Meso 1,9-diketones (six to seven stereocenters)are readily obtained by stepwise or simultaneous two-directional aldol reactions of tetrahydro-4H-thiopyran-4-one with a thiopyran-derived aldehyde. Enantioselective enolizations of these diketones with the lithium amide from (R,R)-bis(1-phenylethyl)amine occur with simultaneous kinetic resolution to give the mono-TMS enol ethers in >90% yields based on recovered starting material (BORSM) and >90% ee. The developed methodology was applied in synthetic studies towards the asymmetric synthesis of denticulatin A.

Meso 1,9-diketones (six to seven stereocenters)are readily obtained by stepwise or simultaneous two-directional aldol reactions of tetrahydro-4H-thiopyran-4-one with a thiopyran-derived aldehyde. Enantioselective enolizations of these diketones with the lithium amide from (R,R)-bis(1-phenylethyl)amine occur with simultaneous kinetic resolution to give the mono-TMS enol ethers in >90% yields based on recovered starting material (BORSM) and >90% ee. The developed methodology was applied in synthetic studies towards the asymmetric synthesis of denticulatin A.

Thesis advisor: James P. Morken / This dissertation describes the development of four metal-catalyzed carbon-carbon bond forming methods. The first project presented is a palladium-catalyzed proparyl-allyl cross-coupling which proceeds via a kinetic resolution to give enantioenriched 1,5-enynes. Next the asymmetric rhodium-catalyzed hydroformylation of 1-alkenes is described. This reaction delivers synthetically useful a-chiral aldehydes in up to 98:2 er and up to 15:1 branched to linear ratio. The development of a unique nickelcatalyzed asymmetric Kumada coupling of cyclic sulfates is presented. Mechanistic studies reveal the reaction proceeds via an SN2 oxidative addition of a chiral nickelcomplex. Finally, a-Substituted allyl bis(boronic) esters, which are derived from 1,2-diboration of 1,3-dienes are shown to undergo allylation and subsequent Suzuki coupling with aldehydes tethered to sp2 electrophiles. The carbocycle products obtained bear three contiguous stereocenters and were used as intermediates in the synthesis of complex molecules. / Thesis (PhD) — Boston College, 2017. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

The first chapter of this thesis describes the development of a general method for indirectly effecting radical carbocyclization of an alkyl chain onto an aromatic ring. This process involves a Birch reductive alkylation of aromatic tert-butyl esters, chromium(VI)-mediated oxidation and radical cyclization. The cyclized products are easily aromatized by Saegusa oxidation and treatment with bismuth trichloride. This method forms five- and six-membered benzo-fused carbocycles. Modification allows both formation of non-phenolic products, and the introduction of an additional substituent on the original aromatic ring. The second chapter describes a method for converting tert-butyl benzoates or tert-butyl 1-naphthoates into derivatives having a substituted alkyl group in a 1,4-relationship to an alkyl, aryl, alkenyl or alkynyl group. Key steps in the process involve addition of an organometallic species to a cross-conjugated cyclohexadienone followed by treatment with bismuth trichloride, which results in spontaneous decarboxylative aromatization. The method was successfully applied to the synthesis of the antimicrobial fungal metabolite culpin. The last chapter of this thesis describes synthetic studies towards the marine antileukemic alkaloid, sorbicillactone A. Studies towards the core structure of sorbicillactone A have resulted in a new method of desymmetrization of cross-conjugated cyclohexadienones. The key step involves a highly diastereoselective iodoetherification and radical cyclization, which affords a product that can be elaborated into a -lactone.

No description available.

Thesis advisor: Jason Kingsbury / Recent findings have led to the discovery that the Sc-catalyzed addition of substituted diazoalkanes to aldehydes elegantly affords a net carbon insertion into the C-H bond, delivering the requisite ketone in one simple step with no need for a readjustment in oxidation state. This chemistry is much improved over the century old diazomethane chemistry which requires stoichiometric amounts of a promoter and is limited in both application and scope. The new catalytic method has now been utilized as the key step in the synthesis of the pseduosymmetric precursor to the natural product achyrofuran, which has been named “pre-achyrofuran.” Subsequently, a related project was pursued involving the desymmetrization of bicyclic β-diketones by catalytic carbon insertion with trimethylsilyldiazomethane as the reagent. Preliminary developments in this area are disclosed. / Thesis (BS) — Boston College, 2010. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: Chemistry Honors Program. / Discipline: Chemistry.

Chiral molecules as with biological activity are plentiful in nature and the chemical literature; however they represent a smaller portion of the pharmaceutical drug market. As asymmetric methodologies grow more powerful, the tools are becoming available to synthesize chiral molecules in an enantioselective and efficient manner. Recent breakthroughs in our understanding of phosphoric acid now allow for Lewis acid catalysis via pairing with alkaline earth metals. Using alkaline earth metals with chiral phosphates is an emerging approach to asymmetric methodology, but already has an influential record. The development of new conditions for the phosphoric acid-catalyzed highly enantioselective ring-opening of meso-aziridines with a series of functionalized aromatic thiol nucleophiles is described in this thesis. This methodology utilizes commercially available aromatic thiols, a series of meso-aziridines, and a catalytic amount of VAPOL calcium phosphate to explore the substrate scope of this highly enantioselective reaction. Additionally, the development of new conditions for a catalytic asymmetric aza-Darzens aziridine synthesis mediated by a vaulted biphenanthrol (VAPOL) magnesium phosphate salt is described in this thesis. Using simple substrates, this methodology explores the scope and reactivity of a new magnesium catalyst for an aziridination reaction capable of building chirality and complexity simultaneously.

Orientador: Fernando Antonio Santos Coelho / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-25T19:28:01Z (GMT). No. of bitstreams: 1 Teodoro_BrunoViniciusMotta_M.pdf: 11061427 bytes, checksum: 006abc673338577da39655293c55243c (MD5) Previous issue date: 2014 / Resumo: Esta dissertação de mestrado está dividida em duas partes. Na primeira parte descrevemos os resultados obtidos na síntese de núcleos indolizidínicos, a partir de adutos de Morita-Baylis-Hillman (MBH). Na segunda parte, descrevemos os resultados obtidos na avaliação de uma reação de dessimetrização de adutos de MBH. Os núcleos indolizidínicos representam um padrão estrutural de grande interesse sintético, pois existem inúmeros alcaloides, com atividade biológica pronunciada, que contêm este núcleo. A metodologia desenvolvida nesse trabalho permite a preparação de núcleos indolizidínicos, a partir de adutos de MBH, em duas etapas. Assim, uma reação de ciclização intramolecular de um aduto, gera indolizinas que, após uma reação de hidrogenação total, conduz as indolizidinas. A rota desenvolvida é rápida, simples, eficiente e estereosseletiva. Os rendimentos globais variaram de 43 a 55%. Os excessos diastereoisoméricos obtidos variaram entre 68 e 86%, em favor do isômero cis. Nesta parte do trabalho avaliamos também um procedimento para preparar tetraidroindolizinas, a partir da hidrogenação parcial das indolizinas. Usando a mesma estratégia, descrevemos a preparação de tetraidroindolizinas com rendimentos que variaram entre 40-93%. Na segunda parte desse trabalho avaliamos uma alternativa de dessimetrização de adutos de MBH. A redução de ?-ceto-?-metileno-ésteres, obtidos a partir de uma reação de oxidação de adutos de MBH racêmicos, nos permite acessar a esses adutos em suas formas enantiomericamente puras. Após realizar uma triagem de catalisadores de redução assimétrica, a melhor condição encontrada nos forneceu o aduto de MBH enantioenrriquecidos, com um rendimento de 25% e um excesso enantiomérico de 68%, utilizando o catalisador CBS. A partir deste dado, outros estudos poderão ser realizados visando verificar a generalidade do método desenvolvido / Abstract: This work is divided in two parts. In the first part, we described the development of a strategy for preparing indolizidine skeletons starting from Morita-Baylis-Hillman (MBH) adducts. In the second part, the preliminary results of study for the desymmetrization of MBH adducts is reported. The indolizidine core is a structural pattern of great synthetic interest since it's present in the structure of several alkaloids with remarkable biological activity. The two-step methodology developed in this work allowed the efficient preparation of indolizidine nucleus from MBH adducts. Thus, an intramolecular cyclization reaction of MBH adducts derived from 2-pyridine-carboxaldehyde followed by platinum mediated hydrogenation affords the indolizidines in good overall yield. The developed methodology is simple, fast and stereoselective. The overall yields ranged from 43 and 55% and the diastereoisomeric excesses obtained ranged from 68 to 86%, in favor of the cis isomer. The partial hydrogenation of the indolizines allowed the preparation of tetrahydroindolizines. Thus, using the same strategy, we also described the preparation of tetrahydroindolizines with yields ranging from 40-93 %. In the second part of this work we described the preliminary results of an evaluation of an alternative desymmetrization strategy of MBH adducts. The reduction of ?-keto-?-methylene esters obtained from an oxidation of racemic MBH adducts could allow us to access these adducts in their enantiomerically pure forms. A screening of asymmetric reduction catalysts showed us that the CBS catalyst provided the best condition. An enantioenriched MBH adduct was obtained in 25% yield and 68% enantiomeric excess. This result will stimulate new studies in order to check the scope of this method / Mestrado / Quimica Organica / Mestre em Química

京都大学 / 0048 / 新制・論文博士 / 博士(農学) / 乙第13178号 / 論農博第2857号 / 新制||農||1061(附属図書館) / 学位論文||H30||N5100(農学部図書室) / (主査)教授 小川 順, 教授 栗原 達夫, 教授 三上 文三 / 学位規則第4条第2項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

Submitted by (lucia.rodrigues@ufrpe.br) on 2017-02-13T15:29:49Z No. of bitstreams: 1 Edmilson Clarindo de Siqueira.pdf: 4674633 bytes, checksum: c618a0d261dbc9f5432627199fd82f3a (MD5) / Made available in DSpace on 2017-02-13T15:29:49Z (GMT). No. of bitstreams: 1 Edmilson Clarindo de Siqueira.pdf: 4674633 bytes, checksum: c618a0d261dbc9f5432627199fd82f3a (MD5) Previous issue date: 2012-04-13 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / In this study we investigated the resolution of rac-1,2-propanediol and rac-2,3- isopropylidene glycerol using chiral amines (R)- and (S)-1-phenylethylamine (27). The alcohols are esterified to form hemi-phthalates, and treated with the enantiomers of 27 resulting in the following salts (R)-27.(±)-52 and (S)-27.(±)-52 in good yields. However, salts (R)-27.(±)-33 and (S)-27.(±)-33 did not form crystalline material. In addition we studied the resolution of (±)-14 and (±)-31 through the use of amino acids benzyl esters and brucine as auxiliaries. Attempts to obtain the benzyl ester of L-tryptophan (59) were negative; attempts to obtain benzyl esters of Lphenylalanine (58) and L-lysine (57) were also negative. In the case of brucine (35) there was no noticeable diastereoisomeric enrichment during repeated crystallizations. As an extension to this, we performed dehydration of D-mannitol (40) in an acid medium. Modifications of the published method resulted in obtaining a new derivative, the 2,5-anhydro-1,3-O-benzyl-D-mannitol (81) whose structure was established via x-ray study. / Neste trabalho foi avaliada a resolução dos alcoóis rac-1,2-propanodiol (14) e rac-2,3-isopropilideno glicerol (31) pelas aminas quirais (R)- e (S)-1-feniletilamina (27) via processo de dessimetrização: os alcoóis foram esterificados, na forma de ftalatos, e tratados com os enantiômeros de 27 que resultou nos seguintes sais (R)-27.(±)-52 e (S)-27.(±)-52 em bons rendimentos. Todavia, os sais (R)-27.(±)-33 e (S)-27.(±)-33 não foram isolados em sua forma cristalina. Adicionalmente, foi estudada a resolução de (±)-14 e (±)-31 através do uso de aminoácidos, na sua forma benzílica, e brucina como auxiliares quirais. Tentativas de obter o éster benzil de L-triptofano (59), foram negativas. Alternativas de usar Lfenilalanina (58) e L-lisina (57) também foram negativas. Condizente com este tipo de resolução foi ensaiada também o alcalóide brucina (35), porém não houve enriquecimento diastereoisomérico durante repetidas cristalizações. Como extensão ao trabalho realizado com os alcoóis, foi investigada a desidratação do D-manitol (40) em meio ácido. Modificações desta metodologia conduziram à obtenção de um novo derivado deste substrato, o 2,6-anidro-1,3-di-Obenzil- D-manitol (81), que foi caracterizado por raios-X.