ingest cdrApp 2019-01-04T15:22:28.911Z 2a9effba-8beb-4434-9ac1-3dd15c1ac330 modifyDatastreamByValue RELS-EXT fedoraAdmin 2019-01-04T15:23:26.666Z Setting exclusive relation addDatastream MD_TECHNICAL fedoraAdmin 2019-01-04T15:23:39.513Z Adding technical metadata derived by FITS addDatastream MD_FULL_TEXT fedoraAdmin 2019-01-04T15:24:06.043Z Adding full text metadata extracted by Apache Tika modifyDatastreamByValue RELS-EXT fedoraAdmin 2019-01-04T15:24:31.390Z Setting exclusive relation modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2019-01-22T16:00:16.491Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2019-02-28T00:58:29.160Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2019-03-19T20:15:02.496Z Blane Zavesky Author Department of Chemistry College of Arts and Sciences Enhancing the Synthetic Utility of Enantioconvergent Addition Reactions and Progress Towards a Convergent, De Novo Synthesis of Jervine I. Direct Zn(II)-Catalyzed Enantioconvergent Additions of Terminal Alkynes to α-Keto Esters The addition of terminal alkynes to β-stereogenic α-keto esters was achieved in high levels of stereoselectivity, affording versatile tertiary propargylic alcohols containing two stereocenters. This environmentally benign enantioconvergent reaction proceeds with perfect atom economy, requires no solvent, and is catalyzed by an abundant and non-toxic zinc salt. The alkyne moiety can be leveraged in downstream transformations including hydrogenation to the corresponding saturated tertiary alcohol, which represents the product of a formal enantioconvergent aliphatic nucleophile addition. II. Palladium-Catalyzed β-Arylation of α-Keto Esters A catalyst system derived from commercially available Pd2(dba)3 and PtBu3 has been applied to the coupling of α-keto ester enolates and aryl bromides. The reaction provides access to a versatile array of β-stereogenic α-keto esters. When the air stable ligand precursor PtBu3·HBF4 is employed, the reaction can be carried out without use of a glovebox. The derived products are of broad interest given the prevalence of the β-keto acid substructure in biologically important molecules. III. Progress Towards a Convergent, De Novo Synthesis of Jervine A convergent approach towards the synthesis of the Veratrum alkaloid jervine is presented. The two requisite complex fragments were stereoselectively and efficiently fashioned from cheap and readily available reagents. Key to this route were the uses of a highly diastereoselective Ireland-Claisen rearrangement to set the relative configuration of the amine and exocyclic methyl group present on the tetrahydrofuran ring, and a selenoetherification reaction, which enabled the assembly of the quaternary stereocenter present at the D and E ring junction. IV. Progress Towards the First Asymmetric Synthesis of Matrine The captivating biological activity of matrine has been of interest since its isolation in 1889 from the traditional medical herb Sophora flavescens, however no asymmetric synthesis of the molecule exists. Herein, we disclose the synthesis of an advanced enantiopure piperidone building block beginning from commercial L-aspartic acid β-methyl ester hydrochloride, and show our efforts in addressing the remaining synthetic challenges. Winter 2018 2018 Organic chemistry Cataysis, Dynamic Kinetic Resolution, Enolate Arylation, Jervine, Matrine, Natural Product Synthesis eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Chemistry Jeffrey Johnson Thesis advisor Erik Alexanian Thesis advisor Michael Crimmins Thesis advisor Michel Gagné Thesis advisor Frank Leibfarth Thesis advisor text Blane Zavesky Creator Department of Chemistry College of Arts and Sciences Enhancing the Synthetic Utility of Enantioconvergent Addition Reactions and Progress Towards a Convergent, De Novo Synthesis of Jervine I. Direct Zn(II)-Catalyzed Enantioconvergent Additions of Terminal Alkynes to α-Keto Esters The addition of terminal alkynes to β-stereogenic α-keto esters was achieved in high levels of stereoselectivity, affording versatile tertiary propargylic alcohols containing two stereocenters. This environmentally benign enantioconvergent reaction proceeds with perfect atom economy, requires no solvent, and is catalyzed by an abundant and non-toxic zinc salt. The alkyne moiety can be leveraged in downstream transformations including hydrogenation to the corresponding saturated tertiary alcohol, which represents the product of a formal enantioconvergent aliphatic nucleophile addition. II. Palladium-Catalyzed β-Arylation of α-Keto Esters A catalyst system derived from commercially available Pd2(dba)3 and PtBu3 has been applied to the coupling of α-keto ester enolates and aryl bromides. The reaction provides access to a versatile array of β-stereogenic α-keto esters. When the air stable ligand precursor PtBu3·HBF4 is employed, the reaction can be carried out without use of a glovebox. The derived products are of broad interest given the prevalence of the β-keto acid substructure in biologically important molecules. III. Progress Towards a Convergent, De Novo Synthesis of Jervine A convergent approach towards the synthesis of the Veratrum alkaloid jervine is presented. The two requisite complex fragments were stereoselectively and efficiently fashioned from cheap and readily available reagents. Key to this route were the uses of a highly diastereoselective Ireland-Claisen rearrangement to set the relative configuration of the amine and exocyclic methyl group present on the tetrahydrofuran ring, and a selenoetherification reaction, which enabled the assembly of the quaternary stereocenter present at the D and E ring junction. IV. Progress Towards the First Asymmetric Synthesis of Matrine The captivating biological activity of matrine has been of interest since its isolation in 1889 from the traditional medical herb Sophora flavescens, however no asymmetric synthesis of the molecule exists. Herein, we disclose the synthesis of an advanced enantiopure piperidone building block beginning from commercial L-aspartic acid β-methyl ester hydrochloride, and show our efforts in addressing the remaining synthetic challenges. 2018 2018-12 Organic chemistry Cataysis; Dynamic Kinetic Resolution; Enolate Arylation; Jervine; Matrine; Natural Product Synthesis eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Chemistry Jeffrey Johnson Thesis advisor Erik Alexanian Thesis advisor Michael Crimmins Thesis advisor Michel Gagné Thesis advisor Frank Leibfarth Thesis advisor text Blane Zavesky Creator Department of Chemistry College of Arts and Sciences Enhancing the Synthetic Utility of Enantioconvergent Addition Reactions and Progress Towards a Convergent, De Novo Synthesis of Jervine I. Direct Zn(II)-Catalyzed Enantioconvergent Additions of Terminal Alkynes to α-Keto Esters The addition of terminal alkynes to β-stereogenic α-keto esters was achieved in high levels of stereoselectivity, affording versatile tertiary propargylic alcohols containing two stereocenters. This environmentally benign enantioconvergent reaction proceeds with perfect atom economy, requires no solvent, and is catalyzed by an abundant and non-toxic zinc salt. The alkyne moiety can be leveraged in downstream transformations including hydrogenation to the corresponding saturated tertiary alcohol, which represents the product of a formal enantioconvergent aliphatic nucleophile addition. II. Palladium-Catalyzed β-Arylation of α-Keto Esters A catalyst system derived from commercially available Pd2(dba)3 and PtBu3 has been applied to the coupling of α-keto ester enolates and aryl bromides. The reaction provides access to a versatile array of β-stereogenic α-keto esters. When the air stable ligand precursor PtBu3·HBF4 is employed, the reaction can be carried out without use of a glovebox. The derived products are of broad interest given the prevalence of the β-keto acid substructure in biologically important molecules. III. Progress Towards a Convergent, De Novo Synthesis of Jervine A convergent approach towards the synthesis of the Veratrum alkaloid jervine is presented. The two requisite complex fragments were stereoselectively and efficiently fashioned from cheap and readily available reagents. Key to this route were the uses of a highly diastereoselective Ireland-Claisen rearrangement to set the relative configuration of the amine and exocyclic methyl group present on the tetrahydrofuran ring, and a selenoetherification reaction, which enabled the assembly of the quaternary stereocenter present at the D and E ring junction. IV. Progress Towards the First Asymmetric Synthesis of Matrine The captivating biological activity of matrine has been of interest since its isolation in 1889 from the traditional medical herb Sophora flavescens, however no asymmetric synthesis of the molecule exists. Herein, we disclose the synthesis of an advanced enantiopure piperidone building block beginning from commercial L-aspartic acid β-methyl ester hydrochloride, and show our efforts in addressing the remaining synthetic challenges. 2018 2018-12 Organic chemistry Cataysis; Dynamic Kinetic Resolution; Enolate Arylation; Jervine; Matrine; Natural Product Synthesis eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Chemistry Jeffrey Johnson Thesis advisor Erik Alexanian Thesis advisor Michael Crimmins Thesis advisor Michel Gagné Thesis advisor Frank Leibfarth Thesis advisor text Blane Zavesky Creator Department of Chemistry College of Arts and Sciences Enhancing the Synthetic Utility of Enantioconvergent Addition Reactions and Progress Towards a Convergent, De Novo Synthesis of Jervine I. Direct Zn(II)-Catalyzed Enantioconvergent Additions of Terminal Alkynes to α-Keto Esters The addition of terminal alkynes to β-stereogenic α-keto esters was achieved in high levels of stereoselectivity, affording versatile tertiary propargylic alcohols containing two stereocenters. This environmentally benign enantioconvergent reaction proceeds with perfect atom economy, requires no solvent, and is catalyzed by an abundant and non-toxic zinc salt. The alkyne moiety can be leveraged in downstream transformations including hydrogenation to the corresponding saturated tertiary alcohol, which represents the product of a formal enantioconvergent aliphatic nucleophile addition. II. Palladium-Catalyzed β-Arylation of α-Keto Esters A catalyst system derived from commercially available Pd2(dba)3 and PtBu3 has been applied to the coupling of α-keto ester enolates and aryl bromides. The reaction provides access to a versatile array of β-stereogenic α-keto esters. When the air stable ligand precursor PtBu3·HBF4 is employed, the reaction can be carried out without use of a glovebox. The derived products are of broad interest given the prevalence of the β-keto acid substructure in biologically important molecules. III. Progress Towards a Convergent, De Novo Synthesis of Jervine A convergent approach towards the synthesis of the Veratrum alkaloid jervine is presented. The two requisite complex fragments were stereoselectively and efficiently fashioned from cheap and readily available reagents. Key to this route were the uses of a highly diastereoselective Ireland-Claisen rearrangement to set the relative configuration of the amine and exocyclic methyl group present on the tetrahydrofuran ring, and a selenoetherification reaction, which enabled the assembly of the quaternary stereocenter present at the D and E ring junction. IV. Progress Towards the First Asymmetric Synthesis of Matrine The captivating biological activity of matrine has been of interest since its isolation in 1889 from the traditional medical herb Sophora flavescens, however no asymmetric synthesis of the molecule exists. Herein, we disclose the synthesis of an advanced enantiopure piperidone building block beginning from commercial L-aspartic acid β-methyl ester hydrochloride, and show our efforts in addressing the remaining synthetic challenges. 2018 2018-12 Organic chemistry Cataysis; Dynamic Kinetic Resolution; Enolate Arylation; Jervine; Matrine; Natural Product Synthesis eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Jeffrey Johnson Thesis advisor Erik Alexanian Thesis advisor Michael Crimmins Thesis advisor Michel Gagné Thesis advisor Frank Leibfarth Thesis advisor text Zavesky_unc_0153D_18254.pdf uuid:2cda8102-a315-4274-a271-1faa1aabfa2f 2020-12-31T00:00:00 2018-12-06T02:23:18Z proquest application/pdf 5361854