{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/102894"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/102894","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Rhodium-catalyzed asymmetric synthesis of beta-branched amides and gamma-branched amines and hydroaminomethylation of alkenes via photoredox catalysis","abstract":"Embargo set by: Seth Robbins for item 109920 Lift date: 2021-02-08T18:43:54Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system","abstract_html":"Embargo set by: Seth Robbins for item 109920 Lift date: 2021-02-08T18:43:54Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system","abstract_has_math":false,"creators":["Wu, Zhao"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":["Hull, Kami L.","Moore, Jeffrey S.","Zimmerman, Steven C.","Fout, Alison R."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-02-08T18:39:40Z","date_published":"2019-02-08T18:39:40Z","updated_at":"2026-07-22T22:24:42Z","subjects":["asymmetric isomerization","oxidative amidation","reductive amination","hydroaminomethylation","photoredox catalysis"],"languages":["en"],"rights":["Copyright 2018 Zhao Wu"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/102894","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Hull, Kami L.","Moore, Jeffrey S.","Zimmerman, Steven C.","Fout, Alison R."]},{"key":"dc:creator","label":"Author","values":["Wu, Zhao"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2019-02-08T18:39:40Z","2021-02-09T10:15:12Z","2018-09-12","2018-12"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["asymmetric isomerization","oxidative amidation","reductive amination","hydroaminomethylation","photoredox catalysis"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2018 Zhao Wu"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/102894"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Embargo set by: Seth Robbins for item 109920 Lift date: 2021-02-08T18:43:54Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system","Nitrogen-containing organic molecules with adjacent stereocenters represent one of the most common motifs in modern pharmaceuticals and agrochemicals. Therefore, there have been tremendous efforts focusing on general, efficient, selective, and atom-economical syntheses of enantiopure amides and amines. However, the direct enantioselective synthesis of β-branched amides and γ-branched amines still requires multiple steps including asymmetric hydrogenation. As a result, these methods are very substrate dependent, meaning that a minor change on the stereocenter often requires re-examining of metal/ligand scaffolds. In this thesis, we will describe methods developed in our lab to address these challenges. We have first developed a tandem isomerization/oxidative amidation approach from allylic alcohols or aldehydes to synthesize β-branched amides using acetone or styrene as the hydrogen acceptor. The conditions are general, affording the products in good to excellent yields with a wide array of amine and aniline nucleophiles, and chemoselective, other alcohols do not participate in the oxidation reaction. Utilization of biphasic conditions is critical, as they promote an equilibrium between the imine/enamine intermediate and the hemiaminal, which can then undergo oxidation to the amide. The enantioselective isomerization/amidation was then achieved utilizing allylic amine as the precursor. After the known asymmetric isomerization, the chiral enamine intermediate, instead of being oxidized to the undesired byproduct, undergoes an exchange with exogenous amine nucleophile followed by oxidation to afford the chiral β-branched amide in one step. The enamine exchange allows for a rapid and modular synthesis of various amides, including challenging β-diaryl and β-cyclic. These kinds of substrates often require privileged ligands in asymmetric hydrogenation. We have further extended this method to synthesize amines with remote stereocenters in a reductive fashion. By intercepting the aforementioned chiral enamine intermediate with a highly chemoselective reduction, a general asymmetric route for the one-pot synthesis of chiral γ-branched amines was developed. This protocol is suitable for establishing various tertiary stereocenters, including those containing dialkyl, diaryl, cyclic, trifluoromethyl, difluoromethyl, and silyl substituents. To demonstrate the synthetic utility of this method, Terikalant and Tolterodine are synthesized using this method with high levels of enantioselectivity. Finally, an alternative method for γ-branched amine synthesis was realized through photoredox-catalyzed hydroaminomethylation of alkenes. The reaction conditions are very mild, and tolerate various functional groups, such as alkyl alkene, ester, ketone, lactone, indole, and tertiary amine, a great improvement compared to two-electron hydroaminomethylation. This reaction is also regiospecific: only linear amine products are formed regardless of the electronic property of alkene substrates. Three bioactive pheniramines are synthesized using this method on gram-scale with only 0.1% catalyst loading.","Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2020-12-01","The student, Zhao Wu, accepted the attached license on 2018-09-11 at 15:32.","The student, Zhao Wu, submitted this Dissertation for approval on 2018-09-11 at 15:33.","This Dissertation was approved for publication on 2018-09-12 at 14:32.","DSpace SAF Submission Ingestion Package generated from Vireo submission #13008 on 2019-02-08 at 11:37:55","Made available in DSpace on 2019-02-08T18:39:40Z (GMT). No. of bitstreams: 3 WU-DISSERTATION-2018.pdf: 10000135 bytes, checksum: 4f19c1d8c3b3ad0fba3d3608a45c3232 (MD5) LICENSE.txt: 4204 bytes, checksum: edcd06c9a778a2b8e4c9be61da3e9928 (MD5) PROQUEST_LICENSE.txt: 4550 bytes, checksum: e34e9b5cb9633953caa0cc03986746fa (MD5) Previous issue date: 2018-09-12","Embargo set by: Seth Robbins for item 109920 Lift date: 2021-02-08T18:40:00Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system","Embargo set by: Seth Robbins for item 109920 Lift date: 2021-02-08T18:42:23Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system","Embargo set by: Seth Robbins for item 109920 Lift date: 2021-02-08T18:44:50Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system","Limited Restriction Lifted for Item 109920 on 2021-02-09T10:15:12Z."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Rhodium-catalyzed asymmetric synthesis of beta-branched amides and gamma-branched amines and hydroaminomethylation of alkenes via photoredox catalysis"]}]}],"canonical_facts":{"dc:contributor":["Hull, Kami L.","Moore, Jeffrey S.","Zimmerman, Steven C.","Fout, Alison R."],"dc:creator":["Wu, Zhao"],"dc:date":["2019-02-08T18:39:40Z","2021-02-09T10:15:12Z","2018-09-12","2018-12"],"dc:description":["Embargo set by: Seth Robbins for item 109920 Lift date: 2021-02-08T18:43:54Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system","Nitrogen-containing organic molecules with adjacent stereocenters represent one of the most common motifs in modern pharmaceuticals and agrochemicals. Therefore, there have been tremendous efforts focusing on general, efficient, selective, and atom-economical syntheses of enantiopure amides and amines. However, the direct enantioselective synthesis of β-branched amides and γ-branched amines still requires multiple steps including asymmetric hydrogenation. As a result, these methods are very substrate dependent, meaning that a minor change on the stereocenter often requires re-examining of metal/ligand scaffolds. In this thesis, we will describe methods developed in our lab to address these challenges. We have first developed a tandem isomerization/oxidative amidation approach from allylic alcohols or aldehydes to synthesize β-branched amides using acetone or styrene as the hydrogen acceptor. The conditions are general, affording the products in good to excellent yields with a wide array of amine and aniline nucleophiles, and chemoselective, other alcohols do not participate in the oxidation reaction. Utilization of biphasic conditions is critical, as they promote an equilibrium between the imine/enamine intermediate and the hemiaminal, which can then undergo oxidation to the amide. The enantioselective isomerization/amidation was then achieved utilizing allylic amine as the precursor. After the known asymmetric isomerization, the chiral enamine intermediate, instead of being oxidized to the undesired byproduct, undergoes an exchange with exogenous amine nucleophile followed by oxidation to afford the chiral β-branched amide in one step. The enamine exchange allows for a rapid and modular synthesis of various amides, including challenging β-diaryl and β-cyclic. These kinds of substrates often require privileged ligands in asymmetric hydrogenation. We have further extended this method to synthesize amines with remote stereocenters in a reductive fashion. By intercepting the aforementioned chiral enamine intermediate with a highly chemoselective reduction, a general asymmetric route for the one-pot synthesis of chiral γ-branched amines was developed. This protocol is suitable for establishing various tertiary stereocenters, including those containing dialkyl, diaryl, cyclic, trifluoromethyl, difluoromethyl, and silyl substituents. To demonstrate the synthetic utility of this method, Terikalant and Tolterodine are synthesized using this method with high levels of enantioselectivity. Finally, an alternative method for γ-branched amine synthesis was realized through photoredox-catalyzed hydroaminomethylation of alkenes. The reaction conditions are very mild, and tolerate various functional groups, such as alkyl alkene, ester, ketone, lactone, indole, and tertiary amine, a great improvement compared to two-electron hydroaminomethylation. This reaction is also regiospecific: only linear amine products are formed regardless of the electronic property of alkene substrates. Three bioactive pheniramines are synthesized using this method on gram-scale with only 0.1% catalyst loading.","Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2020-12-01","The student, Zhao Wu, accepted the attached license on 2018-09-11 at 15:32.","The student, Zhao Wu, submitted this Dissertation for approval on 2018-09-11 at 15:33.","This Dissertation was approved for publication on 2018-09-12 at 14:32.","DSpace SAF Submission Ingestion Package generated from Vireo submission #13008 on 2019-02-08 at 11:37:55","Made available in DSpace on 2019-02-08T18:39:40Z (GMT). No. of bitstreams: 3 WU-DISSERTATION-2018.pdf: 10000135 bytes, checksum: 4f19c1d8c3b3ad0fba3d3608a45c3232 (MD5) LICENSE.txt: 4204 bytes, checksum: edcd06c9a778a2b8e4c9be61da3e9928 (MD5) PROQUEST_LICENSE.txt: 4550 bytes, checksum: e34e9b5cb9633953caa0cc03986746fa (MD5) Previous issue date: 2018-09-12","Embargo set by: Seth Robbins for item 109920 Lift date: 2021-02-08T18:40:00Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system","Embargo set by: Seth Robbins for item 109920 Lift date: 2021-02-08T18:42:23Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system","Embargo set by: Seth Robbins for item 109920 Lift date: 2021-02-08T18:44:50Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system","Limited Restriction Lifted for Item 109920 on 2021-02-09T10:15:12Z."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/2142/102894"],"dc:language":["en"],"dc:rights":["Copyright 2018 Zhao Wu"],"dc:subject":["asymmetric isomerization","oxidative amidation","reductive amination","hydroaminomethylation","photoredox catalysis"],"dc:title":["Rhodium-catalyzed asymmetric synthesis of beta-branched amides and gamma-branched amines and hydroaminomethylation of alkenes via photoredox catalysis"],"dc:type":["text"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:24:42Z"}