Synthesis Of Complex Organic Molecules Research Articles

An Exceptional Valorization of CuO Nanoparticles in Ionic Liquids as an Efficient Medium for the Electrophilic Substitution of Indole Towards the Formation of Bis(indolyl)methanes

Aim: Ionic liquids are promising green solvents with simple but unique structure-related physical properties such as negligible vapour pressure, exceptional thermal conductivity, remarkable thermal stability and their suitability and inertness towards a broad range of catalytic applications. CuO NPs have been addressed as a cost-effective and a reagent of a choice that necessitates only mild reaction conditions to offer a high yield of the desired products with exceptional selectivity in a short duration of time. Therefore, in the present work, attempts have been made to explore the catalytic potentials of CuO NPs in an ionic liquid medium to synthesize biologically important bis(indolyl)methanes. Background: Catalytic explorations of metal oxide nanoparticles in ionic liquids offers a cooperative effect that has a significant impact on the kinetics as well as on the outcome of the reaction. Therefore, such catalytic systems in the present times have seized the scientific community's interest from the perspectives of sustainable development in synthetic organic chemistry. The combination of metal oxide nanoparticles with highly tunable ionic liquids is not only used to synthesize simple organic molecules but also explored in the synthesis of complex organic molecules of high commercial and biological relevance. Objectives: The current work offers a rapid and robust protocol for synthesizing bis(indolyl)methanes via electrophilic substitution reaction between indole and various aldehydes in the presence of a CuO nanoparticles-ionic liquid system. The discussion focuses on the high tolerance of different functionalities by the catalytic system leading to the synthesis of bis(indolyl)methanes. Methods: CuO NPs have been synthesized via the co-precipitation method using ionic liquid. The applicability of metal oxide nanoparticles-IL matrix was further investigated in synthesizing bis(indolyl)methanes. Results: The FT-IR absorption below 600 cm-1 and the XRD pattern showing all the peaks in the diffraction diagram revealed the formation of CuO NPs. FESEM images show the flake-shaped morphology of CuO NPs and are found to be separated from the agglomerated clusters Conclusion: Ionic liquid-CuO NPs matrix reveals good to exceptional catalytic properties, and their advancements as a catalytic system at room temperature open new avenues for synthetic organic chemists.

Soluble individual metal atoms and ultrasmall clusters catalyze key synthetic steps of a natural product synthesis

Metal individual atoms and few-atom clusters show extraordinary catalytic properties for a variety of organic reactions, however, their implementation in total synthesis of complex organic molecules is still to be determined. Here we show a 11-step linear synthesis of the natural product (±)-Licarin B, where individual Pd atoms (Pd1) catalyze the direct aerobic oxidation of an alcohol to the carboxylic acid (steps 1 and 6), Cu2-7 clusters catalyze carbon-oxygen cross couplings (steps 3 and 8), Pd3-4 clusters catalyze a Sonogashira coupling (step 4) and Pt3-5 clusters catalyze a Markovnikov hydrosylilation of alkynes (step 5), as key reactions during the synthetic route. In addition, the new synthesis of Licarin B showcases an unexpected selective alkene hydrogenation with metal-free NaBH4 and an acid-catalyzed intermolecular carbonyl-olefin metathesis as the last step, to forge a trans-alkene group. These results, together, open new avenues in the use of metal individual atoms and clusters in organic synthesis, and confirm their exceptional catalytic activity in late stages during complex synthetic programmes.

Transition‐Metal Catalyzed C−H Alkylation Using Epoxides as Alkylating Reagents

AbstractThe alkylation of arenes is one of the most fundamental transformations in synthetic chemistry and the transition‐metal‐catalyzed direct C−H alkylation represents a straightforward and attractive approach from both atom and step‐economy perspectives. Epoxides, the smallest three‐membered saturated O‐heterocycles that can be easily prepared in racemic or enantioenriched forms, are highly useful building blocks for the synthesis of complex organic molecules. Owing to their inherent high ring‐strain, epoxides readily undergo ring‐opening reactions and have been used as alkylating reagents for C−H alkylation catalyzed by transition metals. This review summarizes recent advances in utilizing epoxides as alkylating reagents in transition‐metal‐catalyzed C−H alkylation as well as their synthetic applications in organic synthesis.

Deoxygenative Transformation of Alcohols via Phosphoranyl Radical from Exogenous Radical Addition

AbstractA general approach to the direct deoxygenative transformation of primary, secondary, and tertiary alcohols has been developed. It undergoes through phosphoranyl radical intermediates generated by the addition of exogenous iodine radical to trivalent alkoxylphosphanes. Since these alkoxylphosphanes are readily in situ obtained from alcohols and commercially available, inexpensive chlorodiphenylphosphine, a diverse range of alcohols with various functional groups can be utilized to proceed deoxygenative cross‐couplings with alkenes or aryl iodides. The selective transformation of polyhydroxy substrates and the rapid synthesis of complex organic molecules are also demonstrated with this method.

Deoxygenative Transformation of Alcohols via Phosphoranyl Radical from Exogenous Radical Addition.

A general approach to the direct deoxygenative transformation of primary, secondary, and tertiary alcohols has been developed. It undergoes through phosphoranyl radical intermediates generated by the addition of exogenous iodine radical to trivalent alkoxylphosphanes. Since these alkoxylphosphanes are readily in situ obtained from alcohols and commercially available, inexpensive chlorodiphenylphosphine, a diverse range of alcohols with various functional groups can be utilized to proceed deoxygenative cross-couplings with alkenes or aryl iodides. The selective transformation of polyhydroxy substrates and the rapid synthesis of complex organic molecules are also demonstrated with this method.

A Brief Review on Recent Developments in Diels-Alder Reactions.

The [4+2] Diels-Alder cycloaddition has been widely used for the synthesis of six-mem-ber scaffolds. In recent years, there have been significant developments in this area, including the discovery and design of novel dienes and dienophiles with improved reactivity and selectivity. These new building blocks can be used to develop diverse molecular structures with functional group compatibility. Additionally, there is the use of catalytic systems and metal-mediated reactions to enable asymmetric [4+2] cycloadditions, resulting in enantiomerically enriched products. Over-all, recent studies related to [4+2] Diels-Alder cycloaddition using numerous dienes, dienophiles, and catalysts in different reaction conditions have significantly improved the efficiency, selectivity, and versatility of the reaction, making it an increasingly important tool in the synthesis of complex organic molecules as presented in this review. These advancements offer exciting possibilities for the development of new methods and reagents for the construction of six-membered rings and the synthesis of bioactive compounds.

Kinetics of direct and water‐mediated tautomerization reactions of nucleobases at low temperatures ⩽200 K

AbstractDetailed chemical kinetic mechanisms for the synthesis of complex organic molecules in the interstellar medium are at an early stage of developement. That such synthesis must take place is well‐known from chemical analysis of sampled asteroids. As molecular complexity increases the number of possible structural isomers also increases with the consequence that the nascent species may adopt a different spatial arrangement, to the lowest energy one. As part of a program of investigations of the hydrogen atom transfer reaction or tautomerization of imidic acid–amide species H‐O=C‐N‐ O=C‐N‐H we have studied the kinetics for a number of nucleobases, namely cytosine, thymine and uracil where a cyclic form of tautomerism (lactim–lactam) is encountered. Together with a fourth, 5‐aza‐uracil (1,3,5‐triazine‐2,4(1H,3H)‐dione), we report on the rates of reaction at low temperatures 50–200 K for both the direct unimolecular process and the similar transformation mediated by an additional water molecule. We show that these tautomerization reactions can be categorized into three classes, and highlight the importance of quantum mechanical tunneling on the rate constants at these low temperatures. We further present some thermochemistry data, such as formation enthalpies, entropies, isobaric heat capacities and enthalpy functions.

Catalytic Alkyne Allylboration: A Quest for Selectivity.

Catalytic methodologies that enable the synthesis of complex organic molecules from simple and readily available starting materials represent a goal in modern synthetic chemistry. In particular, multicomponent carboboration reactions that provide stereoselective access to densely functionalized building blocks are particularly valuable to achieve molecular diversity. This Perspective covers the developments in the area of catalytic allylboration of alkynes and highlights the key features that have allowed for the control of the regio-, diastereo-, and enantioselectivity in these transformations.

Recent Advances in Multicomponent Electro‐Organic (Electrochemical) Synthesis of Heterocycles

AbstractIn terms of pharmaceuticals and biological applications, synthesis of complex organic molecules is a significant and fast‐developing area. In this context, organic electrosynthesis is an alternative way to the traditional methods for chemo‐, regio‐, and stereoselective syntheses. Electro‐organic reactions occur at room temperature and normal pressure, through transferring electrons. It has been found that electrosynthesis is a mild approach for preparing electrophilic substrates, bases, and nucleophiles in situ, from highly stable and low‐level reagents; which can be further applied to make heterocycles more accessible. While several promising methods exist, multi‐component reactions (MCRs) have drawn much attention both in academia and industry worldwide, since they are cost‐efficient and environmentally friendly. Combining the electrosynthesis and MCRs has produced a great strategy in the field of organic synthesis for industry and research. This review focuses on recent advances in the electrochemical synthesis of heterocyclic compounds via multi‐component reactions, reported between 2015 and March 2023.

C−H Functionalized Molecules: Synthesis, Reaction Mechanism, and Biological Activity

AbstractReplacement of traditionally unreactive C−H bond with C−C or C−X (X=Hetero atom) has emerged as one of the widely accepted methods over the last few decades for the synthesis of complex organic molecules which can act as important intermediates for the synthesis of biologically active compounds. Selective functionalization of the C−H bond especially in the presence of a more reactive C−H bond has remained one of the biggest challenges for synthetic organic chemists. The hybridization state of the C−H bond, substitution pattern, and presence of directive groups are some of the factors which have been exploited by researchers over the years for achieving fruitful results. A considerable amount of work has been reported in the literature on the use of metal catalysts for C−H bond functionalization leading to the formation of a C−M (carbon‐metal) bond which is also known as C−H bond activation. This review aims to summarize various synthetic strategies reported for the C−H functionalization, which has led to the development of targeted complex molecules with medicinal properties.

Heterogeneous Catalysis under Continuous Flow Conditions

Abstract: Heterogeneous catalysis using continuous flow processing is one of the most demanding subjects from the viewpoint of manufacturing industrial-scale organic compounds. An amalgamation of the two areas of technology, i.e., heterogeneous catalysis and flow chemistry, has opened new avenues for green synthetic chemistry. These processes are particularly convenient in terms of short diffusion paths and improved mixing due to the sensing of high local concentration of catalytic species on solid catalytic surface when the liquid/ gaseous reagents pass through the column, ultimately resulting in quicker and more efficient reaction with increased reaction rates and higher turnover numbers. It imparts several key benefits over conventional batch systems, such as time and energy-saving methodologies, better productivity, reproducibility, economic viability, waste reduction, and ecofriendly nature. Also, it eradicates the need for any intermediate isolation, separation of catalysts, and use of excess reagents. The present review article focuses on heterogeneous catalysis under continuous flow conditions. Various key reactions, for instance, carbon-carbon bond formation, hydrogenation, condensation, and oxidation, are presented well, along with their recent developments in the manufacturing of active pharmaceutical ingredients and platform chemicals. Asymmetric catalysis has also been discussed with its applications in the synthesis of complex organic molecules. It is anticipated that the review article will proliferate significant interest in modernizing chemical syntheses through continuous flow processes.

Research progress on application of multi-enzyme-catalyzed cascade reactions in enzymatic synthesis of natural products

As a biocatalyst, enzyme has the advantages of high catalytic efficiency, strong reaction selectivity, specific target products, mild reaction conditions, and environmental friendliness, and serves as an important tool for the synthesis of complex organic molecules. With the continuous development of gene sequencing technology, molecular biology, genetic manipulation, and other technologies, the diversity of enzymes increases steadily and the reactions that can be catalyzed are also gradually diversified. In the process of enzyme-catalyzed synthesis, the majority of common enzymatic reactions can be achieved by single enzyme catalysis, while many complex reactions often require the participation of two or more enzymes. Therefore, the combination of multiple enzymes together to construct the multi-enzyme cascade reactions has become a research hotspot in the field of biochemistry. Nowadays, the biosynthetic pathways of more natural products with complex structures have been clarified, and secondary metabolic enzymes with novel catalytic activities have been identified, discovered, and combined in enzymatic synthesis of natural/unnatural molecules with diverse structures. This study summarized a series of examples of multi-enzyme-catalyzed cascades and highlighted the application of cascade catalysis methods in the synthesis of carbohydrates, nucleosides, flavonoids, terpenes, alkaloids, and chiral molecules. Furthermore, the existing problems and solutions of multi-enzyme-catalyzed cascade method were discussed, and the future development direction was prospected.

Formation of H2CO and CH3OH in the Protoplanetary Disks

It is known that the complex organic molecules in planetary systems may be formed by the organic chemistry of gases and particles in protoplanetary disks. Among these molecules, H2CO and CH3OH are potential precursors of essential organic compounds like glycolaldehyde. We calculate the physical and chemical structures of the protoplanetary disks around LkCa 15 and MWC 480 stars, compare the obtained column densities with the observed values. Our results mostly show reasonable agreements with observations. We identify the formation of H2CO to be through the both gas-phase and dust surface reactions, while CH3OH is dominantly formed by surface chemistry in the original astrolabe and then released into the gas-phase by surface exothermic chemical reactions in the LkCa 15 disk. We studied the synthesis of complex organic molecules (NH2CHO and CH3OCHO) in the protoplanetary disk to predict the observable species and Molecular abundance. In the disks around LkCa 15 and MWC 480 stars, we suggest that the strong spectral line observation of NH2CHO belonging to band 4 may obtain good results with ALMA, the observation of CH3OCHO may be challenging.

Photoredox‐mediated Multicomponent Reactions

AbstractMulticomponent reactions (MCR's) provide a unique opportunity for synthetic chemists to achieve the synthesis of complex organic molecules in a single step. Although MCR are known for more than a century, their utility, in general, is limited to a narrow set of reactions due to the inherent difficulties in controlling the desired reactivity & selectivity with three or more components. Photoredox catalysis on the other hand has recently gathered more attention from synthetic chemists due to its simplicity and the new type of reactivity it can offer. In this direction, many new multicomponent reactions mediated by photoredox catalysis are reported. Given the importance of thsis special type of reaction and in order to further design new photomediated multicomponent reactions, a review of the existing reports is very essential. We have broadly divided this review based on the type of photocatalyst used for the multicomponent reaction such as metal photocatalysis, organophotoredox catalysis & dual transition metal‐photoredox catalysis.

A Photoredox Nozaki‐Hiyama Reaction Catalytic in Chromium

AbstractOrganochromium(III) species are multipurpose nucleophiles used in the synthesis of complex organic molecules due to their high functional group tolerance and extraordinary chemoselectivity for aldehydes. The preparation of organochromium(III) species starting from organic halides requires the use of a stoichiometric amount of chromium(II) salts or a catalytic amount of chromium(III) salts in the presence of stoichiometric reductants (such as Mn(0)). Recently, radicals formation from readily available alkenes, followed by their trapping with stoichiometric or catalytic amount of chromium(II) salts were reported in photoredox conditions for the generation of Cr(III) organometallic species. In this paper we disclose a real Nozaki‐Hiyama reaction (NH) in which photoredox conditions enable the preparation of Cr(III) allyl reagents starting from available allyl halides and stable Cr(III) salts.

Organocatalysis: An Overview of its Application in Oxidation and Reduction Reactions

: Organocatalysis was established to be a wide-applicable approach from its inception and rediscovery in the year 2000, where proline was used as a catalyst in aldol condensation and soon after the successful emergence of iminium catalysed reactions in organic synthesis. Development of new potential catalytic systems is always an important as well as an uphill task for scientists and researchers. The fundamental organic synthesis majorly deals with metal based catalysts, whereas there is a constant surge of developing metal free reaction condition to make the reactions environmental friendly. For the synthesis of complex organic molecules, reduction and oxidation reactions are always needed and there are plenty of catalysts available for these reactions. Organocatalysts are also developed and applied for these two elementary reactions. This review focuses on some of the latest developments and applications of organocatalysts in oxidation and reduction reactions in fundamental organic synthesis.

Lithiation–borylation methodology in the total synthesis of natural products

Robust synthetic methods that show a broad substrate scope are of great utility in the synthesis of complex organic molecules. Within this arena, synthetic methods that employ boronic esters are especially useful because they undergo a wide variety of transformations with very high levels of stereoselectivity. In particular, boronic esters can undergo single or multiple homologations using enantioenriched metal carbenoids. The addition of a suitable enantioenriched lithium or magnesium carbenoid to a boronic ester, with subsequent 1,2-migration, gives a homologated boronic ester with high stereocontrol. This process, termed lithiation–borylation, can be iterative, which allows a carbon chain to be extended one atom at a time with remarkable precision. The iterative homologation has been likened to a molecular assembly line and resembles the way nature assembles natural products, for example, in polyketide synthase machinery. The application of lithiation–borylation chemistry to the synthesis of a broad variety of natural products is discussed in this Review.

Controlling enzyme reactions by supramolecular protection and deprotection of oligosaccharide substrates.

Protection/deprotection is a powerful strategy in the total synthesis of complex organic molecules but similar tools are nearly absent in enzymatic reactions. We here report supramolecular protective receptors that outcompete an enzyme in the binding of oligosaccharides. The strong binding inhibits the enzymatic reaction and addition of an even stronger ligand for the receptor releases the substrate. These receptors could be used to control products from the same substrate/enzyme mixture and regulate enzymatic reactions reversibly.

A New “Non-energetic” Route to Complex Organic Molecules in Astrophysical Environments: The C + H2O → H2CO Solid-state Reaction

Abstract The solid-state reaction C + H2O → H2CO was studied experimentally following the co-deposition of C atoms and H2O molecules at low temperatures. In spite of the reaction barrier and absence of energetic triggering, the reaction proceeds fast on the experimental timescale pointing to its quantum tunneling mechanism. This route to formaldehyde shows a new “non-energetic” pathway to complex organic and prebiotic molecules in astrophysical environments. Energetic processing by UV irradiation of the ice produced by co-deposition of C and H2O reactants leads mainly to the destruction of H2CO and the formation of CO2, challenging the role of energetic processing in the synthesis of complex organic molecules under astrophysically relevant conditions.

X-ray-Induced CO2 Formation via CO Reaction with TiO2 at Cryogenic Temperature.

Cosmic rays, γ-rays, and X-ray-driven reactions on interstellar grains have been the main focus in understanding the extraterrestrial synthesis of complex organic molecules. Herein, using temperature-programmed desorption and X-ray photoelectron spectroscopy, we report for the first time X-ray-induced CO2 production from a CO-covered rutile TiO2(110) surface at 110 K, in addition to X-ray-induced CO desorption. The X-ray-induced CO2 production was found to follow a Mars and van Krevelen (MvK) mechanism via the reaction between adsorbed CO and surface lattice oxygen of TiO2. Defects of TiO2 suppress the X-ray-induced CO2 production but promote the X-ray-induced CO desorption. These findings suggest a novel X-ray-induced CO-to-CO2 reaction on oxide surfaces at cryogenic temperature likely occurring in the interstellar medium and also warn us to keep in mind the possibility of X-rays inducing chemical reactions during structural characterizations of oxides with X-ray-involved techniques.