{"id":{"repo_id":"cambridge","oai_identifier":"oai:www.repository.cam.ac.uk:1810/317373"},"canonical_url":"https://search.dev.ndltd.org/etd/cambridge/oai:www.repository.cam.ac.uk:1810/317373","repository":{"repo_id":"cambridge","name":"Cambridge University","base_url":"https://api.repository.cam.ac.uk/server/oai/request"},"display":{"title":"Charge-Transfer Complexes for Amine Synthesis","abstract":"A method to generate α-amino radicals, via a photoinduced charge-transfer complex, is reported. A multicomponent radical fragmentation-cyclization reaction was developed, combining secondary amines, cyclopropyl carboxaldehydes and alkenes, to generate cyclopentyl methylamines. To initiate the fragmentation step, single-electron reduction of alkyliminium ions to α-amino radicals was achieved, using an aromatic thiol and visible light irradiation. Mechanistic and computational studies supported the formation of a transient, ion-pair charge-transfer complex between iminium and thiolate ions. DFT calculations indicated that irradiation of the complex with visible light could promote intra-complex electron transfer from the thiolate HOMO to the iminium LUMO. This method of α-amino radical formation was extended to acyclic aldehydes, by development of a radical reductive amination, using thiol as the single-electron reductant and hydrogen atom source. Subsequently, the chemoselective reductive amination of secondary amines over primary amines was attempted. Preliminary studies on a di-amine drug indicated that the radical reductive amination had high selectivity for primary aminothiazoles over secondary amines, contrasting with existing polar reductive amination techniques.","abstract_html":"A method to generate α-amino radicals, via a photoinduced charge-transfer complex, is reported. A multicomponent radical fragmentation-cyclization reaction was developed, combining secondary amines, cyclopropyl carboxaldehydes and alkenes, to generate cyclopentyl methylamines. To initiate the fragmentation step, single-electron reduction of alkyliminium ions to α-amino radicals was achieved, using an aromatic thiol and visible light irradiation. Mechanistic and computational studies supported the formation of a transient, ion-pair charge-transfer complex between iminium and thiolate ions. DFT calculations indicated that irradiation of the complex with visible light could promote intra-complex electron transfer from the thiolate HOMO to the iminium LUMO. This method of α-amino radical formation was extended to acyclic aldehydes, by development of a radical reductive amination, using thiol as the single-electron reductant and hydrogen atom source. Subsequently, the chemoselective reductive amination of secondary amines over primary amines was attempted. Preliminary studies on a di-amine drug indicated that the radical reductive amination had high selectivity for primary aminothiazoles over secondary amines, contrasting with existing polar reductive amination techniques.","abstract_has_math":false,"creators":["Kohara, Keishi"],"institution":"University of Cambridge","degree_name":null,"degree_level":"Doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Gaunt, Matthew"],"committee_chairs":[],"committee_members":[],"year":2020,"date_issued":"2020-08-23","date_published":"2020-08-23","updated_at":"2026-07-22T22:24:30Z","subjects":["Organic Chemistry","Synthetic Methodology","Photochemistry","Charge-Transfer Complexes","Radical Chemistry"],"languages":["eng"],"rights":[],"rights_urls":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/36f0af7a-ee43-4512-986f-cf006ab351dd/download","https://www.rioxx.net/licenses/all-rights-reserved/"],"identifier_entries":[]},"links":{"outbound_url":"https://doi.org/10.17863/CAM.64486","outbound_label":"DOI","outbound_source":"dc:identifier.doi"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Gaunt, Matthew"]},{"key":"dc:creator","label":"Author","values":["Kohara, Keishi"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2020-08-23"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Cambridge"]},{"key":"dc:relation.isreferencedby.uri","label":"Dc Relation Isreferencedby URI","values":["https://www.repository.cam.ac.uk/handle/1810/317373"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Doctoral"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Organic Chemistry","Synthetic Methodology","Photochemistry","Charge-Transfer Complexes","Radical Chemistry"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/36f0af7a-ee43-4512-986f-cf006ab351dd/download","https://www.rioxx.net/licenses/all-rights-reserved/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.doi","label":"DOI","values":["10.17863/CAM.64486"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/6d7e5d7c-adb5-44ae-a097-59a7af14b13c/download"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["A method to generate α-amino radicals, via a photoinduced charge-transfer complex, is reported. 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Preliminary studies on a di-amine drug indicated that the radical reductive amination had high selectivity for primary aminothiazoles over secondary amines, contrasting with existing polar reductive amination techniques."]},{"key":"dc:format.checksum.md5","label":"Dc Format Checksum Md5","values":["d46aa0eb269850234782c6f3119c14fe","353adac0d1ebdfd65ab16480263c3c87"]},{"key":"dc:title","label":"Title","values":["Charge-Transfer Complexes for Amine Synthesis"]}]}],"canonical_facts":{"dc:contributor.advisor":["Gaunt, Matthew"],"dc:creator":["Kohara, Keishi"],"dc:date.issued":["2020-08-23"],"dc:description.abstract":["A method to generate α-amino radicals, via a photoinduced charge-transfer complex, is reported. A multicomponent radical fragmentation-cyclization reaction was developed, combining secondary amines, cyclopropyl carboxaldehydes and alkenes, to generate cyclopentyl methylamines. To initiate the fragmentation step, single-electron reduction of alkyliminium ions to α-amino radicals was achieved, using an aromatic thiol and visible light irradiation. Mechanistic and computational studies supported the formation of a transient, ion-pair charge-transfer complex between iminium and thiolate ions. DFT calculations indicated that irradiation of the complex with visible light could promote intra-complex electron transfer from the thiolate HOMO to the iminium LUMO. This method of α-amino radical formation was extended to acyclic aldehydes, by development of a radical reductive amination, using thiol as the single-electron reductant and hydrogen atom source. Subsequently, the chemoselective reductive amination of secondary amines over primary amines was attempted. 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