Thesis (PH. D)--Columbia University, 1942. / On t.p., "alpha, beta" following the "Delta" are superscript. Lithoprinted. Vita. Bibliography: p. 19.

Thesis (Ph. D.)--Columbia University, 1941. / Lithoprinted. Vita. Bibliography: p. 19-20, 41-42.

Thesis (PH. D)--Columbia University, 1942. / Lithoprinted. Vita. Bibliography: p. 19.

No description available.

Thesis (Ph. D.)--Columbia University, 1942. / Vita. Bibliography: p. 9, 15, 18.

Le système spirocyclique (7,5) est un motif récurrent dans un certain nombre de produits naturels tels que les Micrandilactones ou les Rubriflordilactones. Ces structures polycycliques représentent un réel défi synthétique pour les chimistes organiciens puisqu'elles présentent au moins neuf centres stéréogènes dont plusieurs sont quaternaires. L'objectif principal de ce travail était de développer de nouvelles réactions de cycloaddition [3+2] et de les utiliser comme étape clé afin d'obtenir rapidement et efficacement le squelette polycylique de ces composés. La première partie de ces travaux a été consacrée au développement d'une réaction de cycloaddition [3+2] intra- et intermoléculaire mettant un jeu un nouveau partenaire dipolarophile, les γ-alkylidènes-buténolides. Cette étape clé conduit à la formation de cycloadduits hautement fonctionnalisés de façon rapide et efficace avec d'excellents rendements et de façon hautement chimio-, régio- et diastéréosélective. De plus, des calculs théoriques ont permis d'appréhender le mécanisme réactionnel entre un 2-diazo-1,3-cétoester et la protoanémonine catalysé par un sel de rhodium mis en jeu dans ce type de processus et ainsi d'expliquer les résultats obtenus.Dans une deuxième partie, deux approches aux cœurs ABC et CD de la micrandilactone C ont été développées mettant respectivement en jeu une cycloaddition [3+2] formellement intermoléculaire utilisant un lien de type acétal de silicium et suivie par une réaction de Diels Alder. Ainsi, le motif tétracyclique devrait être rapidement accessible après quelques aménagements de la voie de synthèse initiale. / The spiro (7, 5) ring system is a recurring structural moiety in numerous natural products such as Micrandilactones and Rubriflordilactones. In term of complexity, these polycyclic structures represent a synthetic challenge for organic chemist. Indeed, these molecules present at least nine stereogenic centres including several quaternary ones. The main goal of this work was to use unprecedented partners in the [3+2] cycloaddition reaction to obtain quickly and efficiently the polycyclic core of those natural products. The first part of these studies was dedicated to the development of an intra- and intermolecular [3+2] cycloaddition using for the first time a γ-alkylidene-butenolide dipolarophile. This approach provides rapid and facile access to highly functionalised polycyclic molecules along with excellent regio-, chemo- and stereoselectivities. In addition, thanks to computational studies an overall picture of the mechanism of the intermolecular rhodium catalysed [3+2] cycloaddition between 2-diazo-1,3-ketoester and protoanemonin was apprehended, and experimental results have been rationalised.Finally, two approaches to the ABC and CD cores of Micrandilactone C were developed using respectively a formal intermolecular [3+2] cycloaddition reaction in presence of a silicon acetal linker followed by a Diels Alder reaction. The ACDE tetracyclic moiety should be quickly accessible after few modifications of the initial strategy.

Made available in DSpace on 2015-03-26T13:00:03Z (GMT). No. of bitstreams: 1 texto completo.pdf: 802007 bytes, checksum: bcc020909e933a451dfda4bc8f17dee0 (MD5) Previous issue date: 2007-10-29 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / The nostoclides belong to a class of natural compounds called γ-alkylidenebutenolides that have several representatives with biological application. To contribute to the study of this class of compounds, this present work aimed to synthesize new butenolides analogous to the nostoclides from furan-2 (5H)-one [8] and evaluate the phytotoxic activity of theses compounds on the development of sorghum and cucumber root growing. For the synthesis of the analogues to the nostoclides, the furan-2(5H)-one was converted in the compound 2-furyl-N,N,N',N'-tetraethyldiamide-phosphate that treated with 3-chlorobenzyl bromide resulted in the formation of the intermediary 3-(3-chlorobenzyl)furan-2(5H)-one [15]. The aldolic addition reaction between the lactone [15] and various aromatic aldehydes with subsequent elimination reaction provided the achievement of the following analogous to the nostoclides: (5Z)-3-(3-chlorobenzyl)-5-(3,4- methylenedioxybenzylidene)furan-2(5H)-one [17], (5Z)-3-(3- chlorobenzyl)-5-(4-fluorobenzylidene)furan-2(5H)one [18], (5Z)-3-(3-chlorobenzyl)-5-(4-bromobenzylidene)furan-2(5H)- one [19], (5Z)-3-(3-chlorobenzyl)-5-(2- bromobenzylidene)furan-2(5H)-one [20], (5Z)-3-(3-chlorobenzyl)-5-(4-trifluormethylbenzylidene)furan-2(5H)-one [21], (5Z)-3-(3-chlorobenzyl)-5-(2,5-dimethoxybenzylidene) furan-2(5H)-one [22], (5E)-3-(3-chlorobenzyl)-5-(2,4,6- trimethoxybenzylidene)furan-2(5H)-one [23], (5Z)-3-(3- chlorobenzyl)-5-(3-nitrobenzylidene)furan-2(5H)-one [24], (5Z)-3-(3-chlorobenzyl)-5-benzylidenefuran-2(5H)-one [25]. The nine news synthesized compounds were submitted to the evaluation of the herbicide activity, in concentrations of 10 and 100 ppm, using cucumber (Cucumis sativus) and sorghum (Sorghum bicolor) as test plants in Petri dishes. All the compounds were active, inhibiting the root system of the seeds of sorghum in two concentrations. By the statistical analysis, in the concentration of 10 ppm, the presence of substituents in the benzylidene group in the compounds [17], [18], [20], [22], [23] and [24] showed less herbicide activity than the compound [25], not replaced. The phytotoxic activity was not dependent on the presence of substituents groups in the compounds [19] and [21], since the results did not differ statistically between themselves, compared to the compound [25], not replaced. For the test using cucumber seeds, the compounds [17] and [23], in the concentration of 100 ppm, showed a contrary action, stimulating the root growth of that culture. The same behavior was observed for the compounds [23] and [24], in the concentration of 10 ppm. Among the tested substances, the one that showed greater inhibition to the sorghum culture was the compound [17] with percentage of inhibition of 70.7% (10 ppm) and 75.8% (100 ppm) and to the cucumber culture the compound [19] was the one that presented greater percentage of inhibition, 41.9% (10 ppm) and 41.1% (100 ppm). / Os nostoclídeos pertencem à classe de compostos naturais denominados γ-alquilidenobutenolídeos que possuem vários representantes com aplicação biológica. Para contribuir com o estudo dessa classe de compostos, este trabalho teve como objetivo sintetizar novos butenolídeos análogos aos nostoclídeos a partir da furan-2(5H)-ona [8] e avaliar a atividade fitotóxica desses compostos sobre o desenvolvimento radicular de sorgo e pepino. Para a síntese dos análogos aos nostoclídeos a furan-2(5H)-ona foi convertida no composto 2-furil-N,N,N ,N - tetraetildiamidofosfato que ao ser tratado com brometo de 3- clorobenzila resultou na formação do intermediário 3-(3- clorobenzil)furan-2(5H)-ona [15]. A reação de adição aldólica entre a lactona [15] e diferentes aldeídos aromáticos com posterior reação de eliminação proporcionou a obtenção dos seguintes análogos aos nostoclídeos: (5Z)-3-(3-clorobenzil)- 5-(3,4-metilenodi-oxibenzilideno)furan-2(5H)-ona [17], (5Z)- 3-(3-clorobenzil)-5-(4-fluorobenzili-deno)furan-2-(5H)ona [18], (5Z)-3-(3-clorobenzil)-5-(4-bromo-benzilideno)furan-2 (5H)-ona [19], (5Z)-3-(3-clorobenzil)-5-(2-bromobenzilideno) furan-2(5H)-ona [20], (5Z)-3-(3-clorobenzil)-5-(4- trifluorometilbenzilideno)furan-2(5H)-ona [21], (5Z)-3-(3- clorobenzil)-5-(2,5-dimetóxibenzilideno)furan-2(5H)-ona [22], (5E)-3-(3-clorobenzil)-5-(2,4,6-trimetóxibenzilideno) furan-2(5H)-ona [23], (5Z)-3-(3-clorobenzil)-5-(3- nitrobenzilide-no)furan-2(5H)-ona [24], (5Z)-3-(3- clorobenzil)-5-benzilidenofuran-2(5H)-ona [25]. Os nove novos compostos sintetizados foram submetidos à avaliação da atividade herbicida, nas concentrações de 10 e 100 ppm, utilizando como planta teste pepino (Cucumis sativus) e sorgo (Sorghum bicolor), em ensaio de Placa de Petri. Todos os compostos se mostraram ativos inibindo o sistema radicular das sementes de sorgo nas duas concentrações estudadas. Pela análise estatística, na concentração de 10 ppm, a presença de substituintes no grupo benzilideno para os compostos [17], [18], [20], [22], [23] e [24] conferiu uma diminuição da atividade herbicida em relação ao composto [25] não substituído. Já para os compostos [19] e [21] a atividade fititóxica não se mostrou dependente da presença dos grupos substituintes, uma vez que os resultados não diferem estatisticamente entre si, em relação ao composto [25] não substituído. Já para o ensaio utilizando sementes de pepino, os compostos [17] e [23], na concentração de 100 ppm, apresentaram ação contrária, estimulando o crescimento radicular dessa cultura. Esse mesmo comportamento foi observado para os compostos [23] e [24], na concentração de 10 ppm. Dentre as substâncias testadas, a que mostrou maior inibição frente à cultura de sorgo foi o composto [17] com porcentagem de inibição de 70,7% (10 ppm) e 75,8% (100 ppm) e para a cultura de pepino o composto [19] foi o que apresentou maior porcentagem de inibição, 41,9% (10 ppm) e 41,1% (100 ppm).

The thesis entitled “Controlling Stereochemistry at the Quaternary Center Using Bifunctional (Thio)urea Catalysis” is divided into five chapters. Chapter 1: Catalytic Enantioselective Construction of Quaternary Stereocenters through Direct Vinylogous Michael Addition of Deconjugated Butenolides to Nitroolefins The direct use of deconjugated butenolides in asymmetric C–C bond forming reaction is a powerful but challenging task because of the additional problem of regioselectivity along with the issues of diastereo- and enantioselectivity. In this chapter, a direct asymmetric vinylogous Michael addition of deconjugated butenolides to nitroolefins has been demonstrated for the construction of quaternary stereocenter at the γ-position of butenolides. A novel thiourea-based bifunctional organocatalyst, containing two elements of chirality, was synthesized starting from commercially available quinine and (S)-tert-leucine. Remarkably, the sense of stereoinduction in this process is dominated by the tert-leucine segment of the catalyst. Synthetically versatile & highly functionalized γ-butenolides with contiguous quaternary and tertiary stereocenters were synthesized stereoselectively. The reaction was found to be general and a wide range of nitroolefins, with both electron-rich and electron-deficient substituents, underwent smooth reaction under these mild conditions. Similarly, deconjugated butenolides, having various substituents at the γ-position were well tolerated under these reaction conditions and the products were obtained in excellent yields and with uniformly high diastereo- and enantioselectivities. Reference: Manna, M. S.; Kumar, V.; Mukherjee, S. Chem. Commun. 2012, 48, 5193–5195. Chapter 2: Catalytic Asymmetric Direct Vinylogous Michael Addition of Deconjugated Butenolides to Maleimides for the Construction of Quaternary Stereogenic Center In this chapter, a mild and operationally simple protocol for the direct vinylogous Michael addition of deconjugated butenolides to maleimides has been illustrated. Using bifunctional tertiary amino thiourea organocatalyst, derived from a ‘matched’ combination of trans-(1R,2R)-diaminocyclohexane (DACH) and (S)-tert-leucine, the Michael adducts were obtained in excellent yields and with good to high diastereoselectivities and outstanding enantioselectivities. Application of the corresponding diastereomeric catalyst indicated the dominance of the ‘DACH’ unit over the chiral side chain in determining the sense of stereoinduction. The practicality of this protocol is illustrated by substantial low catalyst loading (down to 5 mol%) and one-pot catalyst recycling. Based on the X-ray structure of the catalyst and observed stereochemistry of the Michael adduct, a stereochemical model is proposed which was further supported by additional experiment. Reference: Manna, M. S.; Mukherjee, S. Chem.–Eur. J. 2012, 18, 15277–15282. Chapter 3: Enantioselective Desymmetrization of Cyclopentenedione through Direct Catalytic Vinylogous Michael Addition of Deconjugated Butenolides Five-membered carbocycles containing one or more stereogenic centers on the ring are privileged structural motifs found in many biologically active natural and non-natural compounds. Among various methods for accessing these enantioenriched carbocyclic frameworks, desymmetrization of prochiral or meso-compounds through catalytic enantioselective transformations represents a powerful strategy. The biggest advantage of such asymmetric desymmetrization reactions lies in their ability in controlling stereochemistry remote from the reaction site. This chapter deals with a highly efficient desymmetrization protocol for 2,2-disubstituted cyclopentene-1,3-diones via direct vinylogous nucleophilic addition of deconjugated butenolides with the help of a tertiary amino thiourea bifunctional catalyst. In contrast to the existing desymmetrization protocols, this method represents a unique example where quaternary stereocenter is generated not only within the ring but also outside the cyclopentane ring. Densely functionalized products are obtained in excellent yields and with outstanding diastereo- and enantioselectivities. The robustness screening indicated that the reaction is highly tolerant to a variety of competing electrophiles and nucleophiles. The remarkable influence of the secondary catalyst site on the enantioselectivity points towards an intriguing mechanistic scenario. To the best of our knowledge, this is the first time such an effect is observed in the context of asymmetric catalysis. Reference: (1) Manna, M. S.; Mukherjee, S. Chem. Sci. 2014, 5, 1627–1633. (2) Manna, M. S.; Mukherjee, S. Org. Biomol. Chem. 2015, 13, 18–24. (Perspective) Chapter 4: Enantioselective Desymmetrization of Cyclopentenediones through Organocatalytic C(sp2)–H Alkylation Organic compounds are characterized by the presence of various C–H bonds. Functionalization of a specific C–H bond in a molecule with a selected atom or group are among the most straightforward and desirable synthetic transformations in organic chemistry. In this chapter, a simple protocol for the direct alkylation of olefinic C(sp2)–H bond has been developed, not only enantioselectively using an organocatalyst but more importantly without using any directing group. This alkylative desymmetrization of prochiral 2,2-disubstituted cyclopentene-1,3-diones is catalyzed by a dihydroquinine-based bifunctional urea derivative. Using easily accessible, inexpensive and air-stable nitroalkanes as the alkylating agent, this C(sp2)−H alkylation represents a near-ideal desymmetrization and delivers products containing an all-carbon quaternary stereogenic center in good to excellent yields and with high enantioselectivities. The mild reaction conditions allow for the introduction of various functionalized alkyl groups. The possibility of a second alkylation and its applications has also been demonstrated. This protocol is the first example of the use of nitroalkane as the alkyl source in an enantioselective transformation. It is expected that, these findings would have broader consequences and applications to other alkylative and related transformations. Reference: Manna, M. S.; Mukherjee, S. J. Am. Chem. Soc. 2015, 137, 130–133. (Highlighted in Synform 2015, 67–70) Chapter 5: Enantioselective Desymmetrization of Cyclopentenediones through Organocatalytic Formal C(sp2)–H Vinylation The development of catalytic enantioselective C(sp2)–H vinylation reactions remained relatively underexplored for a long time because of various challenges associated with it. As C(sp2)–H functionalization reactions do not generate any stereocenter at the reaction site, development of enantioselective C(sp2)−H functionalization must rely on desymmetrization of prochiral or meso-substrates. More important issue is the identification of a suitable directing group which can efficiently control the regioselectivity during the activation of C(sp2)−H bond. In this chapter, an efficient formal C(sp2)−H vinylation of prochiral 2,2-disubstituted cyclopentene-1,3-dione is developed without using any directing group. This formal C(sp2)−H vinylation of 2,2-disubstituted cyclopentene-1,3-dione is realized using a two-step operation: catalytic enantioselective Michael addition of deconjugated butenolides followed by a base mediated decarboxylation. The vinylated products, containing a remote all-carbon quaternary stereogenic center, are obtained in good yields and with good to high enantioselectivities. Synthetic utility of this protocol is demonstrated by converting the resulting chiral electron-deficient diene into various important building blocks. Significant erosion in enantioselectivity during the decarboxylation process was explained by a plausible mechanism, which was further supported by control experiments. Reference: Manna, M. S.; Sarkar, R.; Mukherjee, S. manuscript under preparation.