Carbon-heteroatom Bond Formation Research Articles

Evolution of High-Valent Nickela-Electrocatalyzed C-H Activation: From Cross(-Electrophile)-Couplings to Electrooxidative C-H Transformations.

C−H activation has emerged as one of the most efficient tools for the formation of carbon–carbon and carbon–heteroatom bonds, avoiding the use of prefunctionalized materials. In spite of tremendous progress in the field, stoichiometric quantities of toxic and/or costly chemical redox reagents, such as silver(I) or copper(II) salts, are largely required for oxidative C−H activations. Recently, electrosynthesis has experienced a remarkable renaissance that enables the use of storable, safe and waste‐free electric current as a redox equivalent. While major recent momentum was gained in electrocatalyzed C−H activations by 4d and 5d metals, user‐friendly and inexpensive nickela‐electrocatalysis has until recently proven elusive for oxidative C−H activations. Herein, the early developments of nickela‐electrocatalyzed reductive cross‐electrophile couplings as well as net‐redox‐neutral cross‐couplings are first introduced. The focus of this Minireview is, however, the recent emergence of nickel‐catalyzed electrooxidative C−H activations until April 2020.

Microwave-accelerated Carbon-carbon and Carbon-heteroatom Bond Formation via Multi-component Reactions: A Brief Overview

Multi-Component Reactions (MCRs) have emerged as an excellent tool in organic chemistry for the synthesis of various bioactive molecules. Among these, one-pot MCRs are included, in which organic reactants react with domino in a single-step process. This has become an alternative platform for the organic chemists, because of their simple operation, less purification methods, no side product and faster reaction time. One of the important applications of the MCRs can be drawn in carbon- carbon (C-C) and carbon-heteroatom (C-X; X = N, O, S) bond formation, which is extensively used by the organic chemists to generate bioactive or useful material synthesis. Some of the key carbon- carbon bond forming reactions are Grignard, Wittig, Enolate alkylation, Aldol, Claisen condensation, Michael and more organic reactions. Alternatively, carbon-heteroatoms containing C-N, C-O, and C-S bond are also found more important and present in various heterocyclic compounds, which are of biological, pharmaceutical, and material interest. Thus, there is a clear scope for the discovery and development of cleaner reaction, faster reaction rate, atom economy and efficient one-pot synthesis for sustainable production of diverse and structurally complex organic molecules. Reactions that required hours to run completely in a conventional method can now be carried out within minutes. Thus, the application of microwave (MW) radiation in organic synthesis has become more promising considerable amount in resource-friendly and eco-friendly processes. The technique of microwaveassisted organic synthesis (MAOS) has successfully been employed in various material syntheses, such as transition metal-catalyzed cross-coupling, dipolar cycloaddition reaction, biomolecule synthesis, polymer formation, and the nanoparticle synthesis. The application of the microwave-technique in carbon-carbon and carbon-heteroatom bond formations via MCRs with major reported literature examples are discussed in this review.

Structure- and Functionality-Based Molecular Design of Azoles and Thiophenes

Abstract Heteroaromatic structures are widely found in a variety of organic molecules such as π-extended oligomers/polymers, pharmaceutical drugs, agrochemicals, etc. Considerable efforts have been made for the wide use of heteroaromatic compounds. It is therefore of great interest to develop efficient and practical synthetic methodology in organic chemistry. In this account, the focus is on the molecular design of five-membered heteroaromatic compounds such as azoles and thiophenes covering transition metal-catalyzed carbon–carbon and carbon–heteroatom bond formation at the C–H bond, polymerization reactions employing coupling reactions, and a new class of structural design of heterobiaryls showing molecular asymmetry.

Chemoselective Cross-Coupling of gem-Borazirconocene Alkanes with Aryl Halides.

The direct and chemoselective conversion of the carbon-metal bond of gem-dimetallic reagents enables rapid and sequential formation of multiple carbon-carbon and carbon-heteroatom bonds, thus representing a powerful method for efficiently increasing structural complexity. Herein, we report a visible-light-induced, nickel-catalyzed, chemoselective cross-coupling reaction between gem-borazirconocene alkanes and diverse aryl halides, affording a wide range of alkyl Bpin derivatives in high yields with excellent regioselectivity. This practical method features attractively simple reaction conditions and a broad substrate scope. Additionally, we systematically investigated a Bpin-directed chain walking process underlying the regioselectivity of alkylzirconocenes, thus uncovering the mechanism of the remote functionalization of internal olefins achieved with our method. Finally, DFT calculations indicate that the high regioselectivity of this reaction originates from the directing effect of the Bpin group.

Applications of Micelles in Catalyzing Organic Reactions

: Micellar chemistry is gaining considerable interest among organic chemists because these reactions are carried out in environmentally benign solvents like water. Owing to the exhaustive use of toxic solvents in carrying out the different chemical reactions, there is a pressing need for alternative approaches either environmental friendly or having minimum impact on the environment. In this article, we aim to discuss the various aspects of micellar chemistry viz-a-viz its role in guiding the chemical reactions. Micelles help to drive various kinds of organic reactions including oxidations, reductions, carbon-carbon bond formation, carbon-heteroatom bond formation, multi-component reactions, Pd-coupling reaction, olefin metathesis reaction, Morita-Baylis-Hillman reaction, etc. in water.

Chiral <italic>N</italic>,<italic>N</italic>ʹ-dioxide and their metal complexes in asymmetric catalysis

Chirality is a fundamental property of nature. Chiral compounds are closely related to life science, human health, material science, and so on. Asymmetric catalysis is one of the most efficient and important synthetic methodologies to obtain chiral compounds, which meets the requirement of green chemistry. Metal-catalyzed asymmetric reactions attract much attention in the past few years, and thousands of chiral ligands have been synthesized, however, widely applicable, so-called privileged chiral ligands are still very limited. Therefore, the design and synthesis of highly efficient and selective chiral ligands becomes the most important and challenging goal. Our group is committed to asymmetric catalysis and develope a novel type of C 2-symmetric chiral ligand of N , N ʹ-dioxide amide compounds which is easily synthesized from cheap chiral amino acids and amines. Such conformationally flexible privileged ligands break through the notion of the rigid feature of previously privileged ligands. Naturally, it would guide the creation of new ideal chiral ligands and catalysts. N , N ʹ-dioxides are not only used as bifunctional organocatalysts, but also provide an arsenal of chiral metal complexes upon coordination with a variety of metal salts, such as alkaline-earth metal salts, transition metal salts and rare-earth metal salts. This powerful catalyst system has been proved to be highly effective for more than fifty types of asymmetric reactions with wide substrate generality under mild conditions, including carbon-carbon bond formation, and carbon-heteroatom bond formation reactions. The concerns of controlling chemo-, regio-, and stereoselectivity of involved reactions are well addressed. Some new and challengling asymmetric reactions are realized, for intances, the first asymmetric Roskamp reaction is achieved with a N , N ʹ-dioxide/Sc(III) complex at low catalyst loading, which updates the comment about β-keto esters in text of Organic Chemistry , Oxford, and the reaction is amended as “Roskamp-Feng reaction” in Elsevier’s Organic Synthesis Based on Name Reactions . The asymmetric amination of ketones with α-diazoesters shed light on the diversity of diazo chemistry. N , N ʹ-dioxide/La(III) complex catalyzed sulfa-Michael reaction exhibits very strong chiral amplification effect. N , N ʹ-dioxide/Ni(II) complex acts as both chiral Lewis catalyst and metal-carbene promotor in Doyle-Kirmse reaction, [ 2 , 3 ] -Stevens rearrangement and Sommelet-Hauser rearrangement of a new type of designed α-diazo pyrazoleamides. Such the creation of catalytic systems and catalytic asymmetric methods provide simple, efficient, precise, green access to several biologically active drug molecules and natural products, such as Paroxetine, Pregabalin, Thiazesim, KAE609 and so on. Now, N , N ʹ-dioxides have become commercially available chiral ligands and have been successfully applied by many research groups and companies. The above original and systematic research achievements make important contribution to the chirality science.

Intermolecular Radical C-H Bond Activation: A Powerful Tool for Late Stage Functionalization.

The synthesis of complex molecules via radical reactions involving carbon-carbon and carbon-heteroatom bonds has become a very successful approach. Radical chemistry has long been dominated by the use of tin-based reagents. Those strongly contributed to the development of the field, allowing one to achieve spectacular transformations, most of which being difficult or impossible to achieve under ionic conditions, and giving access to invaluable kinetics data that paved the way for the development of improved protocols and the design of new synthetic strategies. However, tin reagents and tin byproducts are often toxic and they proved to make purification steps sometimes tedious. In this context, tin-free methods have progressively gained in interest. This short review aims at providing the reader with alternative methods employing C-H bonds in place of the classical alkyl halides to generate, via an intermolecular hydrogen atom transfer (HAT), the radical species. Examples of carbon-carbon and carbon-heteroatom bond formation using this type of C-H bond activation approach will be provided, from early reports to the more recent developments.

Remote Nickel-Catalyzed Cross-Coupling Arylation via Proton-Coupled Electron Transfer-Enabled C-C Bond Cleavage.

Cross-coupling reactions for carbon-carbon and carbon-heteroatom bond formation are of great importance in modern chemical synthesis. In addition to classical cross-couplings involving preformed or preactivated coupling partners, more recently breakthroughs have been made in the selective, direct coupling of abundant aliphatic carbon-hydrogen bonds using hydrogen atom transfer reactions in which the bond-dissociation energy is the thermodynamic driving force. The more challenging carbon-carbon bond activation is still rather underdeveloped due to the bond inertness. Herein, we report a mild and general strategy for the activation of a diverse set of readily available cyclic alcohols for the remote and site-specific arylation of ketones via the combination of photoredox-mediated multisite concerted proton-electron transfer (MS-PCET) and nickel catalysis. The current cross-coupling proceeds with the generation of an alkoxy radical utilizing bond-dissociation free energy (BDFE) as the thermodynamic driving force. Subsequently, the resulting remote carbon-centered radicals formed by C-C cleavage merge with the nickel catalytic cycle to create the challenging C(sp3)-C(sp2) bonds.

Design of Carbon-carbon and Carbon-heteroatom Bond Formation Reactions under Green Conditions

:The development of C-C and C-heteroatom (C-N, C-O and C-P) bond reactions is a field of significant interest and has received momentous attention in modern organic chemistry. These reactions have been exploited in the synthesis of pharmaceuticals, agrochemicals and molecules of interest in materials science. With the increasing awareness of global warming and the use of renewable energies, it is of paramount importance to reduce the usage of hazardous chemicals in both industrial and academic research and to achieve a healthier environment through green practices. Green chemistry is a rapidly emerging approach that shows us a path for the sustainable growth of future science and technologies. In the recent past, healthy growth has been recorded in a number of organic reactions in aqueous media, which are environment-friendly and energy conserving. This review documents the literature on the development of green methodologies involving the design of C-C, C-O, C-N and C-P bond formations of coupling and condensed reactions. It emphasizes the exceptional practices and important advances achieved using alternative green tools, such as microwave (MW), high-speed ball milling (HSBM) and ultrasound irradiation techniques, and a variety of reusable catalysts and green solvents, with attention to water.

Tertiary Amine Lewis Base Catalysis in Combination with Transition Metal Catalysis.

The cooperation between two orthogonal catalytic events during the formation of carbon-carbon and carbon-heteroatom bonds has emerged as an effective strategy for enantioselective chemical synthesis. In recent years, a number of pioneering investigations have described useful chemical synthesis methods whereby the reactivity or nucleophile-electrophile combinations can be fine-tuned or extended far beyond the effect and influence of a single catalyst. The recognition of this has had profound implications for the development cooperative catalysis as a field and has provided a foundation for the development of broadly useful chemical synthesis methods. This chapter focuses on the combination of tertiary amine Lewis base and transition metal catalysts, which the authors hope will simulate further developments and advances.

Carbon-Hydrogen Bond Functionalization in Aqueous Medium: A Brief Review

In the last few decades, considerable research has led to the introduction of selective and efficient green as well as sustainable synthetic methods of functionalization of carbon-hydrogen bonds to form new carbon-carbon and carbon-heteroatom bonds. In this emerging field, significant development has been attained under various environmentally benign conditions including aqueous medium. In this review, we have summarized the current development of C-H functionalization carried out in an aqueous medium and its synthetic applications according to carbon-carbon and carbon-heteroatom bond formations under green conditions.

Organocatalytic Asymmetric Annulation of ortho‐Alkynylanilines: Synthesis of Axially Chiral Naphthyl‐C2‐indoles

AbstractA chiral Brønsted base catalyzed asymmetric annulation of ortho‐alkynylanilines has been developed to access axially chiral naphthyl‐C2‐indoles via vinylidene ortho‐quinone methide (VQM) intermediates. This strategy provides a unique organocatalytic atroposelective route to axially chiral aryl‐C2‐indole skeletons with excellent enantioselectivity and functional‐group tolerance. This transformation was applicable to decagram‐scale preparation (50.0 g) with perfect enantioselectivity through simple recrystallization. Moreover, the utility of this reaction was demonstrated by a variety of transformations towards chiral naphthyl‐C2‐indoles for a series of carbon–heteroatom bond formations. Furthermore, the prepared axially chiral naphthyl‐C2‐indoles were applied as a chiral skeleton for organocatalytic aza‐Baylis–Hillman reaction and asymmetric formal [4+2] tandem cyclization to give the corresponding adducts in high yields with improved enantioselectivity and diastereoselectivity.

Organocatalytic Asymmetric Annulation of ortho-Alkynylanilines: Synthesis of Axially Chiral Naphthyl-C2-indoles.

A chiral Brønsted base catalyzed asymmetric annulation of ortho-alkynylanilines has been developed to access axially chiral naphthyl-C2-indoles via vinylidene ortho-quinone methide (VQM) intermediates. This strategy provides a unique organocatalytic atroposelective route to axially chiral aryl-C2-indole skeletons with excellent enantioselectivity and functional-group tolerance. This transformation was applicable to decagram-scale preparation (50.0 g) with perfect enantioselectivity through simple recrystallization. Moreover, the utility of this reaction was demonstrated by a variety of transformations towards chiral naphthyl-C2-indoles for a series of carbon-heteroatom bond formations. Furthermore, the prepared axially chiral naphthyl-C2-indoles were applied as a chiral skeleton for organocatalytic aza-Baylis-Hillman reaction and asymmetric formal [4+2] tandem cyclization to give the corresponding adducts in high yields with improved enantioselectivity and diastereoselectivity.

Metal Doped-C3N4/Fe2O4: Efficient and Versatile Heterogenous Catalysts for Organic Transformations

The polymeric graphitic carbon nitride (g-C3N4) has been one of the interesting earth abundant elements. Though g-C3N4 finds application as a photocatalyst, its photocatalytic behaviour is limited because of low efficiency, mainly due to rapid charge recombination. To overcome this problem, several strategies have been developed including doping of metal/non-metal in the cavity of g-C3N4. Moreover, the CoFe2O4 NPs have been used in many organic transformations because of its high surface area and easy separation due to its magnetic nature. This review describes the role of cobalt ferrite as magnetic nanoparticles and metal-doped carbon nitride as efficient heterogeneous catalysts for new carbon-carbon and carbon-hetero atom bond formation followed by heterocyclization. Reactions which involved new catalysts for selective activation of readily available substrates has been reported herein. Since nanoparticles enhance the reactivity of catalyst due to higher catalytic area, they have been employed in various reactions such as addition reaction, C-H activation reaction, coupling reaction, cyclo-addition reaction, multi-component reaction, ring-opening reaction, oxidation reaction and reduction reactions etc. The driving force for choosing this topic is based-on huge number of good publications including different types of spinels/metal doped-/graphitic carbon nitride reported in the literature and due to interest of synthetic community in recent years. This review certainly will represent the present status in organic transformation and for exploring further their catalytic efficiency to new organic transformations involving C-H activation reaction through coupling, cyclo-addition, multi-component, ring-opening, oxidation and reduction reactions.

Aromatic Chemistry in the Excited State: Facilitating Metal-Free Substitutions and Cross-Couplings.

Transition-metal-catalyzed cross-couplings between aromatic electrophiles and nucleophiles have revolutionized modern chemical syntheses. Nevertheless, transition-metal-free approaches are preferable, considering the various issues caused by metal catalysts. This Minireview summarizes the recent progress in the light-enabled transition-metal-free formation of carbon-carbon and carbon-heteroatom bonds in aromatics, which opens a new avenue in aromatic reactions. From the mechanistic perspective, it classifies different reaction types of aryl electrophiles in an excited state with various nucleophiles. We believe this will provide more rationales for metal-free aromatic substitutions and cross-couplings with light, and guide the development of novel transformations of aromatic compounds facilitated by light.

Photochemical Strategies for Carbon–Heteroatom Bond Formation

Photochemistry enables new synthetic means to form carbon–heteroatom bonds. Photocatalysts can catalyze carbon–heteroatom cross‐couplings by electron or energy transfer either alone or in combination with a second catalyst. Photocatalyst‐free methods are possible using photolabile substrates or by generating photoactive electron donor‐acceptor complexes. This review summarizes and discusses the strategies used in light‐mediated carbon–heteroatom bond formations based on the proposed mechanisms.

Palladium(II)-Catalyzed Cascade Reactions of Ene-Ynes Tethered to Cyano/Aldehyde: Access to Naphtho[1,2-b]furans and Benzo[g]indoles.

An efficient palladium(II)-catalyzed cascade reaction of ene-yne substrates carrying cyano/aldehyde group is described. It involves successive hetero- and benz-annulations in one pot via trans-oxo/aminopalladation onto alkyne, followed by 1,2-addition to cyano/aldehyde, providing a convenient synthesis of both naphtho[1,2-b]furans and benzo[g]indoles. The reaction constitutes a fast intramolecular assembly through several carbon-carbon and carbon-heteroatom bond formations taking place in one pot. The reactions are operationally simple, compatible with a range of functional groups and atom-economical in nature.

Enantioselective Carbon-Carbon Bond Cleavage for Biaryl Atropisomers Synthesis

Summary Development of new synthetic strategies for enantioselective carbon-carbon and carbon-heteroatom bond formation is one of the pillars of modern organic chemistry. Whereas significant advances have been achieved in center chirality construction, catalytically asymmetric construction of axial chirality is still under development. Moreover, axially chiral molecules constructed through carbon-carbon and carbon-heteroatom bond cleavage are extremely limited. Here, we report an asymmetric synthesis of biaryl atropisomers via palladium-catalyzed chemoselective carbon-carbon cleavage of 9-aryl-9H-fluoren-9-ols. The reaction demonstrated broad substrate scope and produced the atropisomers in high yields and enantioselectivity. The ring-opening reactivity was considerably accelerated by the torsional strain created by the steric repulsion between two ortho-substituents of the biaryl skeleton in the substrates. The high enantiocontrol hinges on the evolvement of a new TADDOL-based phosphoramidite as ligand. These findings set up a new platform for the development of novel synthetic methods via asymmetric carbon-carbon cleavage.

Nickel-Catalyzed Decarbonylative Stannylation of Acyl Fluorides under Ligand-Free Conditions.

Nickel-catalyzed decarbonylative stannylation of acyl fluorides under ligand-free conditions was disclosed. A variety of aromatic acyl fluorides are capable of reacting with silylstannanes in the presence of cesium fluoride. A one-pot decarbonylative stannylation/Migita-Kosugi-Stille reaction of benzoyl fluoride, giving rise to the direct formation of the corresponding cross-coupled products, further demonstrated the synthetic utility of the present method. This newly developed methodology with a good functional-group compatibility via C–F bond cleavage and C–Sn bond formation under nickel catalysis opens a new area for the functionalization of acyl fluorides in terms of carbon-heteroatom bond formation.

Silicon-Tethered Frameworks as Directing Groups for Carbon–Carbon and Carbon–Heteroatom Bond Formation

Recent advances in the use of silicon-tethered frameworks as directing groups for the efficient construction of C–C, C–B, C–O and C–X (X = halogen) bonds are discussed in this short review. In addition, mechanistic insights are briefly discussed. Hence, the goal of this short review is to give an overview of the state of the art in this field, encompassing the reactivity, selectivity and efficiency of different processes.1 Introduction2 Carbon–Carbon Bond Formation2.1 Alkenylation2.2 Arylation2.3 Carbonylation3 Carbon–Boron Bond Formation4 Carbon–Oxygen and Carbon–Halogen Bond Formation5 Conclusion