Complexity-Generating Annulation Reactions in the Synthesis of Natural Products and Materials Scaffolds PDF Download
Are you looking for read ebook online? Search for your book and save it on your Kindle device, PC, phones or tablets. Download Complexity-Generating Annulation Reactions in the Synthesis of Natural Products and Materials Scaffolds PDF full book. Access full book title Complexity-Generating Annulation Reactions in the Synthesis of Natural Products and Materials Scaffolds by Robert Bergstrand Susick. Download full books in PDF and EPUB format.
Author: Robert Bergstrand Susick
Publisher:
ISBN:
Category :
Languages : en
Pages : 333
Get Book Here
Book Description
This dissertation encompasses several studies pertaining to natural product total synthesis, reaction methodology development, and organic materials. Given that natural product structures inspire the development of new agrochemicals and pharmaceuticals, their syntheses remain a worthwhile pursuit in organic chemistry. Furthermore, the successful completion of a total synthesis endeavor can confirm proposed molecular structures and biological activities, in addition to serving as a testing ground for new synthetic methods. Similarly, organic materials impact many areas of humanity, including technology, health, and energy conversion. Therefore, developing new reaction methodologies is crucial for expanding the architectures, and thereby properties, of organic materials. Specifically, photocatalysts and organic light-emitting diodes (OLEDs) often rely on photophysical properties imparted by N-containing polycyclic aromatic hydrocarbon (PAH) ligands. As such, new methods that provide access to unique N-containing heterocyclic scaffolds are highly desirable. Chapter one offers a current perspective on the field of natural product total synthesis. Although historically viewed as a highly competitive field, several recent syntheses demonstrate a growing spirit of collaboration in total synthesis. By forming alliances with chemists in other fields, industries, or laboratories, total synthesis chemists have made many breakthroughs that would arguably not have been possible if working independently. Chapter two describes our laboratory's total syntheses of several bioactive akuammiline alkaloids, including strictamine, 2(S)-cathafoline, akuammiline, -akuammigine, and 10-demethoxyvincorine. Our strategic approach to the natural products focused on the use of a modern variant of a classic reaction, the Fischer indolization, to install several rings and the common quaternary center found in each target. This strategy allowed for the first total syntheses of akuammilines bearing a methanoquinolizidine core, as well as those that bear vicinal quaternary centers. In addition, rearrangements of the methanoquinolizidine core were developed that allowed us to access pyrrolidinoindoline-containing akuammilines. Chapter three describes synthetic studies of the reactive intermediates 2,3-pyridyne and 4,5-pyrimidyne. Heterocycles bearing one or more nitrogen atom are privileged motifs in natural products and pharmaceuticals. Therefore, methodologies that decorate such heterocycles are of great interest to the synthetic and biological communities. Arynes are highly reactive, transient species that can efficiently build multiple bonds in a single transformation, and our lab is particularly interested in accessing new, heterocyclic arynes to study their reactivity. This study demonstrates the synthetic utility of 2,3-pyridyne and the undesired reactivity of a 4,5-pyrimidyne precursor. Chapter four describes synthetic studies toward the development of new methods to manipulate polypyridyl organometallic scaffolds. Ruthenium- and iridium-based polypyridyl organometallic complexes have been known for nearly a century and have broadly impacted the scientific community, including the areas of catalysis, bioimaging, and energy conversion. Despite decades of study, methods to synthesize polypyridyl ligands are limited to relatively few transformations, particularly when extending -conjugation. We detail the use of arynes to extend the conjugation of polypyridyl ligands "on-the-complex," thereby overcoming traditional limitations in ligand synthesis. We also disclose the first generation and trapping of a ligand-bound aryne on an organometallic complex. Chapter five describes the synthesis of a novel -extended carbazole ligand for the study of structure-property relationships in two-coordinate metal complexes. Recently, linear two-coordinate metal complexes of the general structure donor-metal-acceptor have been identified as promising dopants for OLEDs. Both the donor and acceptor ligand play a crucial role in tuning the photophysical properties of these complexes. However, donor ligands with extended -conjugation have not been studied in this context. Our approach leverages heterocyclic arynes to synthesize -extended donor ligands in a modular fashion, which can also apply to other PAHs. Subsequent photophysical studies of -extended two-coordinate metal complexes identify a new dopant that displays up to 80% photoluminescence efficiency.
Author: Robert Bergstrand Susick
Publisher:
ISBN:
Category :
Languages : en
Pages : 333
Get Book Here
Book Description
This dissertation encompasses several studies pertaining to natural product total synthesis, reaction methodology development, and organic materials. Given that natural product structures inspire the development of new agrochemicals and pharmaceuticals, their syntheses remain a worthwhile pursuit in organic chemistry. Furthermore, the successful completion of a total synthesis endeavor can confirm proposed molecular structures and biological activities, in addition to serving as a testing ground for new synthetic methods. Similarly, organic materials impact many areas of humanity, including technology, health, and energy conversion. Therefore, developing new reaction methodologies is crucial for expanding the architectures, and thereby properties, of organic materials. Specifically, photocatalysts and organic light-emitting diodes (OLEDs) often rely on photophysical properties imparted by N-containing polycyclic aromatic hydrocarbon (PAH) ligands. As such, new methods that provide access to unique N-containing heterocyclic scaffolds are highly desirable. Chapter one offers a current perspective on the field of natural product total synthesis. Although historically viewed as a highly competitive field, several recent syntheses demonstrate a growing spirit of collaboration in total synthesis. By forming alliances with chemists in other fields, industries, or laboratories, total synthesis chemists have made many breakthroughs that would arguably not have been possible if working independently. Chapter two describes our laboratory's total syntheses of several bioactive akuammiline alkaloids, including strictamine, 2(S)-cathafoline, akuammiline, -akuammigine, and 10-demethoxyvincorine. Our strategic approach to the natural products focused on the use of a modern variant of a classic reaction, the Fischer indolization, to install several rings and the common quaternary center found in each target. This strategy allowed for the first total syntheses of akuammilines bearing a methanoquinolizidine core, as well as those that bear vicinal quaternary centers. In addition, rearrangements of the methanoquinolizidine core were developed that allowed us to access pyrrolidinoindoline-containing akuammilines. Chapter three describes synthetic studies of the reactive intermediates 2,3-pyridyne and 4,5-pyrimidyne. Heterocycles bearing one or more nitrogen atom are privileged motifs in natural products and pharmaceuticals. Therefore, methodologies that decorate such heterocycles are of great interest to the synthetic and biological communities. Arynes are highly reactive, transient species that can efficiently build multiple bonds in a single transformation, and our lab is particularly interested in accessing new, heterocyclic arynes to study their reactivity. This study demonstrates the synthetic utility of 2,3-pyridyne and the undesired reactivity of a 4,5-pyrimidyne precursor. Chapter four describes synthetic studies toward the development of new methods to manipulate polypyridyl organometallic scaffolds. Ruthenium- and iridium-based polypyridyl organometallic complexes have been known for nearly a century and have broadly impacted the scientific community, including the areas of catalysis, bioimaging, and energy conversion. Despite decades of study, methods to synthesize polypyridyl ligands are limited to relatively few transformations, particularly when extending -conjugation. We detail the use of arynes to extend the conjugation of polypyridyl ligands "on-the-complex," thereby overcoming traditional limitations in ligand synthesis. We also disclose the first generation and trapping of a ligand-bound aryne on an organometallic complex. Chapter five describes the synthesis of a novel -extended carbazole ligand for the study of structure-property relationships in two-coordinate metal complexes. Recently, linear two-coordinate metal complexes of the general structure donor-metal-acceptor have been identified as promising dopants for OLEDs. Both the donor and acceptor ligand play a crucial role in tuning the photophysical properties of these complexes. However, donor ligands with extended -conjugation have not been studied in this context. Our approach leverages heterocyclic arynes to synthesize -extended donor ligands in a modular fashion, which can also apply to other PAHs. Subsequent photophysical studies of -extended two-coordinate metal complexes identify a new dopant that displays up to 80% photoluminescence efficiency.
Author: Jie Jack Li
Publisher: Springer Science & Business Media
ISBN: 3642340652
Category : Science
Languages : en
Pages : 292
Get Book Here
Book Description
'Total Synthesis of Natural Products' is written and edited by some of today's leaders in organic chemistry. Eleven chapters cover a range of natural products, from steroids to alkaloids. Each chapter contains an introduction to the natural product in question, descriptions of its biological and pharmacological properties and outlines of total synthesis procedures already carried out. Particular emphasis is placed on novel methodologies developed by the respective authors and their research groups. This text is ideal for graduate and advanced undergraduate students, as well as organic chemists in academia and industry.
Author: Jason Chari
Publisher:
ISBN:
Category :
Languages : en
Pages : 475
Get Book Here
Book Description
This dissertation describes the development of synthetic methodologies and approaches that leverage strain-driven reactivity to access complex molecules, as well as enzymatic studies and advances in the field of chemical education. The high potential energy stored within strained bonds offers a powerful tool in organic synthesis for the construction of new covalent bonds. Controlling the reactivity of strained molecules, while challenging in many cases, offers a means to form multiple bonds in a single step, under mild reaction conditions, and generate products that may be inaccessible by other means. Herein, several synthetic endeavors are described that seek to leverage strain release to push our understanding of chemical reactivity and gain new entryways into important classes of organic and organometallic compounds. Moreover, two studies in the area of biosynthesis and are described, which take advantage of synergy between chemical synthesis and enzymatic chemistry to access bioactive compounds with high selectivity. Finally, studies in the area of chemical education are described. These efforts seek to make organic chemistry accessible to wider audiences through the development of interactive, globally available educational tools and the creation of a new undergraduate lecture course that highlights the role of organic chemistry in the world around us. Chapter one describes a perspective on the field of complex molecule synthesis (i.e., total synthesis), with a focus on the power of collaborations across research groups. Although historically competitive, there is a growing spirit of teamwork and collaboration in the field of total synthesis. This chapter discusses recent breakthroughs in both academic and industrial laboratories that have succeeded as a direct result of alliances between research groups. Chapter two describes progress toward the total synthesis of dodecahedrane, a complex and highly symmetrical hydrocarbon that bears twelve fused rings arranged in a cage-like architecture. Central to our approach is an ambitious [2+2+2+2+2] poly-ene cyclization cascade which would serve to provide new insights into chemical reactivity. Current efforts center around constructing key linkages found in the target by harnessing the strain release of norbornene ring systems to form new carbon-carbon bonds. Chapter three describes a concise and scalable synthetic approach to precursors to strained intermediates. Although historically avoided due to their high reactivity, strained cyclic alkynes and allenes have demonstrated value in the synthesis of medicinally privileged, polycyclic compounds. These efforts, which provide efficient access to silyl triflate precursors to cyclohexyne and 1,2-cyclohexadiene, serve to enable further studies involving strained alkynes and allenes. Chapters four and five describe the development of new methodologies that exploit strained aryne intermediates in the synthesis of complex organic and organometallic materials. Both chapters investigate the controlled generation and reactivity of aryne intermediates, as well as engagement of these intermediates in Pd-catalysis to build new ring systems. Chapter four specifically details the development of aryne chemistry "on-the-complex," wherein fleeting aryne intermediates are reacted with pre-coordinated metal-ligand complexes to form new carbon-carbon bonds. These studies, performed in the context of privileged, photoactive polypyridyl metal complexes, provide an effective strategy to annulate organometallic complexes and access complex metal-ligand scaffolds, while furthering the synthetic utility of strained intermediates in chemical synthesis. Chapter five details the development of Pd-catalyzed reactions of indole and carbazole-based arynes (i.e., hetarynes) to access [pi]-extended heterocyclic materials. The products obtained were applied as ligands in two-coordinate metal complexes to access new OLED emitters. Chapters six and seven are concerned with uncovering and investigating highly selective reactions catalyzed by fungal enzymes. In particular, chapter six describes the discovery of two groups of enzymes that catalyze distinct reactions, an Alder-ene reaction (previously unknown in biology) and a stereoselective hetero-Diels-Alder reaction. Chapter seven presents studies pertaining to the aminoacylation and thiolation of polyketides in fungi, with a focus on elucidating mechanistic pathways. Both chapters showcase important synergy between chemical synthesis and enzymatic chemistry, and elucidate new enzymatic pathways that ultimately give rise to molecular complexity. Chapters eight and nine illustrate advances in chemical education. Chapter eight specifically details the development and execution of a new undergraduate course taught by graduate students. The course, entitled Catalysis in Modern Drug Discovery, served to highlight the central role of organic chemistry in drug discovery, while also conveying key concepts in catalysis. Moreover, the course spotlighted the various careers that organic chemists play in the development of new medicines. Chapter nine presents a perspective that highlights our recent efforts to develop interactive resources in chemical education for worldwide usage. In particular, these efforts seek to promote a spirit of innovation in chemical education and spur the development of widely accessible resources that improve learning outcomes and promote positive perception of chemistry in the broader community
Author: Charles K. Zercher
Publisher: John Wiley & Sons
ISBN: 1118117824
Category : Science
Languages : en
Pages : 1606
Get Book Here
Book Description
Continuing the tradition of providing significant and interesting procedures, Organic Syntheses, Collective Volume XII is a compilation of revised editions of Annual Volumes 85 through 89. The contents of this volume are organized by primarily by reaction type, with the precise classification made according to the bias of the editor, who attempted to ascertain the primary purpose or utility of the procedure.
Author: Andrew Vincent Kelleghan
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
Get Book Here
Book Description
This dissertation describes the development of methodologies that engage strained cyclic intermediates in complexity-generating reactions. One major effort involves the transition metal-catalyzed interception of strained cyclic allenes, which has been accomplished using asymmetric nickel catalysis and palladium catalysis. Additionally, the study of alternative minimally explored strained intermediates including cyclic 1,2,3-trienes and 2,3-heterocyclic allenes are reported. These studies expand on fundamental understanding of structure and reactivity of strained compounds and give rise to diverse libraries of polycyclic products. Studies relating to the in situ generation of various strained cyclic intermediates are also reported. Specifically, these include experimental evaluation of the safety associated with the use of silyl triflates as benzyne precursors as well as the synthesis and evaluation of silyl tosylates as precursors to strained alkynes and allenes. Chapters one and two are related to the development of metal-catalyzed reactions of strained cyclic allenes. Chapter one describes the first catalytic asymmetric reaction involving a strained cyclic allene, which was achieved through the use of nickel catalysis. The scope of the asymmetric annulation reaction is reported, and computational studies performed in collaboration with the Houk Laboratory elucidate the origin of asymmetric induction in the transformation. Chapter two describes the development of a modular annulation reaction of strained allenes enabled by a palladium catalyst. This methodology employs aryl halides and cyclic allene precursors to generate fused heterocyclic products via the formation of two new bonds and a sp3 center. The development of these metal-catalyzed reactions demonstrates that despite their high reactivity and short lifetimes, strained cyclic intermediates can be efficiently engaged in catalysis, to access complex products, often with absolute stereocontrol. Chapter three describes the development of strained 1,2,3-cyclohexatrienes, which have remained underexplored historically, as synthetic building blocks. Studies of the reactivity of the unsubstituted 1,2,3-cyclohexatriene, as well as its mono- and disubstituted derivatives are reported, drastically expanding the scope of reactions known for such intermediates. Combined computational and experimental studies elucidate the factors controlling regioselectivity in reactions of an unsymmetrical strained triene. Furthermore, the potential utility of strained trienes in rapidly generating complex scaffolds is demonstrated through the integration of triene trapping reactions into multistep synthetic sequences to access sp3-rich polycyclic products. These studies highlight the potential of these traditionally avoided species in synthetic chemistry. Chapter four details the study of unsymmetrical strained heterocyclic allenes, particularly 2,3-azacyclohexadienes. Computational studies of the structure of such species, as well as the development of a synthetic route to access precursors to the same, are reported. Scope studies demonstrate the utility of 2,3-azacyclic allenes for accessing complex nitrogen-containing heterocycles, and trends in the regio- and diastereoselectivity observed therein are explored through control experiments. The extension of this study to 2,3-oxacyclic allenes enables their generation under mild conditions for the first time, as well as the first demonstration of their reactivity in dipolar cycloadditions and transition metal-catalyzed reactions. Collectively, this study demonstrates the potential value of unsymmetrical aza- and oxacyclic allenes in heterocycle synthesis. Chapter five describes an evaluation of the safety profile associated with benzyne generation from a silyl triflate precursor which was performed in collaboration with the process development group at Boehringer Ingelheim. Calorimetric analysis supports the safe nature of generating high energy aryne intermediates from silyl triflates under fluoride-mediated conditions. Chapter six illustrates the development of an alternative precursor toward strained cyclic allenes and alkynes. Our studies of strained cyclic allenes revealed that, in some cases, silyl triflate precursors were inaccessible. This study shows that silyl tosylates can serve as alternative precursors to strained cyclic allenes and alkynes.
Author: Florian de Nanteuil
Publisher: Springer
ISBN: 3319230069
Category : Science
Languages : en
Pages : 329
Get Book Here
Book Description
This thesis presents a general approach to accessing nitrogen-substituted hetero- and carbocycles. In short, the annulation reactions developed in the thesis make it possible to access nitrogen-substituted four-, five- and six-membered rings, all essential building blocks for the synthesis of bioactive molecules. Many natural products display a saturated polycyclic core allowing a well-defined arrangement of functional groups in space. As such, they can interact with biological targets with a high degree of affinity and selectivity, surpassing many synthetic drugs. Nevertheless, the efficient synthesis of such complex ring systems poses a challenge for organic chemistry. Through careful tuning of the electronic properties of a nitrogen donor group and a diester acceptor group, the first [3+2] annulation reaction between aminocyclopropanes and enol ethers or carbonyl compounds is now possible. The reaction proceeded under mild catalytic conditions, and the building blocks obtained can be found at the core of bioactive alkaloids, drugs such as Ramipril and biomolecules such as DNA and RNA. Thanks to the dynamic kinetic asymmetric annulation of aminocyclopropanes with enol ethers and aldehydes, access to enantioenriched compounds is also now possible. Lastly, a synthesis of donor-acceptor aminocyclobutanes via [2+2] cycloaddition using a cheap iron catalyst was developed, allowing them to be used in [4+2] annulations to access cyclohexylamines.
Author: Jun Yang
Publisher: OAE Publishing Inc.
ISBN:
Category : Science
Languages : en
Pages : 54
Get Book Here
Book Description
Chiral spirolactones, including spiropropyllactones, spirobutyrolactones, and spirovalerolactones, are important heterocyclic frameworks that attracted the attention of organic and medicinal chemists because these motifs constitute the core structure of several natural products and bioactive molecules. The absolute configuration and the substituents on the fully substituted spirocyclic stereocenter of the lactone can potentially enhance specificity for ligand-protein binding and enhance bioavailability, potency, and metabolic stability. So, intensive attention from chemists has been paid to the synthetic methods leading to such prominent structural motifs. The synthetic methods can be divided into two main classes. The first approach takes advantage of the presence of the existing lactone structure and focuses on its functionalization. The second approach is the lactone framework constructed from various precursors in a direct spirolactonization reaction. In this review, for convenience in reading, the recent advances in the synthesis of spirolactones are summarized and discussed according to the two major organocatalytic asymmetric synthetic routes: (i) using the lactone-related frameworks as building blocks; and (ii) direct spirolactonization reaction using various reagents. This review also describes both the mechanisms and related transformations, and gives some insights into challenging issues in this research field, which will enlighten the future development of this field.
Author: Ramon Rios Torres
Publisher: John Wiley & Sons
ISBN: 1118308638
Category : Science
Languages : en
Pages : 422
Get Book Here
Book Description
The Pauson-Khand reaction is an important reaction in the field of organic chemistry. It involves the transition-metal catalysed cycloaddition of an alkyne, an alkene and carbon monoxide, to produce cyclopentenones. The importance of this reaction originates from its high value in transforming simple components into the synthetically useful cyclopentenone unit, in which a high degree of molecular complexity can be achieved in a single step, with impressive stereochemical and regiochemical control. The Pauson-Khand Reaction investigates the nature and many variations of this reaction. Topics covered include: the mechanisms of Pauson‐Khand-type reactions non chiral intramolecular and intermolecular versions of Pauson‐Khand reactions asymmetric Pauson‐Khand reaction using chiral auxiliaries the enantioselective Pauson‐Khand reaction Pauson‐Khand reactions catalysed by metals other than cobalt unconventional Pauson‐Khand reactions the Pauson‐Khand reaction in total synthesis Presenting a comprehensive overview of this fundamental reaction, The Pauson-Khand Reaction will find a place on the bookshelves of any organic or organometallic chemist.
Author: Mark G. Moloney
Publisher: John Wiley & Sons
ISBN: 1119716802
Category : Science
Languages : en
Pages : 629
Get Book Here
Book Description
Organic Reaction Mechanisms 2020, the 56th annual volume in this highly successful and unique series, surveys research on organic reaction mechanisms described in the available literature dated 2020. The following classes of organic reaction mechanisms are comprehensively reviewed: Reaction of Aldehydes and Ketones and their Derivatives Reactions of Carboxylic, Phosphoric, and Sulfonic Acids and their Derivatives Oxidation and Reduction Nucleophilic Aromatic Substitution Electrophilic Aromatic Substitution Carbocations Nucleophilic Aliphatic Substitution Carbanions and Electrophilic Aliphatic Substitution Elimination Reactions Polar Addition Reactions Cycloaddition Reactions Molecular Rearrangements Transition Metal Coupling Radicals An experienced team of authors compile these reviews every year, so that the reader can rely on a continuing quality of selection and presentation.
Author: Wei Zhang
Publisher: John Wiley & Sons
ISBN: 1119288177
Category : Science
Languages : en
Pages : 730
Get Book Here
Book Description
An updated overview of the rapidly developing field of green techniques for organic synthesis and medicinal chemistry Green chemistry remains a high priority in modern organic synthesis and pharmaceutical R&D, with important environmental and economic implications. This book presents comprehensive coverage of green chemistry techniques for organic and medicinal chemistry applications, summarizing the available new technologies, analyzing each technique’s features and green chemistry characteristics, and providing examples to demonstrate applications for green organic synthesis and medicinal chemistry. The extensively revised edition of Green Techniques for Organic Synthesis and Medicinal Chemistry includes 7 entirely new chapters on topics including green chemistry and innovation, green chemistry metrics, green chemistry and biological drugs, and the business case for green chemistry in the generic pharmaceutical industry. It is divided into 4 parts. The first part introduces readers to the concepts of green chemistry and green engineering, global environmental regulations, green analytical chemistry, green solvents, and green chemistry metrics. The other three sections cover green catalysis, green synthetic techniques, and green techniques and strategies in the pharmaceutical industry. Includes more than 30% new and updated material—plus seven brand new chapters Edited by highly regarded experts in the field (Berkeley Cue is one of the fathers of Green Chemistry in Pharma) with backgrounds in academia and industry Brings together a team of international authors from academia, industry, government agencies, and consultancies (including John Warner, one of the founders of the field of Green Chemistry) Green Techniques for Organic Synthesis and Medicinal Chemistry, Second Edition is an essential resource on green chemistry technologies for academic researchers, R&D professionals, and students working in organic chemistry and medicinal chemistry.
