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The peroxygenases are ideal biocatalysts for the selective oxyfunctionalisation of stable C-H bonds. However, the catalytic efficiency of this approach is limited due to enzyme lability toward oxidant H2O2. Although the reported in-situ H2O2 generation system enables the stable biocatalytic process without deactivating the enzyme, the greatest catalytic potential of peroxygenases still cannot be fulfilled effectively. To address the above issue, a H2O2 generation-detection-regulation platform that integrated an effective organocatalyst-driven H2O2 generation system, a precise electrochemical H2O2 real-time detection device, and a convenient H2O2 regulation strategy was first developed. The suitable range of H2O2 generation rate for maximizing the catalytic efficiency of perox-ygenases while minimizing inactivation of the enzyme was firstly obtained by simply adjusting the amount of organocatalyst. According to the determined suitable range, the C-H oxyfunctionalisation efficiency of peroxygenases for each substrate was significantly boosted, achieving ~3-fold of the reported highest turnover frequency. [ABSTRACT FROM AUTHOR]

C–H bonds are common in organic molecules, and the functionalization of these inactive C–H bonds has become one of the most powerful methods used to assemble complicated bioactive molecules from readily available starting materials. However, a central challenge in these reactions is controlling their stereoselectivity. Recently, significant progress has been made in the development of enantioselective C–H activation enabled by different chiral ligands for the formation of C–C and C–X bonds bearing a chiral center. In this paper, we focus on some archetypal chiral ligands for enantioselective C–H functionalization developed in recent years and analyze the mechanism of these methods, aiming to accelerate related research and to search for more efficient strategies. [ABSTRACT FROM AUTHOR]

In this study, 2‐(benzylamino)naphthalene‐1,4‐dione (4a) was used as the starting material to carry out a one‐pot catalytic reaction in acetic acid with divalent palladium metal Pd(OAc)2 in a nitrogen atmosphere. Two compounds, 5a and 6a, were observed unexpectedly. Both compounds were characterized by spectroscopic methods as well as X‐ray single crystal determination. The crystal structure of 5a reveals that a nitrogen‐containing six‐membered ring is formed; while the crystal structure of 6a shows that both oxazole and pyridine ring are generated. The optimized condition for making 6a was pursued. Derivatives of 4a, such as 4b and 4c, were also used as starting materials to proceed under the aforementioned optimal reaction conditions. Although the yields are not satisfactory, obviously the same patterns of corresponding compounds can be synthesized. The reaction of a 4a‐structural related compound 9 under similar condition, two unexpected oxazole‐containing compounds, 10 and 11, were obtained. The diverse pathways for this type of reactions even starting with slightly different substituents on the quinone indeed provides chemists with a perpetual motivation for further studies. [ABSTRACT FROM AUTHOR]

The palladium‐catalyzed [3+2] annulation of aromatic amides with maleimides via the activation of ortho benzylic C−H and meta C−H bonds is reported. Carboxamide and anilide type substrates that contain a 2‐methylthiophenyl group both participate in this [3+2] annulation, indicating that the presence of a 2‐methylthiophenyl directing group is a key for the success of the reaction. The first C−H bond activation at the benzylic C−H bond is followed by a second C−H bond activation at the meta C−H bond to give five‐membered cyclic products. The cleavage of these C−H bonds is irreversible. [ABSTRACT FROM AUTHOR]

An effective Pd(II)/Ag(I)‐promoted intramolecular cross‐dehydrogenative coupling (CDC) of substituted 1‐benzylimidazoles under air provides, for the first time, a simple access to several functionalized imidazo[2,1‐a]isoindoles, an interesting class of polycyclic heteroaromatic compounds. The direct involvement of two unactivated carbon–hydrogen bonds, without any directing group, grants an elevated atom economy of the whole process. [ABSTRACT FROM AUTHOR]

Carboxylic acids are important in a variety of research fields and applications. As a result, substantial efforts have been directed towards the C–H functionalization of such compounds. While the use of the carboxylic acid moiety as a native directing group for C(sp2)–H functionalization reactions is well established, as yet there is no general solution for the C(sp3)–H activation of aliphatic carboxylic acids and most endeavors have instead relied on the introduction of stronger directing groups. Recently however, novel ligands, tools, and strategies have emerged, which enable the use of free aliphatic carboxylic acids in C–H-activation-based transformations. 1 Introduction 2 Challenges in the C(sp3)–H Bond Activation of Carboxylic Acids 3 The Lactonization of Aliphatic Carboxylic Acids 4 The Directing Group Approach 5 The Direct C–H Arylation of Aliphatic Carboxylic Acids 6 The Direct C–H Olefination of Aliphatic Carboxylic Acids 7 The Direct C–H Acetoxylation of Aliphatic Carboxylic Acids 8 Summary [ABSTRACT FROM AUTHOR]

Peptide macrocycles are widely used in fields ranging from medicinal chemistry to materials science. Efficient chemical methods for the synthesis of cyclic peptides with novel three-dimensional structures are highly desired to facilitate the development of this unique class of compounds. However, the range of methods available for constructing peptide macrocycles is limited compared with that for small molecules. We recently developed new methods for synthesizing highly constrained cyclic peptides with C–C crosslinks through Pd-catalyzed C–H activation reactions. These methods use endogenous backbone amides as directing groups and, therefore, have the potential for use in late-stage functionalization of peptide natural products. [ABSTRACT FROM AUTHOR]

A catalyst‐ and additive‐free simple and straightforward method for regioselective direct sp2 C–H acetoxylation reaction of aldehyde hydrazones has been achieved at ambient temperature employing PIDA as an acetoxy source. The scope of the reaction has been successfully verified with a wide range of biologically important aldehyde hydrazones with diverse functional group tolerance. The method is highly selective, mild and efficient, operationally simple, rapid and high‐yielding. [ABSTRACT FROM AUTHOR]

Peptide modifications via C–C bond formation have emerged as valuable tools for the preparation and alteration of non-proteinogenic amino acids and the corresponding peptides. Modification of glycine subunits in peptides allows for the incorporation of unusual side chains, often in a highly stereoselective manner, orchestrated by the chiral peptide backbone. Moreover, modifications of peptides are not limited to the peptidic backbone. Many side-chain modifications, not only by variation of existing functional groups, but also by C–H functionalization, have been developed over the past decade. This account highlights the synthetic contributions made by our group and others to the field of peptide modifications and their application in natural product syntheses. 1 Introduction 2 Peptide Backbone Modifications via Peptide Enolates 2.1 Chelate Enolate Claisen Rearrangements 2.2 Allylic Alkylations 2.3 Miscellaneous Modifications 3 Side-Chain Modifications 3.1 C–H Activation 3.1.1 Functionalization via Csp3 –H Bond Activation 3.2.2 Functionalization via Csp2 –H Bond Activation 3.2 On Peptide Tryptophan Syntheses 4 Conclusion [ABSTRACT FROM AUTHOR]

A variety of ligands are being explored extensively to achieve enhanced performance for ligand assisted C‐H bond activation/functionalization reactions. We explored here several readily available biomass‐derived ligands as effective additives to significantly enhance the catalytic activity of arene‐Ru(II) dimer for ortho C‐H bond arylation in a water‐based catalytic reaction. We achieved almost 7‐fold enhancement in the catalytic activity with [(η6‐p‐cymene)RuCl2]2 catalyst in the presence of levulinic acid ligand at 80 °C. Mass investigations revealed the in‐situ formation of a ruthenium‐levulinate complex, which presumably plays a crucial role in the formation of the important cycloruthenated intermediate by facilitating the initial activation of ortho C‐H bond of 2‐phenylpyridine. Density functional theoretical studies also inferred that the ligand assisted route is energetically more favorable, where the acetyl group is found to be involved in the deprotonation step. [ABSTRACT FROM AUTHOR]

Pd-catalyzed C–H silylation reactions remain underdeveloped. General strategies usually rely on the use of complex bidentate directing groups. C,C- Palladacycles exhibit extremely high reactivity towards hexamethyldisilane and can be disilylated very efficiently. The C,C- palladacycles are prepared through halide-directed C–H activation. This account introduces Pd-catalyzed C–H silylation reactions with di-silanes as the silyl source, and is focused on studies on the silylation of C,C- palladacycles. 1 Introduction and Background 2 Allylic C–H Silylation Reaction 3 Coordinating-Ligand-Directed C–H Silylation Reaction 4 Disilylation of C (sp2), C (sp2) - Palladacycles That are Generated by C(sp2)–H activation 5 Disilylation of C (sp2), C (sp3) - Palladacycles That are Generated by C(sp3)–H Activation 6 Disilylation of C , C- Palladacycles That are Generated through Domino Processes 7 Summary and Outlook [ABSTRACT FROM AUTHOR]

A continuous flow process for the synthesis of trifluoromethylthioethers is reported. The palladium-catalyzed C-H trifluoromethylthiolation of amides derived from the 8-aminoquinoline using N-[(trifluoromethyl)thio]phthalimide produced the desired products in moderate to good yields with a residence time of 20 min. In comparison with the batch process, the reaction time was decreased by a factor of 100 to 200, demonstrating the positive effect of continuous flow processes for this type of reaction. [ABSTRACT FROM AUTHOR]

Abstract A one-pot, multicomponent-type, solvent-free Pd(II)-catalyzed direct β -C-H activation/arylation of carboxamides involving anhydrides as substrates via in situ installation of directing group (DG) is reported. Typically, the DG-assisted β -C-H activation/arylation of carboxamides is a two-step process comprising the installation of DG and Pd(II)-catalyzed C H arylation. We attempted a multicomponent-type reaction comprising an anhydride, a DG (e.g. 8-aminoquinoline), an aryl iodide in the presence of the Pd(II) catalyst and an appropriate additive. Different anhydrides, DGs, aryl iodides, catalysts and additives were screened to reveal the scope of this multicomponent-type C H arylation reaction process and various β -C-H arylated carboxamides were obtained in satisfactory to good yields. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

A novel palladium(II)/copper(II)‐catalyzed sulfidation of the C–H bond in electron‐rich arenes and in pentafluorobenzene with disulfides was developed. This catalytic system can be used to efficiently produce various types of either unsymmetrical aryl sulfides or alkyl aryl sulfides. The present protocol could also be applied to the direct preparation of unsymmetrical aryl selenides via C–H selenation. C–H sulfidation or selenation of arenes by a Pd(II)/Cu(II) catalytic system: Preparation of unsymmetrical sulfides or selenides by C–H functionalization has been disclosed. This protocol could be applied a various of arenes. In the case of using an indolizine and pentafluorobenzene, bis‐sulfidated product were obtained. [ABSTRACT FROM AUTHOR]

A method for the formal β-functionalization of aliphatic ketones via a palladium-catalyzed sp3 C–H activation pathway is reported. An N,O-ketal directs an aliphatic C–H carbonylation to form γ-lactams which upon hydrolysis generate γ-keto carboxylic acids. This C–C bond-forming reaction is tolerant of a range of functional groups, enabling the synthesis of a range of synthetically important building blocks. Furthermore, the concepts underlying this transformation have also enabled the development of a related C–H alkenylation process to highly functionalised heterocycles. [ABSTRACT FROM AUTHOR]

We present a new method for the selective C(sp3)–H cyanation of adamantane derivatives with PINO as the hydrogen abstracting reagent. A cyano radical is thereby transferred from p - toluenesulfonyl cyanide, allowing the cyanation of adamantane derivatives in up to 71% yield. The protocol presents a novel way to orthogonally functionalized adamantanes that are otherwise difficult to prepare. Mechanistic studies support the hypothesis of a radical pathway. [ABSTRACT FROM AUTHOR]

Abstract An unprecedented Rh(III)-catalyzed C–H activation of N -(pivaloyloxy)benzamide was recently reported by Feng et al. In this transformation, the substituent on the alkyne controls the chemoselectivity (annulation or hydroarylation). Given the importance of this novel strategy, we performed a density functional theory study to clarify the origins of the experimentally observed chemoselectivity. The results of our calculations showed that the conventional annulation of N -(pivaloyloxy)benzamide with an alkynone was kinetically favored, whereas the hydroarylation of α,α-difluoromethylene alkynes was kinetically favored. We found that the inductive effect of a fluorine substituent on the alkyne polarizes the Rh–C bond, and this facilitates the protonation step. Our calculations also explain the experimentally observed regioselectivity, which mainly arises from the interaction energy. Graphical abstract Image 1 Highlights • Origin of substituent-controled chemoselectivity (annulation or hydroarylation) was clarified. • Experimentally observed regioselectivity was explained. • Fluorine substituents in alkyne play an essential role in diverting the reaction sequence from the conventional pathway. • Protonation of the alkenyl group precedes formation of a Rh(V) nitrenoid intermediate. [ABSTRACT FROM AUTHOR]

As pioneered by Corey and Chaykovsky, sulfoxonium ylides have had widespread application in organic synthesis for more than a half century. In most of the reactions, sulfoxonium ylides were used to react with electrophiles. Under suitable reaction conditions these ylides can generate metal carbenoids and react with nucleophiles. By combining the typical reactivity of sulfoxonium ylides with transition-metal catalysis, a growing number of investigations have expanded their application in organic synthesis. This review provides an update on the preparation of sulfoxonium ylides and their applications in carbenoid transfer reactions. [ABSTRACT FROM AUTHOR]

This review summarizes the synthetic approaches towards 1,2-substitution pattern on the adamantane framework. Selected are the works containing the directed C–H functionalization step. [ABSTRACT FROM AUTHOR]

The functionalization of otherwise unreactive C–H bonds holds great promise for reducing reliance on existing functional groups while improving energy efficiency and atom economy. One of the most powerful strategies exploits chelation assistance through reversible coordination with metal catalysts. This microreview summarizes the most recent advances in the use of 1,2,3‐triazoles as versatile directing groups in the field of C–H functionalization. The main feature is the modular and straightforward assembly of the required triazoles through "click" chemistry, and such procedures therefore constitute practical synthetic tools of utmost importance for the late‐stage diversification of "click compounds", which are ubiquitous moieties in drug discovery and material science. Click&Go! Recent advances in the use of 1,2,3‐triazoles as versatile directing groups in C–H functionalization are reviewed. The main feature is the straightforward, modular assembly of the required triazoles in "click" fashion, making the procedures practical synthetic tools of key importance for late‐stage diversification of "click compounds" – prevalent moieties in drug discovery and materials science. [ABSTRACT FROM AUTHOR]

A Ru0‐catalyzed direct C‐H arylation and alkenylation of furfural imines with aryl‐ or alkenyl‐boronates, in the presence of benzylideneacetone as a sacrificial hydride acceptor, is disclosed. This reaction provides access, after hydrolysis, to C3‐arylated or vinylated furfural derivatives, and thus valorizes these relevant building‐blocks obtained from lignocellulosic biomass. This approach, involving C‐H activation by a Ru0/RuII, cycle offers several advantages, notably simple, mild and neutral reaction conditions. Furfural activated again: a Ru‐catalyzed arylation and alkenylation of furfural imines with aryl‐ or alkenyl‐boronates, involving a directed C‐H activation occurring at C3 of the furan ring, was developed. It was revealed that an electron‐rich aromatic imine, such as a p‐dimethylaminophenyl‐imine, enables the coupling with good yields. After the coupling, a smooth hydrolytic removal of the imine directing‐group releases the C3‐functionalized furfurals. [ABSTRACT FROM AUTHOR]

The luminescence of oxazolones R1‐C6H4CH=CC(O)O‐CN(R2) (1a–1j) and imidazolones R1‐C6H4CH=CC(O)NR3CN(R2) (1k–1q) has been examined. The new GFP‐like imidazolones (GFP = Green Fluorescent Protein) (1k–1q) have been prepared by reaction of the oxazolones with amines H2NR3 and bis(trimethylsilyl)acetamide. The most intense fluorescence was found in push‐pull systems containing simultaneously strong electron‐donating and electron‐withdrawing substituents. The incorporation of the Pd atom into the molecular skeleton of oxazolones and imidazolones notably changes their luminescence. The reaction of oxazolones (1a–1j) and imidazolones (1k–1q) with Pd(OAc)2 (1:1 molar ratio) in carboxylic acids gives the dinuclear [Pd{R1‐C6H3CH=CC(O)OCN(R2)}(µ‐carboxylate)]2 (2a–2j) and [Pd{R1‐C6H3CH=CC(O)NR3CN(R2)}(µ‐carboxylate)]2 (2k–2q) through regioselective C–H bond activation of the ortho position of the respective 4‐arylidene rings. Complexes 2a–2q react with LiCl in MeOH to give the chloride‐bridge derivatives [Pd{R1‐C6H3CH=CC(O)OCN(R2)}(µ‐Cl)]2 (3a–3j) and [Pd{R1‐C6H3CH=CC(O)NR3CN(R2)}(µ‐Cl)]2 (3k–3q), which further react with Tl(acac) (acac = acetylacetonate) to give the mononuclear species [Pd(R1‐C6H3CH=CC(O)OCN(R2)(acac)] (4a–4j) and [Pd{R1‐C6H3CH=CC(O)NR3CN(R2)(acac)}] (4k–4q). Complexes 4o and 4q, having an orthopalladated push‐pull imidazolone, are strongly fluorescent, showing a notable increase of the quantum yield with respect to the free ligands 1o and 1q up of one order of magnitude. The orthopalladation of 4‐aryliden‐5(4H)‐oxazolones and ‐imidazolones through C–H bond activation is regioselective and gives dimers where only the ortho position of the 4‐arylidene ring is activated. The carboxylate ligands can be replaced by acetylacetonate, affording rigid neutral mononuclear complexes. The photophysical properties of these rigid mononuclear complexes have been examined and confirm the importance of rigidification of imidazolones. [ABSTRACT FROM AUTHOR]

Reaction optimization for C–H bond functionalization reactions with transition‐metal catalysts is traditionally based on long and tedious screening of multiple conditions. In this contribution we have applied a deconvolution strategy to identify reaction conditions suitable for the C–H bond heteroarylation of 1,2,3‐triazoles with a ruthenium catalyst by performing only 18 experiments with mixtures of reagents instead of the theoretically 576 experiments that should have been considered individually. The activation and functionalization takes place at the ortho position of the phenyl ring attached to the 1,2,3‐triazole directing group as confirmed by X‐ray crystallographic studies. The bis‐ vs. mono‐heteroarylation was controlled by tuning the stoichiometry of the reagents. Such methodology was also applicable to aryl bromide coupling partners bearing ortho and meta substituents. The application of a deconvolution strategy to ruthenium‐catalyzed C–H bond functionalization provided appropriate reaction conditions to perform the unprecedented heteroarylation of triazole scaffolds in good yields. This was possible after screening 22 parameters (three solvents, three ruthenium complexes as pre‐catalysts, eight carboxylate salts as co‐catalysts and eight bases) in only 18 designed experiments. [ABSTRACT FROM AUTHOR]

The reactivity of positions C9 and C10 of 9‐ or 10‐bromophenanthrenes in palladium‐catalyzed direct heteroarylations was investigated. A wide variety of heteroarenes such as thiazoles, (benzo)thiophenes, (benzo)furans, pyrroles, selenophenes or imidazopyridazines was successfully introduced at phenanthrene C9‐position via palladium‐catalyzed direct arylations, using 0.5–0.1 mol‐% of phosphine‐free Pd(OAc)2 catalyst. Then, C10‐bromination of the 9‐heteroarylated phenanthrenes, followed by a second palladium‐catalyzed direct heteroarylation gives access to symmetrical and non‐symmetrical 9,10‐di(heteroaryl)phenanthrenes. Successive palladium‐catalyzed direct heteroarylations of 9‐ and 10‐bromophenanthrenes provides a convenient route for access to symmetrical and non‐symmetrical 9,10‐di(heteroarylated) phenanthrenes. A wide variety of heteroarenes such as thiazoles, (benzo)thiophenes, (benzo)furans, pyrroles, selenophenes, or imidazopyridazines was successfully employed. [ABSTRACT FROM AUTHOR]

The reactivity of (poly)halo‐substituted benzenesulfonyl chlorides in palladium‐catalyzed ortho‐directed C–H bond sulfonylation of 2‐arylpyridines was investigated. The use of Ag2CO3 in concert with Cu(OAc)2 was found to be critical to promote the chemoselective sulfonylation reaction. Fluoro‐, chloro‐, bromo‐, and even iodo‐benzenesulfonyl chlorides react nicely to afford halo‐substituted diarylsulfones in good to high yields without cleavage of the C–halo bonds, allowing further transformations. A one‐step procedure for the synthesis of (poly)halo‐substituted diarylsulfones was developed. The reaction involves ortho C–H bond sulfonylation of 2‐arylpyridines with (poly)halo‐substituted benzenesulfonyl chlorides. These reaction conditions tolerated C–F, C–Cl, C–Br and even C–I bonds. [ABSTRACT FROM AUTHOR]

Ruthenium(II)‐catalysed C–H bond activation of arenes containing a functional directing group depends on the ligand coordinated to ruthenium(II). In this study, 2‐phenylpyridine C–H activation catalysed by a "piano‐stool" ruthenium(II) complex containing a fluorinated β‐diketonate ligand was examined by ESI‐MS in combination with CID experiments. [Ru(β‐diketonate)(CTPhPy)Cl]+ was identified as an active intermediate, and its collisional activation leads to C–H activation. CID analysis indicates proton transfer from the phenylpyridine to the chlorine anion, showing HCl elimination, while the β‐diketonate ligand is retained in the complex together with the activated phenylpyridine. Furthermore, DFT calculations were performed for the neutral analogue [Ru(β‐diketonate)(PhPy)Cl] to identify all ruthenium intermediates along the C–H activation reaction pathway. The results suggest that the most stable structure of [Ru(β‐diketonate)(PhPy)Cl] has pre‐activated 2‐phenylpyridine with a partly developed Ru–H bond. Further, we show that K2CO3 is not directly involved in the C–H activation step and it serves in the reaction as a base. 2‐Phenylpyridine C–H activation catalysed by a ruthenium(II) β‐diketonate complex was studied by ESI‐MS and CID. We have identified [Ru(β‐diketonate)(CTPhPy)Cl]+ as an active intermediate, and its collisional activation leads to C–H activation. DFT calculations were performed to identify all ruthenium intermediates along the C–H activation reaction pathway. [ABSTRACT FROM AUTHOR]

C–H activation has emerged as a viable alternative to traditional C–C bond forming reactions such as the Suzuki–Miyaura, Stille, Negishi and others. However, C–H activation is rarely employed in total synthesis or fine chemical manufacture, particularly as an end‐game strategy. This may be due to the harsh conditions typically required. For C–H activation to become a truly useful and versatile methodology, conditions must emerge which are applicable to compounds with multiple functionalities. In this review, we hope to inspire the chemistry community to focus their efforts on milder conditions for C–H activation and cross‐dehydrogenative coupling. To this end, we have focused on describing C–H activation as it has been applied to several classes of biologically interesting, but chemically sensitive motifs: the 2‐pyrones, 2‐pyridones, 2‐coumarins and 2‐quinolones. In this review, we hope to inspire the chemistry community to focus their efforts on milder conditions for C–H activation and cross‐dehydrogenative coupling. To this end, we have focused on describing C–H activation as it has been applied to several classes of biologically interesting, but chemically sensitive motifs: the 2‐pyrones, 2‐pyridones, 2‐coumarins and 2‐quinolones. [ABSTRACT FROM AUTHOR]

In this study, a simple and appropriate procedure for the synthesis of functionalized benzothiadiazine 1,1-dioxide with good yields via the Cu-catalyzed intramolecular C-H activation reaction from benzenesulfonylchloride and N,N′,N′′-trisubstitutedguanidines, generated by copper(II) oxide-catalyzed hydroamination of carbodiimides, is reported. [ABSTRACT FROM AUTHOR]

An N‐heterocyclic carbene palladium(II) complex containing two anthracene side arms was immobilized on the surface of reduced graphene oxide (rGO) by π‐stacking. The activity of the homogeneous analogue and the supported complex in undirected C–H acetoxylation reaction of arenes was studied. The results show that the catalytic efficiency in acetoxylation of benzene is improved in the immobilized materials compared to the homogeneous analogue. According to XPS analysis, the immobilized catalyst maintains the original oxidation state of PdII after the catalytic reaction. π‐Stacking an NHC Pd system with anthracene side arms on a reduced graphene oxide surface is a simple procedure and gives a material that is an effective, recyclable catalyst in the acetoxylation of benzene. The complex remains molecular palladium(II) also on the graphene surface and the activity is comparable to other supported NHC–Pd complexes with more elaborate support procedures. [ABSTRACT FROM AUTHOR]

Proximity effects permit C–H activation reactions without directing groups. Here competitive reactions of selected substrates were investigated which allow a domino‐carbopalladation/Mizoroki–Heck reaction and a domino‐carbopalladation/C–H activation reaction. In the Pd‐catalyzed transformation of the enantio‐ and diastereopure alkyne 8a the tetra‐substituted alkenes 10 and 11 were formed almost exclusively through a domino carbopalladation/Mizoroki–Heck reaction. In contrast, the diastereomer 8c only led to the acenaphthylenes 12c and 13c through a domino carbopalladation/C–H activation reaction. Moreover, in the reaction of 20, 24 and 27 containing a naphthyl moiety only the tetra‐substituted alkenes 23, 25/26 and 28/29, respectively were obtained, whereas in the reaction of 34, containing a phenanthrene moiety, compound 37 was the only product, formed via a C–H activation reaction. Proximity effects allow C–H‐activation reactions without directing groups in competition with domino‐carbopalladation or Mizoroki–Heck reactions. Vinly–Pd species can be assumed as intermediates, which either react with a double bond or a naphthyl or phenanthryl moiety. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Combination of triazole with thiazole and oxazole. • C–H activation/decarboxylation cross-coupling. • 1,2,3-Triazole directing group. Abstract An efficient palladium-catalyzed selective decarboxylation/C–H activation coupling of aryl acid with thiazole and oxazole under the assistance of 1,2,3-triazole ring were developed. This work provides an effective access to build functionalized 1,2,3-triazoles bearing thiazole and oxazole moieties. This method has good substrate compatibility to compose a series of selective heterocyclic compounds in moderate to good yields. [ABSTRACT FROM AUTHOR]

Graphical abstract A spin-crossover cobalt(II) complex is found to be a catalyst for the oxidation of weak C–H bonds by the two-electron oxidants iodosobenzene and meta -chloroperbenzoic acid. The complex is incapable of being oxidized to a cobalt(III)-peroxo species and cannot participate in aldehyde deformylation reactions. Highlights • A non-organometallic cobalt(II) complex was found to catalyze the oxidation of weak C–H bonds by two two-electron oxidants. • The cobalt(II) complex differs from the other known non-organometallic catalyst in that it is not entirely high-spin. • The cobalt(II) complex cannot form a cobalt(III)-peroxo complex and cannot participate in aldehyde deformylation. Abstract We recently found that a high-spin Co(II) complex with N,N' -dibenzyl- N,N' -bis(2-pyridylmethyl)-1,2-cyclohexanediamine (bbpc) was capable of catalyzing the oxidation of weak sp3 C–H bonds by iodosobenzene (PhIO) and meta -chloroperbenzoic acid (MCPBA). The bbpc compound could also be oxidized to a Co(III)-peroxo species capable of reacting with aldehydes. The ligand N -benzenesulfonyl- N,N’ -bis(2-pyridylmethyl)-1,2-cyclohexanediamine (bsbpc) reacts with Co(ClO 4) 2 to yield a spin-crossover complex, [Co(bsbpc)(MeCN) 2 ](ClO 4) 2. The bsbpc complex catalyzes the oxidation of benzylic and allylic C–H bonds by PhIO and MCPBA to approximately the same extent as the high-spin bbpc compound. The bsbpc complex differs more substantially from the bbpc compound in that it cannot be oxidized to a stable Co(III)-peroxo complex and shows no reactivity with aldehydes. [ABSTRACT FROM AUTHOR]

An IrIII‐catalyzed cascade reaction consisting of C–H activation/annulation of benzimidates with hydroxylisopropylalkynes is reported. A broad range of isoquinolines has been prepared in one step with good functiona‐group tolerance and high efficiency. [ABSTRACT FROM AUTHOR]

Abstract Vinyl acetate is used as an acetylene equivalent in rhodium(III)-catalysed C-H activation/annulation with aryl ketoxime esters. Extension to an aldoxime ester allows for a concise formal synthesis of decumbenine B. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

A simple and facile protocols for copper‐catalyzed regionselective C4 nitration and azidation of 1‐naphthylamines via remote C–H activation that use of pyridyl amide fragment as the removable directing group have been firstly developed. These reactions proceed under mild conditions without any additives, tolerate a wide variety of functional groups, and afford a wide range of products in good to excellent yields. Control experiments suggest that those C–H activation reactions are likely to proceed through a single‐electron‐transfer (SET) process. [ABSTRACT FROM AUTHOR]

A simple, one-pot, three-component, green synthesis of a wide range of propargylamines is reported by A3-coupling (aldehyde, alkyne and amine) via C-H activation of alkynes using [Zn(L-proline)2] as an efficient and reusable heterogeneous catalyst. High catalytic activity was achieved in comparatively low temperature under solvent-free conditions. All reactions were carried out in an open atmosphere without the use of any co-catalyst/additive.Graphical Abstract: [ABSTRACT FROM AUTHOR]

The first RhIII‐catalyzed activation of ortho‐C–H bonds of arylcarboxylic esters for monoselective coupling with ethenesulfonyl fluoride (ESF) was developed. This protocol provides a convenient access to a class of otherwise difficult to access 2‐arylethenesulfonyl fluorides possessing ortho‐carboxylic esters functionality. The synthesized 25 examples in up to 99 % isolated yields of 2‐arylethenesulfonyl fluorides bearing versatile carboxylic groups make this method remarkably applicable in developing biologically and pharmacologically active ethenesulfonyl fluorides, which are potential covalent drug candidates. [ABSTRACT FROM AUTHOR]

α-Cyanocarbanion complexes feature nitrile ligands containing deprotonated α-carbon atoms. This short review will focus on the various synthetic methods employed to prepare these complexes, the different binding modes they exhibit and their applications to the synthesis of alkylnitriles including β-hydroxy- and β-aminonitriles, the formation of unique coupling products and as key intermediates in the reaction of acrylonitrile with various substrates in hydrophosphination and copolymerisation reactions. [ABSTRACT FROM AUTHOR]

Hydrogen isotope exchange (HIE) is a versatile method for the introduction of deuterium to organic compounds. Herein, regioselective deuteration of sulfonamides is achieved by palladium-Catalyzed HIE reaction. By using amino acid as weakly coordination-directing auxiliary, a variety of sulfonamides are efficiently deuterated at the ortho -position. Placing competing directing groups on the aromatic ring does not affect the site-selectivity. [ABSTRACT FROM AUTHOR]

Indole is an important heterocyclic motif that occurs ubiquitously in bioactive natural products and pharmaceuticals. Immense efforts have been devoted to the synthesis of indoles starting from the Fisher indole synthesis to the recently developed C-H activation/functionalization- based methods. Herein, we have reviewed the progress made on the regioselective synthesis of functionalized indoles, including 2-substituted, 3-substituted and 2,3-disusbstituted indoles, since the year 2010. [ABSTRACT FROM AUTHOR]

This work reports the synthesis of p-hydroxybenzoates directly from phenols by oxidative carbonylation of phenolic C–H bonds, proceding through oxidative iodination. The developed methodology is efficient and economically attractive because phenols are cheap and easily available starting materials. This one-pot strategy was expediently applied to thesynthesis of a variety of p-hydroxybenzoates by utilizing simple primary and secondary alcohols with different phenols under mild reaction conditions. Advantageously, the procedure has no need for co-catalysts, co-solvents or external ligands. The utilization of molecular oxygen as a terminal oxidant for C–H bond oxidation represents an additional benefit. [ABSTRACT FROM AUTHOR]

A simple and efficient selective diacetoxylation of 1,4-disubstituted 1,2,3-triazoles by Pd-catalyzed C-H bond activation is described. PhI(OAc)2 was used as an acetyloxy source to convert aromatic sp2 C-H bonds into C-O bonds with high selectivity by employing a 1,2,3-triazole ring as an elegant directing group. A range of 1,2,3-triazoles bearing two acetyloxy groups can be readily synthesized by the reaction. [ABSTRACT FROM AUTHOR]

The transition metal catalyzed direct site‐selective carbon –hydrogen functionalization is ubiquitous in organic synthesis and has reached an impressive level of sophistication and efficiency emerging as a powerful synthetic strategy for C–C bond and C–X bond formation to access various useful arylated organic molecules. For the past two decades, directing group strategy has been used for selective activation and functionalization of certain inert C–H bonds. Despite the enormous development in this field, still, the majority of systems require two redundant steps, i. e. installation and removal of DGs. To overcome these limitations, recently, traceless and multitasking groups were invented as a partial solution to DG release however installation still remains unsolved. Ideally, use of the catalytic directing group, which can be reversibly linked to the substrate and can serve as an efficient directing role would circumvent this problem and is considered as one of the most efficient and powerful strategies for the non‐activated C–H functionalization (C(sp2)–H or C(sp3)–H). In this review, we describe the enormous advances in this field for direct selective C–H functionalization without involving additional steps, i. e. installation and removal of directing groups and also discuss less explored but significant non‐covalent interactions such as hydrogen bonding or ion pairing, which helps to control the selectivity of a substrate in a catalytic organic reaction. Transition‐metal‐catalyzed C−H functionalization can be carried out via transient directing group strategy, which represents the most direct and efficient method in introducing the second functional group on organic molecules. [ABSTRACT FROM AUTHOR]

Many Pd-catalyzed C–H functionalization reactions utilize stoichiometric Ag(I)-salts as additives. Ag additives are typically used either as a terminal oxidant or as a halide scavenger for Pd catalyst regeneration. However, recent experimental and computational studies have shown that Ag(I)-salts may play additional roles in C–H activation processes. Notably, cooperative Pd–Ag bimetallic C–H activations and Ag(I)-mediated Pd-catalyzed C–H arylations can occur. The non-oxidative roles of Ag(I) salts in Pd-catalyzed C-H activation are highlighted in this mini-review. [ABSTRACT FROM AUTHOR]

Abstract: Direct transformation of carbon–hydrogen bond (C–H) has emerged to be a trend for construction of molecules from building blocks with no or less prefunctionalization, leading high atom and step economy. Directing group (DG) strategy is widely used to achieve higher reactivity and selectivity, but additional steps are usually needed for installation and/or cleavage of DGs, limiting step economy of the overall transformation. To meet this challenge, we proposed a concept of automatic DG (DGauto), which is auto‐installed and/or auto‐cleavable. Multifunctional oxime and hydrazone DGauto were designed for C–H activation and alkyne annulation to furnish diverse nitrogen‐containing heterocycles. Imidazole was employed as an intrinsic DG (DGin) to synthesize ring‐fused and π‐extended functional molecules. The alkyne group in the substrates can also be served as DGin for ortho‐C–H activation to afford carbocycles. In this account, we intend to give a review of our progress in this area and brief introduction of other related advances on C–H functionalization using DGauto or DGin strategies. [ABSTRACT FROM AUTHOR]

Roll-over cyclometalation is a special case of cyclometalation. While in classical cyclometalation, C,H-activation (deprotonation or oxidative addition) has to occur at the ligand to result in a metallacycle, in roll-over cyclometalation the ligand in principle has the chance to undergo chelating coordination without cleavage of a C-H bond (e.g. κ 2 - N , N′ - vs. κ 2 - C , N -coordination at 2,2′-bipyridines). Nature thus can decide for which route shall be followed. In this review, the basic parameters for bringing a system into roll-over cyclometalation are discussed, followed by an overview on compounds that have been published in this field during the last years. The major emphasis of this review however is on applications of roll-over cyclometalation in catalysis, a rather new field in coordination and organometallic chemistry. [ABSTRACT FROM AUTHOR]

Noncovalent interactions play a fundamental role in molecular biology, crystal engineering, supramolecular chemistry, drug design, sensing applications, and many other research fields in the chemical sciences. Because of this importance, thorough research efforts have been focused on the interpreting and quantifying these interactions, which include H-bonding, electrostatic effects, π π interaction, cation-π interaction, hydrophobic-hydrophobic interaction, van der Waals forces, and other such type of interactions. However, on the synthetic standpoint, use of these noncovalent interactions are rare, although might be beneficial for the site-selective C H bond activation and functionalization by transition metal catalysis. In this context, iridium-catalyzed C H borylation has gained immense popularity due to the versatility conferred to the C B bonds. Very recently, researchers have started employing these interactions as a governing factor for attaining regioselectivity in arene C H borylation. In this perspective, we will focus on the advancements made so far by the use of various noncovalent interactions in Ir-catalyzed borylations. [ABSTRACT FROM AUTHOR]

Fused-ring systems containing heterocycles are attractive templates for drug discovery. Biologically active 6-5-5+6 fused-ring systems that possess heterocycles are available, but these require a relatively large number of synthetic steps for preparation. Therefore, pyrazolofuropyrazine was designed as a 6-5-5+6 ring system template that incorporates ready accessibility for drug discovery. Pyrazolofuropyrazines were successfully constructed in only a few steps via one-pot SNAr reaction/intramolecular C-H direct arylation. As a drug candidate, pyrazolofuropyrazine has earned a favorable LogP, although significant biological activity has yet to be established; the ready accessibility of pyrazolofuropyrazine template, however, offers an opportunity for the rapid development of promising new drug candidates. [ABSTRACT FROM AUTHOR]

Water‐soluble ruthenium(II)–arene complexes [(η6‐arene)Ru(κ2‐L)]n+ (n = 0, 1) ([Ru]‐1–[Ru]‐10) containing pyridine‐based bischelating N,O/N,N donor ligands (L1–L5) are synthesized and employed for the catalytic C–H bond activation/arylation of a wide range of 2‐phenylpyridines and aryl halides in water, affording the corresponding mono‐ and biarylated products. Exploring the reactivity of the synthesized complexes, our investigations, including time‐dependent 1H NMR spectroscopic studies with ruthenium–arene catalysts, demonstrate a remarkable structure–activity relationship for the ligand‐tuned C–H activation/arylation of 2‐phenylpyridine, where the complexes with bischelating N,O donor‐based ligands (acteylpyridine and picolinate) outperform those with N,N donor ligands (iminopyridine). Moreover, among the N,O donor ligands, a distinct effect of the nature of the coordinating oxygen donor on the catalytic activity is also observed, where ruthenium–arene complexes having N,O donor ligands (acetylpyridine) with neutral oxygen‐donor atoms exhibit enhanced catalytic activity over those with anionic oxygen‐donor atoms (picolinate). The observed trend in the catalytic activity is attributed to the ligand‐promoted facile deprotonation and coordination–decoordination interconversion behavior. In addition, molecular structures for a few of the representative complexes ([Ru]‐2, [Ru]‐4, and [Ru]‐5) are authenticated by single‐crystal X‐ray diffraction studies. [ABSTRACT FROM AUTHOR]