Acide carboxylique | EPFL Graph Search

thumb|Modèle éclaté d'un groupe carboxyle. Le terme acide carboxylique désigne une molécule comprenant un groupe carboxyle (–C(O)OH). Ce sont des acides et leurs bases conjuguées sont appelées ions carboxylate. En chimie organique, un groupe carboxyle est un groupe fonctionnel composé d'un atome de carbone, lié par une double liaison à un atome d'oxygène et lié par une liaison simple à un groupe hydroxyle : -OH. Généralités En chimie, les acides carboxyliques R-COOH constituent avec les acides sulfoniques R-SO3H les deux types d'acides de la chimie organique. On les trouve de manière abondante dans la nature, sous la forme d'acide gras (lipide) et ils sont très importants en chimie industrielle. Par exemple, l'acide acétique est non seulement une brique importante pour les molécules complexes que l'on trouve en biologie, mais est aussi une molécule produite industriellement et qu'on retrouve dans le vinaigre. Un des plus connus est l'acide acétylsalicylique ou aspirine.

Aliphatic Carboxylic Acids as Coupling Partners in Carbon-Heteroatom Bond-Forming Reactions

Runze Mao

Carboxylic acids are one of the most suitable starting materials for synthesis. They are readily available and therefore inexpensive, stable and non-toxic. Many carboxylic acids can be obtained directly from natural resources, thus avoiding the extraction of fossil resources, such as oil or natural gas, in the production of chemicals. Furthermore, renewable carboxylic acids derived from biomass have a wide structural diversity (e.g., amino acids, fatty acids and sugar acids), which not only holds greater potential for the synthesis of complex molecules, but also advances the development of green chemistry. In this context, this thesis aims at establishing new carbon-heteroatom coupling reactions with carboxylic acids as versatile coupling partners. These reactions are hitherto unknown, which not only fill some of the gaps in synthetic organic chemistry, but also provide solutions for the rapid assembly of bioactive molecules. In order to overcome the challenge of forming C(sp3)-heteroatom bonds, Chapters 4, 5 and 6 detail the development of photoredox/copper bi-catalytic systems and their applications in decarboxylative C(sp3)-N and C(sp3)-O coupling reactions. These methods are not only compatible with numerous functional groups, but also allow for rapid late-stage functionalization. More importantly, these methods can simplify the pathway for building drug core skeletons, highlighting the potential of these methods to expedite drug discovery. To bridge the disconnection in the synthesis of trifluoromethylthioesters from carboxylic acids, Chapter 7 describes the establishment of a "umpolung" strategy and its application in the conversion of carboxylic acids to trifluoromethylthioesters. This approach provides the most concise synthetic pathway to date for the synthesis of trifluoromethylthioesters, which not only accommodates a variety of functional groups, but also allows for the rapid functionalization of carboxylic acid-containing natural products and drug molecules. In summary, this thesis illustrates how novel catalytic methods can be used to convert inexpensive, readily available and environmentally benign aliphatic carboxylic acids into high value-added compounds.

EPFL2020

Photoredox-Catalyzed Decarboxylation for the Transfer of Alkynes and Nitriles Using Hypervalent Iodine Reagents

Franck Le Vaillant

Aliphatic alkynes and nitriles are privileged motifs in organic chemistry. Therefore, alkynes and nitriles have played a central role for the exploration and development of novel strategies to forge C-C bonds in efficient manner. They are broadly used as versatile building blocks for applications in every fields of chemistry, from pharmaceuticals to material sciences. Alkynes are also of paramount importance in chemical biology for labelling experiments due to their bio orthogonality. In this context, radical chemistry provides endless alternatives to nucleophilic and electrophilic alkynylation and cyanation reactions. For decades, organic chemists have designed and improved the structure of alkynylating reagents in order to enhance the efficiency of group transfer process. Methods enabling alkynylation and cyanation of alkyl radicals have emerged and while providing useful tools, they set the basis for further improvements. Notably, the formation of alkyl radicals is limited to harsh conditions using peroxides, elevated temperature and radical initiators. To overcome these major limitations, photoredox catalysis has emerged as a powerful tool for the generation of alkyl radicals under ambient conditions. The combination of photocatalysts and alkynylating reagents allowed the photoredox-catalyzed alkynylation of organoboron trifluoroborates salt and N-phtalimide esters. In this regard, the goal of my PhD was first to extend the photoredox catalyzed alkynylation to carboxylic acids. Indeed, carboxylic acids are broadly available from biomass, and widely occurring in drugs and fine chemicals, thus making them attractive starting materials. Their conversion to alkynes would provide efficient disconnections for the construction of Csp3-Csp, and find useful applications in chemical biology. Ethynyl Benziodoxolone (EBX) reagents, CsOBz and iridium photocatalysts were identified as a promising combination for the development of this novel transformation, in which silyl, aryl and alkyl substituted alkynes were transferred. ï¡ïamino, ï¡ïoxy and non-heteroatom stabilized radicals could be alkynylated in good to excellent yields upon visible light irradiation. This strategy was next applied to the decarboxylative cyanation of carboxylic acids. In that regard, Cyano Benziodoxolone CBX was introduced for the first time in photoredox-catalyzed cyanation. The combination of CBX, CsOBz and the same iridium photocatalyst allowed the smooth conversion of amino and oxy acids to their corresponding nitriles, and this novel method was applied to the synthesis of important intermediates in the synthesis of APIs. During scope investigations, hydantoins were isolated as side products. This background reaction was further optimized as a novel and efficient synthesis of chiral hydantoins starting from amino acids and CBX. Finally, investigations of the reaction mechanisms of the photoredox-catalyzed decarboxylations revealed that the cyanation followed a divergent mechanism compared to alkynylation. A additional redox step between CBX and ï¡-amino radical allows the generation of cyanide and iminium, which upon recombination affords the nitrile product. Then, the second goal of my PhD was to implement the photoredox mediated alkynylation and cyanation to other starting materials. In this regard, the use of carboxylic acids as starting materials to initiate photoredox catalyzed radical fragmentations was an appealing strategy.

EPFL2019