Triple-Bond Directed Csp2−N Bond Formation with N-Fluorobenzenesulfonimide as Aminating Source: One-Step Transformation of Aldehydes into Amines

A metal-free, versatile triple-bond directed approach for the decarbonylative C−H amination of ortho-alkynyl quinoline/pyridine aldehydes using N-fluorobenzenesulfonimide as nitrogen source under mild reaction conditions has been described. The designed reaction strategy was triggered by trapping of fluorine by base with subsequent attack of bis(phenylsulfonyl)-λ²-azane on the carbonyl carbon of a heterocycle, which was gradually converted into the corresponding amine through a Curtius type rearrangement. This protocol provides a one-step approach for the conversion of aldehydes into amines in good yields. The synthesized amines were successfully transformed into biologically important pyrroloquinolines/pyridines.     

Pd-Catalyzed Regioselective Domino C−C Bond Formation to Access N-Fused Benzimidazo-Indolo-Isoquinoline Heterocycles

Regioselective synthesis of N-fused benzimidazo-indolo-isoquinoline heterocycles via Pd-catalyzed domino coupling reaction of 1-(1-methyl-1H-indol-2-yl)-1H-benzimidazoles and aryl halides was developed. This one pot methodology proceeded via a five-member carbopalladacycle intermediate and provided direct and facile route to access structurally complex polyheterocycles in moderate to good yields. These unique hybrid molecules resembled structural similarity with naturally isolated alkaloids. Notably, the present domino process occurred through activation of three C−H bonds and the simultaneous formation of two new C−C bonds in one-shot. These molecules exhibited strong solid and solution phase fluorescence and their emission spectra in both the medium are reported here.     

N−H Bond Formation at a Diiron Bridging Nitride

Despite their connection to ammonia synthesis, little is known about the ability of iron-bound, bridging nitrides to form N−H bonds. Herein we report a linear diiron bridging nitride complex supported by a redox-active macrocycle. The unique ability of the ligand scaffold to adapt to the geometric preference of the bridging species was found to facilitate the formation of N−H bonds via proton-coupled electron transfer to generate a μ-amide product. The structurally analogous μ-silyl- and μ-borylamide complexes were shown to form from the net insertion of the nitride into the E−H bonds (E=B, Si). Protonation of the parent bridging amide produced ammonia in high yield, and treatment of the nitride with PhSH was found to liberate NH₃ in high yield through a reaction that engages the redox-activity of the ligand during PCET.     

Visible-Light-Driven C−H Oxidation of Cyclic Tertiary Amines: Access to Synthetic Strychnos Alkaloids with Antiviral Activity

Air and visible light have been used in facile direct C−H oxidation of cyclic tertiary amines at ambient conditions, employing organic dyes as photocatalysts and LED. Tolerance of this new environmentally compatible protocol to various side-chain derivatizations of tryptoline and tetrahydroisoquinoline substrates was demonstrated. The developed method provides a straightforward and sustainable route towards δ-lactams, which feature strong antiviral properties (EC₅₀ down to 4.6±1.8 μm ) against human cytomegalovirus (HCMV). The clear advantages, which are easily available and inexpensive reagents, organic dyes, visible light, air/O₂ and atom efficiency, make this system highly appealing for synthesis of versatile Strychnocarpine alkaloid derivatives with antiviral activity.     

Aerobic C−N Bond Formation through Enzymatic Nitroso-Ene-Type Reactions**

The biocatalytic oxidation of acylated hydroxylamines enables the direct and selective introduction of nitrogen functionalities by activation of allylic C−H bonds. Utilizing either laccases or an oxidase/peroxidase couple for the formal dehydrogenation of N-hydroxycarbamates and hydroxamic acids with air as the terminal oxidant, acylnitroso species are generated under particularly mild aqueous conditions. The reactive intermediates undergo C−N bond formation through an ene-type mechanism and provide high yields both in intramolecular and intermolecular enzymatic aminations. Investigations on different pathways of the two biocatalytic systems and labelling studies provide more insight into this unprecedented promiscuity of classical oxidoreductases as catalysts for nitroso-based transformations.     

Tunable Electrochemical C−N versus N−N Bond Formation of Nitrogen-Centered Radicals Enabled by Dehydrogenative Dearomatization: Biological Applications

Herein, an environmentally friendly electrochemical approach is reported that takes advantage of the captodative effect and delocalization effect to generate nitrogen-centered radicals (NCRs). By changing the reaction parameters of the electrode material and feedstock solubility, dearomatization enabled a selective dehydrogenative C−N versus N−N bond formation reaction. Hence, pyrido[1,2-a]benzimidazole and tetraarylhydrazine frameworks were prepared through a sustainable transition-metal- and exogenous oxidant-free strategy with broad generality. Bioactivity assays demonstrated that pyrido[1,2-a]benzimidazoles displayed antimicrobial activity and cytotoxicity against human cancer cells. Compound 21 exhibited good photochemical properties with a large Stokes shift (approximately 130 nm) and was successfully applied to subcellular imaging. A preliminary mechanism investigation and density functional theory (DFT) calculations revealed the possible reaction pathway.     

Metal-Free,Visible-Light-Induced Selective C−C Bond Cleavage of Cycloalkanones with Molecular Oxygen

A metal-free, visible-light-induced oxidative C−C bond cleavage of cycloketones with molecular oxygen is described. Cooperative Brønsted-acid catalysis and photocatalysis enabled selective C−C bond cleavage of cycloketones to generate an array of γ-, δ- and ϵ-keto esters under very mild conditions. Mechanistic studies indicate that singlet molecular oxygen (¹O₂) is responsible for this transformation.     

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.     

Ruthenium Catalyzed Intramolecular C−X (X=C,N, O,S) Bond Formation via C−H Functionalization: An Overview

Ruthenium catalyzed C−H activation is well known for its high tolerance towards the functional group and broad applicability in organic synthesis and molecular sciences, with significant applications in pharmaceutical industries, material sciences, and polymer industry. In the last few decades, enormous progress has been observed with ruthenium-catalyzed C−H activation chemistry. Notably, the vast majority of the C−H functionalization known in the literature are intermolecular, although the intramolecular variant provides fascinating new structural facet starting from the simple molecular scaffolds. Intramolecular C−H functionalization is atom economical and step efficient, results in less formation of undesired products which is easy to purify. This has created a lot of interest in organic chemistry in developing new synthetic strategies for such functionalization. The focus of this review is to present the relatively unexplored intramolecular functionalization of C−H bonds into C−X (X=C, N, O, S) bonds utilizing versatile ruthenium catalysts, their scope, and brief mechanistic discussion.     

Chalcogen-Transfer Rearrangement: Exploring Inter- versus Intramolecular P−P Bond Activation

tert-Butyl-substituted diphospha[2]ferrocenophane has been used as a stereochemically confined diphosphane to explore the addition of O, S, Se and Te. Although the diphosphanylchalcogane has been obtained for tellurium, all other chalcogens give diphosphane monochalcogenides. The latter transform via chalcogen-transfer rearrangement to the corresponding diphosphanylchalcoganes upon heating. The kinetics of this rearrangement has been followed with NMR spectroscopy supported by DFT calculations. Intermediates during rearrangement point to a disproportionation/synproportionation mechanism for the S and Se derivatives. Cyclic voltammetry together with DFT studies indicate ferrocene-centred oxidation for most of the compounds presented.     

High-Performance Near-Infrared Chlorinated Rylenecarboximide Fluorophores via Consecutive C−N and C−C Bond Formation

A new class of near-infrared (NIR) fluorophores, PAI , is obtained by consecutive C−N/C−C bond formation between diphenylamines and 9,10-dibromoperylenecarboximide. Owing to the rigid structure, extended π-conjugation and pronounced push-pull substitution, these fluorophores show emission maxima up to 804 nm and large Stokes shifts. The extraordinarily high fluorescence quantum yields from 47 % to 70 % are attributed to chloro substitution in the bay positions of the perylene core. These characteristics, together with high photostability, qualify them as useful NIR emitters for applications as biomarkers and security inks.     

Intramolecular Nitrene Insertion into Saturated C−H-Bond-Mediated C−N Bond Cleavage of a Coordinated NHC Ligand

Ruthenium(II) complexes bearing a tridentate bis(N-heterocyclic carbene) ligand reacted with iminoiodanes (PhI=NR) resulting in the formation of isolable ruthenium(III)–amido intermediates, which underwent cleavage of a C−N bond of the tridentate ligand and formation of an N-substituted imine group. The Ru^III–amido intermediates have been characterized by ¹H NMR, UV/Vis, ESI-MS, and X-ray crystallography. DFT calculations were performed to provide insight into the reaction mechanism.     

Carbon–Carbon Bond Formation via Catalytically Generated Aminocarbene Complexes: Rhodium-Catalyzed Hydroaminative Cyclization of Enynes with Secondary Amines

We report a hydroaminative cyclization of enynes using phosphine-quinolinolato rhodium catalysts. The hydroaminative cyclization of 2-vinylphenylacetylene derivatives with secondary amines gives 2-aminoindenes in good yields. The reaction is considered to proceed through carbon–carbon bond formation on a catalytically generated aminocarbene ligand.     

Visible-Light-Mediated Charge Transfer Enables C−C Bond Formation with Traceless Acceptor Groups

The development and application of traceless acceptor groups in photochemical C−C bond formation is described. This strategy was enabled by the photoexcitation of electron donor–acceptor (EDA) complexes with visible light. The traceless acceptors, which were readily prepared from amino acid and peptide feedstocks, could be used to alkylate a wide range of heteroarene and enamine donors under metal- and peroxide-free conditions. The crucial role of the EDA complexes in the mechanism of these reactions was explored through combined experimental and computational studies.     

Carbon Monoxide Activation by a Molecular Aluminium Imide: C−O Bond Cleavage and C−C Bond Formation

Anionic molecular imide complexes of aluminium are accessible via a rational synthetic approach involving the reactions of organo azides with a potassium aluminyl reagent. In the case of K₂[( NON )Al(NDipp)]₂ ( NON =4,5-bis(2,6-diisopropylanilido)-2,7-di-tert-butyl-9,9-dimethyl-xanthene; Dipp=2,6-diisopropylphenyl) structural characterization by X-ray crystallography reveals a short Al−N distance, which is thought primarily to be due to the low coordinate nature of the nitrogen centre. The Al−N unit is highly polar, and capable of the activation of relatively inert chemical bonds, such as those found in dihydrogen and carbon monoxide. In the case of CO, uptake of two molecules of the substrate leads to C−C coupling and C≡O bond cleavage. Thermodynamically, this is driven, at least in part, by Al−O bond formation. Mechanistically, a combination of quantum chemical and experimental observations suggests that the reaction proceeds via exchange of the NR and O substituents through intermediates featuring an aluminium-bound isocyanate fragment.     

Isolable Tetragold(0) Clusters with Polarity-Tunable exo-Au−Au Bond via Intramolecular σ-Aromatization

Intramolecular π-aromatization is a trait of many organic compounds that enhances the stability of their structures and polarizes related C−C π bonds. In contrast, rare study is focused on this phenomenon in metal clusters. Many existing homometallic clusters exhibit aromaticity, often characterized by nonpolar metal-metal bonds and a high degree of symmetry. However, synthesizing low-symmetric homometallic clusters with high-polar metal-metal bonds is challenging due to their limited thermodynamic stability. Herein, we report a facile strategy for the synthesis of [Au(μ₂-ER₂)]₃−AuPMe₃ (E=Ge, Sn; R₂=1,1,4,4-tetrakis(trimethylsilyl)butane-1,4-diyl) clusters and reveal a novel stabilization mode, intramolecular σ-aromatization. Our electronic structure analyses show that these low-symmetric clusters possess a ten-electron σ-aromatic system, which is achieved via intramolecular σ-aromatization. Moreover, the strength of σ-aromaticity gives rise to a polarity-tunable exo-Au−Au bond.     

Chiral-Directing-Group-Assisted Rhodium(III)-Catalyzed Asymmetric Addition of Inert Arene C−H Bond to Aldimines with Subsequent Intramolecular Cyclization

By using a chiral directing group, an asymmetric rhodium(III)-catalyzed C−H bond addition to aldimines followed by intramolecular cyclization to form chiral isoindolinones has been achieved (up to 68 % yield, up to 93 % ee). A three-component variant that resembles Mannich reaction was also realized (41 % yield, 83 % ee). Product elaborations and preliminary mechanistic studies were described.     

Cobalt Nanoparticles-Catalyzed Widely Applicable Successive C−C Bond Cleavage in Alcohols to Access Esters

Selective cleavage and functionalization of C−C bonds have important applications in organic synthesis and biomass utilization. However, functionalization of C−C bonds by controlled cleavage remains difficult and challenging because they are inert. Herein, we describe an unprecedented efficient protocol for the breaking of successive C−C bonds in alcohols to form esters with one or multiple carbon atoms less using heterogeneous cobalt nanoparticles as catalyst with dioxygen as the oxidant. A wide range of alcohols including inactive long-chain alkyl aryl alcohols undergo smoothly successive cleavage of adjacent −(C−C)_n− bonds to afford the corresponding esters. The catalyst was used for seven times without any decrease in activity. Characterization and control experiments disclose that cobalt nanoparticles are responsible for the successive cleavage of C−C bonds to achieve excellent catalytic activity, while the presence of Co-N_x has just the opposite effect. Preliminary mechanistic studies reveal that a tandem sequence reaction is involved in this process.     

Pivotal Role of the Basic Character of Organic and Salt Catalysts in C−N Bond Forming Reactions of Amines with CO2

Organocatalysts promote a range of C−N bond forming reactions of amines with CO₂. Herein, we review these reactions and attempt to identify the unifying features of the catalysts that allows them to promote a multitude of seemingly unrelated reactions. Analysis of the literature shows that these reactions predominantly proceed by carbamate salt formation in the form [BaseH][RR′NCOO]. The anion of the carbamate salt acts as a nucleophile in hydrosilane reductions of CO₂, internal cyclization reactions or after dehydration as an electrophile in the synthesis of urea derivatives. The reactions are enhanced by polar aprotic solvents and can be either promoted or hindered by H-bonding interactions. The predominant role of all types of organic and salt catalysts (including ionic liquids, ILs) is the stabilization of the carbamate salt, mostly by acting as a base. Catalytic enhancement depends on the combination of the amine, the base strength, the solvent, steric factors, ion pairing and H-bonding. A linear relationship between the base strength and the reaction yield has been demonstrated with IL catalysts in the synthesis of formamides and quinazoline-2,4-diones. The role of organocatalysts in the reactions indicates that all bases of sufficient strength should be able to catalyze the reactions. However, a physical limit to the extent of a purely base catalyzed reaction mechanism should exist, which needs to be identified, understood and overcome by synergistic or alternative methods.     

Cobalt-Catalyzed Hiyama-Type C−H Activation with Arylsiloxanes: Versatile Access to Highly ortho-Decorated Biaryls

Versatile direct Hiyama-type C−H arylations of benzamides were accomplished with organosiloxanes by chelation-assisted cobalt catalysis. The C−H arylation featured broad substrate scope, including challenging C(sp³)−H activation, the use of γ-valerolactone as biomass-derived solvent, and selectively provided the desired biaryls, even when being highly sterically hindered.