Transition Metal-Free Aromatic C−H,C−N,C−S and C−O Borylation

Aromatic organoboron compounds are highly valuable building blocks in organic chemistry. They were mainly synthesized through aromatic C−H and C−Het borylation, in which transition metal-catalysis dominate. In the past decade, with increasing attention to sustainable chemistry, numerous transition metal-free C−H and C−Het borylation transformations have been developed and emerged as efficient methods towards the synthesis of aromatic organoboron compounds. This account mainly focuses on recent advances in transition metal-free aromatic C−H, C−N, C−S, and C−O borylation transformations and provides insights to where further developments are required.     

Elucidating the N−N and C−N Bond-breaking Mechanism in the Photoinduced Formation of Nitrile Imine

In this study, we revealed the significance of chemical bonding for the photochemically induced mechanism of 2-phenyl tetrazole derivatives generating nitrile imines. The correlated electron localization function shows that the formation of imine nitrile involves two key bond events: (i) the heterolytic C−N breakage taking place in the T₁ state and (ii) the homolytic N−N rupture occurring in the T₂ excited state. In particular, a cation-radical specie results from the C−N cleavage, whereas the N−N rupture creates a biradical resonant form of imine nitrile. Additionally, we noticed that the substantial pair delocalization of the C−C-N bonded structure could play a significant role in the conversion of the biradical imine nitrile into both the propargylic and allenic forms via the T₁→S₀ deactivation.     

Iron-Catalyzed Oxidative C−O and C−N Coupling Reactions Using Air as Sole Oxidant**

We describe the oxygenation of tertiary arylamines, and the amination of tertiary arylamines and phenols. The key step of these coupling reactions is an iron-catalyzed oxidative C−O or C−N bond formation which generally provides the corresponding products in high yields and with excellent regioselectivity. The transformations are accomplished using hexadecafluorophthalocyanine−iron(II) (FePcF₁₆) as catalyst in the presence of an acid or a base additive and require only ambient air as sole oxidant.     

RASS-Enabled S/P−C and S−N Bond Formation for DEL Synthesis

DNA encoded libraries (DEL) have shown promise as a valuable technology for democratizing the hit discovery process. Although DEL provides relatively inexpensive access to libraries of unprecedented size, their production has been hampered by the idiosyncratic needs of the encoding DNA tag relegating DEL compatible chemistry to dilute aqueous environments. Recently reversible adsorption to solid support (RASS) has been demonstrated as a promising method to expand DEL reactivity using standard organic synthesis protocols. Here we demonstrate a suite of on-DNA chemistries to incorporate medicinally relevant and C−S, C−P and N−S linkages into DELs, which are underrepresented in the canonical methods.     

Rhoda-Electrocatalyzed C−H Methylation and Paired Electrocatalyzed C−H Ethylation and Propylation

The use of electricity over traditional stoichiometric oxidants is a promising strategy for sustainable molecular assembly. Herein, we describe the rhoda-electrocatalyzed C−H activation/alkylation of several N-heteroarenes. This catalytic approach has been successfully applied to several arenes, including biologically relevant purines, diazepam, and amino acids. The versatile C−H alkylation featured water as a co-solvent and user-friendly trifluoroborates as alkylating agents. Finally, the rhoda-electrocatalysis with unsaturated organotrifluoroborates proceeded by paired electrolysis.     

Aryne-Enabled C−N Arylation of Anilines

Anilines are potentially high-value arylating agents, but are limited by the low reactivity of the strong C−N bond. We show that the reactive intermediate benzyne can be used to both activate anilines, and set-up an aryl transfer reaction in a single step. The reaction does not require any transition metal catalysts or stoichiometric organometallics, and establishes a metal-free route to valuable biaryl products by functionalizing the aniline C−N bond.     

Copper-Catalyzed Borylative Couplings with C−N Electrophiles

Copper-catalyzed borylative multicomponent reactions (MCRs) involving olefins and C−N electrophiles are a powerful tool to rapidly build up molecular complexity. The products from these reactions contain multiple functionalities, such as amino, cyano and boronate groups, that are ubiquitous in medicinal and process chemistry programs. Copper-catalyzed MCRs are particularly attractive because they use a relatively abundant and non-toxic catalyst to selectively deliver high-value products from simple feedstocks such as olefins. In this Minireview, we explore this rapidly emerging field and survey the borylative union of allenes, dienes, styrenes and other olefins, with imines, nitriles and related C−N electrophiles.     

Divergent Coupling of Benzocyclobutenones with Indoles via C−H and C−C Activations

Highly selective divergent coupling reactions of benzocyclobutenones and indoles, in which the chemoselectivity is controlled by catalysts, are reported herein. The substrates undergo C2(indole)–C8(benzocyclobutenone) coupling to produce benzylated indoles and benzo[b]carbazoles in the Ni- and Ru-catalyzed reactions. A completely different selectivity pattern C2(indole)–C2(benzocyclobutenone) coupling to form arylated indoles is observed in the Rh-catalyzed reaction. Preliminary mechanistic studies suggest C−H and C−C activations in the reaction pathway. Synthetic utility of this protocol is demonstrated by the selective synthesis of three different types of carbazoles from the representative products.     

Electronic structures of C36 fulleride anions: C36− and C362−

Electronic structures for mono- and dianionic species of two promising C₃₆ fullerene isomers, 14 and 15, are investigated by means of the hybrid Hartree–Fock (HF)/density functional (DF) method. Structural deformations, charge distributions, and spin densities upon one- or two-electron reduction are explained in light of the lowest unoccupied molecular orbitals (LUMOs) of each neutral isomer. First electron affinities for the neutral isomers 14 and 15 are predicted to be 2.3 and 2.5 eV, respectively, facilitating n-type doping for C₃₆ solids. The degrees of local aromaticity of the isomers 14 and 15 tend to decrease with reduction in contrast with C₆₀.     

Structures and stability of N9, N9 − and N9 + clusters

 Ab initio molecular orbital calculations for N₉, N⁻ ₉ and N⁺ ₉ isomers were carried out at the HF/ 6-31G*, B3PW91/6-31G*, B3LYP/6-31G* and MP2/ 6-31G* levels of theory. Stable equilibrium geometric structures were determined by harmonic vibrational frequency analyses at the HF/6-31G*, B3PW91/6-31G* and B3LYP/6-31G* levels of theory. The most stable free-radical N₉ cluster is structure 1 with C _{2 v} symmetry and that of anion N⁻ ₉ is structure 3 with C _s symmetry. Only one stable structure of the N⁺ ₉ cation with C _{2 v} symmetry was predicted. Their potential application as high-energy-density materials has been examined. Received: 15 June 1999 / Accepted: 11 October 1999 / Published online: 14 March 2000     

Ni(II) Precatalysts Enable Thioetherification of (Hetero)Aryl Halides and Tosylates and Tandem C−S/C−N Couplings

Ni-catalyzed C−S cross-coupling reactions have received less attention compared with other C-heteroatom couplings. Most reported examples comprise the thioetherification of most reactive aryl iodides with aromatic thiols. The use of C−O electrophiles in this context is almost uncharted. Here, we describe that preformed Ni(II) precatalysts of the type NiCl(allyl)(PMe₂Ar’) (Ar’=terphenyl group) efficiently couple a wide range of (hetero)aryl halides, including challenging aryl chlorides, with a variety of aromatic and aliphatic thiols. Aryl and alkenyl tosylates are also well tolerated, demonstrating, for the first time, to be competent electrophilic partners in Ni-catalyzed C−S bond formation. The chemoselective functionalization of the C−I bond in the presence of a C−Cl bond allows for designing site-selective tandem C−S/C−N couplings. The formation of the two C-heteroatom bonds takes place in a single operation and represents a rare example of dual electrophile/nucleophile chemoselective process.     

Insight into Iron Leaching from an Ascorbate-Oxidase-like Fe−N−C Nanozyme and Oxygen Reduction Selectivity**

Ascorbate (H₂A) is a well-known antioxidant to protect cellular components from free radical damage and has also emerged as a pro-oxidant in cancer therapies. However, such “contradictory” mechanisms underlying H₂A oxidation are not well understood. Herein, we report Fe leaching during catalytic H₂A oxidation using an Fe−N−C nanozyme as a ferritin mimic and its influence on the selectivity of the oxygen reduction reaction (ORR). Owing to the heterogeneity, the Fe-N_x sites in Fe−N−C primarily catalyzed H₂A oxidation and 4 e⁻ ORR via an iron-oxo intermediate. Nonetheless, trace O₂⋅⁻ produced by marginal N−C sites through 2 e⁻ ORR accumulated and attacked Fe-N_x sites, leading to the linear leakage of unstable Fe ions up to 420 ppb when the H₂A concentration increased to 2 mM. As a result, a substantial fraction (ca. 40 %) of the N−C sites on Fe−N−C were activated, and a new 2+2 e⁻ ORR path was finally enabled, along with Fenton-type H₂A oxidation. Consequently, after Fe ions diffused into the bulk solution, the ORR at the N−C sites stopped at H₂O₂ production, which was the origin of the pro-oxidant effect of H₂A.     

Asymmetric Synthesis of Axially Chiral C−N Atropisomers

Molecules with restricted rotation around a single bond or atropisomers are found in a wide number of natural products and bioactive molecules as well as in chiral ligands for asymmetric catalysis and smart materials. Although most of these compounds are biaryls and heterobiaryls displaying a C−C stereogenic axis, there is a growing interest in less common and more challenging axially chiral C−N atropisomers. This review offers an overview of the various methodologies available for their asymmetric synthesis. A brief introduction is initially given to contextualize these axially chiral skeletons, including a historical background and examples of natural products containing axially chiral C−N axes. The preparation of different families of C−N based atropisomers is then presented from anilides to chiral five- and six-membered ring heterocycles. Special emphasis has been given to modern catalytic asymmetric strategies over the past decade for the synthesis of these chiral scaffolds. Applications of these methods to the preparation of natural products and biologically active molecules will be highlighted along the text.     

C−C Cross-Couplings from a Cyclometalated Au(III) C N Complex: Mechanistic Insights and Synthetic Developments

In recent years, the reactivity of gold complexes was shown to extend well beyond π-activation and to hold promises to achieve selective cross-couplings in several C−C and C−E (E=heteroatom) bond forming reactions. Here, with the aim of exploiting new organometallic species for cross-coupling reactions, we report on the Au(III)-mediated C(sp²)−C(sp) occurring upon reaction of the cyclometalated complex [Au(C^CH2N)Cl₂] ( 1 , C^CH2N=2-benzylpyridine) with AgPhCC. The reaction progress has been monitored by NMR spectroscopy, demonstrating the involvement of a number of key intermediates, whose structures have been unambiguously ascertained through 1D and 2D NMR analyses (¹H, ¹³C, ¹H-¹H COSY, ¹H-¹³C HSQC and ¹H-¹³C HMBC) as well as by HR-ESI-MS and X-ray diffraction studies. Furthermore, crystallographic studies have serendipitously resulted in the authentication of zwitterionic Au(I) complexes as side-products arising from cyclization of the coupling product in the coordination sphere of gold. The experimental work has been paralleled and complemented by DFT calculations of the reaction profiles, providing valuable insight into the structure and energetics of the key intermediates and transition states, as well as on the coordination sphere of gold along the whole process. Of note, the broader scope of the cross-coupling at the Au(III) C^CH2N centre has also been demonstrated studying the reaction of 1 with C(sp²)-based nucleophiles, namely vinyl and heteroaryl tin and zinc reagents. These reactions stand as rare examples of C(sp²)−C(sp²) cross-couplings at Au(III).     

Generation of FeIV=O and its Contribution to Fenton-Like Reactions on a Single-Atom Iron−N−C Catalyst

Generating Fe^IV=O on single-atom catalysts by Fenton-like reaction has been established for water treatment; however, the Fe^IV=O generation pathway and oxidation behavior remain obscure. Employing an Fe−N−C catalyst with a typical Fe−N₄ moiety to activate peroxymonosulfate (PMS), we demonstrate that generating Fe^IV=O is mediated by an Fe−N−C−PMS* complex—a well-recognized nonradical species for induction of electron-transfer oxidation—and we determined that adjacent Fe sites with a specific Fe₁−Fe₁ distance are required. After the Fe atoms with an Fe₁-Fe₁ distance <4 Å are PMS-saturated, Fe−N−C−PMS* formed on Fe sites with an Fe₁-Fe₁ distance of 4–5 Å can coordinate with the adjacent Fe^II−N₄, forming an inter-complex with enhanced charge transfer to produce Fe^IV=O. Fe^IV=O enables the Fenton-like system to efficiently oxidize various pollutants in a substrate-specific, pH-tolerant, and sustainable manner, where its prominent contribution manifests for pollutants with higher one-electron oxidation potential.     

Electrophilic 1,3-C→N− and-N→C− migrations in saturated systems

A new type of intramolecular electrophilic rearrangements involving the shift of COOAlk groups from carbon to an N-anionic center is considered. Carbanionic species with COOAlk groups at anionic centers containing no acidic hydrogen react unusually with alkyl(aryl) iso(thio)cyanates giving carbamates as a result of insertion of RNCX into the C−C bond. The kinetics and mechanism of insertion of aryl isocyanates into the C−C bond of the phosphonium zwitterion obtained from triisopropylphosphine and ethyl 2-cyanoacrylate are discussed. The reaction of α-carbanions derived fromN,N-disubstituted amides with methyl trifluoromethanesulfonate results inO-methylation. Some possibilities of back N→C⁻ migrations are considered. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1643–1648, September, 1999.     

On-Surface Synthesis of One-Dimensional Carbon-Based Nanostructures via C−X and C−H Activation Reactions

The past decades have witnessed the emergence of low-dimensional carbon-based nanostructures owing to their unique properties and various subsequent applications. It is of fundamental importance to explore ways to achieve atomically precise fabrication of these interesting structures. The newly developed on-surface synthesis approach provides an efficient strategy for this challenging issue, demonstrating the potential of atomically precise preparation of low-dimensional nanostructures. Up to now, the formation of various surface nanostructures, especially carbon-based ones, such as graphene nanoribbons (GNRs), kinds of organic (organometallic) chains and films, have been achieved via on-surface synthesis strategy, in which in-depth understanding of the reaction mechanism has also been explored. This review article will provide a general overview on the formation of one-dimensional carbon-based nanostructures via on-surface synthesis method. In this review, only a part of the on-surface chemical reactions (specifically, C−X (X=Cl, Br, I) and C−H activation reactions) under ultra-high vacuum conditions will be covered.     

Preparation and some properties of ionic salts of C 60 − and C 60 2− fullerides with phthalocyanine cations

Ionic fullerides of C ₆₀ ^? and C ₆₀ ^2? with the silicon phthalocyanines cations were obtained in the reaction of PcSi(OH)₂ with fullerene C₆₀ in the presence of KOH in DMSO or in xylene and THF with the addition of 15C5 crown ether. The fullerides were characterized by electron absorption, ¹H NMR and electron spin resonance spectra, and their reaction with O₂ and CF₃COOH were carried out.     

Asymmetric Pd(II)-Catalyzed C−O,C−N,C−C Bond Formation Using Alkenes as Substrates: Insight into Recent Enantioselective Developments

This Review summarizes the advances in the catalytic enantioselective mono- and difunctionalization of alkenes, highlighting the fundamental role of ligands. Several types of asymmetric reactions have been developed involving different bonds formation, C−O, C−N and C−C, highlighting the urgency to go ahead in the search for new ligands and synthetic methodologies in order to improve the control over the reaction selectivity and activity and thus, to increase the applications in the synthesis of heterocyclic scaffolds and biologically active compounds. The Review is organized into paragraphs, which discuss the type of bond formed during the nucleopalladation, C−O, C−N, C−C bonds, and the type of reaction involved.     

Synthesis, spectral and thermal studies of N,N − -pyridine-2,6-diyl bis[N −-phenyl(thiourea)] and its metal complexes

Four new metal complexes with the general formula, [ML·mH₂O]nH₂O (where, M = Cu(I), Co(II), Ni(II) or Zn(II); L = N,N ^?-pyridine–2,6-diyl bis[N ^?-phenyl (thiourea)] (PDPT); m = 1 or 3 and n = 0.5 or 4.0), have been synthesized and characterized by elemental analyses, spectral analyses (IR, UV–Vis., ¹H-NMR and MS), thermal analyses (TGA), conductivity and magnetic measurements. The results showed that the ligand (PDPT) acts in a mononegative tridentate manner towards Cu(I) ion coordinating via the two thiol sulfurs and pyridyl nitrogen groups with displacement of only one hydrogen atom from the thiol group, while the ligand behaves in a binegative tridentate manner towards the Co(II), Ni(II) and Zn(II) ions with displacement of two hydrogen atoms from the two thiol groups. The value of magnetic measurements showed a diamagnetic character of the copper complex indicating the reduction of Cu(II) to Cu(I). Semi-empirical calculations of the ligand and its metal complexes have been used to study the molecular geometry using ZINDO/1, PM3 and AM1. Also, the harmonic vibration spectra of the ligand and its metal complexes have been investigated with the purpose to assist the experimental assignment of metal complexes. The results of the optical absorption studies reveal that the optical transition is direct with band gaps energy (E_g) values 2.62, 1.98 and 1.85 eV for Cu, Co and Ni complexes, respectively, indicating that these complexes can behave as semi-conductors.