Copper-Catalyzed Sequential C(sp2)−H/C(sp3)−H Annulation of Indoles with Propargylic Alcohols to Access Hydrobenzo[b]carbazoles

Herein, we describe a copper-catalyzed sequential C(sp²)−H/C(sp³)−H annulation of indoles with propargylic alcohols for the synthesis of diversely functionalized hydrobenzo[b]carbazole scaffolds. The reaction involves a Friedel-Crafts addition, 1,5-H shift, 6π electrocyclization, and dearomatization-aromatization cascade. Importantly, this is a report of the use of 2-(diarylmethyl)indoles as three-carbon synthons in a (3+3) annulation reaction involving C(sp³)−H indole functionalization under oxidant-free conditions.     

An Update on Distal C(sp3)−H Functionalization Involving 1,5-HAT Emerging from Nitrogen Radicals

Methods to selectively functionalize any one sp³ C−H bond among all others, has been well documented in literature. Radical reactions, which are essentially mild reaction conditions has provided a significant improvement over the standard functionalization pathways. Although radical recombinations are fast and feasible, the selectivity is always guided by the electronic biasness in the system. 1,n-Hydrogen atom transfer (HAT) reactions are extremely useful in determining regioselectivity, the involvement of a 1,5-HAT protocol made the reaction pathway energetically much more favourable to functionalize the desired remote C(sp³)−H bond. In this review we are going to give a brief overview of the methods involved in the functionalization of distal aliphatic C−H bond by 1,5-HAT transformation pathway.     

Ruthenium(II)-Catalyzed Selective C(sp2)−H Acyloxylation of 2-Aroyl-Pyridine Derivatives with Sodium Carboxylate

A ruthenium-catalyzed C(sp²)−H acyloxylation of 2-aroyl pyridine derivatives with simple sodium carboxylate utilizing transformable directing groups is described. This protocol features broad functional group tolerance and chemo- and regio-selectivity, providing the acyloxylation products in 45%-84%yield. Furthermore, the synthetic utility of this protocol was demonstrated by the late-stage functionalization of pharmaceutical compounds. Notably, the acyloxylation products could be further transformed into a variety of useful heterocycles under mild conditions.     

Substrate-induced Selective α-C(sp3)−H Activation of N-alkyl Amines: Synthesis of Coumarin-fused Quinolinones under Air

A substrate-induced synthesis of coumarin-fused quinolinones is achieved from 4-(phenylamino)-2H-chromen-2-ones using N-alkyl amines as the solvent and a carbon source under air conditions without any catalysts in one pot. This protocol highlights the special roles of 4-(phenylamino)-2H-chromen-2-ones which were not only used as reactants but also as an internal oxidant selectively activated N-α-C(sp³)−H bond. This reaction features catalyst-free, broad substrate scopes (N-alkyl amines 27 examples and quinolinones 24 examples), operationally simple for the one-step synthesis, and recovery and recycling of the solvent.     

Aryl Ketone-Catalyzed Light-Driven Radical Oxy-Functionalization of Non-Acidic C(sp3)−H Bonds Enabled by Triple Role of TEMPO

A light-driven radical oxy-functionalization of non-acidic aliphatic and benzylic C(sp³)−H bonds was achieved with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) in a single-step by employing an aryl ketone as a sole catalyst. The transformation was initiated by homolysis of a C(sp³)−H bond in the starting substance by the photo-excited aryl ketone. The derived carbon radical was then promptly trapped by TEMPO leading to the formation of the TEMPO-adduct. The derived TEMPO-adduct is synthetically versatile as an alcohol equivalent since it can be readily converted to the corresponding ketone by oxidation and to the corresponding alcohol by reduction. The key to realizing the present catalytic reaction relies on the distinctive triple role of TEMPO, which acts as the precursor of the oxygen functionality, the oxidant to regenerate the aryl ketone, and the protective group for the derived TEMPO-adduct from over-oxidation.     

FeCl3-Catalyzed C(sp3)−H Heteroarylation Enabled by Photoinduced Ligand-to-Metal Charge Transfer

Herein, we report a strategy for pyrimidination of inert alkanes via synergistic visible light-driven redox reaction and FeCl₃ catalysis. This transformation involves C−H activation by a chlorine radical generated during the iron-promoted ligand-to-metal charge transfer process, triggering subsequent C−H pyrimidination. The substrates and catalysts are inexpensive and readily available, while the reaction conditions and procedures are simple without the need for external oxidants. This work provides a practical approach for synthesizing pyrimidine derivatives with high structural diversity.     

Tackling Remote sp3 C−H Functionalization via Ni-Catalyzed “chain-walking” Reactions

Nickel catalysts have recently played an important role for rapidly and reliably converting feedstock chemicals into valuable compounds of interest for both pharmaceutical and academic laboratories. Herein, we summarize the recent advances on the ability of nickel catalysts to trigger olefin isomerization via “chain-walking”, causing a displacement of the nickel catalyst throughout the alkyl chain while opening up new grounds for forging C−C and C-heteroatom linkages at remote, yet unfunctionalized, sp³ C−H bonds.     

A DFT Survey of the Effects of d-Electron Count and Metal Identity on the Activation and Functionalization of C−H Bonds for Mid to Late Transition Metals

The contribution of metal identity to the activation and functionalization of methane by a series of three-coordinate imide complexes is evaluated in silico for a 3-by-3 block of metals from Fe to Pt. Three mechanisms were studied: oxidative addition (OA) to the metal; hydrogen atom abstraction (HAA) by the imide nitrogen; and, [2+2] addition across the metal-imide bond. In no studied case, was a [2+2] mechanism preferred, perhaps suggesting this mechanism is largely (entirely?) the domain of d⁰ imides. There is a diagonal relationship within the nonet of metals studied in that OA is preferred for earlier, heavier (5d) members of the series, transitioning to an HAA mechanism for later, lighter (3d) imides. DFT indicates that important parameters in partitioning between HAA and OA mechanisms include the strength of the metal-imide π-bond, the ability of larger metals to accommodate increases in formal oxidation state and coordination number, and the soft acid/base compatibility of larger transition metals with soft hydride and methyl ligands     

Electrochemical Ruthenium-Catalysed Directed C−H Functionalization of Arenes with Boron Reagents

Ortho-directed electrochemical C−H functionalization of aromatics with boron-based coupling partners has been achieved under ruthenium catalysis through an oxidatively induced reductive elimination mechanism. Our method provides a single set of conditions delivering C−H arylation, alkenylation and methylation, yielding ortho-functionalized products with good functional group tolerance, including examples of late-stage functionalization in synthetically useful yields. By harnessing electricity as a ‘green’ oxidant, this method circumvents the need for stoichiometric quantities of chemical oxidants, enhancing our sustainability metrics.     

Preparation and Catalytic Performance of Al2O3, TiO2 and SiO2 Supported Vanadium Based-Catalysts for C–H Activation

A series of Al₂O₃, SiO₂ and TiO₂-supported vanadium oxide catalysts with different vanadium loadings has been prepared by two different methods: wet impregnation using ammonium metavanadate as a vanadium precursor and grafting using VOCl₃. Characterization of these catalysts by XRD, FTIR, TEM, SEM, EDX, DR and TGA techniques revealed that the structure of vanadium oxide VO _x species depends on the preparation method, the type of the support and loadings of vanadium on the oxides surfaces. Monomeric vanadium oxide species are predominant at low vanadium loadings while polymeric vanadium oxide species increase with higher loadings. The catalytic activity of the prepared catalysts was evaluated for the liquid-phase oxidation of cyclohexane as a model reaction to obtain cyclohexylhydroperoxide, cyclohexanol and cyclohexanone with PCA as co-catalyst. The results show that the catalysts exhibit good cyclohexane conversion and remarkable selectivity to the target products and high turnover numbers (TON).     

Synthesis of [60]Fullerene‐Fused Tetralones via Palladium‐ Catalyzed Ketone‐Directed sp2 C?H Activation and sp3 C?H Functionalization

The palladium‐catalyzed ketone‐directed dual sp² C H activation and sp³ C H functionalization has been applied for fullerene functionalization for the first time. The sec‐alkyl aryl ketones have been exploited to react with [60]fullerene (C₆₀) to provide the novel and scarce C₆₀‐fused tetralones. The combined use of a highly active cationic palladium(II) catalyst and trifluoromethanesulfonic acid is crucial for the improvement of the reaction yield. A plausible reaction mechanism leading to the observed products has been proposed, and the electrochemistry of the fullerene products has also been investigated.

     

Selective C−H Bond Functionalization of Unprotected Indoles by Donor-Acceptor Carbene Insertion

Copper catalysts containing alkoxydiaminophosphine (ADAP) ligand catalyze the selective C3−H functionalization of unprotected indoles upon carbene transfer from donor-acceptor diazo compounds, the N−H bond remaining unaltered during the transformation. Mechanistic studies, including DFT calculations, allows proposing the existence of two competitive pathways, none of them occurring through the formation of cyclopropane intermediates, at variance with previously reported systems.     

Monofluoromethylation of Tetrahydroisoquinolines by Visible‐light Induced Direct C(sp3)?H Bond Activation

A visible‐light photoredox‐catalyzed reaction of tetrahydroisoquinolines with β‐fluorinated gem‐diols results in the formation of C1‐monofluoromethylated tetrahydroisoquinolines via C(sp³) H bond activation. This protocol provides a new method to introduce a CF group with stable, easily‐prepared monofluorinated gem‐diol as CF source. A mechanistic investigation is presented based on control experiments.

     

Palladium(II)‐Catalyzed Cycloamidination via C(sp2)?H Activation and Isocyanide Insertion

An efficient method for the synthesis of nitrogen heterocycles containing a cyclic amidine moiety has been developed. The process involves palladium‐catalyzed C(sp²) H activation and isocyanide insertion starting with readily accessible ortho‐heteroarene‐substituted aniline derivatives under mild conditions.     

C−N-Coupled Metabolites Yield Insights into Dynemicin A Biosynthesis

The biosynthesis of the three structural subclasses of enediyne antitumor antibiotics remains largely unknown beyond a common C₁₆-hexaene precursor. For the anthraquinone-fused subtype, however, an unexpected iodoanthracene γ-thiolactone was established to be a mid-pathway intermediate to dynemicin A. Having deleted a putative flavin-dependent oxidoreductase from the dynemicin biosynthetic gene cluster, we can now report four metabolites that incorporate the iodoanthracene and reveal the formation of the C−N bond linking the anthraquinone and enediyne halves emblematic of this structural subclass. The coupling of an aryl iodide and an amine is familiar from organometallic chemistry, but has little or no precedent in natural product biosynthesis. These metabolites suggest further that enediyne formation occurs early in the overall biosynthesis, and that even earlier events might convert the C₁₆-hexaene to a common C₁₅ intermediate that partitions to enediyne and anthraquinone building blocks for the heterodimerization.     

Sequential Functionalization of the O?H and C(sp2)?O Bonds of Tropolones by Alkynes and N‐Sulfonyl Azides

Sequential copper‐catalyzed [3+2] cycloaddition, rhodium‐catalyzed O H insertion, intramolecular 1,8‐addition, and rearrangement starting from 1‐alkynes, N‐sulfonyl azides, and tropolones is demonstrated for the synthesis of the 2‐functionalized aminotropones in one pot. These results indicate that sequential functionalization of O H and C(sp²) O bonds smoothly occurs in the C(sp²) O H bonds of tropolone

     

Insights into the electrochemical activity of nanosized α-LiFeO2

In recent work [J. Morales, J. Santos-Peña, Electrochem. Commun. 9 (2007) 2116], we prepared nanosized α-LiFeO₂ with increased electrochemical activity in lithium cells relative to various lithium ferrite polymorphs. In this work, we studied the previous electrodes in different charge states in order to obtain a more accurate picture of the phenomena occurring during cycling. Exsitu X-ray photoelectron spectroscopy (XPS) measurements confirmed the oxidation/reduction of iron atoms during the charge/discharge process. The electrochemical impedance spectroscopy results suggested that the electrolyte is not oxidised during the first charge, but rather than a solid electrolyte interface is formed after one cycle. Also, thermal tests revealed that Fe(IV) present in the electrodes reacted with the electrolyte to form oxidised carbon species. Finally, α-LiFeO₂ was tested as a positive electrode material in a lithium battery under different regimes. Stabilised capacities up to 150 mAh g⁻¹ were obtained under a C/4 regime. This lithium ferrite is therefore an attractive alternative to LiCoO₂.     

Iodine‐Mediated Synthesis of Aromatic Thioethers with Aromatic Amines and Sulfonyl Hydrazides in High Regioselectivity via C(sp2)?H Bond Functionalization

An iodine‐mediated synthesis of aromatic thioethers from aromatic amines and sulfonyl hydrazides via C(sp²) H bond functionalization and C S bond formation has been developed. In this procedure, various substituents on the sulfonyl hydrazides, such as alkyl, methoxyl, chloro, bromo and fluoro groups, and aromatic amines are tolerated in the thiolation which generates the desired products in moderate to good yields.