ingest cdrApp 2017-07-06T13:13:41.756Z f230b17a-68de-497f-ac05-5cb17af9fe4f modifyDatastreamByValue RELS-EXT cdrApp 2017-07-06T13:18:11.450Z Setting exclusive relation modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2017-08-15T12:25:38.335Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-01-24T23:31:14.198Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-01-26T23:15:51.783Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-03-13T17:20:04.071Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-05-16T15:32:21.875Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-07-10T17:10:51.947Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-07-17T13:40:01.335Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-07-25T18:09:03.287Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-08-02T13:29:46.266Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-08-08T13:05:38.679Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-08-09T13:18:20.147Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-08-09T14:56:59.250Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-08-16T13:05:55.245Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-09-21T10:56:04.162Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-09-26T13:16:11.262Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-10-10T14:04:23.087Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-10-11T14:37:07.719Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2019-02-27T22:25:19.280Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2019-03-19T17:55:12.149Z Trandon Bender Author Department of Chemistry College of Arts and Sciences METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity. Spring 2017 2017 Chemistry Biomass, Catalysis, Hydrosilylation, Lewis acid, Natural Products eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Chemistry Michele Gagne Thesis advisor Alex Miller Thesis advisor Maurice Brookhart Thesis advisor Joesph Templeton Thesis advisor Eric Brustad Thesis advisor text Trandon Bender Author Department of Chemistry College of Arts and Sciences METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity. Spring 2017 2017 Chemistry Biomass Catalysis Hydrosilylation Lewis acid Natural Products eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Chemistry Michele Gagne Thesis advisor Alex Miller Thesis advisor Maurice Brookhart Thesis advisor Joesph Templeton Thesis advisor Eric Brustad Thesis advisor text Trandon Bender Creator Department of Chemistry College of Arts and Sciences METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity. Spring 2017 2017 Chemistry Biomass Catalysis Hydrosilylation Lewis acid Natural Products eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Chemistry Michele Gagne Thesis advisor Alex Miller Thesis advisor Maurice Brookhart Thesis advisor Joesph Templeton Thesis advisor Eric Brustad Thesis advisor text Trandon Bender Creator Department of Chemistry College of Arts and Sciences METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity. Spring 2017 2017 Chemistry Biomass Catalysis Hydrosilylation Lewis acid Natural Products eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Chemistry Michele Gagne Thesis advisor Alex Miller Thesis advisor Maurice Brookhart Thesis advisor Joesph Templeton Thesis advisor Eric Brustad Thesis advisor text Trandon Bender Creator Department of Chemistry College of Arts and Sciences METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity. 2017-05 2017 Chemistry Biomass Catalysis Hydrosilylation Lewis acid Natural Products eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Chemistry Michele Gagne Thesis advisor Alex Miller Thesis advisor Maurice Brookhart Thesis advisor Joesph Templeton Thesis advisor Eric Brustad Thesis advisor text Trandon Bender Creator Department of Chemistry College of Arts and Sciences METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity. 2017 Chemistry Biomass Catalysis Hydrosilylation Lewis acid Natural Products eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Chemistry Michele Gagne Thesis advisor Alex Miller Thesis advisor Maurice Brookhart Thesis advisor Joesph Templeton Thesis advisor Eric Brustad Thesis advisor text 2017-05 Trandon Bender Creator Department of Chemistry College of Arts and Sciences METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity. 2017 Chemistry Biomass Catalysis Hydrosilylation Lewis acid Natural Products eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Chemistry Michele Gagne Thesis advisor Alex Miller Thesis advisor Maurice Brookhart Thesis advisor Joesph Templeton Thesis advisor Eric Brustad Thesis advisor text 2017-05 Trandon Bender Creator Department of Chemistry College of Arts and Sciences METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity. 2017 Chemistry Biomass Catalysis Hydrosilylation Lewis acid Natural Products eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Chemistry Michele Gagne Thesis advisor Alex Miller Thesis advisor Maurice Brookhart Thesis advisor Joesph Templeton Thesis advisor Eric Brustad Thesis advisor text 2017-05 Trandon Bender Creator Department of Chemistry College of Arts and Sciences METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity. 2017 Chemistry Biomass Catalysis Hydrosilylation Lewis acid Natural Products eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Chemistry Michele Gagne Thesis advisor Alex Miller Thesis advisor Maurice Brookhart Thesis advisor Joesph Templeton Thesis advisor Eric Brustad Thesis advisor text 2017-05 Trandon Bender Creator Department of Chemistry College of Arts and Sciences METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity. 2017 Chemistry Biomass Catalysis Hydrosilylation Lewis acid Natural Products eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Chemistry Michel Gagne Thesis advisor Alexander Miller Thesis advisor Maurice Brookhart Thesis advisor Joseph Templeton Thesis advisor Eric Brustad Thesis advisor text 2017-05 Trandon Bender Creator Department of Chemistry College of Arts and Sciences METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity. 2017 Chemistry Biomass Catalysis Hydrosilylation Lewis acid Natural Products eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Chemistry Michel Gagne Thesis advisor Alexander Miller Thesis advisor Maurice Brookhart Thesis advisor Joseph Templeton Thesis advisor Eric Brustad Thesis advisor text 2017-05 Trandon Bender Creator Department of Chemistry College of Arts and Sciences METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity. 2017 Chemistry Biomass Catalysis Hydrosilylation Lewis acid Natural Products eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Chemistry Michele Gagne Thesis advisor Alex Miller Thesis advisor Maurice Brookhart Thesis advisor Joesph Templeton Thesis advisor Eric Brustad Thesis advisor text 2017-05 Trandon Bender Creator Department of Chemistry College of Arts and Sciences METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity. 2017 Chemistry Biomass Catalysis Hydrosilylation Lewis acid Natural Products eng Doctor of Philosophy Dissertation Chemistry Michel Gagne Thesis advisor Alexander Miller Thesis advisor Maurice Brookhart Thesis advisor Joseph Templeton Thesis advisor Eric Brustad Thesis advisor text 2017-05 University of North Carolina at Chapel Hill Degree granting institution Trandon Bender Creator Department of Chemistry College of Arts and Sciences METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity. 2017 Chemistry Biomass Catalysis Hydrosilylation Lewis acid Natural Products eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Chemistry Michele Gagne Thesis advisor Alex Miller Thesis advisor Maurice Brookhart Thesis advisor Joesph Templeton Thesis advisor Eric Brustad Thesis advisor text 2017-05 Trandon Bender Creator Department of Chemistry College of Arts and Sciences METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity. 2017 Chemistry Biomass Catalysis Hydrosilylation Lewis acid Natural Products eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Chemistry Michele Gagne Thesis advisor Alex Miller Thesis advisor Maurice Brookhart Thesis advisor Joesph Templeton Thesis advisor Eric Brustad Thesis advisor text 2017-05 Trandon Bender Creator Department of Chemistry College of Arts and Sciences METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity. 2017 Chemistry Biomass Catalysis Hydrosilylation Lewis acid Natural Products eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Chemistry Michele Gagne Thesis advisor Alex Miller Thesis advisor Maurice Brookhart Thesis advisor Joesph Templeton Thesis advisor Eric Brustad Thesis advisor text 2017-05 Trandon Bender Creator Department of Chemistry College of Arts and Sciences METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity. 2017 Chemistry Biomass Catalysis Hydrosilylation Lewis acid Natural Products eng Doctor of Philosophy Dissertation Chemistry Michel Gagne Thesis advisor Alexander Miller Thesis advisor Maurice Brookhart Thesis advisor Joseph Templeton Thesis advisor Eric Brustad Thesis advisor text 2017-05 University of North Carolina at Chapel Hill Degree granting institution Trandon Bender Creator Department of Chemistry College of Arts and Sciences METHODS FOR THE SELECTIVE MODIFICATION OF CARBOHYDRATES AND NATURAL PRODUCTS Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity. 2017 Chemistry Biomass Catalysis Hydrosilylation Lewis acid Natural Products eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Chemistry Michel Gagne Thesis advisor Alexander Miller Thesis advisor Maurice Brookhart Thesis advisor Joseph Templeton Thesis advisor Eric Brustad Thesis advisor text 2017-05 Trandon Bender Creator Department of Chemistry College of Arts and Sciences Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity. 2017 Chemistry Biomass Catalysis Hydrosilylation Lewis acid Natural Products eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Chemistry Michel Gagne Thesis advisor Alexander Miller Thesis advisor Maurice Brookhart Thesis advisor Joseph Templeton Thesis advisor Eric Brustad Thesis advisor text 2017-05 Trandon Bender Creator Department of Chemistry College of Arts and Sciences Selective modification of complex molecular scaffolds in the form of carbohydrates and natural products in a controllable way is a long-standing challenge. In carbohydrates, this problem results from the difficulty of activating carbon oxygen (C–O) bonds that are similar in reactivity making it difficult to differentiate between which bonds are activated. Natural products present a completely unique challenge in that they often contain disparate functional groups that present cross reactivity issues making activation of a natural product in a controllable way challenging. Each presents its own challenge, but the ability to perform selective modification of carbohydrates and natural products offers new routes to valuable chiral synthons from a renewable source and the opportunity to create new chemical space in molecular scaffolds that are often mined for biologically active drug candidates, respectively. Fluoroarylborane-based catalysts (such as B(C6F5)3) are uniquely capable in this regard as they heterolytically activate Si–H bonds to generate an oxophilic silylium (R3Si+) equivalent along with a reducing borohydride (H–BR3–). Although silylium ions are notoriously oxophilic and aggressive electrophiles that would seemingly be a poor choice for carrying out selective chemistry on a complex molecule, much less one with diverse (often oxygenated) functionality, together these components enable the selective activation and reduction C–O bonds in carbohydrates and complex natural products. Imperative to the selective deoxygenation of carbohydrates was the realization that selective neighboring group participation results in chemoselective formation of cyclic intermediates which are reduced with high diastereoselectivity to generate chiral synthons. With the observation that cyclic intermediates guide selective activation in polyoxygenated substrates, we expanded this application to include selective allylic C–O bond reduction in linear styryl-carbohydrates which also relied on cyclic intermediates to achieve high levels of selectivity. Ultimately, neighboring group participation in styryl-carbohyrates was harnessed to realize carbon-carbon bond formation to generate carbocycles in a highly diastereoselective fashion where cyclic intermediates are again implicated in the highly selective transformations. Investigating fluroarylborane-based catalyst activation of natural products required that addition of an exogenous phosphine Lewis base to modify the catalyst speciation and enable aggressive silylium ions to be harnessed for the selective modification of natural product scaffolds. Importantly, manipulation of the catalyst, the silane reagent, and the reaction conditions provide good control over which (and how) the functional groups are modified. The application of this methodology on complex bioactive compounds (natural products or drugs) thus provides a powerful tool for assessing how structural diversifications of these bioactive compounds correlates with bioactivity. 2017 Chemistry Biomass Catalysis Hydrosilylation Lewis acid Natural Products eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Michel Gagne Thesis advisor Alexander Miller Thesis advisor Maurice Brookhart Thesis advisor Joseph Templeton Thesis advisor Eric Brustad Thesis advisor text 2017-05 Bender_unc_0153D_16931.pdf uuid:c3276209-40d9-401c-b75a-a54bcd3d2dfc 2019-07-06T00:00:00 2017-04-27T13:48:56Z proquest yes