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1
Rajinder, Kaur Maya. "Gold(I) Catalyzed Tandem Cyclization Reactions." Thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for kjemi, 2012. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-19239.
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Through this study it has been observed that in contrast to propargyl esters which give cyclopropyl products, the high reactivity of propargyl acetals allows a new tandem cyclization to take place, resulting in bicyclic products. It has also been found that steric effects may cause propargyl acetals to react by unexpected pathways. NMR studies confirmed a particularly high reactivity of propargyl acetal compared to propargyl ester. These results show how molecular diversity can easily be achieved by varying the substrates in gold(I) catalysis.
2
Lam, Tin Yiu. "Synthesis of indoles via a tandem benzannulation-cyclization strategy." Thesis, Massachusetts Institute of Technology, 2008. http://hdl.handle.net/1721.1/46045.
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Vita.Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2008.
Includes bibliographical references.
Vinylketenes (generated in situ from cyclobutenones or a-diazo ketones) react with ynamides via a pericyclic cascade process to produce highly-substituted aniline derivatives. Cyclization of the benzannulation products can then be achieved via several alternate procedures leading to indoles that are highly substituted on the six-membered ring. The cyclization approaches investigated as the second step in this tandem strategy included aromatic substitution, palladium-catalyzed oxidative amination, and nucleophilic cyclization. This thesis discusses the scope and limitations of this tandem strategy.
by Tin Yiu Lam.
Ph.D.
3
Mamaliga, Galina. "Progress towards the synthesis of tetracyclic heteroaromatic compounds via tandem benzannulation-cyclization strategies." Thesis, Massachusetts Institute of Technology, 2011. http://hdl.handle.net/1721.1/78512.
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Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Chemistry, February 2012.Cataloged from PDF version of thesis.
Includes bibliographical references.
A tandem benzannulation-cyclization strategy was successfully applied to the synthesis of a tetracyclic heteroaromatic compound expected to have interesting electronic properties. Benzannulation of a diazo ketone and a ynamide yielded a highly substituted aniline that was cyclized to indole according to protocols developed in our laboratory previously.
by Galina Mamaliga.
S.B.
4
Willumstad, Thomas P. (Thomas Paul). "Synthesis of highly substituted benzo-fused nitrogen heterocycles via tandem benzannulation/cyclization strategies." Thesis, Massachusetts Institute of Technology, 2013. http://hdl.handle.net/1721.1/84379.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2013.Cataloged from PDF version of thesis.
Includes bibliographical references.
Benzannulations employing ynamides and vinylketenes (generated in situ from [alpha]-diazo ketones) were investigated. Irradiation of the diazo ketones using a batch or continuous-flow reactor leads to the formation of vinylketenes via a photo-Wolff rearrangement. The vinylketenes then react with ynamides via a pericyclic cascade process to produce highly substituted aniline derivatives. Using this vinylketene-based benzannulation, tandem strategies for the synthesis of highly substituted benzo-fused nitrogen heterocycles were investigated. A tandem benzannulation-iodocyclization method for the synthesis of polysubstituted quinolines was established. In addition, a tandem strategy for the synthesis of carbazoles was developed and applied in the total synthesis of the carbazole alkaloid carazostatin as well as formal syntheses of the alkaloids carbazoquinocin C and antiostatin A₄.
by Thomas P. Willumstad.
Ph.D.
5
Shah, Parin Ajay. "Synthesis of terpenoids using a tandem cationic cascade cyclization-electrophilic aromatic substitution reaction." Diss., University of Iowa, 2018. https://ir.uiowa.edu/etd/6639.
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The terpene and terpenoid family of compounds is considered to be the largest group of natural products. These compounds not only display great diversity in their structural features but are also known to have a multitude of biological activities including but not limited to anti-bacterial, anti-cancer, anti-inflammatory, and anti-HIV properties. Remarkably, all the terpenoids formed in nature come from two molecules viz. isopentenyl pyrophosphate and its isomer, dimethylallyl pyrophosphate both consisting of just five carbons but assembled in many ways. Nature utilizes highly efficient, enzyme-mediated cascade reactions to transform simple linear molecules to more complex cyclic scaffolds.
Cascade or domino reactions are organic chemistry’s most powerful tools that, if executed correctly, mimic the extreme complexity of reactions occurring in nature. Our group has successfully utilized cationic cascade cyclization reactions, to prepare a large library of natural products along with their analogues. It was during the synthesis of one such natural product that it was discovered that a methoxymethyl (MOM) “protecting group” had been transferred within the same molecule. The optimization of this process not only allowed the synthesis of the desired tricyclic framework but also resulted in the liberated MOM group doing an EAS reaction which gave a new C-C bond. This transferred MOM group was further elaborated to different functional groups.
Use of the tandem reaction sequence in an attempt to prepare radulanin E has been described. Total syntheses of two chalcone-based analogous meroterpenoids have been successfully completed using the aforementioned sequence. An advanced intermediate for an entire new class of acridine-based schweinfurthins has been elaborated. The results will be discussed in detail.
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Krismanich, Anthony. "Studies Related to Tandem Reactivity of 1-Carbomethoxy-5-dicyanomethyl-1,3-cyclohexadiene." Thesis, University of Waterloo, 2006. http://hdl.handle.net/10012/2954.
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A set of studies centered around the reactions of the active methine compound 1-carbomethoxy-5-dicyanomethyl-1,3-cyclohexadiene (the "ring-opened adduct"), obtained by base-induced ring-opening of the Diels-Alder adduct of 5,5-dicyanocyclopentadiene and methyl acrylate, has been carried out. A plan was devised for the anionic (at the dicyanomethyl carbon) ring-opened adduct whereby its reaction with electrophiles, for example Michael reactions with double-bond acceptors, would generate reactive intermediates that would undergo cyclization by tandem conjugate addition to the a,ß,?,d-unsaturated ring p-system to generate bicyclic compounds. In practice, reaction with di-tert-butyl methylidenemalonate, methyl vinyl ketone, and cyclopentenone generated intermediates that exhibited greater tandem reactivity than was anticipated: the bicyclic enolates were found to cyclize further by Thorpe-Ziegler-like reaction with the proximal nitrile to generate, after facile acid hydrolysis, substituted known tricyclic skeleta termed homobrendanes, specifically, tricyclo[5. 2. 1. 04,8]decenes. An attempt was made to generalize the reaction to other substrates, among them singly-activated Michael acceptors and 1,2-heteroatom electrophiles, but the generalization of the homobrendane forming reaction did not meet with success. Attempted functional group manipulations to probe the conversion of the homobrendane derived from di-tert-butyl methylidenemalonate to the homobrendane natural product 2-isocyanoallopupukeanane revealed the unreactivity of the skeletal double-bond toward electrophiles and the high reactivity of the ring ketone toward nucleophiles, among them mCPBA which brought about Baeyer-Villiger reaction, and chloride and hydroxide, which brought about addition/elimination reactions to cleave the last-formed homobrendane ring. The ring-opened adduct was also envisaged as a potential substrate in intramolecular Heck reactions. To this end, Heck substrates were generated from the ring-opened adduct anion and iodo- and bromo-benzyl halides. A key observation at this stage pertained to the unexpected acidity of the ring-opened adduct C5 proton, which could be deprotonated by DBU to bring about allylic isomerization, a finding that would provide a key insight to the pattern of reactivity later evidenced with alkyl propiolates. Optimization of the Heck substrate-generating reaction was followed by Heck reactions under Jeffery's conditions, which generated angular tricycles as intended, accompanied by aromatic compounds generated by base-induced HCN elimination/rearrangement and dehydrogenation. The Jeffery's conditions were optimized to limit the production of aromatics.
The possibility of ring-opened adduct-derived vinyl silane intermediates undergoing cationic cyclizations led to a minor study based upon the bromination of allylsilanes and the elimination of TMSBr from 1,2-dibromo-3-trimethylsilyl compounds, accessible compounds unaccounted for in the review literature. It was determined that the combination of HBr and Br2 (perhaps as HBr3) was required to eliminate TMSBr, in contravention of the textbook account of electrophilic substitutions being the inherent reactions of allylsilanes and Br2.
Unexpected tandem reactivity was observed in the reactions of the anionic ring-opened adduct and alkyl propiolates under catalytic DBU conditions. Rather than tandem cyclization or simple adduct formation, the allenolate intermediates were determined to undergo extremely facile formal allenolate Cope rearrangements involving the ?,d-double-bond of the parent ring. Excess base intercepted the allenolate by deprotonating ring C5 and effecting 1,2-vinyl transfer by 3-exo-trig addition-elimination. The chemistry of the highly delocalized side-chain carbanion in the Cope product was studied in detail.
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Yip, Kai-tai, and 葉啟泰. "Oxidative palladium catalysis under aerobic condition: studies on monocyclization of {221}-Keto amides and tandem cyclization ofAlkenyl anilines." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B34860605.
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Xing, Dong, and 邢栋. "Transition metal-catalyzed C-N bond formation via addition of nitrogennucleophiles towards alkenes and related tandem cyclization reactions." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B46589156.
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Sandoval, Sergio. "Tandem conjugate addition - cyclization reactors of L-methyl prolinate with [alpha,beta]-unsaturated ketones catalyzed by L-proline /." View online ; access limited to URI, 2008. http://0-digitalcommons.uri.edu.helin.uri.edu/dissertations/AAI3314459.
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Yip, Kai-tai. "Oxidative palladium catalysis under aerobic condition : studies on monocyclization of [beta]-Keto amides and tandem cyclization of Alkenyl anilines /." Click to view the E-thesis via HKUTO, 2005. http://sunzi.lib.hku.hk/hkuto/record/B34860605.
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Patil, Dadasaheb V. "Intramolecular cyclization strategies for synthesizing medium-ring polycycles and the total synthesis of natural products." Diss., Georgia Institute of Technology, 2012. http://hdl.handle.net/1853/50118.
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Carbo- and heterocyclic compounds are of great interest to chemists. Intramolecular cyclization strategies of donor-acceptor (D-A) cyclopropanes and alkylidene malonate monoamides have excellent potential for synthesis as they offer easy access to structurally-diverse compounds. The work described in this thesis accesses the scope of the In(OTf)3-catalyzed cyclization reaction of cyclopropanes and alkylidene malonate monoamides. In(OTf)3-catalyzed reactions of alkenyl and heteroaryl cyclopropyl ketones were examined in the synthesis of functionalized cyclohexenone-based derivatives (Chapter 2). Subsequent efforts to utilize a tandem cyclopropane ring-opening/Friedel-Crafts alkylation sequence of methyl 1-(1H-indolecarbonyl)-1-cyclopropanecarboxylates to prepare functionalized hydropyrido[1,2-a]indole-6(7H)-ones is discussed in Chapter 3. The extension of this tandem protocol towards the total synthesis of (±)-deethyleburnamonine is the subject of Chapter 6. Intramolecular Friedel-Crafts alkylation of N-indolyl alkylidene malonate monoamides was also examined. An In(OTf)3-catalyzed cyclization of substituted methyl 2-(1H-indole-1-carbonyl) acrylates afforded a series of 1H-pyrrolo[1,2-a]indole-3(2H)-ones (Chapter 4), whereas substrates with the indole 2-position blocked provided access to substituted 4H-pyrrolo[3,2,1-ij]quinolin-4-ones (Chapter 5).
12
Sandelier, Matthew James. "Tandem reduction/cyclization of o-nitrophenyl propargyl alcohols--a novel synthesis of 2- & 2,4-disubstituted quinolines and application to the synthesis of streptonigrin." College Park, Md.: University of Maryland, 2008. http://hdl.handle.net/1903/8471.
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Thesis (Ph. D.) -- University of Maryland, College Park, 2008.Thesis research directed by: Dept. of Chemistry. Title from t.p. of PDF. Includes bibliographical references. Published by UMI Dissertation Services, Ann Arbor, Mich. Also available in paper.
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Loertscher, Brad M. "Studies Toward the Synthesis of Lyconadin A and Cranomycin." BYU ScholarsArchive, 2013. https://scholarsarchive.byu.edu/etd/4243.
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Lyconadin A is a pentacyclic Lycopodium alkaloid isolated from the club moss Lycopodium companatum with anticancer activity. Our approach sought to incorporate a 7-exo–6-exo acyl radical cyclization cascade to access the bicyclo[5.4.0]undecane framework of lyconadin A. Our studies created methodology for the synthesis of 5-alkyl and 3,5-dialkyl-6-carbomethoxy-2-pyridones and sterically demanding epoxide substrates. These epoxide substrates underwent an unanticipated Payne rearrangement.Cranomycin is a potent antibiotic with antiprotozoal activity. Structurally it is a cyclopentane ring system with substitution at each carbon in the ring. Another interesting structural aspect is the existence of three contiguous quaternary stereocenters including two tertiary alcohols and a tert-alkylamine. Our strategy led to the development of a highly diastereoselective synthesis of vicinal tertiary diol systems. We have successfully synthesized the cyclopentenone system shown above, from which we hope to assemble cranomycin.
14
Mariaule, Gaëlle. "Accès original aux hétérocycles par la catalyse organométallique : développement de nouveaux inhibiteurs de kinases." Thesis, Paris 5, 2014. http://www.theses.fr/2014PA05P612/document.
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Cette thèse est composée de deux parties distinctes ayant comme thématique commune, la synthèse d’hétérocycles via la catalyse organométallique.Nous nous sommes intéressés, dans un premier temps, à une voie de synthèse permettant un accès rapide au squelette tétrahydrocyclopenta[c]acridine. Ces composés polyfonctionnalisés sont obtenus très efficacement en seulement trois étapes dans des conditions particulièrement douces. L’étape clé de cette synthèse est une réaction de Pauson-Khand intramoléculaire catalysée au cobalt. Certains composés issus de la famille des tétrahydrocyclopenta[c]acridines présentent une activité d’inhibition sélective envers les kinases dépendantes des cyclines (CDKs), et plus particulièrement la CDK2. Un composé chef de file est identifié, puis grâce aux données de co-Cristallisation avec CDK2 et de modélisation moléculaire, suivi de l’étude des relations structure-Activité, la conception rationnelle d’une deuxième génération de molécules est rendue possible. Le composé le plus avancé présente une CI50 de 300 nM envers CDK2/cyclin A et un excellent profil de stabilité métabolique.Dans un deuxième temps, nous avons étudié et développé une réaction tandem d’addition/cyclisation catalysée par l’argent, avec des nucléophiles carbonés sur des substrats ortho-Alcynylbenzaldéhydes. La stratégie de synthèse conduit à des dérivés 1H-Isochromènes par création de deux nouvelles liaisons (C-C et C-O). Une étude approfondie de la réaction tandem nous a permis d’obtenir une large gamme de dérivés d’isochromènes en mettant en évidence l’influence de différents substituants, portés par le groupement alcyne ou le substrat, ainsi que l’utilisation de différents nucléophiles carbonés (alcynes, aromatiques, hétéroaromatiques). Les limitations de la réaction tandem ont également pu être identifiéesMy thesis proJect is organized around two main topics having in common organometallic chemistry and the synthesis of heterocycles.Firstly, we were interested in a methodology for the synthesis of tetrahydrocyclopenta[c]acridines. These compounds are synthesized in three steps from various quinolines. The key step is a cobalt-Catalyzed intramolecular Pauson-Khand reaction. Some compounds of this family exhibit selective Cyclin Dependent Kinases (CDKs) inhibition, particulary against CDK2, in the submicromolar range. A hit compound has been identified, and then using data from co-Crystallization with CDK2 and molecular modeling, followed by the study of structure-Activity relationships, the rational design of a second generation of molecules has been investigated. The most advanced compound has an IC50 of 300 nM against CDK2/cyclin A with an excellent metabolic profile. In the second axis of research, we have studied and developed a new silver-Catalyzed tandem addition/cyclization reaction with carbon nucleophiles. The systems studied are (hetero)aromatics compounds having an aldehyde group and in ortho-Position an alkynyl group. The synthetic strategy leads to 1H-Isochromene derivatives by creating two new bonds. A thorough study of the tandem reaction allowed us to obtain a wide range of isochromene derivatives, highlighting the influence of different substituents carried by the alkyne group or on the (hetero)aromatic substrates; and also to investigate the use of different carbon nucleophiles (alkynes, aromatics and heteroaromatics). The limitations of the tandem reaction have also been identified
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Laio, Fang-Yu, and 廖芳瑜. "The Study of Free Radical Tandem Cyclization Reactions of Acylsilanes." Thesis, 2004. http://ndltd.ncl.edu.tw/handle/12163839257229825597.
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Chang, Yi-Hsuan, and 張怡萱. "The Study of Tandem Radical Cyclization of Vinyl Radical with Acylsilanes." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/63313572445229254747.
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Hsu, Jen-Yu, and 徐仁佑. "The Study of Tandem Radical Cyclization of Vinyl Radical with Acylsilanes." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/01886288224108411631.
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碩士國立臺灣大學
化學研究所
96
According to previous research in our laboratory, cyclizations of acylsilanes with vinyl radicals have been studied. This process involved intramolecular free radical cyclizations of a vinyl radical to the carbonyl group of acylsilane to give a β-silyl alkoxy radical. This radical then undergoes a radical Brook rearrangement to afford an α-silyloxy radical. Due to the presence of the vinyl group, this α-silyloxy radical is also an allylic radical. Finally, hydrogen abstraction occurs at the γ-position of this allylic system to give an enol silyl ether. Generally, 1,5-exo-cyclizations are more efficient than 1,6-exo-cyclizations. In this research we exploited this system further in the context of tandem radical cyclizations. We have constructed two systems in which the intermediate allylic radicals are trapped intramolecularly at the γ-position by radicalphilic groups. Specifically, we have synthesized acylsilanes with vinyl iodide tethered to an alkynyl functional group. The scope and limitations of this type of tandem cyclizations were studied.
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Ordner, Ciara Mary. "Synthesis of Enantioenriched Heterocycles by Tandem Sakurai Allylation/Intramolecular Cyclization Processes." Thesis, 2018. https://thesis.library.caltech.edu/11238/1/CMO%20Senior%20Thesis%20-%20FINAL.pdf.
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Organosilanes are advantageous in organic synthesis due to their ability to act as both stable products and reactive intermediates. A stereospecific one-pot cascade reaction that converts chiral allylic silanes into chiral heterocycles was developed using Lewis acid catalysis. We report on the development of this cascade reaction, optimization to benchtop- scale chemistry, and preliminary investigation into the synthetic scope. In our studies, we were successful in varying the cyclization ring size, investigating cyclization preference in the presence of multiple electrophilic leaving groups, and altering the functional groups present on the aldehyde starting material. Ultimately, we envision this method will be useful in the synthesis of a variety of enantioenriched heterocycles found in bioactive natural products, many of which have may find use as potential drug targets.
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Hsu, Jen-Yu. "The Study of Tandem Radical Cyclization of Vinyl Radical with Acylsilanes." 2008. http://www.cetd.com.tw/ec/thesisdetail.aspx?etdun=U0001-2207200813360000.
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Dhoro, Francis. "Part I, Interrupted Nazarov cyclization on silica gel: Part II, Tandem alkylation-cyclization process via an O,C dianion." Thesis, 2006. http://hdl.handle.net/10125/20467.
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Kumar, Anil. "C-H Bond Functionalization and Tandem Cyclization with Alkynoates and Maleimides Using Directing Group Strategy." Thesis, 2022. https://etd.iisc.ac.in/handle/2005/5797.
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The thesis presents manganese‒ and rhodium‒catalyzed C‒H bond activation and tandem cyclization reactions. These reactions lead to the construction of carbon‒carbon bonds using directing group strategy. The thesis is divided into two sections. Section‒A is presented in three chapters, which describes the C‒H bond functionalization of N‒pyrimidylindoles, imines, and benzoic/acrylic acids with 4‒hydroxy‒2‒alkynoate as a coupling partner. This alkynoate is a highly functionalized unsymmetrical internal alkyne that can undergo regioselective alkenylation/annulation and lactonization after C‒H bond activation. The developed reactions are highly efficient, step economical, and require a single set of reaction conditions. Section‒B is presented in two chapters employing maleimides as a coupling partner with 2‒alkenylphenols and sulfoximines for [5+1] and diastereoselective [4+1] spirocyclization reactions, respectively, using Rh(III)‒catalytic system.
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Chen, Pei-Min, and 陳佩敏. "Tandem Cyclization of Enynes Containing an Ether Linkage and a Cyclopropyl Group via Ruthenium Metal Complex." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/72759808192027849035.
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碩士國立臺灣大學
化學研究所
102
We study chemical reactions of [Ru]Cl ([Ru] = Cp(PPh3)2Ru) with three 1,8-enyne compounds containing cyclopropyl group (1, 7 and 11) in which the triple bond is associated with propargylic alcohol and the ole&;#64257;nic group has various substituted methyl groups. The reaction of [Ru]Cl and 1, containing one methyl group added to the internal carbon of the allyl group, affords the vinylidene complex 2 with a newly formed seven-membered ring. Furthermore, tandem cyclization reaction of 1 in MeOH/CHCl3 catalyzed by [Ru]NCCH3+PF6－ at 60 oC leads to the product 6 with spiro-cyclopropyl ring, formed possibly via sequential allenylidene vinylidene cyclization followed by a nucleophilic addition of alkoxide. In CHCl3, the catalytic reaction by [Ru]NCCH3+ PF6－ gives the isolable organic cyclization intermediate enyne 5. Treatment of the propargylic alcohol 7 containing two terminal methyl groups at the O-allylic group, with [Ru]Cl yields a mixture of two diastereomers of the vinylidene complex 8 containing a newly formed six-membered ring in a ratio of ca. 10:1. Among diastereoisomers only the anti-isomer is isolated for complex 8. The cyclization reaction is proposed to proceed via the formation of a six-membered ring boat-like transition state with bulkiest group in the pseudo-equatorial position to reduce the 1,3-diaxial interactions. The catalytic reaction by [Ru]NCCH3+PF6－ in CHCl3 at 60 oC affords anti-9 and syn-9 in a ratio of 3:1. The thermal energy increases amount of product syn-9. The subsequent cyclization carried out in a cosolvent of ROH/CHCl3 at 60 oC affords bicyclic product 10. In the reaction of [Ru]Cl with 11, containing no methyl group, no C&;#8722;C bond formation is observed. The reaction of 11with [Ru]Cl in the presence of NH4PF6 in CH2Cl2 affords a mixture of the allenylidene complex 12 and phosphonium acetylide 13. Interestingly, thermal treatment of 11 leads to a ring expansion of the cyclopropyl group, giving the vinylidene complex 16 with a five-membered ring. This ring expansion proceeds by C-C bond formation between Cβ of the cumulative double bond and a methylene group of the cyclopropyl ring. Reaction of 1,3-diol 18 with [Ru]Cl in CH2Cl2 yields a mixture of the alkoxy carbene 17 and 19 in a ratio of 1:2. The spontaneous dehydration of 19 to 17 by elevating temperature is failed. Fortunately, complex 17 could be the only product when the reaction is carried out in MeOH. Overall, tandem cyclizations of two 1,8-enynes with methyl-substituents have been achieved. Ring-expansion of a cyclopropyl group in a 1,8-enyne with no methyl-substituent is also accomplished.
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Nagaraju, CH. "Construction of Complex Polycyclic Systems using Gold Catalyzed Intramolecular Diyne/Enyne/ Hydroalkoxylation Reactions." Thesis, 2015. http://etd.iisc.ac.in/handle/2005/3840.
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First section of chapter 1 deals with gold catalyzed synthesis of ring fused furo[3,2,b]pyrans and furo[3,2,b]furans. Furo[3,2,b]pyrans and furo[3,2,b]furans are ubiquitous structural segments found in a number of natural products including polyether containing marine toxins. Synthesis of furo[3,2,b]pyrans 2a was accomplished from the bis-propargyl ethers 1a, while the synthesis of furo[3,2,b]furans 2b was accomplished from the prenyl propargyl ethers 1b.
Scheme 1: Synthesis of furo[3,2,b]pyrans and furo[3,2,b]furans
Second section of chapter 1 describes an unusual ring-contraction rearrangement route to functionalized 2,8-oxymethano-bridged di and triquinane. During the course of investigations concerning the total synthesis of 6-oxabicyclo[3.2.1]octane framework containing natural products, an unusual ring-contraction rearrangement sequence was observed in the reaction of 5-substituted 1-methyl-4-isopropenyl-6-oxabicyclo[3.2.1]octan-8-ones 4 to the 2,8-oxymethano-bridged diquinanes 5. The reaction was further demonstrated in the synthesis of triquinane 7 framework.
Scheme 2: Synthesis of functionalized di and triquinane
In third section of chapter 1 gold catalyzed synthesis of isochromanones and isoquinolones from suitable substituted allyl propargyl ethers was discussed. Synthesis of isochromanones and isoquinolones comprising a quaternary center with high diastereoselectivity was realized via AuCl3 catalyzed tandem intramolecular exo-dig heterocyclization/enol isomerization/Claisen rearrangement sequence in excellent yields. The reaction was general and amenable for the synthesis of structurally diverse analogues.
Scheme 3: Synthesis of isochromanones and isoquinolones
Forth section of chapter 1 consists of gold catalyzed intramolecular hydroalkoxylation assisted ring opening of furans to the corresponding saturated -keto esters. During the course investigations concerning gold catalyzed intramolecular enyne cyclization reactions, an interesting ring opening of furans in furyl propargyl alcohols to the corresponding tetrahydrofuran appended saturated -keto esters exclusively driven by intramolecular hydroalkoxylation of the alkyne was observed. Reaction of furyl propargyl alcohols without free hydroxyl group, under similar conditions afforded the conjugated enynes involving dehydration/ketalization.
Scheme 4: Synthesis of saturated -keto esters and enynes
Chapter 2 delineates the enantiospecific synthesis of bicyclo[4.2.2]decadienes 15 via gold catalyzed tandem enyne cyclization, semipinacol rearrangement reaction. Bicyclodecadienes are key structural units of natural products nakafuran-8 and pallescensin B.
Scheme 5: Synthesis of bicyclo[4.2.2]decadienes
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Nagaraju, CH. "Construction of Complex Polycyclic Systems using Gold Catalyzed Intramolecular Diyne/Enyne/ Hydroalkoxylation Reactions." Thesis, 2015. http://etd.iisc.ernet.in/2005/3840.
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First section of chapter 1 deals with gold catalyzed synthesis of ring fused furo[3,2,b]pyrans and furo[3,2,b]furans. Furo[3,2,b]pyrans and furo[3,2,b]furans are ubiquitous structural segments found in a number of natural products including polyether containing marine toxins. Synthesis of furo[3,2,b]pyrans 2a was accomplished from the bis-propargyl ethers 1a, while the synthesis of furo[3,2,b]furans 2b was accomplished from the prenyl propargyl ethers 1b.
Scheme 1: Synthesis of furo[3,2,b]pyrans and furo[3,2,b]furans
Second section of chapter 1 describes an unusual ring-contraction rearrangement route to functionalized 2,8-oxymethano-bridged di and triquinane. During the course of investigations concerning the total synthesis of 6-oxabicyclo[3.2.1]octane framework containing natural products, an unusual ring-contraction rearrangement sequence was observed in the reaction of 5-substituted 1-methyl-4-isopropenyl-6-oxabicyclo[3.2.1]octan-8-ones 4 to the 2,8-oxymethano-bridged diquinanes 5. The reaction was further demonstrated in the synthesis of triquinane 7 framework.
Scheme 2: Synthesis of functionalized di and triquinane
In third section of chapter 1 gold catalyzed synthesis of isochromanones and isoquinolones from suitable substituted allyl propargyl ethers was discussed. Synthesis of isochromanones and isoquinolones comprising a quaternary center with high diastereoselectivity was realized via AuCl3 catalyzed tandem intramolecular exo-dig heterocyclization/enol isomerization/Claisen rearrangement sequence in excellent yields. The reaction was general and amenable for the synthesis of structurally diverse analogues.
Scheme 3: Synthesis of isochromanones and isoquinolones
Forth section of chapter 1 consists of gold catalyzed intramolecular hydroalkoxylation assisted ring opening of furans to the corresponding saturated -keto esters. During the course investigations concerning gold catalyzed intramolecular enyne cyclization reactions, an interesting ring opening of furans in furyl propargyl alcohols to the corresponding tetrahydrofuran appended saturated -keto esters exclusively driven by intramolecular hydroalkoxylation of the alkyne was observed. Reaction of furyl propargyl alcohols without free hydroxyl group, under similar conditions afforded the conjugated enynes involving dehydration/ketalization.
Scheme 4: Synthesis of saturated -keto esters and enynes
Chapter 2 delineates the enantiospecific synthesis of bicyclo[4.2.2]decadienes 15 via gold catalyzed tandem enyne cyclization, semipinacol rearrangement reaction. Bicyclodecadienes are key structural units of natural products nakafuran-8 and pallescensin B.
Scheme 5: Synthesis of bicyclo[4.2.2]decadienes
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Moon, David Thompson. "The Conjugate Addition of Novel Nucleophiles and Catalytic Intramolecular Tandem [1,5]-Hydride Shift / Cyclization and Friedel-Crafts Acylation with Alkylidene Meldrum’s Acid Derivatives." Thesis, 2008. http://hdl.handle.net/10012/4061.
Full textAbstract:
Investigations into the conjugate addition of phenols and sp3-hybridized carbons bound to tin, boron and silicon by transition metal catalysts through novel transmetallation pathways were undertaken with limited success. An intramolecular Lewis acid-catalyzed tandem [1,5]-hydride shift / cyclization and Friedel-Crafts acylation reaction with alkylidene Meldrum’s acid derivatives has been accomplished.
The use of metal phenolates as nucleophiles for transition metal catalyzed conjugate addition onto alkylidene Meldrum’s acids is explored, and the ambident nucleophilic property of metal phenolates allow for the C-alkylation and O-acylation with alkylidene Meldrum’s acids, producing substituted 3,4-dihydrocoumarins in modest yields.
The transmetallation of rhodium complexes with alkyl boron, tin and silicon derivatives and subsequent conjugate addition onto alkylidene Meldrum’s acid derivatives is investigated without success.
An intramolecular Lewis acid-catalyzed [1,5]-hydride shift / cyclization reaction promoted by electron-rich aromatic rings is employed with alkylidene Meldrum’s acid derivatives to furnish spiro Meldrum’s acids in excellent yields. These can subsequently be used as electrophiles in the Friedel-Crafts acylation reaction, and a tandem, one-pot variation of this reaction has been accomplished in moderate to good yields. Preliminary investigations into the scope and limitations of this transformation are outlined.
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"Part I, total synthesis of (±)-pallambins C and D: and, Part II, gold-catalyzed tandem cyclization towards substituted bicyclo[3.2.1]octenone derivatives : lead to total synthesis of dhilirolides A-D." 2013. http://library.cuhk.edu.hk/record=b5549785.
Full textAbstract:
半日花烷型二萜天然產物 pallambins A-D 是從中國苔植物Pallavicinia ambigua 中分獲取的，這二萜中的許多化合物都呈現出有趣的生物活性。從分子結構觀點看，pallambins C 和D 由獨特的梯型[6-5-5-5]四環骨架構成，該分子骨架中包含7 個毗的體中心及三烯部分。並且，二環[3.2.1]辛烷酮片段的橋接部分分別由個橋頭甲基以及橋中的乙烯基密集取代。該分子的骨架新穎性及潛在的生物活性激發我們去進相關的全合成探。在此，我們將報導pallambins C 和D 的首次全合成。本文第一章首先概述pallavicinin 系的天然源，結構特點以及生物學效用。此外，重點介紹pallambins C 和D 的分，結構鑒定以及反合成分析。
第二章討消旋體pallambins C 和D 的全合成細節。該合成以消旋Wieland-Miescher ketone (WMK)為起始原，經38 步線性步驟得到最終產物。該合成線突出以下個重要的化學轉化：a) 一個由Grob 碎及分子內aldol成環反應組成的多米式程，構建目標分子內關鍵的二環[3.2.1]辛烷酮單元；b) 一個由脲/鈀體系催化的烷氧羰基化增環反應，構建稠環型四氫呋喃/γ 內酯雙環框架。
第三章總結本文的相關研究工作。
第四章給出相關工作的詳細實驗據。
Naturally occurring pallambins A-D isolated from the Chinese liverwort Pallavicinia ambigua are classified as modified labdane-type diterpenoids, many of which exhibit interesting biological activities. From a structural perspective, pallambins C and D are consisting of trienes and an unprecedented ladder-shaped [6-5-5-5] tetracyclic skeleton bearing seven contiguous stereogenic centers. Furthermore, the bridge of the bicyclo[3.2.1]octane segment is densely substituted with two methyl groups on the bridge-heads and a vinyl group on the carbon bridge. The skeletal novelty and potential bioactivities of pallambins C and D inspired us to explore their total synthesis. In this thesis, the first total synthesis of (±)-pallambins C and D is described.
In Chapter 1, a general introduction to the natural occurrence, structural features and biological potency of pallavicinin family is presented briefly. In addition, the background of pallambins C and D including isolation, structural elucidation and retrosynthetic analysis is emphasized.
In Chapter 2, detailed synthesis of (±)-pallambins C and D involving a linear 38 steps starting from the known (±)-Wieland-Miescher ketone is discussed. The synthetic approach features the following two key conversions: a) a domino process including Grob fragmentation and intramolecular aldol cyclization to build up the bicyclo[3.2.1]octanone embedded in the target molecules; b) a thiourea/palladium-catalyzed alkoxycarbonylative annulation to assemble the fused tetrahydrofuran/γ-lactone bicyclic framework.
Chaper 3 provides a conclusion of this research work.
Chapter 4 is concerned with the experimental details.
[With images.]
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Xu, Xuesong.
Thesis (Ph.D.)--Chinese University of Hong Kong, 2013.
Includes bibliographical references.
Abstracts also in Chinese.
ACKNOWLEDGEMENTS --- p.I
CONTENTS --- p.II
ABBREVIATIONS --- p.V
PART I:
ABSTRACT --- p.1
Chapter CHAPTER 1. --- INTRODUCTION
Chapter 1.1 --- General background --- p.4
Chapter 1.1.1 --- General introduction to liverworts --- p.4
Chapter 1.1.2 --- General introduction to terpenoids in liverworts --- p.5
Chapter 1.2 --- Introduction to pallavicinin family --- p.9
Chapter 1.2.1 --- Isolation and structural elucidation of pallavicinin compounds --- p.9
Chapter 1.2.2 --- Synthetic advances on pallavicinin family --- p.13
Chapter 1.3 --- Introduction to the present research --- p.16
Chapter 1.3.1 --- Structural elucidation and features of pallambins C and D --- p.16
Chapter 1.3.2 --- Biogenetic hypothesis and retrosynthetic analysis of pallambins C and D --- p..20
Chapter 1.4 --- Aim of the present work --- p.22
Chapter CHAPTER 2. --- RESULTS AND DISCUSSION --- p.24
Chapter 2.1 --- Previous synthetic effort on pallambin D (2) --- p.24
Chapter 2.2 --- Successful synthetic approach to 1 and 2 --- p.25
Chapter 2.2.1 --- Synthesis of compound 24 --- p.25
Chapter 2.2.2 --- Synthesis of compound 14 --- p.30
Chapter 2.2.3 --- Synthesis of compound 13 --- p.37
Chapter 2.2.4 --- Synthesis of compound 12 --- p.43
Chapter 2.2.5 --- Synthesis of 1 and 2 --- p.53
Chapter CHAPTER 3. --- CONCLUSION --- p.60
Chapter CHAPTER 4. --- EXPERIMENTAL SECTION --- p.62
REFERENCES --- p.104
PART II:
ABSTRACT --- p.110
Chapter CHAPTER 1. --- INTRODUCTION --- p.113
Chapter 1.1 --- Introduction to bicyclo[3.2.1]octane skeleton --- p.113
Chapter 1.1.1 --- Structural features of bicyclo[3.2.1]octane --- p.113
Chapter 1.1.2 --- Bicyclo[3.2.1]octane-containing bioactive natural products --- p.114
Chapter 1.1.3 --- Methodologies for synthesis of bicyclo[3.2.1]octane derivatives --- p.116
Chapter 1.1.4 --- Gold-catalyzed construction of bicyclo[3.2.1]octane unit --- p.117
Chapter 1.2 --- Background of the present research --- p.119
Chapter 1.2.1 --- Introduction to dhilirolides A-D --- p.119
Chapter 1.2.2 --- Retrosynthetic analysis of dhilirolide A (1) --- p.121
Chapter 1.3 --- Aim of the present work --- p.122
Chapter CHAPTER 2. --- RESULTS AND DISCUSSION --- p.124
Chapter 2.1 --- Synthesis of the key acetal allene precursor 6 --- p.124
Chapter 2.1.1 --- Preparation of the starting dimethoxyl ketone 7 --- p.124
Chapter 2.1.2 --- Preparation of alkynyl furan 11 --- p.126
Chapter 2.1.3 --- Preparation of acetal allene 6 --- p.128
Chapter 2.2 --- Synthesis of bicyclo[3.2.1]octenone derivative 5 --- p.134
Chapter 2.3 --- Synthesis of mono-tosylate 26 --- p.138
Chapter CHAPTER 3. --- CONCLUSION --- p.141
Chapter CHAPTER 4. --- EXPERIMENTAL SECTION --- p.143
REFERENCES --- p.162
APPENDIX --- p.167
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Açıkalın, Serdar [Verfasser]. "Enantioselective synthesis of cyclic β-amino [beta amino] alcohols via tandem hydroalumination cyclization reduction of ethoxycarbonyl vinyl sulfoximines and application to the synthesis of potential aggrecanase inhibitors / vorgelegt von Serdar Açıkalın." 2009. http://d-nb.info/999784145/34.
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"Synthesis of nordihydroguaiaretic acid (NDGA) analogues and their oxidative metabolism." Thesis, 2015. http://hdl.handle.net/10388/ETD-2015-06-1915.
Full textAbstract:
Nordihydroguaiaretic acid (NDGA), is a naturally-occurring lignan isolated from the creosote bush (Larrea tridentata). The aqueous extract of this shrub, commonly referred to as Chaparral tea, was listed in the American pharmacopeia as an ethnobotanical used to treat tuberculosis, arthritis and cancer. Other documented traditional applications of creosote bush extract include treatment for infertility, rheumatism, arthritis, diabetes, gallbladder and kidney stones, pain and inflammation among many others. In spite of the numerous pharmacological properties, NDGA use has been associated with toxicities including hepatotoxicity in humans. Previous studies in our group showed that oxidative cyclization of NDGA (a di-catechol) at physiological pH forms a dibenzocyclooctadiene that may have therapeutic benefits whilst oxidation to ortho-quinone likely mediates toxicological properties.
In order to investigate the structural features responsible for pharmacological and toxicological properties, a series of NDGA analogues were designed, synthesized and characterized for the purpose of studying their oxidative metabolism. Literature procedures were modified to successfully prepare seven lignan analogues via multi-step synthesis. In our effort to understand the mechanisms of NDGA intramolecular cyclization, the prepared analogues were incubated under previously established conditions where NDGA autoxidized to yield the dibenzocyclooctadiene derivative. We also evaluated the stability of the analogues under the conditions of this study. Furthermore, we evaluated bioactivation potential of the prepared analogues with a goal of eliminating reactive metabolite liability through rational structural modification. We incubated NDGA and its analogues in rat liver microsomes (RLM) in the presence of glutathione as a nucleophilic trapping agent. Standards for comparison were generated by performing glutathione trapping experiments with chemical and enzyme oxidation systems. The potential of the dibenzocyclooctadiene lignan 2 derived from NDGA under physiological conditions to contribute to toxicological properties via reactive metabolite formation was also evaluated. Glutathione conjugates were detected by electrospray ionization-mass spectrometry (ESI-MS) scanning for neutral loss (NL) 129 Da or 307 Da in positive ion mode or precursor ion (PI) scanning for 272 Da in negative ion mode and further characterized by liquid chromatography–tandem mass spectrometry (LC–MS/MS) or in a single LC-MS run using multiple reactions monitoring (MRM) as a survey scan to trigger acquisition of enhanced product ion (EPI) data.
We determined that NDGA autoxidation at pH 7.4 is dependent on substituents and/or substitution pattern on the two aromatic rings. In particular, spontaneous intramolecular cyclization to a dibenzocyclooctadiene required a di-catechol lignan, raising the possibility that o-Q formation may not be necessary for cyclization to occur. Cyclization was significantly inhibited in the presence of excess GSH which supports the involvement of free radicals as opposed to o-Q in the intramolecular cyclization process. The mono-catechol analogues A1 and A4 underwent oxidation to o-Q but no evidence of cyclization was found implying that electrophilic substitution cannot account for NDGA cyclization. The phenol-type analogues were oxidatively more stable in comparison with the catechol-type analogues at pH 7.4. The results demonstrate that electrophilic substitution makes no contribution to the intramolecular cyclization process and that a radical mediated process accurately describes the situation for NDGA.
Oxidative metabolism and bioactivation studies on NDGA and its analogues revealed that reactive metabolites formation is dependent on substitution and/or substitution pattern of the aromatic rings. Cytochrome P450-mediated oxidation of NDGA and its catechol-type analogues yielded electrophilic intermediates which reacted with GSH. The GSH mono-conjugates were identified as ring adducts derived from o-Q although the position at which the GSH binds to the aromatic rings could not be determined. We also found that NL 129 or 307 scanning in positive ionization mode has potential diagnostic utility in distinguishing between aromatic and benzylic GSH conjugates although further studies may be required for validation. We found no evidence of p-QM either directly or via isomerization of o-Q intermediates suggesting that o-Q is the major reactive toxicophore responsible for reactive metabolite mediated toxicities associated with NDGA use. In addition, we demonstrated that the NDGA-derived dibenzycyclooctadiene lignan (cNDGA 2) undergoes P450-mediated oxidation to a reactive metabolite which might have toxicological implications. There was no evidence of P450-mediated oxidation to reactive metabolites for the phenol-type NDGA analogues. It is concluded that structural modification efforts should focus on phenol-type analogues to potentially enhance the safety profile of NDGA.
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Lin, Chi-Feng, and 林其鋒. "The Study of Tandem Free Radical Cyclizations of Acylsilanes Involving Alkyne as Terminator." Thesis, 2002. http://ndltd.ncl.edu.tw/handle/55165756602313426084.
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Chang, Ching-Jung, and 張慶榮. "Tandem Radical Cyclizations initiated by α-Carbonyl Radicals: (1) Total synthesis of (+)-Paniculatine .(2) Synthetic studies for Total Synthesis of Ingenol." Thesis, 1998. http://ndltd.ncl.edu.tw/handle/85392832879732180827.
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