{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/102779"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/102779","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Ligand design principles for perfecting stereoretention in Suzuki-Miyaura cross-coupling of unactivated CSP3 boronic acids","abstract":"The strategy of building block-based, iterative synthesis has revolutionized the preparation of oligonucleotides and oligopeptides. However, small molecules possess greater structural diversity than these classes of macromolecules. The development of an iterative, building block-based synthetic strategy could nonetheless accelerate the discovery of new small molecule functions. A key challenge in building block assembly is finding reactions to forge carbon-carbon bonds between a range of structurally diverse building blocks. Iteration of metal-mediated cross-coupling reactions represents a promising direction, and such an approach has already been automated and used to make many different small molecules. Still, the lack of methods for Csp3 coupling dramatically limits the scope of building block-based synthesis. With the goal of developing a stereospecific cross-coupling reaction for unactivated secondary alkylboronic acids, it was critical to understand the competition between stereoretentive and stereoinvertive transmetalation mechanisms. Achieving perfect transfer of stereochemistry from building blocks to products required that one of these transmetalation pathways be completely mitigated. By systematically studying the effect of the phosphine ligand on the outcome of a model Csp3 cross-coupling reaction, we have elucidated ligand steric and electronic design principles for maximizing stereoretention. These ligand design principles are applicable across different reaction conditions and a broad substrate scope. Continued progress in stereocontrolled Csp3 couplings will accelerate the generalization of building block-based synthesis.","abstract_html":"The strategy of building block-based, iterative synthesis has revolutionized the preparation of oligonucleotides and oligopeptides. However, small molecules possess greater structural diversity than these classes of macromolecules. The development of an iterative, building block-based synthetic strategy could nonetheless accelerate the discovery of new small molecule functions. A key challenge in building block assembly is finding reactions to forge carbon-carbon bonds between a range of structurally diverse building blocks. Iteration of metal-mediated cross-coupling reactions represents a promising direction, and such an approach has already been automated and used to make many different small molecules. Still, the lack of methods for Csp3 coupling dramatically limits the scope of building block-based synthesis. With the goal of developing a stereospecific cross-coupling reaction for unactivated secondary alkylboronic acids, it was critical to understand the competition between stereoretentive and stereoinvertive transmetalation mechanisms. Achieving perfect transfer of stereochemistry from building blocks to products required that one of these transmetalation pathways be completely mitigated. By systematically studying the effect of the phosphine ligand on the outcome of a model Csp3 cross-coupling reaction, we have elucidated ligand steric and electronic design principles for maximizing stereoretention. These ligand design principles are applicable across different reaction conditions and a broad substrate scope. Continued progress in stereocontrolled Csp3 couplings will accelerate the generalization of building block-based synthesis.","abstract_has_math":false,"creators":["Lehmann, Jonathan W."],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":["Burke, Martin D.","Denmark, Scott E.","Hergenrother, Paul J.","Moore, Jeffrey S."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-02-07T20:35:53Z","date_published":"2019-02-07T20:35:53Z","updated_at":"2026-07-22T22:24:42Z","subjects":["Cross-coupling","methodology","Csp3 coupling","stereospecific","stereospecific coupling","unactivated boronic acid","stereoretentive transmetalation","stereoinvertive transmetalation","transmetalation","beta-hydride elimination","P(o-tol)3","tri-ortho-tol phosphine"],"languages":["en"],"rights":["Copyright 2018 Jonathan W. 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Lehmann"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/102779"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The strategy of building block-based, iterative synthesis has revolutionized the preparation of oligonucleotides and oligopeptides. However, small molecules possess greater structural diversity than these classes of macromolecules. The development of an iterative, building block-based synthetic strategy could nonetheless accelerate the discovery of new small molecule functions. A key challenge in building block assembly is finding reactions to forge carbon-carbon bonds between a range of structurally diverse building blocks. Iteration of metal-mediated cross-coupling reactions represents a promising direction, and such an approach has already been automated and used to make many different small molecules. Still, the lack of methods for Csp3 coupling dramatically limits the scope of building block-based synthesis. With the goal of developing a stereospecific cross-coupling reaction for unactivated secondary alkylboronic acids, it was critical to understand the competition between stereoretentive and stereoinvertive transmetalation mechanisms. Achieving perfect transfer of stereochemistry from building blocks to products required that one of these transmetalation pathways be completely mitigated. By systematically studying the effect of the phosphine ligand on the outcome of a model Csp3 cross-coupling reaction, we have elucidated ligand steric and electronic design principles for maximizing stereoretention. These ligand design principles are applicable across different reaction conditions and a broad substrate scope. Continued progress in stereocontrolled Csp3 couplings will accelerate the generalization of building block-based synthesis.","Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2020-12-01","The student, Jonathan Lehmann, accepted the attached license on 2018-09-16 at 09:43.","The student, Jonathan Lehmann, submitted this Dissertation for approval on 2018-09-16 at 10:18.","This Dissertation was approved for publication on 2018-10-05 at 11:58.","DSpace SAF Submission Ingestion Package generated from Vireo submission #13015 on 2019-02-07 at 14:16:35","Made available in DSpace on 2019-02-07T20:35:53Z (GMT). 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However, small molecules possess greater structural diversity than these classes of macromolecules. The development of an iterative, building block-based synthetic strategy could nonetheless accelerate the discovery of new small molecule functions. A key challenge in building block assembly is finding reactions to forge carbon-carbon bonds between a range of structurally diverse building blocks. Iteration of metal-mediated cross-coupling reactions represents a promising direction, and such an approach has already been automated and used to make many different small molecules. Still, the lack of methods for Csp3 coupling dramatically limits the scope of building block-based synthesis. With the goal of developing a stereospecific cross-coupling reaction for unactivated secondary alkylboronic acids, it was critical to understand the competition between stereoretentive and stereoinvertive transmetalation mechanisms. Achieving perfect transfer of stereochemistry from building blocks to products required that one of these transmetalation pathways be completely mitigated. By systematically studying the effect of the phosphine ligand on the outcome of a model Csp3 cross-coupling reaction, we have elucidated ligand steric and electronic design principles for maximizing stereoretention. These ligand design principles are applicable across different reaction conditions and a broad substrate scope. Continued progress in stereocontrolled Csp3 couplings will accelerate the generalization of building block-based synthesis.","Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2020-12-01","The student, Jonathan Lehmann, accepted the attached license on 2018-09-16 at 09:43.","The student, Jonathan Lehmann, submitted this Dissertation for approval on 2018-09-16 at 10:18.","This Dissertation was approved for publication on 2018-10-05 at 11:58.","DSpace SAF Submission Ingestion Package generated from Vireo submission #13015 on 2019-02-07 at 14:16:35","Made available in DSpace on 2019-02-07T20:35:53Z (GMT). No. of bitstreams: 2 LEHMANN-DISSERTATION-2018.pdf: 24444786 bytes, checksum: 38738c5e2f53e3f9be972e5d576a547f (MD5) LICENSE.txt: 4213 bytes, checksum: 432e4bf265c5bec0d5a129c86da92e71 (MD5) Previous issue date: 2018-10-05","Embargo set by: Seth Robbins for item 109803 Lift date: 2021-02-07T20:36:09Z Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system","Embargo set by: Seth Robbins for item 109803 Lift date: 2021-02-07T20:39:46Z Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system","Embargo set by: Seth Robbins for item 109803 Lift date: 2021-02-07T20:44:35Z Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system","U of I Only Restriction Lifted for Item 109803 on 2021-02-08T10:15:25Z."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/2142/102779"],"dc:language":["en"],"dc:rights":["Copyright 2018 Jonathan W. Lehmann"],"dc:subject":["Cross-coupling","methodology","Csp3 coupling","stereospecific","stereospecific coupling","unactivated boronic acid","stereoretentive transmetalation","stereoinvertive transmetalation","transmetalation","beta-hydride elimination","P(o-tol)3","tri-ortho-tol phosphine"],"dc:title":["Ligand design principles for perfecting stereoretention in Suzuki-Miyaura cross-coupling of unactivated CSP3 boronic acids"],"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"}