This thesis is divided into four chapters that describe the new development in rhodium-catalyzed addition reactions and asymmetric ring opening (ARO) reactions of strained alkenes. Chapter 1 describes a regioselective Rh(I)-catalyzed addition reaction of arylboronic acids to unactivated alkenes - protected allylic amines and allyl sulfones. These formal hydroarylation processes have significantly advanced the substrate scope. Comprehensive studies were carried out to optimize the reaction conditions and a wide range of arylboronic acids were employed. The reaction was found to be linear-selective and a mechanism based on functional group- directing effects has been proposed. Chapter 2 discloses the discovery of Rh(I)-catalyzed addition of arylboronic acids to (benzyl- /arylsulfonyl)acetonitriles. Novel β-sulfonylvinylamine products were formed in a stereoselective fashion (Z-alkene). Upon hydrolysis, β-keto sulfones were obtained with a broad scope of aryl and sulfonyl substituents. These (Z)-β-sulfonylvinylamines were useful synthons in the synthesis of unsymmetrical polysubstituted pyridines via 1-aza-allyl anion intermediates as well as 1,4- benzothiazine derivatives via intramolecular cyclization. Chapter 3 reports the use of two new nucleophiles in Rh(I)-catalyzed ARO of oxabicyclic alkenes - water and triethylamine trihydrofluoride. In the water-induced ARO, an unprecedented domino ARO/isomerization process was discovered which led to the formation of 2-hydroxy-1- tetralones. By modifying the reaction conditions, trans-1,2-diols can be obtained in excellent enantioselectivity. Using triethylamine trihydrofluoride as a nucleophile, an aliphatic C-F bond was constructed enantioselectively in the ring-opening process which provided fluorinated building blocks containing both allylic fluoride and fluorohydrin units. Finally, Chapter 4 details the development of a one-pot synthesis of a chiral dihydrobenzofuran framework using Rh-catalyzed asymmetric ring opening and Pd-catalyzed C-O coupling. The product can be obtained in excellent enantioselectivity without isolation of intermediates. Systematic metal-ligand studies were carried out to investigate the compatibility of each catalytic system using product enantiopurity as an indicator.

This thesis is divided into four chapters that describe the new development in rhodium-catalyzed addition reactions and asymmetric ring opening (ARO) reactions of strained alkenes. Chapter 1 describes a regioselective Rh(I)-catalyzed addition reaction of arylboronic acids to unactivated alkenes - protected allylic amines and allyl sulfones. These formal hydroarylation processes have significantly advanced the substrate scope. Comprehensive studies were carried out to optimize the reaction conditions and a wide range of arylboronic acids were employed. The reaction was found to be linear-selective and a mechanism based on functional group- directing effects has been proposed. Chapter 2 discloses the discovery of Rh(I)-catalyzed addition of arylboronic acids to (benzyl- /arylsulfonyl)acetonitriles. Novel β-sulfonylvinylamine products were formed in a stereoselective fashion (Z-alkene). Upon hydrolysis, β-keto sulfones were obtained with a broad scope of aryl and sulfonyl substituents. These (Z)-β-sulfonylvinylamines were useful synthons in the synthesis of unsymmetrical polysubstituted pyridines via 1-aza-allyl anion intermediates as well as 1,4- benzothiazine derivatives via intramolecular cyclization. Chapter 3 reports the use of two new nucleophiles in Rh(I)-catalyzed ARO of oxabicyclic alkenes - water and triethylamine trihydrofluoride. In the water-induced ARO, an unprecedented domino ARO/isomerization process was discovered which led to the formation of 2-hydroxy-1- tetralones. By modifying the reaction conditions, trans-1,2-diols can be obtained in excellent enantioselectivity. Using triethylamine trihydrofluoride as a nucleophile, an aliphatic C-F bond was constructed enantioselectively in the ring-opening process which provided fluorinated building blocks containing both allylic fluoride and fluorohydrin units. Finally, Chapter 4 details the development of a one-pot synthesis of a chiral dihydrobenzofuran framework using Rh-catalyzed asymmetric ring opening and Pd-catalyzed C-O coupling. The product can be obtained in excellent enantioselectivity without isolation of intermediates. Systematic metal-ligand studies were carried out to investigate the compatibility of each catalytic system using product enantiopurity as an indicator.

ABSTRACT SYNTHESIS OF 1,2,3,5-TETRASUBSTITUTED PYRROLE DERIVATIVES VIA 5-EXO-DIG TYPE CYCLIZATION AND STEREOSELECTIVE FUNCTIONALISATION OF FERROCENE DERIVATIVES Metin Kayalar M.S., Department of Chemistry Supervisor: Prof. Dr. Ayhan S. Demir January 2005, 102 pages A convenient and new method for the synthesis of 1,2,3,5-tetrasubstituted pyrrole derivatives starting from 1,3,-dicarbonyl compounds through acid catalyzed cyclization reaction is described. Alkylation of 1,3-dicarbonyl compound with propargyl bromide followed by one step cyclization with the introduction of primary amines in the presence of catalytic amount of triflouroacetic acid (TFA) affords the corresponding pyrrole derivatives in high yields. The investigations on the studies of developing a new method for catalytic and stereoselective functionalisation of ferrocene derivatives were summarized. Functionalisation studies were carried out in three main strategy the first one of which is carboxylation, second one is arylation and the last one is oxidative cross-coupling with &amp / #945 / , &amp / #946 / -unsaturated carbonyl compounds.

143 f. / Submitted by Ana Hilda Fonseca (anahilda@ufba.br) on 2013-09-24T14:26:15Z No. of bitstreams: 1 Dissertação Maria Candeia Kuliakita.pdf: 4339184 bytes, checksum: 54063fe95edeaa2662c649acf009c9ae (MD5) / Approved for entry into archive by Ana Hilda Fonseca(anahilda@ufba.br) on 2013-09-24T14:27:50Z (GMT) No. of bitstreams: 1 Dissertação Maria Candeia Kuliakita.pdf: 4339184 bytes, checksum: 54063fe95edeaa2662c649acf009c9ae (MD5) / Made available in DSpace on 2013-09-24T14:27:50Z (GMT). No. of bitstreams: 1 Dissertação Maria Candeia Kuliakita.pdf: 4339184 bytes, checksum: 54063fe95edeaa2662c649acf009c9ae (MD5) Previous issue date: 2012 / CNPq / Desenvolveram-se neste trabalho atividades experimentais empregando as reações de Mannich, utilizando-se o dímero di-hidróxi-acetona, um derivado da glicerina. A glicerina obtém-se como co- produto da produção de biodiesel. Sem êxitos nas tentativas feitas para a reação de Mannich, partiu-se então para reações aldólicas organocatalisadas. Nesta rota preparou-se a di-hidroxi-acetona sililada (97% de rendimento), que foi empregada como reagente na reação aldólica com o 4-nitrobenzaldeído. O aldol foi obtido como mistura enantiomérica enriquecida, na proporção diastereoisomérica de 5:1 (syn/anti). Posterior acetilação em 90% de rendimento permitiu avaliar, através de HPLC com coluna quiral, o excesso enantiomérico em cerca de 90%. O aldol acetilado teve seu grupo TBS primário removido (96-100 % de rendimento). No entanto, as tentativas de oxidação e preparação do ácido não foram exitosas. Como alternativa, reações de redução para a obtenção de dióis foram feitas obtendo-se dióis com estreoquímica relativa 1,3-anti em rendimento de 80%. Reações de redução por aminação também foram realizadas, mas sem resultados satisfatórios. Em paralelo a estas reações foram preparados derivados de ácidos triterpênicos (ácidos betulínico e ursólico), triterpenos (lupeol) e esteroides (estigmasterol e β-sitosterol) com ácidos oleico e hexanoico, preparando-se compostos com potencial atividade anticâncer e anti-AIDS. / Salvador

This diploma thesis deals with the stereoselective addition reaction of benzothiophenone derivatives to ketimines derived from isatin using bifunctional organocatalysis. The stereoselective addition reaction was optimized to provide the appropriate reaction conditions which were subsequently used to study the scope of the reaction. Keywords Organocatalysis, stereoselective synthesis, bifunctional organocatalysts, ketimines, sulphur heterocykles.

No description available.

Thesis advisor: Amir H. Hoveyda / Chapter 1. In Situ Methylene Capping: A Key Strategy in Catalytic Stereoretentive Olefin MetathesisA general approach for in situ methylene capping that significantly expands the scope of catalyst-controlled stereoselective olefin metathesis is presented. By incorporation of stereodefined 2-butene as the capping reagent, the catechothiolate Ru complex is enabled to catalyze olefin metathesis reactions of terminal alkenes. Substrates bearing a carboxylic acid, an aldehyde, an aryl substituent, an α substituent were thus converted to the desired products in 47–88% yield and 90:10–98:2 Z:E selectivity. The capping strategy was also applied in ring-closing metathesis reactions leading to 14- to 21-membered macrocyclic alkenes (96:4–98:2 Z:E). The utility of this method was highlighted through synthesis of a platelet aggregate inhibitor and two members of the prostaglandin family compounds by cross-metathesis reaction, as well as a strained 14-membered ring stapled peptide by macrocyclic ring-closing metathesis. Examples of the corresponding E-selective cross-processes are provided as well. Chapter 2. Synthesis of Z- or E-Trisubstituted Allylic Alcohols and Ethers by Kinetically Controlled Catalytic Cross-MetathesisKinetically controlled Ru-catalyzed cross-metathesis reactions that generate Z- or E-trisubstituted alkenes are discussed. Reactions were catalyzed by catechothiolate Ru complex to generate trisubstituted allylic alcohols and ethers in up to 81% yield and >98% stereoisomeric purity. The approach is applicable to synthesis of products containing an alcohol, an aldehyde, a carboxylic acid or an alkenyl substituent. Mechanistic models that account for the observed trends in efficiency and stereoselectivity will be provided. Chapter 3. A New Ru-Based Catechothiolate Complex Bearing an Unsaturated NHC Ligand for Synthesis of Z-α,β-Unsaturated Carbonyl Compounds by Cross Metathesis Design and development of a new Ru catechothiolate complex that may be used to promote Z-selective cross-metathesis transformations that afford Z-α,β-unsaturated esters, acids, and amides (including Weinweb amides) are discussed. Comparison between Ru catechothiolate complexes with an unsaturated NHC and a saturated NHC ligand will be provided. Utility of the approach is demonstrated by an eight-step synthesis (15% overall yield) of an intermediate for synthesis of stagonolide E, and a five-step synthesis of a precursor to dihydrocompactin / Thesis (PhD) — Boston College, 2020. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

This thesis deals with the synthesis and characterization ofnovel polyhydroxyl surfactants. The first part describes thesynthesis of a number of stereoisomers of a polyhydroxylsurfactant, and the second part concerns surface chemicalcharacterization. A stereodivergent route for preparation of the hydrophilichead group was developed, featuring consecutive stereoselectivedihydroxylations of a diene. This afforded in total fourdifferent polyhydroxyl head groups. These surfactant headgroups were natural and unnatural sugar analogues, and wereused for the coupling with two different hydrophobic tailgroups. Three of these surfactants were used to investigate thechiral discrimination in Langmuir monolayers at an air-waterinterface. The isotherms showed a remarkable difference incompressibility between surfactants of diastereomericrelationship and also a pronounced chiral discriminationbetween racemic and enantiomerically pure surfactants favoringheterochiral discrimination. / <p>NR 20140805</p>

Indiana University-Purdue University Indianapolis (IUPUI) / A version of this thesis was published as: Masters AR, McCoy M, Jones DR, and Desta Z. Stereoselective method to quantify bupropion and its three major metabolites, hydroxybupropion, erythro-dihydrobupropion, and threo-dihydrobupropion using HPLC-MS/MS. J Chromatography B Analyt Technol Biomed Life Sci 1015-1016:201-208, 2016. / Bupropion is a dual dopamine-norepinephrine uptake inhibitor and a nicotine receptor antagonist. Clinically, bupropion is given as a racemate for the management of depression, smoking cessation aid, and for the management of weight. Bupropion has also been targeted as a phenotypic probe of CYP2B6 activity. Bupropion metabolites are formed via oxidation (4-hydroxybupropion) through CYP2B6, and reduction (erythro- and threo-dihydrobupropion) through carbonyl reductases. These metabolites exhibit pharmacological activity, but little is known regarding their stereoselective disposition due to the lack of a chiral assay. A novel reversed phase chiral-HPLC-MS/MS method involving a simple liquid-liquid extraction procedure and a small plasma sample volume (50µL) was developed that allowed simultaneous separation and quantification of enantiomers of bupropion, 4-hydroxybupropion, and those of threo- and erythro-dihydrobupropion in human plasma. This method was successfully implemented to determine the unique stereoselective disposition of bupropion and its metabolites in 15 human volunteers administered a single 100 mg oral dose of racemic bupropion. Significant differences (p<0.05) in the stereoselective metabolism were observed for all of the enantiomers. The highest plasma exposure (AUC0-∞) was (2R, 3R)-4-hydoxybupropion, almost 65 fold higher, than (2S, 3S)-4-hydoxybupropion, and over 32 fold greater than the parent R-bupropion. The second highest plasma exposure was threo-dihydrobupropion A, which was almost 5 fold higher than threo-dihydrobupropion B. (Nomenclature of the enantiomers for erythro- and threo-dihydrobupropion was based on the chromatography of the first eluting peak as “A” and the second eluting peak as “B”.) Threo-dihydrobupropion A and B showed the most significant difference between the racemic and enantiomer profiles. Although the AUC was greater for threo-dihydrobupropion B, threo-dihydrobupropion A had a significantly (p<0.05) higher Cmax. The half-life for threo-dihydrobupropion A and erythro-dihydrobupropion A were the longest for all analytes, which could indicate accumulation in multiple dosing. The importance of this study was, for the first time, to be able to characterize the stereoselective metabolism of bupropion and its three major metabolites. This new method and subsequent pharmacokinetic data should enhance further research into bupropion stereoselective metabolism, drug interactions, and effect. / A version of this thesis was published as: Masters AR, McCoy M, Jones DR, and Desta Z. Stereoselective method to quantify bupropion and its three major metabolites, hydroxybupropion, erythro-dihydrobupropion, and threo-dihydrobupropion using HPLC-MS/MS. J Chromatography B Analyt Technol Biomed Life Sci 1015-1016:201-208, 2016.

京都大学 / 0048 / 新制・課程博士 / 博士(薬科学) / 甲第21049号 / 薬科博第92号 / 新制||薬科||10(附属図書館) / 京都大学大学院薬学研究科医薬創成情報科学専攻 / (主査)教授 大野 浩章, 教授 竹本 佳司, 教授 高須 清誠 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM