"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Murphy, John J."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2012-10"]},{"key":"dc:date.issued","label":"Date","values":["2012-10"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Chemistry"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["National University of Ireland Maynooth"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://mural.maynoothuniversity.ie/id/eprint/4771/"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["phd"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Chemistry"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://mural.maynoothuniversity.ie/id/eprint/4771/1/Thesis.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["A novel approach to substrate design led to the development of charge de-localized extended Michael acceptors. Using this methodology a family of both alkyl and aryl bis-phenylsulfonyl butadienes were synthesised and characterised. The first enamine activated organocatalytic 1,6- conjugate addition was performed on the sulfonyl acceptors, using aldehydic enamines, giving excellent yields and selectivities (up to 98% yield, uniformly 99% ee). The mechanism of this reaction was explored in detail. The products of these additions were fully characterised and were subsequently used as substrates for the conjugate addition of methyllithium (52% yield, 12 : 1 d.r.) and an organocatalysed inverse electron demand Diels-Alder reaction (DAINV) (76% yield, 3.1 : 1 : 1.5 d.r.). Combining the 1,6-addition and DAINV methodology let to the development of an enamine/iminium ion organocatalytic cascade reaction which delivered a product with 5 contiguous stereocenters (75% yield, 3.1 : 1 : 1.5 d.r.). We attempted to apply our 1,6-conjuagate addition methodology to the synthesis of Sildenafil analogues. Several steps of this challenging synthesis were completed. The step involving the oxidation of a homo-allylic alcohol remains to be solved. Interestingly a DMSO-based oxidation generated a sulfur ylide in high yield (90%), a possible explanation is provided. A second class of butadienes, bis-cyano butadienes, that are suitable substrates for 1,6-conjugate additions, were prepared and characterised. Addition of aldehydic enamines to these acceptors also yielded a regioselective 1,6-adduct in high yield and selectivity (up to 75% yield, up to 99% ee). An experimental investigation was performed into the synthesis of suitable trienes for 1,8-conugate additions. A 1,3-bis-phenylsulfonyl hexatriene was synthesised and characterised which did not undergo a selective 1,8-conjugate addition with aldehydic enamines. Upon heating, this triene was found to undergo an electrocyclisation reaction to give a biphenyl with a near zero twist angle. Synthesis of α,γ,ε-tris activated triene led to the isolation of a bis-phenylsulfonyl-cyano-arene and not the desired triene. A final experimental study was undertaken exploring the use of DNA and a suitable intercalating organocatalyst in asymmetric transformations. The design, synthesis and characterization of a novel achiral DNA-intercalating imidazolidinone was realized in high yield (40% yield over 4 steps). Several synthetic routes to the intercalating imidazolidinone were explored. The catalyst was found to still retain the ability to generate a reactive iminium ion and participate in a Diels-Alder reaction without DNA, albeit in reduced potency (24% yield). Future work will entail the application of the intercalating catalyst with salmon testes DNA."]},{"key":"dc:format","label":"Dc Format","values":["text"]},{"key":"dc:title","label":"Title","values":["Studies in Synthesis and Organocatalysis: (i) The Design and Synthesis of Novel Electron Deficient Dienes and their Application in the First Enamine Activated Organocatalytic 1,6-Conjugate Addition. (ii) The Development of a New Organocatalytic Methodology through the Combination of DNA-Based Catalysis and Organocatalysis"]}]}],"canonical_facts":{"dc:creator":["Murphy, John J."],"dc:date":["2012-10"],"dc:date.issued":["2012-10"],"dc:description.abstract":["A novel approach to substrate design led to the development of charge de-localized extended Michael acceptors. Using this methodology a family of both alkyl and aryl bis-phenylsulfonyl butadienes were synthesised and characterised. The first enamine activated organocatalytic 1,6- conjugate addition was performed on the sulfonyl acceptors, using aldehydic enamines, giving excellent yields and selectivities (up to 98% yield, uniformly 99% ee). The mechanism of this reaction was explored in detail. The products of these additions were fully characterised and were subsequently used as substrates for the conjugate addition of methyllithium (52% yield, 12 : 1 d.r.) and an organocatalysed inverse electron demand Diels-Alder reaction (DAINV) (76% yield, 3.1 : 1 : 1.5 d.r.). Combining the 1,6-addition and DAINV methodology let to the development of an enamine/iminium ion organocatalytic cascade reaction which delivered a product with 5 contiguous stereocenters (75% yield, 3.1 : 1 : 1.5 d.r.). We attempted to apply our 1,6-conjuagate addition methodology to the synthesis of Sildenafil analogues. Several steps of this challenging synthesis were completed. The step involving the oxidation of a homo-allylic alcohol remains to be solved. Interestingly a DMSO-based oxidation generated a sulfur ylide in high yield (90%), a possible explanation is provided. A second class of butadienes, bis-cyano butadienes, that are suitable substrates for 1,6-conjugate additions, were prepared and characterised. Addition of aldehydic enamines to these acceptors also yielded a regioselective 1,6-adduct in high yield and selectivity (up to 75% yield, up to 99% ee). An experimental investigation was performed into the synthesis of suitable trienes for 1,8-conugate additions. A 1,3-bis-phenylsulfonyl hexatriene was synthesised and characterised which did not undergo a selective 1,8-conjugate addition with aldehydic enamines. Upon heating, this triene was found to undergo an electrocyclisation reaction to give a biphenyl with a near zero twist angle. Synthesis of α,γ,ε-tris activated triene led to the isolation of a bis-phenylsulfonyl-cyano-arene and not the desired triene. A final experimental study was undertaken exploring the use of DNA and a suitable intercalating organocatalyst in asymmetric transformations. The design, synthesis and characterization of a novel achiral DNA-intercalating imidazolidinone was realized in high yield (40% yield over 4 steps). Several synthetic routes to the intercalating imidazolidinone were explored. The catalyst was found to still retain the ability to generate a reactive iminium ion and participate in a Diels-Alder reaction without DNA, albeit in reduced potency (24% yield). Future work will entail the application of the intercalating catalyst with salmon testes DNA."],"dc:format":["text"],"dc:identifier.uri":["https://mural.maynoothuniversity.ie/id/eprint/4771/1/Thesis.pdf"],"dc:language":["en"],"dc:publisher.department":["Chemistry"],"dc:publisher.institution":["National University of Ireland Maynooth"],"dc:relation.isreferencedby":["https://mural.maynoothuniversity.ie/id/eprint/4771/"],"dc:subject":["Chemistry"],"dc:title":["Studies in Synthesis and Organocatalysis: (i) The Design and Synthesis of Novel Electron Deficient Dienes and their Application in the First Enamine Activated Organocatalytic 1,6-Conjugate Addition. (ii) The Development of a New Organocatalytic Methodology through the Combination of DNA-Based Catalysis and Organocatalysis"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["doctoral"],"dc:type.qualificationname":["phd"]},"updated_at":"2026-07-24T03:02:41Z"}