20^th European Organic Chemistry Congress November 28-29, 2024 Paris, France

Biography:

Rammiya Ramanathan graduated from the East Paris University of Creteil (UPEC, France) with a Master's degree in Bioactive Molecules Chemistry in 2022. She is a third-year PhD student in organic chemistry, under the supervision of Dr Michael Rivard, Associate Professor at UPEC. Her thesis focuses on the synthesis and valorization of nitrogen heterocycle derivatives. She is currently working at the East Paris Institute of Chemistry and Materials (ICMPE, France), known for its research in chemistry and materials science, as well as for its works developed at the interface with physics, engineering and biology.

Abstract:

Pyridiniums are six-membered cationic nitrogen-containing heterocycles found in both natural and synthetic compounds. The multiple properties associated with these structures make them usable in materials science or for the synthesis of biologically active natural products. Additionally, pyridiniums serve as important building blocks for the preparation of nitrogenated structures, such as piperidines, which are easily obtained by reduction of the heterocycle (Figure 1a).

Along with sugars, terpenes, alkaloids and fatty acids, amino acids make up one of the five major classes of natural products. Playing an essential role in biology, they and their derivatives are one of the main sources of chiral compounds, valuable for organic synthesis. In this context, we are interested in the conversion of amino acids into their corresponding pyridinium. In 2007, Marazano et al. proposed the use of Zincke salt to achieve this transformation. After a two-step reaction, expected compounds were obtained in poor yields (30%) after five days (Figure 1b). Low yields were primarily due to the need for reduced temperatures (below 45 °C) to avoid unwanted side reactions, such as decarboxylation or racemization. In 2021, Zhao et al. attempted to improve the method (Figure 1b). However, reaction times remained long (around 24 hours) and yields proved substrate-dependent (20-98%).

In this context, we propose an alternative approach using in- situ generated glutaconaldehyde and based on a protocol initially developed for the transformation of anilines and heteroaromatic derivatives (Figure 1c). With our method, amino acids and their esterified derivatives are efficiently converted into their corresponding pyridiniums. The poster will detail the experimental conditions we developed to optimize this reaction and will highlight the advantages of using a potassium salt of glutaconaldehyde as a reagent to perform this transformation. Antibacterial activities of the pyridiniums thus prepared will also be presented.

Biography:

Siddique Khan is a research scholar pursuing his doctoral studies (Ph.D.) under the supervision of Prof. Beeraiah Baire. He joined the Department of Chemistry, at IIT Madras in Jan 2019. His research focuses mainly on strategies for halogenation of the hexadehydro Diels-Alder reaction based Benzynes.

Abstract:

The HDDA reaction forms polycyclic benzyne intermediates via [4+2] cycloaddition between tethered alkyne and 1,3-diyne, yielding complex benzenoid products after trapping reactions.1,2 We devised and developed a versatile method for crafting dihaloarenes by trapping HDDA benzynes using N-halosuccinimides respectively. Here, the iodine- radical trapping reaction of the HDDA-benzynes for the construction of structurally divergent vicinal-diiodo arenes has been discovered and developed. Under thermal conditions, the N-iodosuccinimide was employed as the source of iodine radicals. EPR spectral analysis of the reaction mixture helped us to prove the existence of the radical intermediates and supported the proposed radical mechanism. A series of fruitful control experiments suggested that the 4-iodination (mono-) of the HDDA-benzynes is faster than the 5-iodiniation for both tetraynes as well as triynes. The iodine radical trapping reaction of the HDDA- benzynes was found to be faster than many of the intermolecular trapping reactions. The process is very broad in terms of the nature of the tethering units and substituents on the diynes. To the best of our knowledge, this is only the third report on the 1,2-diradical reactivity of the HDDA-benzynes and first one with experimental support for the radical mechanism.4 This presentation unveils our effort towards HDDA arynes using halogen based reagents.

Biography:

Surabhi Mishra is a research scholar pursuing her doctoral studies (PhD) under the supervision of Prof. Beeraiah Baire. She joined the Department of Chemistry, at IIT Madras in September 2020. Her research is focused mainly on acid catalyzed functionalization of inactivated C(sp3)-H bonds through vinyl carbocation intermediate.

Abstract:

The Prins cyclization reaction holds significance in organic synthesis as it enables the single step formation of both C−C and C−X (heteroatom) bonds. It will provide an access to generate many biologically relevant oxa-polycyclic systems as well spirocyclic frameworks, such as spiroketals. As a result, many biologically active natural products have been successfully synthesized by employing this approach. The spiroketal units are emerging as privileged structures in drug discovery. They are also omnipresent in the natural products domain. Alkyne-Prins cyclization reaction, involve an acid catalyzed condensation of homopropargylic alcohols/amines (in place of homoallylic counterparts; Prins cyclization) with aldehydes and ketones to give the corresponding five (exo-olefin) or six membered (endo-olefin) oxa- as well as aza- heterocyclic systems.

Here in, we developed a Brønsted acid catalyzed alkynyl Prins reaction between ketones/ aldehydes and 2-(1-alkyn-1-yl-n-ol)benzoates giving vinyl carbocation intermediate, which will be attacked by o-carboxylate resulting in intermediate (1), which further underwent rearrangement to give spirolactone product in single step (Scheme). This approach exhibits broad substrate scope with respect to carbonyl compounds and 2- (alkynol)benzoates, with yields ranging between 43–98%. To prove the mechanistic pathway, we performed control experiment and isolated the intermediate (1), which will be demonstrated in detail in the poster.

Biography:

Swati Lekha Mondal is a research scholar, currently pursuing her doctoral studies (PhD) under the supervision of Prof. Md. Mahiuddin Baidya. She joined the Department of Chemistry, IIT Madras in July 2020. Her research studies mainly focus on organocatalytic cascade annulation strategies unraveling the expedient approach towards fused carbocycles and heterocycles.

Abstract:

The isoxazolidine scaffold featuring an N–O bond connectivity in a ring framework is marked as the core constituent of many pharmaceuticals and natural products. In particular, the cyclopentane-fused isoxazolidine derivatives have received significant attention from the contemporary drug discovery regime owing to their promising bioactivities. They are acknowledged for antibacterial, antifungal, anti-cancer, and other significant therapeutic properties. Furthermore, this unique scaffold can also be utilized as an advanced intermediate towards the synthesis of natural products. Consequently, devising succinct catalytic protocols leading to these high-value scaffolds with enriched substitution patterns is highly desirable. Among the diverse methods to construct isoxazolidine scaffolds, the 1,3- dipolar cycloaddition reaction of nitrones with olefins remained most significant. Classically, nitrones are generated by condensing aldehydes with N-substituted hydroxyl amines with suitable nucleophilic N-center to facilitate the condensation event. However, such N-substitutions often constitute the pivotal burden in post synthetic manipulations. In fact, the recent advancements that account for the three-component coupling of diazo compounds, nitrosoarenes, and activated olefins to forge isoxazolidines also suffer a similar issue of N–aryl bond breaking. Grounded on this research gap, we delineated heretofore unrealized synthesis of cyclopentane-fused isoxazolidine frameworks from distal formyl enones 1 with hydroxycarbamates 2 bearing versatile functionalities such as Cbz, Boc, Troc. etc. The protocol is catalyzed by H3PO4 and offers a wide range of desired isoxazolidines 3 in high yields. Of note, these products are isolated as a single observable isomer. The cyclopentane-fused isoxazolidine products were also transformed into valuable cyclopentane-fused γ-lactams through the development of a diastereoselective benzilic amide rearrangement for which literature precedents are currently limited.

Biography:

Siddique Khan is a research scholar pursuing his doctoral studies (PhD) under the supervision of Prof. Beeraiah Baire. He joined the Department of Chemistry, at IIT Madras in Jan 2019. His research focuses mainly on strategies for halogenation of the hexadehydro Diels-Alder reaction based Benzynes.

Abstract:

The HDDA reaction forms polycyclic benzyne intermediates via [4+2] cycloaddition between tethered alkyne and 1,3-diyne, yielding complex benzenoid products after trapping reactions. We devised and developed a versatile method for crafting mono and dihaloarenes by trapping HDDA benzynes using Bismuth halides and N-halosuccinimides respectively. Here, we show how BiX₃ reagents stimulate the hydrohalogenation reactions of HDDA benzynes to produce complicated aryl halides. Each of the three bismuth(III) halides, Cl-, Br-, or I-, can serve as the source for the corresponding halide. The type of substituent at the diyne terminal determines the regiochemical preference for hydrohalogenation. Natures of the linker and the BiX3 reagent have no effect on the regiochemical outcome of these reactions. This process exhibits broad substrate scope in terms of tethering units and diyne substituents, with good yields and moderate regioselectivity. Extending this, HDDA reactions with N-halosuccinimide gives vicinal di-halogenation of arenes as well as radical di-halogenation of HDDA benzynes. This presentation unveils our effort towards HDDA arynes using halogen based reagents.

Biography:

Misba Siddique is a research scholar pursuing her doctoral studies (PhD) under the supervision of Prof. Arnab Rit. She joined the Department of Chemistry, at IIT Madras in July 2020. Her research focuses mainly on the synthesis of organometallic complexes and their catalytic activity in various transformations.

Abstract:

In the domain of metal-based catalysis, a comprehensive understanding of the structure of the metal-ligand complex is essential for assessing its catalytic performance. In this context, the steric and electronic properties of the ligands are important, as they significantly influence the complex's overall reactivity and stability. On the other hand, one-pot methodology offering either alkylation or cyclisation of 1,2- phenylenediamine using alcohol exploiting a single catalyst system remained unexplored. Herein, we report the chemoselective effective alkylation and cyclisation of 1,2- phenylenediamine with alcohol by simply switching the substituent on the supporting NHC ligand of cobalt(III) complexes. This varying catalytic behaviour of the complexes under consideration towards the selective formation of different products was fairly understood by analyzing their electronic properties based on NMR, electrochemical, and DFT studies. Further, the present protocol is compatible with a wide range of structurally diverse substrates offering ample variations of both amines as well as alcohols producing four different types of products starting from 1,2-phenylene diamine. Finally, an array of control experiments including the deuterium labeling and the identification of different intermediates assisted in establishing the proposed mechanism.

Biography:

Sangita Sahoo is a research scholar pursuing his doctoral studies (PhD) under the supervision of Dr. Arnab Rit. She joined the Department of Chemistry, at IIT Madras in July 2020. Her research focuses mainly on the development of effective base metal catalyst systems for various organic transformations.

Abstract:

Direct functionalization of unactivated organic moiety via C-C bond formation has long fascinated the synthetic chemists. Although the base metal systems are steadily emerging in this area, achieving multitasking activity of a single catalyst to execute several such functionalization under mild conditions is challenging. Herein, we report an effective protocol for the diverse selective C-alk(en)ylation of indene/fluorene with alcohol as a green alkylating agent employing a naturally abundant and eco-friendly zinc derived compound. Notably, this study unveiled the unique potential of a bench-stable Zn compound bearing an amide ligand towards C-C bond forming reactions utilizing an array of alcohols, ranging from aliphatic to aromatic and attractively, also the secondary ones. Moreover, this readily scalable protocol which proceeds via a borrowing hydrogen protocol, as established based on a range of control experiments, works effortlessly under mild conditions using low catalyst loading and affords remarkable selectivity towards alkylated or alkenylated products with high level of functional group tolerance and chemoselectivity. Synthetic utility of the obtained products was showcased by their late-stage functionalization to access unsymmetrical 9,9-disubstituted fluorenes, which is potentially useful for various optoelectronic applications.

Biography:

Misba Siddique is a research scholar pursuing her doctoral studies (PhD) under the supervision of Prof. Arnab Rit. She joined the Department of Chemistry, at IIT Madras in July 2020. Her research focuses mainly on the synthesis of organometallic complexes and their catalytic activity in various transformations.

Abstract:

In the domain of metal-based catalysis, a comprehensive understanding of the structure of the metal-ligand complex is essential for assessing its catalytic performance. In this context, the steric and electronic properties of the ligands are important, as they significantly influence the complex's overall reactivity and stability. In this line we have conducted a comprehensive study on the C-C/C-N bond formation with cobalt centers using CO₂ and alcohol. Initially, we synthesized cobalt complexes with a heteroditopic NHC ligand and Cp* as an auxiliary ligand. At room temperature, these complexes were employed for the effective N-formylation of amines with CO₂ but exhibited limited catalytic activity for sterically demanding substrates. Subsequently, when the same catalytic system was applied for the selective alkylation or cyclization of 1,2-phenylenediamine, the corresponding products were generated under relatively harsh reaction conditions. It was observed that the inert Cp* auxiliary ligand might impede the access of these substrates to the active cobalt centers. Consequently, we replaced the Cp* ligand with structurally labile acetylacetonate (acac) ligands and synthesized the Co-NHC complexes to evaluate their performance with structurally demanding substrates. Our findings revealed that the Co-NHC complexes with the acac ligand exhibited superior performance compared to Cp* for ortho-substituted anilines. Furthermore, these acac-containing Co-NHC complexes demonstrated efficacy in the olefination of alcohols using sulfone.