Download or read book New Strategies for the Synthesis of Bioactive Natural and Unnatural Products Via Palladium Catalyzed Asymmetric Allylic Alkylation written by Weiping Tang and published by . This book was released on 2004 with total page 496 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book The Development of Palladium and Copper catalyzed Transformations for the Asymmetric Synthesis of Biologically Active Small Molecules written by James Thomas Masters and published by . This book was released on 2016 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The continued demand for efficient chemo-, regio-, and stereoselective organic transformations motivates the development of new chemical reactions. Transition metal catalysis represents a powerful method for the construction of carbon-carbon, carbon-hydrogen, and carbon-heteroatom bonds in a highly selective fashion. This dissertation describes the development of several new transition metal-catalyzed organic reactions useful in the preparation of various chiral small molecules, including both fundamental organic "building block" compounds and structurally complex natural products and pharmaceutical agents. We report a new strategy for the synthesis of chiral beta-alkynyl esters, ketones, and sulfones via sequential palladium-catalyzed carbon-carbon bond formation and copper-catalyzed carbon-hydrogen bond formation. The process is operationally straightforward, compatible with a broad range of substrates, and delivers the targets in high yields with excellent levels of enantioselectivity. It is compatible with both oxygen and nitrogen functionality, and this enabled the rapid elaboration of the products into a diverse set of chiral heterocycles. The sequential catalysis protocol was employed in a concise, enantioselective synthesis of AMG 837, a potent agonist of G-protein coupled receptor 40. Recognizing both the biological relevance of chiral alkaloids and the synthetic challenges associated with the construction of quaternary, all-carbon stereocenters, we pursued a palladium-catalyzed asymmetric allylic alkylation that effected carbon-carbon bond formation on prochiral oxindole nucleophiles. Although prior research has demonstrated that allylic alkylation reactions of geminal dicarboxylate electrophiles typically yield branched products as the result of ipso-addition, we identify conditions wherein oxindoles react with a dipivaloyl electrophile to afford linear enol pivalate compounds. A mild hydrolysis reaction converts these products into the aldehyde that formally results from asymmetric conjugate addition to acrolein, a challenging transformation with limited literature precedent. These adducts are established precursors to tricyclic alkaloid scaffolds of pharmaceutical interest. Chiral gamma-heteroatom-substituted cycloalkenones are well-established organic "building blocks" that are widely used in the synthesis of complex molecules. The exposure of meso-1,4-allylic dibenzoates to chiral phosphine-ligated palladium salts in the presence of a potassium nitronate nucleophile promotes a unique oxidative desymmetrization reaction. This process yields enantiopure gamma-benzoyloxy cyclopentenones, cyclohexenones, and cycloheptenones. We describe the elaboration of these products into diverse, enantioenriched oxygen- and nitrogen-substituted cycloalkenones via subsequent palladium-catalyzed allylic alkylation reactions involving heteroatom nucleophiles. Separately, we employ enantiopure gamma-benzoyloxy cyclohexenones in short, asymmetric syntheses of enantio- and diastereomerically diverse epoxyquinoid natural products. We further highlight the utility of palladium catalysis in complex molecule synthesis through the development of a unique, intramolecular carbon-carbon bond-forming reaction that generates a strained enyne and through an asymmetric formal synthesis of aliskiren, a renin inhibitor used in the treatment of hypertension.

Download or read book New Frontiers in Palladium catalyzed Asymmetric Allylic Alkylations written by David Andrew Thaisrivongs and published by . This book was released on 2012 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The research described in this dissertation defines two endeavors into the field of palladium-catalyzed allylic alkylation chemistry: the employment of unstabilized nitrogen-containing aromatic heterocycles as nucleophiles and the use of C--H activation to access [pi]-allyl-palladium electrophiles. With regard to the former program, we demonstrate that 2-methylpyridines, substrates whose corresponding anions are too unstabilized to react productively in palladium-catalyzed asymmetric allylic alkylation (AAA) reactions, form complexes when exposed to boron trifluoride diethyl etherate that can be deprotonated with lithium hexamethyldisilazide to afford competent nucleophiles for AAA processes. Investigations into the reaction mechanism establish that the configuration of the allylic stereocenter of the electrophile is retained, a finding that is consistent with the canonical outer sphere mechanism invoked for palladium-catalyzed allylic substitution processes of stabilized anions. We also show that under modified conditions, this protocol is applicable to the highly regio-, diastereo-, and enantioselective allylic alkylation of 2-substituted pyridines, reactions that form homoallylic stereocenters containing alkyl, aryl, heteroaryl, and nitrogen substituents. When the reaction is correspondingly performed with unsymmetric acyclic electrophiles, both linear and branched products may be obtained regio- and enantioselectively by choosing the appropriate regioisomeric starting material and ligand. We further report that this strategy extends to reactions of a variety of nitrogen-containing aromatic heterocycles, including pyrazines, pyrimidines, pyridazines, quinoxalines, benzoimidazoles, and tetrazoles. The mesityl ester, whose steric bulk prevents competitive deacylation of the electrophile from these nucleophiles, is introduced as a new leaving group in allylic alkylation chemistry. We describe the first general palladium-catalyzed allylic alkylation of 1,4-dienes that proceeds via C--H activation. A broad range of nucleophiles undergo reaction with variously substituted 1,4-dienes under relatively mild conditions, providing direct access to the corresponding 1,3-diene-containing products with high regio- and stereocontrol. This is the first catalytic allylic alkylation that proceeds via C--H activation in the absence of sulfoxide ligands, a discovery that provides for further developments in this chemistry enabled by phosphorus-based ligands. This finding is applied to a new assisted tandem catalytic process that effects sequential palladium(0)-catalyzed allylic alkylations via leaving group ionization and palladium(II)-catalyzed allylic alkylations via C--H activation. By employing an oxidative trigger to convert the initial palladium(0) species to a palladium(II) one, both transformations can be conducted in a single reaction vessel using the same precatalyst. This strategy allows for the introduction of otherwise indistinguishable allyl groups by exploiting complementary catalytic redox cycles. Finally, we detail the discovery and development of the first catalytic enantioselective palladium-catalyzed allylic C--H alkylations, an achievement made possible by a novel class of pyroglutamic-based phosphoramidite ligands. A wide array of sterically and electronically diverse allylarenes undergo allylic substitution by 2-acetyl-1-tetralones to form quaternary carbon stereocenters. Control experiments verify that this palladium-catalyzed process involves direct allylic alkylation, rather than initial allylic C--H acetoxylation. This conceptually and mechanistically distinct strategy averts many of the chemoselectivity issues inherent to traditional methods for the synthesis of enantioenriched allylic substitution products, providing the groundwork for the next generation of palladium-catalyzed allylic alkylation methods.

Download or read book The Palladium Catalyzed Asymmetric Allylic Alkylation AAA written by Daniel Edward Patterson and published by . This book was released on 2000 with total page 734 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Palladium Catalyzed Asymmetric Allylic Alkylation and TMM Cycloaddition in Natural Product Syntheses written by Chunhui Jiang and published by . This book was released on 2004 with total page 854 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Palladium catalyzed Asymmetric Allylic Alkylation written by Nathan Bruce Bennett and published by . This book was released on 2013 with total page 1828 pages. Available in PDF, EPUB and Kindle. Book excerpt: The asymmetric construction of quaternary stereocenters is a topic of great interest in the organic chemistry community given their prevalence in natural products and biologically active molecules. Over the last decade, the Stoltz group has pursued the synthesis of this challenging motif via a palladium-catalyzed allylic alkylation using chiral phosphinooxazoline (PHOX) ligands. Recent results indicate that the alkylation of lactams and imides consistently proceeds with enantioselectivities substantially higher than any other substrate class previously examined in this system. This observation prompted exploration of the characteristics that distinguish these molecules as superior alkylation substrates, resulting in newfound insights and marked improvements in the allylic alkylation of carbocyclic compounds.

Download or read book Palladium Catalyzed Asymmetric Allylic Alkylation in Aminochromane and Quinuclidinone Synthesis written by Karna Lyn Sacchi and published by . This book was released on 2002 with total page 266 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Artificial Metalloenzymes and MetalloDNAzymes in Catalysis written by Montserrat Diéguez and published by John Wiley & Sons. This book was released on 2018-02-21 with total page 431 pages. Available in PDF, EPUB and Kindle. Book excerpt: An important reference for researchers in the field of metal-enzyme hybrid catalysis Artificial Metalloenzymes and MetalloDNAzymes in Catalysis offers a comprehensive review of the most current strategies, developed over recent decades, for the design, synthesis, and optimization of these hybrid catalysts as well as material about their application. The contributors—noted experts in the field—present information on the preparation, characterization, and optimization of artificial metalloenzymes in a timely and authoritative manner. The authors present a thorough examination of this interesting new platform for catalysis that combines the excellent selective recognition/binding properties of enzymes with transition metal catalysts. The text includes information on the various applications of metal-enzyme hybrid catalysts for novel reactions, offers insights into the latest advances in the field, and contains an informative perspective on the future: Explores the development of artificial metalloenzymes, the modern and strongly evolving research field on the verge of industrial application Contains a comprehensive reference to the research area of metal-enzyme hybrid catalysis that has experienced tremendous growth in recent years Includes contributions from leading researchers in the field Shows how this new catalysis combines the selective recognition/binding properties of enzymes with transition metal catalysts Written for catalytic chemists, bioinorganic chemists, biochemists, and organic chemists, Artificial Metalloenzymes and MetalloDNAzymes in Catalysis offers a unique reference to the fundamentals, concepts, applications, and the most recent developments for more efficient and sustainable synthesis.

Download or read book Palladium Catalyzed Asymmetric Allylic Alkylation AAA of Prochiral Nucleophiles written by Gretchen Marie Schroeder and published by . This book was released on 2002 with total page 868 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Applications of Palladum sic Catalyzed Asymmetric Allylic Alkylation written by Jennifer Ann Vance and published by . This book was released on 2005 with total page 870 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Applications of Palladum sic Catalyzed Asymmetric Allylic Alkylation written by Jennifer Ann Vance and published by . This book was released on 2005 with total page 656 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Development of Metal catalyzed Asymmetric Allylic Alkylations for the Total Synthesis of Alkaloids and Other Nitrogen Containing Biologically Active Targets written by Maksim Osipov and published by . This book was released on 2014 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation deals with the development of metal-catalyzed asymmetric allylic alklyations, and their use for the synthesis of alkaloids and other nitrogen-containing biologically active compounds. The synthesis of the drug ( -- )-ranirestat is disclosed, which relies on a Pd-catalyzed asymmetric allylic alkylation (Pd-AAA) as a key step. The development and application of pyrroles and indoles as nucleophiles in the Pd-AAA is described. A Pd-catalyzed decarboxylative asymmetric alkylation approach to constructing vicinal all-carbon quaternary stereocenters is disclosed, and this methodology is used to complete the formal synthesis of several cyclotryptamine alkaloids. Finally, a catalytic asymmetric total synthesis of the alkaloid ( -- )-perophoramidine and efforts towards the alkaloid communesin B are described. Both syntheses employ a molybdenum-catalyzed asymmetric allylic alkylation as a key asymmetric step. ( -- )-Ranirestat is a potent aldose reductase inhibitor currently in phase III clinical testing for its ability to treat diabetic neuropathy. We have developed a concise, catalytic asymmetric total synthesis of ( -- )-ranirestat, which was completed in 8 steps and 14% overall yield starting from inexpensive, commercially available 2-(trichloroacetyl)pyrrole. A palladium-catalyzed asymmetric allylic alkylation (Pd-AAA) of an imidomalonate and an allylic carbonate serve as a key transformation to construct the tetrasubstituted stereocenter in the target with high yield and enantioselectivity. Protiodesilylation followed by oxidative cleavage of the allyl moiety and cyclization are used to access ( -- )-ranirestat. Nitrogen heterocycles are found in a variety of natural products and other biologically active compounds. We have demonstrated that pyrroles and indoles bearing electron-withdrawing groups are competent nucleophiles in the Pd-AAA with vinyl aziridines. The resulting alkylated products were obtained with high levels of regio-, chemo-, and enantioselectivity. Both substituted 1H-pyrroles and 1H-indoles were successfully employed to give exclusively the branched N-alkylated products. The synthetic utility of this asymmetric process was demonstrated through the elaboration of pyrrole products into bromopyrrole alkaloids longamide B, longamide B methyl ester, hanishin, agesamides A and B, and cyclooroidin. Likewise, the synthetic utility of the indole products was demonstrated by elaboration into several patented piperazinones and piperazine medicinal chemistry lead compounds. 1H-Pyrroles have also shown to serve as nucleophiles with meso electrophiles in the Pd-AAA. The products from this transformation were obtained as a single regio- and diastereomer in high yield and % ee. To demonstrate synthetic utility, a pyrrole-substituted nucleoside analogue was synthesized employing this methodology as the asymmetric step. Quaternary all-carbon stereocenters are present in many natural products and biologically active compounds. The presence of this structural element greatly complicates the asymmetric assembly of molecules due to steric congestion. The asymmetric assembly is complicated further when a second vicinal, quaternary center is present in a molecular target. We have discovered that a two-fold Pd-DAAA of an oxindole-derived dienol carbonate can be used to construct two vicinal all carbon quaternary stereocenters in a diastereo- and enantioselective fashion. To demonstrate the synthetic utility of this process, the product of this transformation was used to complete the formal syntheses of the cyclotryptamine alkaloids ( -- )-chimonanthine, (+)-calycanthine ( -- )-folicanthine, and ditryptophenaline. Mechanistic investigations have suggested that the two-fold Pd-catalyzed transformation proceeds through an unusual matched and mismatched allylation to deliver the desired product. Perophoramidine was isolated from the ascidian organism Perophora namei and displays cytotoxicity toward the HCT116 colon carcinoma cell line with an IC50 of 60 æM. The complex polycyclic cage-like core of this alkaloid makes it a challenging and interesting target for total synthesis. A catalytic asymmetric total synthesis of ( -- )-perophoramidine was developed employing a molybdenum-catalyzed asymmetric allylic alkylation between an allylic phosphate and an alkyl oxindole as an asymmetric step. This key transformation provides a chiral oxindole product in high yield and with high levels of regio-, diastereo-, and enantioselectivity. The chiral oxindole product, which contains the key quaternary stereocenter present in perophoramidine, was further elaborated to a pentacyclic imino ether using a reductive cyclization, oxidative cleavage and lactamization as key transformations. The imino ether was alkylated with allyl iodide to construct the second vicinal quaternary stereocenter providing an allyl imino ether as a single regio- and diastereomer. The allyl imino ether was converted to an aldehyde via ozonolysis, which was subjected to a reductive amination and cyclization sequence to complete ( -- )-perophoramidine.

Download or read book Synthesis Characterization and Use of New Chiral P N Ligands in the Palladium catalyzed Asymmetric Allylic Alkylation and a New Synthetic Route to the Preparation of Optically Active Cyclomercurated Ferrocenylimines written by Kurtis Thiesen and published by . This book was released on 2010 with total page 296 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Expanding the Scope of the Palladium catalyzed Asymmetric Allylic Alkylation Reaction and Applications Towards Alkaloid Syntheses written by Megan Brennan and published by . This book was released on 2008 with total page 460 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book A Synthesis of Baconipyrone Through New Catalytic Asymmetric Methods written by Dennis Gillingham and published by . This book was released on 2008-09-01 with total page 344 pages. Available in PDF, EPUB and Kindle. Book excerpt: The societal need for optically enriched molecules (e.g. in pharmaceuticals or new materials) continues to drive the development of new synthetic methods for enantioselective synthesis. This work discusses the development of new chiral catalysts and ligands for two important synthetic synthetic methods: Ru-catalyzed asymmetric olefin metathesis, and Cu-catalyzed asymmetric allylic alkylation. These methods were applied to a total synthesis of the marine natural product baconipyrone C. Other highlights include the development of a mild new method for the synthesis of the gamma-pyrone motif and the use of tethered ring-closing olefin metathesis as an alternative to olefin cross-metathesis. Practitioners of organic synthesis should find this book particularly useful for the new carbon-carbon bond-forming methods presented, as well as the novel synthetic strategies.

Download or read book Palladium catalyzed Decarboxylative and Decarbonylative Transformations in the Synthesis of Fine and Commodity Chemicals written by Yiyang Liu and published by . This book was released on 2015 with total page 1012 pages. Available in PDF, EPUB and Kindle. Book excerpt: Decarboxylation and decarbonylation are important reactions in synthetic organic chemistry, transforming readily available carboxylic acids and their derivatives into various products through loss of carbon dioxide or carbon monoxide. In the past few decades, palladium-catalyzed decarboxylative and decarbonylative reactions experienced tremendous growth due to the excellent catalytic activity of palladium. Development of new reactions in this category for fine and commodity chemical synthesis continues to draw attention from the chemistry community. The Stoltz laboratory has established a palladium-catalyzed enantioselective decarboxylative allylic alkylation of beta-keto esters for the synthesis of alpha-quaternary ketones since 2005. Recently, we extended this chemistry to lactams due to the ubiquity and importance of nitrogen-containing heterocycles. A wide variety of alpha-quaternary and tetrasubstituted alpha-tertiary lactams were obtained in excellent yields and exceptional enantioselectivities using our palladium-catalyzed decarboxylative allylic alkylation chemistry. Enantioenriched alpha-quaternary carbonyl compounds are versatile building blocks that can be further elaborated to intercept synthetic intermediates en route to many classical natural products. Thus our chemistry enables catalytic asymmetric formal synthesis of these complex molecules. In addition to fine chemicals, we became interested in commodity chemical synthesis using renewable feedstocks. In collaboration with the Grubbs group, we developed a palladium-catalyzed decarbonylative dehydration reaction that converts abundant and inexpensive fatty acids into value-added linear alpha olefins. The chemistry proceeds under relatively mild conditions, requires very low catalyst loading, tolerates a variety of functional groups, and is easily performed on a large scale. An additional advantage of this chemistry is that it provides access to expensive odd-numbered alpha olefins. Finally, combining features of both projects, we applied a small-scale decarbonylative dehydration reaction to the synthesis of alpha-vinyl carbonyl compounds. Direct alpha-vinylation is challenging, and asymmetric vinylations are rare. Taking advantage of our decarbonylative dehydration chemistry, we were able to transform enantioenriched delta-oxocarboxylic acids into quaternary alpha-vinyl carbonyl compounds in good yields with complete retention of stereochemistry. Our explorations culminated in the catalytic enantioselective total synthesis of (-)-aspewentin B, a terpenoid natural product featuring a quaternary alpha-vinyl ketone. Both decarboxylative and decarbonylative chemistries found application in the late stage of the total synthesis.

Download or read book Palladium Catalyzed Decarboxylative Asymmetric Allylic Alkylation of Unstabilized Enolates written by Jiayi Xu and published by . This book was released on 2008 with total page 1042 pages. Available in PDF, EPUB and Kindle. Book excerpt: