Current Organocatalysis - Volume 6, Issue 2, 2019

Background: Metal nanoparticles have been extensively used in the synthesis of organic molecules during the last few decades especially due to their high catalytic activity. Organic reactions involving C-H functionalisations are very much in demand as they provide a direct method of derivatisation of organic molecules, thus making the process economical. In the recent years, metal nanoparticles catalysed C-H activation reactions have led to the design of useful molecules especially heterocyclic motifs which form the core structure of drugs and thus have high biological and industrial importance. Methods: In this review, we present a collection of reactions where metal nanoparticles are instrumental in the synthesis and functionalization of heterocycles via C-H activation. The review consists of three units namely, Nano-copper catalysed C-H activation reactions, nano-palladium catalysed CH activation reactions and other nano-metals catalysed C-H activation reactions. Results: The discussion reflects the scope of nano-metals as effective catalysts for the synthesis and functionalization of heterocycles as well as the efficiency of nano-metals towards catalysing economic and environmentally viable reaction protocols. Conclusion: The theme of this review is to correlate nanometal catalysis, heterocyclic synthesis and C-H activation, each of which in itself forms an integral part of modern day chemical research. Thus, the review will hopefully highlight the need for future development and research in this area and be instrumental in guiding researchers towards fulfilling that goal.

Background: The continuous increase in challenges associated with the effective treatment of life threatening diseases influences the development of drug therapies with suitable physicochemical properties, efficiency and selectivity. So, organocatalysis is a potential synthetic tool which is accelerating the development of new drug molecules. Methods: Organocatalysis reactions can be carried out at lower temperatures and in milder pH conditions as compared to metal based catalysed reactions. Due to ready availability of catalysts, stability, purity, low toxicity and easy in handling of the chemical reactions, it has become an attractive technique to synthesise complex molecules with diverse structures. Here, the impact of various catalysts in organic synthesis with methods is discussed. Results: Organic catalysts are used widely in various chemical reactions such as Michael Addition, aldol reaction, Diels-Alder reactions and Knoevenagal reactions. It was observed that the use of organocatalyst results in the formation of stereo active molecules with diverse biological activities. Conclusion: This review also focuses on the various scopes and limitations of organocatalytic reactions in the production of medicinally useful drug molecules. Organocatalysts possess several advantages over traditional metal catalysts because they are non-toxic, readily available, stable, efficient, and easy to handle which involves environmentally friendly reaction.

Introduction: The popularity of chitosan is increasing among the researchers due to its environment friendly nature, high activity and easy approachability. Chitosan based catalysts are not only the most active and selective in catalytic reaction, but their “green” accessibility also makes them promising in organic catalysis. Chitosan is commonly extracted from chitin by alkaline deacetylation and it is the second abundant biopolymer in nature after cellulose. Chitosan based catalysts are advantageous by means of non-metallic activation as it involves small organic molecules. The robustness, nontoxicity, the lack of metal leaching possibility, inertness towards moisture and oxygen, easy handling and storage are the main advantages of organocatalysts. Traditional drawbacks associated with the metal-based heterogeneous catalysts, like longer reaction times during any synthesis, metal-leaching after every reaction and structural instability of the catalyst for prolonged recycling experiments are also very negligible for chitosan based catalysts. Besides, these catalysts can contribute more in catalysis due to their reusability and these special features increase their demand as the functionalized and profitable catalysts. Objectives: The thorough description about the preparation of organocatalysts from chitosan and their uniqueness and novel activities in various famous reactions includes as the main aim of this review. Reusable and recycle nature of chitosan based organocatalysts gain the advantages over traditional and conventional catalyst which is further discussed over here. Methods and Discussions: In this article only those reactions are discussed where chitosan has been used both as support in heterogeneous catalysts or used as a catalyst itself without any co-catalyst for some reactions. Owing to its high biodegradability, nontoxicity, and antimicrobial properties, chitosan is widely-used as a green and sustainable polymeric catalyst in vast number of the reactions. Most of the preparations of catalyst have been achieved by exploring the complexation properties of chitosan with metal ions in heterogeneous molecular catalysis. Organocatalysis with chitosan is primarily discussed for carbon-carbon bond-forming reactions, carbon dioxide fixation through cyclo- addition reaction, condensation reaction and fine chemical synthesis reactions. Furthermore, its application as an enantioselective catalyst is also considered here for the chiral, helical organization of the chitosan skeleton. Moreover, another advantage of this polymeric catalyst is its easy recovery and reusability for several times under solvent-free conditions which is also explored in the current article. Conclusion: Important organocatalyzed reactions with either native chitosan or functionalized chitosan as catalysts have attracted great attention in the recent past. Also, chitosan has been widely used as a very promising support for the immobilization of catalytic metals for many reactions. In this review, various reactions have been discussed which show the potentiality of chitosan as catalyst or catalyst support.

Arylazoimidazole brings azoimine (-N=N-C=N-) chelating N(azo), N(imine) (abbreviated - N, N/) centres and forms Ru(II) and Os(II) carbonyl complexes. These complexes act as catalysts for the oxidation of alcohols to aldehydes/ketones by tertiary butyl hydro peroxide (ButOOH), hydrogen peroxide (H2O2) and N-methylmorpholine-N-oxide (NMO) as oxygen sources. Different substituted arylazoimidazoles such as 1-alkyl-2-(arylazo)imidazoles (RaaiR/), 1-alkyl-2-(naphthyl-α/β- azo)imidazoles (α/β-NaiR) and (1-alkyl-2-{(o-thioalkyl)phenylazo}imidazole, SRaaiNR/) are used to prepare Ru/Os-CO complexes. Ancillary ligands like hydride (H-), chloride (Cl-), triphenylphosphine (PPh3) are used to monitor the catalytic efficiency of the complexes. Aromatic and aliphatic alcohols like benzyl alcohol, 2-butanol, cyclopentanol, cyclohexanol, 1-phenylethanol, cinnamyl alcohol, diphenylmethanol, are oxidized to the corresponding benzaldehyde, 2-butanone, cyclopentanone, cyclohexanone, phenylacetone, cinamaldehyde, cyclopentanone, benzophenone, respectively. Different physicochemical analyses (FT-IR, UV-Vis, Mass, NMR) suggest that the complexes react with an oxidant to yield high valent ruthenium/osmium-oxo species (RuIV=O; OsIV=O), which is capable of transferring the oxygen atom to alcohols. GC analysis accounts that percentage conversion order is as follows : Cinnamyl alcohol > Cyclohexanol ~ 1-Phenylethanol > Diphenylmethanol > Cyclopentanol > 2-Butanol > Benzyl alcohol. The oxidation efficiency of the oxidant follows the order : NMO > ButOOH > H2O2. RuII complexes are more potent catalysts than OsII complexes. Out of three series of RuII complexes, [RuCl(CO)(SMeaaiNEt)]ClO4 and [RuCl(CO)(SEtaaiNMe)]ClO4 showed highest catalytic efficiency amongst 32 catalysts.

Background: Catalyst speeds up any chemical reaction without changing the point of the equilibrium. Catalysis process plays a key role in organic synthesis to produce new organic compounds. Similarly, organocatalysis is a type of chemical catalysis in which the rate of a reaction is accelerated by organic catalysts. Methods: Organocatalysts have gained significant utility in organic reactions due to their less of sensitivity towards moisture, readily available, economic, large chiral pool and low toxicity as compared to metal catalysts. Organocatalysts work via both formations of covalent bonds such as enamine and iminium catalysis as well as through non-covalent interactions such as in hydrogen bonding. For example, Bakers’ yeast based organocatalysis is widely used in various organic transformations. Results: Baker’s yeast is a fermentation product and used mainly in the preparation of bread dough. It is produced by aerobic fermentation of yeast strain Saccharomyces cerevisiae. Baker's yeast consists of enzymes which can reduce a carbonyl group into a hydroxyl group with high yield and thereby making it suitable for biotransformations in organic synthesis. Conclusion: Baker's yeast is widely used as a biocatalyst in various organic reactions such as oxidation, reduction, condensation, hydrolysis, cyclization, etc. because it is readily available, inexpensive and easy to handle.

Background: A cheap and commercially available organocatalyst, (1R, 2R)-(+)-1, 2- diammonium cyclohexane-L-tartrate 1 was applied in direct aldol reaction in water. The organocatalyst 1 afforded aldol products from cyclohexanone and substituted aromatic aldehydes with high yield (up to 90%) and good stereoselectivity (up to 99% ee and up to 11.5:1 dr) in large volume of water (10 ml). Methods: The same aldol reaction when carried out in the presence of more expensive organocatalyst e.g. (1R, 2R)-(+)-1,2-diaminocyclohexane and 1,6-hexanediaoic acid as acid additive furnished the aldol products with only 20% yield, 2:1 anti/syn ratio and 92% ee. Results and Conclusion: In summary, we have applied a reasonably cheap and commercially available organocatalyst 1 for highly enantioselective direct aldol reaction in water at room temperature.

Background: While proline can catalyze the asymmetric direct aldol reactions, its catalytic activity and catalyst turnover are both low. To improve the catalytic efficiency, many prolinebased organocatalysts have been developed. In this regard, prolinamide-based bifunctional catalysts have been demonstrated by us and others to be highly efficient catalysts for the direct aldol reactions. Results: Using the β-acetamido- and β-tosylamidoprolinamide catalysts, the highly enantio- and diastereoselective direct aldol reactions between enolizable ketones and aldehydes were achieved (up to >99% ee, 98:2 dr). A low catalyst loading of only 2-5 mol % of the β-tosylamidoprolinamide catalyst was needed to obtain the desired aldol products in good to high yields and high stereoselectivities. Methods: By carefully adjusting the hydrogen bonding ability of the remote β-amide hydrogen of the 1,2-diamine-based prolinamide bifunctional catalysts, the catalytic activity and the asymmetric induction of these catalysts were significantly improved for the direct aldol reaction between aldehydes and enolizable ketones. Conclusion: Some highly efficient 1,2-diamine-based bifunctional prolinamide catalysts have been developed through probing the remote β-amide hydrogen for its hydrogen bonding capability. These catalysts are easy to synthesize and high enantioselectivities may be achieved at very low catalyst loadings.

Background: Recently, organic synthesis using ionic liquids (ILs) via green approach has attracted considerable attention to address the problem associated with environmental pollution. Magnetization of ILs provides added advantages of separation by external magnet. This can be accomplished by incorporation of high-spin iron(III) in the form of tetrachloro or tetrabromoferrate( III). Thus, synthesis of novel magnetically separable ILs for organic transformations is highly desirable. Results: [AcMIm]FeCl4 ionic liquid showed excellent catalytic activity in the one pot threecomponent synthesis tetrahydrobenzo[b]pyran derivatives at room temperature in excellent yields (94-98 %) within short reaction time (15-20 min.). The ILs were recovered and reused for at least six times with the minimum loss of catalytic activity. Methods: Here, we have demonstrated the excellent catalytic activity of acid functionalized magnetic Ils, [AcMIm]FeCl4 in one-pot multicomponent reactions for the synthesis of biologically important tetrahydrobenzo[b]pyran derivatives. Conclusion: A facile and convenient methodology has been developed for the synthesis of bio-active tetrahydrobenzo[b]pyran derivatives using [AcMIm]FeCl4 ionic liquid as an sufficient and reusable catalyst under environment-benign conditions.