{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/91591"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/91591","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Iterative cross-coupling with MIDA boronates","abstract":"Many small molecules targeted for synthesis in the laboratory are inherently modular in their construction. Harnessing this modularity towards a unified strategy for the synthesis of these compounds, this dissertation describes an approach to small molecule making based on the iterative cross-coupling (ICC) of bifunctional haloboronic acid building blocks. Realizing a general ICC approach in the context of small molecule synthesis required the discovery of a ligand with the capacity to attenuate the reactivity of boronic acids under Suzuki-Miyaura cross-coupling (SMC) conditions and then liberate this masked reactivity under mild conditions. Towards this end, N-methyliminodiacetic acid (MIDA) was discovered to be such a ligand, enabling an approach by which the reactivity of boronic acids is modulated via rehybridization of the boron center. Further, MIDA boronates, which result from the condensation of MIDA with boronic acids, were found to possess a number of enabling properties. Specifically, MIDA boronates are uniformly stable to SiO2 chromatography and to storage under ambient air at room temperature. MIDA boronates were also found to be compatible with a broad range of common reagents and reaction conditions, enabling an approach by which relatively simple MIDA boronates can be elaborated through multiple-step organic synthesis en route to structurally complex boronate building blocks. Through a process of rate-controlled in situ release of boronic acids from the corresponding MIDA boronates, MIDA boronates were found to serve as generally effective surrogates for otherwise unstable boronic acids in high-yielding Suzuki-Miyaura cross-coupling reactions with deactivated aryl chlorides. Enabled by these collective discoveries, and towards the goal of a simple and accessible approach to small molecule synthesis, a machine with the capacity to perform fully automated ICC syntheses was developed and was employed in the syntheses of several natural products.","abstract_html":"Many small molecules targeted for synthesis in the laboratory are inherently modular in their construction. Harnessing this modularity towards a unified strategy for the synthesis of these compounds, this dissertation describes an approach to small molecule making based on the iterative cross-coupling (ICC) of bifunctional haloboronic acid building blocks. Realizing a general ICC approach in the context of small molecule synthesis required the discovery of a ligand with the capacity to attenuate the reactivity of boronic acids under Suzuki-Miyaura cross-coupling (SMC) conditions and then liberate this masked reactivity under mild conditions. Towards this end, N-methyliminodiacetic acid (MIDA) was discovered to be such a ligand, enabling an approach by which the reactivity of boronic acids is modulated via rehybridization of the boron center. Further, MIDA boronates, which result from the condensation of MIDA with boronic acids, were found to possess a number of enabling properties. Specifically, MIDA boronates are uniformly stable to SiO2 chromatography and to storage under ambient air at room temperature. MIDA boronates were also found to be compatible with a broad range of common reagents and reaction conditions, enabling an approach by which relatively simple MIDA boronates can be elaborated through multiple-step organic synthesis en route to structurally complex boronate building blocks. Through a process of rate-controlled in situ release of boronic acids from the corresponding MIDA boronates, MIDA boronates were found to serve as generally effective surrogates for otherwise unstable boronic acids in high-yielding Suzuki-Miyaura cross-coupling reactions with deactivated aryl chlorides. Enabled by these collective discoveries, and towards the goal of a simple and accessible approach to small molecule synthesis, a machine with the capacity to perform fully automated ICC syntheses was developed and was employed in the syntheses of several natural products.","abstract_has_math":false,"creators":["Gillis, Eric P"],"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.","Hartwig, John F.","Hergenrother, Paul J."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2016,"date_issued":"2016-09-09T21:14:38Z","date_published":"2016-09-09T21:14:38Z","updated_at":"2026-07-22T22:26:34Z","subjects":["MIDA","N-methyliminodiacetic acid","iterative cross-coupling","slow-release","MIDA boronate","boronate","cross-coupling","Suzuki cross-coupling"],"languages":[],"rights":["Copyright 2010 Eric Gillis"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/91591","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Burke, Martin D.","Denmark, Scott E.","Hartwig, John F.","Hergenrother, Paul J."]},{"key":"dc:creator","label":"Author","values":["Gillis, Eric P"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2016-09-09T21:14:38Z","2018-09-10T09:15:35Z","2010-10-20","2010-12"]},{"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":["MIDA","N-methyliminodiacetic acid","iterative cross-coupling","slow-release","MIDA boronate","boronate","cross-coupling","Suzuki cross-coupling"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2010 Eric Gillis"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/91591"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Many small molecules targeted for synthesis in the laboratory are inherently modular in their construction. Harnessing this modularity towards a unified strategy for the synthesis of these compounds, this dissertation describes an approach to small molecule making based on the iterative cross-coupling (ICC) of bifunctional haloboronic acid building blocks. Realizing a general ICC approach in the context of small molecule synthesis required the discovery of a ligand with the capacity to attenuate the reactivity of boronic acids under Suzuki-Miyaura cross-coupling (SMC) conditions and then liberate this masked reactivity under mild conditions. Towards this end, N-methyliminodiacetic acid (MIDA) was discovered to be such a ligand, enabling an approach by which the reactivity of boronic acids is modulated via rehybridization of the boron center. Further, MIDA boronates, which result from the condensation of MIDA with boronic acids, were found to possess a number of enabling properties. Specifically, MIDA boronates are uniformly stable to SiO2 chromatography and to storage under ambient air at room temperature. MIDA boronates were also found to be compatible with a broad range of common reagents and reaction conditions, enabling an approach by which relatively simple MIDA boronates can be elaborated through multiple-step organic synthesis en route to structurally complex boronate building blocks. Through a process of rate-controlled in situ release of boronic acids from the corresponding MIDA boronates, MIDA boronates were found to serve as generally effective surrogates for otherwise unstable boronic acids in high-yielding Suzuki-Miyaura cross-coupling reactions with deactivated aryl chlorides. Enabled by these collective discoveries, and towards the goal of a simple and accessible approach to small molecule synthesis, a machine with the capacity to perform fully automated ICC syntheses was developed and was employed in the syntheses of several natural products.","Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2012-12-01","The student, Eric Gillis, accepted the attached license on 2010-10-19 at 15:03.","The student, Eric Gillis, submitted this Dissertation for approval on 2010-10-19 at 16:23.","This Dissertation was approved for publication on 2010-10-20 at 09:10.","DSpace SAF Submission Ingestion Package generated from Vireo submission #1326 on 2016-09-09 at 16:06:49","Made available in DSpace on 2016-09-09T21:14:38Z (GMT). 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Harnessing this modularity towards a unified strategy for the synthesis of these compounds, this dissertation describes an approach to small molecule making based on the iterative cross-coupling (ICC) of bifunctional haloboronic acid building blocks. Realizing a general ICC approach in the context of small molecule synthesis required the discovery of a ligand with the capacity to attenuate the reactivity of boronic acids under Suzuki-Miyaura cross-coupling (SMC) conditions and then liberate this masked reactivity under mild conditions. Towards this end, N-methyliminodiacetic acid (MIDA) was discovered to be such a ligand, enabling an approach by which the reactivity of boronic acids is modulated via rehybridization of the boron center. Further, MIDA boronates, which result from the condensation of MIDA with boronic acids, were found to possess a number of enabling properties. Specifically, MIDA boronates are uniformly stable to SiO2 chromatography and to storage under ambient air at room temperature. MIDA boronates were also found to be compatible with a broad range of common reagents and reaction conditions, enabling an approach by which relatively simple MIDA boronates can be elaborated through multiple-step organic synthesis en route to structurally complex boronate building blocks. Through a process of rate-controlled in situ release of boronic acids from the corresponding MIDA boronates, MIDA boronates were found to serve as generally effective surrogates for otherwise unstable boronic acids in high-yielding Suzuki-Miyaura cross-coupling reactions with deactivated aryl chlorides. Enabled by these collective discoveries, and towards the goal of a simple and accessible approach to small molecule synthesis, a machine with the capacity to perform fully automated ICC syntheses was developed and was employed in the syntheses of several natural products.","Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2012-12-01","The student, Eric Gillis, accepted the attached license on 2010-10-19 at 15:03.","The student, Eric Gillis, submitted this Dissertation for approval on 2010-10-19 at 16:23.","This Dissertation was approved for publication on 2010-10-20 at 09:10.","DSpace SAF Submission Ingestion Package generated from Vireo submission #1326 on 2016-09-09 at 16:06:49","Made available in DSpace on 2016-09-09T21:14:38Z (GMT). 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