New Approaches to Heterocycles and Carbocycles

New Approaches to Heterocycles and Carbocycles
Author: Tuanli Yao
Publisher:
Total Pages: 342
Release: 2005
Genre:
ISBN:

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The electrophilic cyclization of functionally-substituted alkynes is a very promising route to an extraordinary range of medicinally interesting, functionally-substituted heterocycles and carbocycles. For instance, a variety of substituted isocoumarins and [alpha]-pyrones are readily prepared in excellent yields under very mild reaction conditions by the reaction of o-(l-alkynyl)benzoates and (Z)-2-alken-4-ynoates with IC1,I2, PhSeCl, p-O2NC6H4SCl, and HI. This methodology accommodates various alkynyl esters and has been successfully extended to the synthesis of polycyclic aromatic and biaryl compounds. Electrophilic cyclization of o-(l-alkynyl)benzamides with IC1, I2, and NBS, affords a variety of substituted isoindolin-1-ones in good to excellent yields. In a few cases, substituted isoquinolin-1-ones were obtained as the major product instead. This methodology accommodates various alkynyl amides and functional groups, and has been successfully extended to heterocyclic starting materials. This chemistry has been successfully applied to the formal synthesis of a biologically interesting alkaloid cepharanone B.A variety of substituted polycyclic aromatics are readily prepared in good to excellent yields under very mild reaction conditions by the reaction of 2-(1-alkynyl)biphenyls with IC1, I2, NBS, and p-O2NC6H4SCl. This methodology readily accommodates various functional groups and has been successfully extended to systems containing a variety of polycyclic and heterocyclic rings. The coupling of 2-(1-alkynyl)-2-alken-1-ones with nucleophiles, either catalyzed by AuCl3 or induced by an electrophile, provides highly substituted furans in good to excellent yields under very mild reaction conditions. Various nucleophiles, including functionalized alcohols, H2O, carboxylic acids, 1,3-diketones and electron-rich arenes, and a range of cyclic and acyclic 2-(1-alkynyl)-2-alken-1-ones readily participate in these cyclizations. Iodine, NIS, and PhSeCl have proven successful as electrophiles in this process. The resulting iodine-containing furans can be readily elaborated to more complex products using known organopalladium chemistry.

Innovative Approaches to Carbocyclic and Heterocyclic Compounds Using Strained Carbocycles

Innovative Approaches to Carbocyclic and Heterocyclic Compounds Using Strained Carbocycles
Author: Lien Hoang Phun
Publisher:
Total Pages:
Release: 2013
Genre: Drug development
ISBN:

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Natural products and small molecules play a major role in drug development. However, using natural products as a source of medicine comes with many challenges, such as lack of natural abundance and difficulty in isolation. Consequently, synthetic organic chemistry is a solution in order to access these compounds in usable quantities. However, synthetic chemisty comes with its own challenges such as efficiency, chemoselectivity, stereoselectivity and enantioselectivity. Therefore, synthetic tools that addresses these challenges are required solve these limitations. This thesis discusses new methodologies using strained carbocycles (cyclopropanes and cyclopropenes) as the reactive subunit for the construction of different carbocyclic and heterocyclic compounds. The homo-Nazarov cyclization of alkenyl and heteroaryl cyclopropyl ketones was used in order to construct cyclohexenones, cyclohexenols, heteroaryl ring-fused cyclohexenones, dihydrofurans, furans and furanones in a mild and efficient manner. Benzofused heteroaromatic compounds were achieved via the Lewis acid-catalyzed cycloisomerization of cyclopropene-3,3-dicarbonyls and furan-3-carboxylates. These heteroaromatic compounds can be applied to medicinal chemistry and material science.

Synthesizing Annulated Carbocycles and Heterocycles

Synthesizing Annulated Carbocycles and Heterocycles
Author: S. Thavaselvan
Publisher:
Total Pages: 0
Release: 2023-05-28
Genre:
ISBN: 9781805292470

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S. Thavaselvan is a renowned scientist in the field of organic chemistry, particularly in the area of synthesizing annulated carbocycles and heterocycles. In this area of research, he has made significant contributions to the development of new methodologies for the synthesis of complex molecules with diverse biological activities. Synthesis of annulated carbocycles and heterocycles is a challenging task due to the presence of multiple functional groups and the complexity of the reaction pathways involved. However, with the development of new methods and strategies, this area of research has seen rapid growth in recent years. Cyclization reactions, which involve the formation of a ring from a linear precursor, are the most common methods used for the synthesis of annulated carbocycles and heterocycles. These reactions can be catalyzed by a variety of transition metals such as palladium, rhodium, ruthenium, nickel, copper, and iron. The choice of metal catalyst and ligand can significantly influence the outcome of the reaction, particularly with respect to stereoselectivity and regioselectivity. Chiral ligands are used to achieve asymmetric synthesis of annulated carbocycles and heterocycles, while non-chiral ligands are used for stereoselective synthesis. Aromatic and aliphatic compounds can be used as starting materials for the synthesis of these complex molecules, and a range of functional groups including nitrogen, oxygen, and sulfur can be incorporated into the final product. The synthesis of annulated carbocycles and heterocycles can also involve nucleophilic substitution, electrophilic substitution, cross-coupling reactions, ring opening reactions, rearrangement, reduction, and oxidation. Grignard reagents, Sonogashira reaction, Suzuki reaction, and Heck reaction are some of the most commonly used reactions for the synthesis of these compounds. Heteroaromatic compounds such as pyridine, indole, quinoline, pyrimidine, pyrazine, benzofuran, benzothiophene, benzimidazole, isoquinoline, and pyrrole are commonly used as building blocks for the synthesis of annulated carbocycles and heterocycles due to their diverse biological activities. In conclusion, S. Thavaselvan's research in the area of synthesizing annulated carbocycles and heterocycles has contributed significantly to the development of new methodologies for the synthesis of complex molecules with diverse biological activities. The use of different metal catalysts, ligands, and functional groups has enabled the development of efficient and selective synthetic methods for the preparation of these complex molecules.

New Palladium-catalyzed Approaches to Heterocycles and Carbocycles

New Palladium-catalyzed Approaches to Heterocycles and Carbocycles
Author: Qinhua Huang
Publisher:
Total Pages: 629
Release: 2004
Genre:
ISBN:

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The tert-butylimines of o-(1-alkynyl)benzaldehydes and analogous pyridinecarbaldehydes have been cyclized under very mild reaction conditions in the presence of I2, ICl, PhSeCl, and p-O2NC6H4SCl to give the corresponding halogen-, selenium-, and sulfur containing disubstituted isoquinolines and naphthyridines, respectively. Monosubstituted isoquinolines and naphthyridines have been synthesized by the metal-catalyzed ring closure of these same iminoalkynes. The Pd(II)-catalyzed cyclization of 2-(1-alkynyl)arylaldimines in the presence of various alkenes provides an efficient way to synthesize a variety of 4-(1-alkenyl)-3-arylisoquinolines in moderate to excellent yields. The introduction of an ortho-methoxy group on the arylaldimine promotes the Pd-catalyzed cyclization and stabilizes the resulting Pd(II) intermediate, improving the yields of the isoquinoline products. Highly substituted naphthalenes have been synthesized by the palladium-catalyzed annulation of a variety of internal alkynes, in which two new carbon-carbon bonds are formed in a single step under relatively mild reaction conditions. This method has also been used to synthesize carbazoles, although a higher reaction temperature is necessary. This method accommodates a variety of functional groups and affords the anticipated highly substituted naphthalenes and carbazoles in good to excellent yields. Novel palladium migration/arylation methodology for the synthesis of complex fused polycycles has been developed, in which one or more sequential Pd-catalyzed intramolecular migration processes involving C-H activation are employed. The chemistry works best with electron-rich aromatics, which is in agreement with the idea that these palladium-catalyzed C-H activation reactions parallel electrophilic aromatic substitution. A relatively efficient synthesis of cyclopropanes has been developed using palladium-catalyzed C-H activation chemistry, in which two new carbon-carbon bonds are formed in a single step. This method involves the palladium-catalyzed activation of relatively unreactive C-H bonds, and provides a very efficient way to synthesize cyclopropapyrrolo[1,2-a]indoles, analogues of the mitomycin antibiotics.

Modern Strategies for Heterocycle Synthesis

Modern Strategies for Heterocycle Synthesis
Author: Gianfranco Favi
Publisher: MDPI
Total Pages: 372
Release: 2021-03-17
Genre: Medical
ISBN: 3036503404

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Heterocycles feature widely in natural products, agrochemicals, pharmaceuticals and dyes, and their synthesis is of great interest to synthetic chemists in both academia and industry. The contributions of recent applications of new methodologies in C–H activation, photoredox chemistry, cross-coupling strategies, borrowing hydrogen catalysis, multicomponent and solvent-free reactions, regio- and stereoselective syntheses, as well as other new, attractive approaches for the construction of heterocyclic scaffolds are of great interest. This Special Issue is dedicated to featuring the latest research that is ongoing in the field of heterocyclic synthesis. It is expected that most submissions will focus on five- and six-membered oxygen and nitrogen-containing heterocycles, but structures incorporating other rings/heteroatoms will also be considered. Original research (communications, full papers and reviews) that discusses innovative methodologies for assembling heterocycles with potential application in materials, catalysis and medicine are therefore welcome.