Catalysis: Current and Future Developments

Chiral spiro compounds have been found to have great importance in organic synthesis because of their presence in a variety of natural alkaloids and pharmaceuticals. Lately, spiro compounds have gained interest because of their engrossing conformational characteristics and their structural connection with biological systems. Enantioselective synthesis of conformationally constrained spiro and bridged acetals can also be performed by organometallic catalysts but we will focus on organocatalytic routes in this chapter. Organocatalytic methodologies are found to be powerful approaches for the synthesis of conformationally rigid spiro and bridged acetal compounds because of their stability, functional group tolerance and easy stereoprediction. In this chapter, the organocatalytic asymmetric approaches for the synthesis of bridged [2.2.1], [2.2.2], [3.1.1], [3.2.1], [3.3.1] bicyclic acetals as well as spiroacetals are discussed in details with examples. The synthesis contains different reactions such as Michael addition reaction, Mannich reaction, cycloaddition reaction, aldol reaction, tandem Friedel Craft/hemiketalization reaction, Knoevenagel, Diels Alder reaction, cyclisation reaction and various other reactions.

The hydrolytic kinetic resolution of terminal epoxides catalyzed by the monometallic chiral salen Co complex follows the cooperative bimetallic mechanism and second order kinetic dependency on the catalyst. In this mechanism, one metal works as an active Lewis acid center for preferential activation of one enantiomer from a racemic substrate and the second metal center stimulates the incoming nucleophile. Mechanistically, rational design and development of bi- and multimetallic chiral complex centers within the sterically, electronically, and co-ordinatively accessible framework of chiral salen ligand provides improved activity and enantioselectivity relative to their corresponding monometallic catalysts. This chapter provides a survey of bimetallic chiral salen Co complexes used in the hydrolytic kinetic resolution of terminal epoxides to procure valuable chiral intermediates, useful for academic interest and in industrial applications.

Catalytic reactions play a major role in industry to produce a number of compounds, which are essential in our daily life. These reactions cover synthesis of biofuels from bio waste, oil refining, cracking of hydrocarbons, hydrogenations, dehydrogenations, partial oxidations and fermentations. In surface catalysis, the catalytic reactions occur mainly on the surface, where number of steps involved are adsorption, diffusion and reaction on the surface and desorption of the products. Producing the target product with a high turnover number (TON) and turnover frequency (TOF) is a major challenge for surface catalysis. Recently, flow systems have been developed to produce high quality chemicals and reduce time and energy. In this direction, polymers, metal oxides like alumina and silica, metal nanoparticles of Pt, Pd, and carbon nanotubes (CNTs)have been modified (or treated)with various chiral ligands to synthesize highly active and enantioselective heterogeneous catalysts for the flow process. The aim of this review is to highlight the potential application of flow systems in heterogeneous catalysis. The unique combination of high levels of selectivity in heterogeneous systems together with ease of separation, purification and recyclability makes this heterogeneous system under flow conditions, one of the most promising strategies for the synthesis of fine chemicals on an industrial scale. This review focuses on the most representative examples of this emerging research field, highlights, and future perspectives of flow systems in heterogeneous catalysis. Recent achievements in this area using metal supported and self-supported organo catalysts are discussed.

Background: Activation of covalent bonds for the initiation of chemical reactions can be achieved by all kinds of energy including light, thermal heating, microwave heating, electrical, sonochemical and mechanical energy. Among these, ball milling is an attractive alternative source of energy for the activation of bonds leading to chemical reactions due to its simplicity, ease of purification of products, mild reaction conditions and greenness of the process.

Methods: Mechano-chemical reaction is defined as “a chemical reaction that is induced by the direct absorption of mechanical energy.” Simply, mechanical energy can be generated by grinding using a mortar and a pestle and the process of milling is carried out in ball mills. The process of milling is more reproducible due to the regulation of parameters like time and energy entry.

Results: The ball milling is mainly applicable in the industry for particle refinement processes, disagglomeration, the cracking of bacteria, etc. However, recently, ball milling has attracted considerable attention in organic synthesis due to its operational simplicity, economy, environment friendliness, and its potential to produce very good yields of products, and as a consequence, several research articles, review papers and book chapters have been published in recent time. The literature studies revealed that various carbon-carbon, carbon-heteroatom bond formation, condensation reactions, coupling reactions and oxidation-reduction reactions have been performed in a ball mill under mild and environmental-friendly reaction conditions.

Conclusion: The aim of this review is to highlight the recent breakthrough of ball milling in organic transformation leading to the synthesis of bioactive molecules in the context of Green Chemistry.

In recent years, the organocatalytic electrophilic fluorination reactions have been extensively explored for the synthesis of organofluorine compounds. The systematic introduction of fluorine atom often improves a number of properties of fluorinated molecules including metabolic stability and various pharmacological properties and thus frequently employed to design fluorinated drugs. The enantioselective electrophilic fluorination via organocatalysis has emerged as the most powerful approach for the synthesis of organofluorine compounds as the organocatalytic approaches have several advantages in terms of economical and environmental benefit. In this chapter, the most important developments of organocatalytic enantioselective electrophilic fluorination are highlighted using new types of electrophilic fluorinating reagents (NFSI, F-TEDA-BF4, F-CA-BF4) in the presence of readily available different types of organocatalysts such as different amine based catalysts, phase-transfer catalysts, Brønsted acid and H-bonding catalysts, which are stable, easy to handle, more efficient and selective. Some recent advances with fascinating examples, mechanism of electrophilic fluorination, mode of activation of catalysts, catalytic cycles, controlling product selectivity and synthesis of chiral fluorine containing drugs have been described.

There has been great interest in the replacement of petroleum-based polyols with biobased polyols in polyurethane applications. However, current products mainly triglyceride-based polyols have many drawbacks, and also do not have the structural efficiency and physical performance characteristics that restrict them to limited applications.

To minimize all these limitations, the synthesis of low molecular weight liquid polyols can be performed via a robust, simple, environmentally friendly, and solvent-free ‘biocatalytic route’. In contrast to chemical methods, enzyme-catalyzed reactions proceed with high enantio- and regioselectivity, under mild conditions, avoiding protection deprotection steps, providing an attractive alternative to conventional chemical methods. Bio-renewable, non-toxic and low-cost monomers, such as 2,5 dihydroxymethyl furan, 1,4 butanediol, glycerol, diglycerol, isosorbide, D-mannitol, D-sorbitol, citric acid, maleic acid, fumaric acid, succinic acid, glutaric acid, adipic acid, sebacic acid and many more can be employed in preparing biobased polyol prepolymers via enzymatic catalysis.

In general, a catalyst is used to enhance the reaction and to complete the reaction quickly or accelerate the reaction involving reactants and catalysts. In the catalysis process, only the chemical structure of reactant changes with time, but the structure of the catalyst remains unaffected throughout the course of the reaction. The varieties of chemicals that can be used as a catalyst in numerous chemical reactions are metals, acids, bases, organic compounds, inorganic complexes, enzymes and polymers. Some specific polymers have the ability to catalyse reactions with the formation of carbon-carbon and carbon-non carbon linkages. Polyvinyl pyridine and sulfonated polystyrene are very useful and simple polymers that can act as catalysts. The catalytic activity of polymers is pronounced due to modification in polymer chains. Further, polymers may also be used as a support for another catalyst. Polymer catalysis can be illustrated with soluble linear polymers, ion exchange resins, polymer-supported phase transfer catalysts, palladium catalysts on polymer supports, etc. The brief review of each is explained by citing important examples along with their basic principles.