New Catalytic Reactions in Carbohydrate Chemistry

Carbohydrates or sugars are some of the most diverse and abundant biological molecules. They are involved in a multitude of processes in the body such as fertilization, cell-cell communication, and cancer metathesis. Because of these vital functions, the study of sugars is rapidly growing field. The field however is limited due to the complex nature of sugars which results in difficulties in obtaining large quantities for study. Protecting group manipulation is a large emphasis area in carbohydrate chemistry due to the need to selectively protect different functional groups of each molecule during synthesis. Catalytic and selective cleavage of protecting groups is a growing area in the field of carbohydrates as current methods are time-consuming and require large excess of reagents. Picoloyl ester is becoming a common protecting group due to its ability to provide a powerful stereodirecting effect in glycosylation reaction. Chapter 2 details the development of a new catalytic approach to remove the picoloyl group in a highly chemoselective manner. Protecting group manipulation is only one part of carbohydrate synthesis. New catalytic methods for glycosylation, a fundamental reaction for connecting two sugar units, are also needed. Chapter 3 describes our recent discovery that catalytic FeCl3 can efficiently activate glycosyl chloride to produce disaccharides in respectable yields in 30 min – 16 h. Chapter 4 further elaborates upon the topic of chemical glycosylation. Described herein is the application of a cooperative Ag2O and triflic acid catalysis to glycosidation of glycosyl chlorides. Fast reaction times and near quantitative yields are the main traits of this method. Lastly, Chapter 5 combines findings described in the previous chapters into development of a new superior platform for oligosaccharide synthesis. Currently used strategies for oligosaccharide synthesis are time consuming, inefficient, and may lead to low yields of oligosaccharides. By combining the catalytic picoloyl group cleavage and activation of glycosyl chlorides using FeCl3 we developed a reverse orthogonal synthetic strategy which combined protecting group cleavage and activation of glycosyl donors in one step. We then showcase how efficiently this concept works for the rapid assembly of oligosaccharide sequences

One-Pot Synthesis of Coumarin Derivatives

Coumarin derivatives have a myriad of applications in medical science, biomedical research, and many industrial branches. For this reason, many efforts are being dedicated to the development of novel and more practical methods for synthesizing these compounds. This chapter describes several methods of one-pot synthesis of coumarin derivatives, including von Pechmann condensation, Knoevenagel condensation, Baylis-Hillman reaction, Michael addition, Kostanecki reaction, vinyl phosphonium salt-mediated electrophilic reaction, and Heck-lactonization reaction. The methods are compared with each other, and the advantages and disadvantages of each of them are addressed

Homogeneous and heterogeneous catalysts for multicomponent reactions

[EN] Organic synthesis performed through multicomponent reactions is an attractive area of research in organic chemistry. Multicomponent reactions involve more than two starting reagents that couple in an exclusive ordered mode under the same reaction conditions to form a single product which contains the essential parts of the starting materials. Multicomponent reactions are powerful tools in modern drug discovery processes, because they are an important source of molecular diversity, allowing rapid, automated and high throughput generation of organic compounds. This review aims to illustrate progress in a large variety of catalyzed multicomponent reactions performed with acid, base and metal heterogeneous and homogeneous catalysts. Within each type of multicomponent approach, relevant products that can be obtained and their interest for industrial applications are presented.The authors wish to gratefully acknowledge the Generalitat Valenciana for the financial support in the project CONSOLIDER-INGENIO 2010 (CSD2009-00050)Climent Olmedo, MJ.; Corma Canós, A.; Iborra Chornet, S. (2012). Homogeneous and heterogeneous catalysts for multicomponent reactions. RSC Advances. 2(1):16-58. https://doi.org/10.1039/c1ra00807bS16582

Chapter 1: Part A: A Unique Approach of Preparing 3,3-Disubstituted Oxindoles from Acyclic Tetrasubstituted Aldehydes: Total Synthesis of (-)-Coerulescine and (-)-Coixspirolactam A, Chapter 1: Part B: Synthetic Scope of Brønsted Acid Catalyzed Reactions of Carbonyl Compounds and Ethyl Diazoacetate,

CHAPTER 1: PART A: A UNIQUE APPROACH OF PREPARING 3,3-DISUBSTITUTED OXINDOLES FROM ACYCLIC TETRASUBSTITUTED ALDEHYDES: TOTAL SYNTHESIS OF (-)-COERULESCINE AND (-)-COIXSPIROLACTAM A(-)-Coerulescine and (-)-coixspirolactam A, two naturally occurring compounds characterized with an all-carbon quaternary center containing a spirooxindole, have been synthesized asymmetrically. The key feature of their total synthesis involves a novel rational construction of the chiral 3,3-disubstituted oxindole core from the acyclic chiral tetrasubstituted aldehyde. The later scaffold was prepared in high enantioselectivity (up to 86%) from the ethyl 3-hydroxy-2-(2-nitrophenyl)acrylate 1 by exploring both intermolecular and intramolecular Pd-mediated asymmetric allylic allylations (Pd-AAA). A through optimization of these approaches is described in this thesis. CHAPTER 1: PART B: SYNTHETIC SCOPE OF BRØNSTED ACID CATALYZED REACTIONS OF CARBONYL COMPOUNDS AND ETHYL DIAZOACETATE The comprehensive study of the reactions of carbonyl compounds and ethyl diazoacetate in the presence of a Brønsted acid catalyst is described. In this, a broad range of 3-oxo esters were synthesized from a variety of ketones, specifically benzophenones and aliphatic ketones. For the diaryl ketones, we have characterized two inseparable products of migration by two-dimensional nuclear magnetic resonance spectroscopy (2D-NMR) and calculated the ratio of their relative migratory tendencies. However, the symmetric and nonsymmetrical aliphatic ketones provided the higher migration for relatively longer alkyl chains length. In case of the aliphatic aldehydes, we got exclusively the expected β-keto ester by a 1,2- hydride shift. CHAPTER 2: INVESTIGATION OF THE C2-ALKYLATION OF 1-(1H-INDOL-3-YL)-N,N-DIMETHYLMETHANAMINE Indole derivatives can be conveniently alkylated at the C2 position by choosing appropriate N-protecting group and appropriate base. However, 1-(1H-indol-3-yl)-N,N-dimethylmethanamine (commercially named as gramine) is also limited to that restricted choice of a protecting group for such alkylation. Herein we explore a the lithiation of gramine with different protecting groups (such as Ms, Ts, Me, TIPS etc.) on the N-heteroatom and investigate the alkylation at the C-2 position by trapping the C-2 lithio species with a variety of electrophiles such as methyl iodide, benzyl bromide, prenyl bromide, allyl bromide, etc

Sustainable C–H Functionalization within Peptide & Heterocyclic Chemistry

224 p.Chemistry is known to play a crucial role in the universal commitment to achieve sustainable methodologies in which the reduction of energy consumption and the production of waste constitute great challenges for the advancement of Science. In this context, Organic and Organometallic Chemistry have experienced exceptional development in recent years, providing access to new environmentally friendly synthetic protocols based on the use of metal catalysts. In particular, cross-coupling reactions for C–H functionalization have emerged as a powerful alternative within modern Chemistry to overcome previous synthetic problems. In this regard, CDC (Cross-Dehydrogenative Coupling) processes are of great interest since they not only minimize the generation of chemical waste but also can be carried out under very mild reaction conditions. Given the experience of our group in the development of robust and general catalytic C–H functionalization events, we envisioned that the use of earth-abundant and often less-toxic first-row transition metals (Cu, Fe, and Co) could be a viable tool for sustainable development. In particular, we became interested in the modification and assembly of amino acid and peptide derivatives, in a sustainable manner, due to their high importance in research areas such as proteomics and drug discovery. Likewise, the use of 1,2,3-triazoles as versatile DGs in the realm of C–H functionalization has not reached yet its full synthetic potential. Thus, we decided to focus our doctoral studies on the development of sustainable methodologies for the diversification of heterocycles and peptides, which are structures of utmost importance in medicinal chemistry

Sustainable C–H Functionalization within Peptide & Heterocyclic Chemistry

224 p.Chemistry is known to play a crucial role in the universal commitment to achieve sustainable methodologies in which the reduction of energy consumption and the production of waste constitute great challenges for the advancement of Science. In this context, Organic and Organometallic Chemistry have experienced exceptional development in recent years, providing access to new environmentally friendly synthetic protocols based on the use of metal catalysts. In particular, cross-coupling reactions for C–H functionalization have emerged as a powerful alternative within modern Chemistry to overcome previous synthetic problems. In this regard, CDC (Cross-Dehydrogenative Coupling) processes are of great interest since they not only minimize the generation of chemical waste but also can be carried out under very mild reaction conditions. Given the experience of our group in the development of robust and general catalytic C–H functionalization events, we envisioned that the use of earth-abundant and often less-toxic first-row transition metals (Cu, Fe, and Co) could be a viable tool for sustainable development. In particular, we became interested in the modification and assembly of amino acid and peptide derivatives, in a sustainable manner, due to their high importance in research areas such as proteomics and drug discovery. Likewise, the use of 1,2,3-triazoles as versatile DGs in the realm of C–H functionalization has not reached yet its full synthetic potential. Thus, we decided to focus our doctoral studies on the development of sustainable methodologies for the diversification of heterocycles and peptides, which are structures of utmost importance in medicinal chemistry

λ5-Phosphorus-Containing α-Diazo Compounds (PCDCs): a valuable tool for accessing phosphorus-functionalized molecules

The compounds characterized by the presence of a λ5-phosphorus functionality at the α-position with respect to the diazo moiety, here referred to as λ5-phosphorus-containing α-diazo compounds (PCDCs), represent a vast class of extremely versatile reagents in organic chemistry and are particularly useful in the preparation of phosphonate- and phosphinoxide-functionalized molecules. Indeed, thanks to the high reactivity of the diazo moiety, PCDCs can be induced to undergo a wide variety of chemical transformations. Among them are carbon–hydrogen, as well as heteroatom–hydrogen insertion reactions, cyclopropanation, ylide formation, Wolff rearrangement, and cycloaddition reactions. PCDCs can be easily prepared from readily accessible precursors by a variety of different methods, such as diazotization, Bamford–Stevens-type elimination, and diazo transfer reactions. This evidence along with their relative stability and manageability make them appealing tools in organic synthesis. This Review aims to demonstrate the ongoing utility of PCDCs in the modern preparation of different classes of phosphorus-containing compounds, phosphonates, in particular. Furthermore, to address the lack of precedent collective papers, this Review also summarizes the methods for PCDCs preparatio