The Role of Catalysts in Functionalization of C-H and C-C Bonds

Catalysis is one of the fundamental pillars of green chemistry. Contemporary research in green organic synthesis focuses on saving energy attainable with the use of green chemistry tools (microwave, ultrasound, ball mill, etc.), also utilizing catalysts. Catalysis has been positioned at the forefront of chemical research concerning the minimization of waste by using catalytic reactions, with catalysts being essential for C-H functionalization and C-C bond formation.

This Special Issue includes fifteen articles in total, out of which thirteen are research articles and two are review papers. The review article published by Maiti’s group [1] screened C-H methylation, as the interest in C-H methylation has grown rapidly due to its biological importance in medicinal chemistry, which is popularly called the “Magic Methyl Effect”. A radical-based approach for the alkylation of heterocycles was first proposed by Francesco Minisci. Later on, various groups developed modified Minisci-type reactions via different strategies viz. photo-redox, electrochemical, mechanochemical, transition metal catalyzed, as well as metal-free. So far, various methyl sources have been discovered, e.g., CH₃OH, CH₃COOH, DMSO, CH₃B(OH)₂, CH₄, DCP, TBHP, etc. Photo-redox and electrochemical approaches usually negate the use of harsh oxidants. The mechanochemical protocol helps to minimize the solvent waste. Metal-free approaches are providing a new direction; to methylate, carbon centers by avoiding the use of a metal catalyst. This helps in reducing the metal contamination. These sustainable approaches for the C-H methylation of both sp² and sp³ carbon centers fueled the remarkable development in its applications. The second review article published by Ke yang et al. was classified into two parts [2]. The first part mainly introduces the nickel-catalyzed intramolecular C-H alkylation and arylation reactions and their role in constructing different heterocycle compounds, including imidazolium and thiazolium salts, pyridones, indolones, dibenzofurans, and others. Furthermore, various chiral derivatives of simple heterocyclic compounds, such as pyridine, 2-pyridone, isoquinoline, quinolinone, 4-pyrimidone, and imidazoles, have been obtained through Ni-catalyzed asymmetric C-H functionalization with a chiral ligand. Additionally, intramolecular C-H amination catalyzed by nickel catalysts provides an important approach to preparing azetidin-2-one and cyclopentylamine derivatives. The second part mainly describes the nickel-catalyzed intermolecular C-H/N-H annulation reactions, leading to the synthesis of isoquinolones, isoquinoline, indoles, isoindoline-1,3-diones, and pyrrole-2,5-diones by using different directing groups, including pyridinylmethylamine, pyrimidin-2-amine, 8-aminoquinoline, and others. While some significant work has been accomplished using these directing groups, there are still many avenues for improvement and utilization in this field. In general, these directing groups often need to be pre-installed on the substrates to promote the C-H functionalization reactions, which limits the efficiency of the process. Therefore, transient ligand-enabled nickel-catalyzed C-H functionalization would be an ideal strategy for heterocycle synthesis. We hope this review will provide some insights for readers and inspire them to explore more novel approaches in nickel-catalyzed C-H functionalization and their utility in heterocycle synthesis. An interesting work by Saleh et al. [3], published for the first time in the literature, has emerged in this Special Issue. They described a novel sonophotoreactor based on an ultrasonic cleaning bath and blue LED light (visible light) that induce copper-catalyzed monoarylation for pharmacologically relevant pyrazoles. The hybrid effect of ultrasonic irradiation and blue LED is discussed to interpret the observed synergistic action. A broad array of pyrazoles coupled with iodobenzene avoids expensive palladium metal or salts, and certain designed substrates were attained. Only comparatively inexpensive copper(I)iodide and 1,10-phenanthroline were used together as the catalyst. The presented technique is a greener way to create the C-H arylation of pyrazoles. It significantly reduces the amount of energy needed. On the other hand, the C-C coupling reaction was studied by El-Shishtawy’s group [4], where three palladium-catalyzed coupling reactions—the Suzuki–Miyaura coupling reaction, Suzuki cross-coupling reaction, and Stille cross-coupling reaction—were presented, utilizing three palladium catalysts—Pd(PPh₃)₄, Pd(PPh₃)₂Cl₂, and Pd(dppf)Cl₂—under mild conditions. PTZ, POZ, and Cz were utilized in the Miyaura borylation reaction to synthesize 17 heteroaromatic pinacol boronate esters decorated with imidazolyl, p-tolyl, or carbaldehyde groups. The best yields of the borylated species were obtained using Pd(dppf)Cl₂ as a catalyst. The electron-deficient QX was decorated with the phenyl and/or thienyl ring, utilizing the Suzuki cross-coupling reaction and the Stille cross-coupling reaction, achieving moderate to excellent yields. Pd(PPh₃)₄ and Pd(dppf)Cl₂ were employed in the Suzuki cross-coupling reaction for the synthesis of 16 PTZ, POZ, and Cz chromophores using commercial boronic acids or synthesized pinacol boronate esters. The semi-hydrogenation of the carbon–carbon triple bond (C≡C) of alkyne to its corresponding alkene (C=C) is a reaction of a high industrial significance [5]. Among them, removing phenylacetylene from styrene feed, via such semi-hydrogenation, during styrene polymerization is essential because phenylacetylene, as an impurity above a concentration of 10 ppm, is poisonous to the polymerization catalysts and promotes quicker catalyst deactivation [5]. Therefore, the selective hydrogenation of phenylacetylene under benign conditions to the intermediate styrene is essential for the polymer industry. With an aim to upgrade the industrial Lindlar catalyst for the semi-hydrogenation of phenyl acetylene to styrene, Y. Zheng et al. [5] demonstrated that newly derived precipitated CaCO₃ (PCC) holds the critical criteria to deliver a superior catalytic performance compared to the commercial Lindlar catalyst. Their low-surface area PCC-derived Pd-Pb catalytic material provided a superior catalytic performance, stability, and robustness compared to its two counterpart materials: i.e., Pd-Pb over both high-surface area PCC materials and the commercial Lindlar catalyst. The low-surface area Pd-Pb/PCC could deliver a similar reactivity and selectivity even after lowering the metallic loading, indicating that the “active-site isolation” and “strong metal-support interaction” (SMSI) features are possibly among the contributing factors that may impact the catalysis. There are seven publications which cover the green chemistry fundamentals using photocatalysis [6,7,8,9], electro-catalysis [10], remediation of organic pollutants from wastewater [11,12], and green protocol was used for the selective oxidation of benzyl alcohol and styrene with molecular oxygen to carbonyl compounds under environmentally benign solvent-free conditions [13]. The last two papers cover the carbon economy [14], and the conversion of glycerol into valuable biofuel additives is essential in the fuel industry [15].

This Special Issue of the Catalysts journal aims to assemble articles provided by the best research groups worldwide, with which readers will be able to find various articles on the topic of “The Role of Catalysts in Functionalization of C-H and C-C Bonds”, including full papers and reviews.