Oxidation‐Induced C—H Functionalization: A Formal Way for C—H Activation

Cross‐coupling reactions have developed widely and provided a powerful means to synthesize a variety of compounds in each chemical field. The compounds which have C—H bonds are widespread in fossil fuels, chemical raw materials, biologically active molecules, etc. Using these readily‐ available substances as substrates is high atom‐ and step‐economy for cross‐coupling reactions. Over the past decades, our research group focused on finding and developing new strategies for C—H functionalization. Compared with classical C—H activation methods, for example, C—H bonds are deprotonated by strong base or converted into C—M bonds, oxidation‐induced C—H functionalization would be another pathway for C—H bond activation. This perspective shows a brief introduction of our recent works in this oxidation‐induced C—H functionalization. We categorized this approach of these C—H bond activations by the key intermediates, radical cations, radicals and cations.     

Hydrogen bonding between aromatic H and F groups leading to a stripe structure with R‐ and S‐columns: the crystal structure of (2,7‐dimethoxynaphthalen‐1‐yl)(3‐fluorophenyl)methanone and comparison with its 1‐aroylnaphthalene analogues

In the molecule of (2,7‐dimethoxynaphthalen‐1‐yl)(3‐fluorophenyl)methanone, C₁₉H₁₅FO₃, (I), the dihedral angle between the plane of the naphthalene ring system and that of the benzene ring is 85.90 (5)°. The molecules exhibit axial chirality, with either an R‐ or an S‐stereogenic axis. In the crystal structure, each enantiomer is stacked into a columnar structure and the columns are arranged alternately to form a stripe structure. A pair of (methoxy)C—H...F hydrogen bonds and π–π interactions between the benzene rings of the aroyl groups link an R‐ and an S‐isomer to form a dimeric pair. These dimeric pairs are piled up in a columnar fashion through (benzene)C—H...O=C and (benzene)C—H...OCH₃ hydrogen bonds. The analogous 1‐benzoylated compound, namely (2,7‐dimethoxynaphthalen‐1‐yl)(phenyl)methanone [Kato et al. (2010). Acta Cryst. E 66 , o2659], (II), affords three independent molecules having slightly different dihedral angles between the benzene and naphthalene rings. The three independent molecules form separate columns and the three types of column are connected to each other via two C—H...OCH₃ hydrogen bonds and one C—H...O=C hydrogen bond. Two of the three columns are formed by the same enantiomeric isomer, whereas the remaining column consists of the counterpart isomer. In the case of the fluorinated 1‐benzoylated naphthalene analogue, namely (2,7‐dimethoxynaphthalen‐1‐yl)(4‐fluorophenyl)methanone [Watanabe et al. (2011). Acta Cryst. E 67 , o1466], (III), the molecular packing is similar to that of (I), i.e. it consists of stripes of R‐ and S‐enantiomeric columns. A pair of C—H...F hydrogen bonds between R‐ and S‐isomers, and C—H...O=C hydrogen bonds between R(or S)‐isomers, are also observed. Consequently, the stripe structure is apparently induced by the formation of R...S dimeric pairs stacked in a columnar fashion. The pair of C—H...F hydrogen bonds effectively stabilizes the dimeric pair of R‐ and S‐enantiomers. In addition, the co‐existence of C—H...F and C—H...O=C hydrogen bonds makes possible the formation of a structure with just one independent molecule.     

Single and Twofold Metal‐ and Reagent‐Free Anodic C−C Cross‐Coupling of Phenols with Thiophenes

The first electrochemical dehydrogenative C−C cross‐coupling of thiophenes with phenols has been realized. This sustainable and very simple to perform anodic coupling reaction enables access to two classes of compounds of significant interest. The scope for electrochemical C−H‐activating cross‐coupling reactions was expanded to sulfur heterocycles. Previously, only various benzoid aromatic systems could be converted, while the application of heterocycles was not successful in the electrochemical C−H‐activating cross‐coupling reaction. Here, reagent‐ and metal‐free reaction conditions offer a sustainable electrochemical pathway that provides an attractive synthetic method to a broad variety of bi‐ and terarylic products based on thiophenes and phenols. This method is easy to conduct in an undivided cell, is scalable, and is inherently safe. The resulting products offer applications in electronic materials or as [OSO]²⁻ pincer‐type ligands.     

RhodiumIII/SilverI Relay Catalyzed C—H Aminomethylation with Imine Equivalents and Lewis Acid Catalyzed [4+2] Cycloaddition of Indoles with Triarylhexahydrotriazine†

A Rh^III/Ag^I relay‐catalyzed C(sp²)—H coupling of indoles with triarylhexahydrotriazine (THT) is reported in this context. Upon merging Rh^III‐catalyzed C(sp²)—H bond activation and silver promoted THT dissociation, an efficient indole's C3 aminomethylation protocol is uncovered, providing C3 aminomethyl indoles in good yields and exhibiting potential applications for the synthesis of complicated bioactive compounds. We revealed the C3‐selectivity of this reaction through a detailed mechanistic investigation. Meanwhile, during the examination of the reaction conditions, we discovered another [4+2] cycloaddition pathway to afford tetrahydro‐indolo[3,2‐c]quinoline scaffold products via silver or Lewis acid catalysis.     

The first crystal structures of six‐ and seven‐membered tellurium‐ and nitrogen‐containing (Te—N) heterocycles: 2H‐1,4‐benzotellurazin‐3(4H)‐one and 2,3‐dihydro‐1,5‐benzotellurazepin‐4(5H)‐one

There is a paucity of data concerning the structures of six‐ and seven‐membered tellurium‐ and nitrogen‐containing (Te—N) heterocycles. The title compounds, C₈H₇NOTe, (I), and C₉H₉NOTe, (II), represent the first structurally characterized members of their respective classes. Both crystallize with two independent molecules in the asymmetric unit. When compared to their sulfur analogs, they exhibit slightly greater deviations from planarity to accommodate the larger chalcogenide atom, with (II) adopting a pronounced twist‐boat conformation. The C—Te—C angles of 85.49 (15) and 85.89 (15)° for the two independent molecules of (I) were found to be somewhat smaller than those of 97.4 (2) and 97.77 (19)° for the two independent molecules of (II). The C—Te bond lengths [2.109 (4)–2.158 (5) Å] are in good agreement with those predicted by the covalent radii. Intermolecular N—H...O hydrogen bonding in (I) forms centrosymmetric R₂²(8) dimers, while that in (II) forms chains. In addition, intermolecular Te...O contacts [3.159 (3)–3.200 (3) Å] exist in (I).     

Transition Metal Catalyzed Direct Oxidative Borylation of C—H Bonds

Organoboron is well‐developed and broadly utilized organometallic reagents in organic synthesis due to its extraordinary performances in transition‐metal catalyzed C‐C and C‐X bonds construction. Catalytic C—H borylation and further transformations catalyzed by transition metal catalysts in the absence of oxidants were well studied in decades. However, as known, transition metal catalyzed oxidative C—H borylations were not reviewed up to date. In this article the oxidative borylation of C(sp²)‐H and C(sp³)‐H bonds were summarized and their mechanisms were also accounted.     

Direct Transformation of Arenols Based on C—O Activation

In the view of substrate availability, atomic efficiency and cost, directly using arenols as coupling partners in cross‐coupling, would be one of the most attractive goals. Up to date, many efforts have been made to activate the C—O bond of phenols with different strategies, for example, through in‐situ formed intermediates, through a catalytic reductive dearomatization‐condensation‐rearomatization sequence or catalytic deoxygenation. In this review, we summarized recent advances in cross‐couplings of arenols as the electrophiles via C—O activation.     

Intermolecular C—H...O and C—H...X interactions in substituted spiroacenaphthylene structures

In the three spiroacenaphthylene structures 5′′‐[(E)‐2,3‐dichlorobenzylidene]‐7′‐(2,3‐dichlorophenyl)‐1′′‐methyldispiro[acenaphthylene‐1,5′‐pyrrolo[1,2‐c][1,3]thiazole‐6′,3′′‐piperidine]‐2,4′′‐dione, C₃₅H₂₆Cl₄N₂O₂S, (I), 5′′‐[(E)‐4‐fluorobenzylidene]‐7′‐(4‐fluorophenyl)‐1′′‐methyldispiro[acenaphthylene‐1,5′‐pyrrolo[1,2‐c][1,3]thiazole‐6′,3′′‐piperidine]‐2,4′′‐dione, C₃₅H₂₈F₂N₂O₂S, (II), and 5′′‐[(E)‐4‐bromobenzylidene]‐7′‐(4‐bromophenyl)‐1′′‐methyldispiro[acenaphthylene‐1,5′‐pyrrolo[1,2‐c][1,3]thiazole‐6′,3′′‐piperidine]‐2,4′′‐dione, C₃₅H₂₈Br₂N₂O₂S, (III), the substituted aryl groups are 2,3‐dichloro‐, 4‐fluoro‐ and 4‐bromophenyl, respectively. The six‐membered piperidine ring in all three structures adopts a half‐chair conformation, the thiazolidine ring adopts a slightly twisted envelope and the pyrrolidine ring an envelope conformation; in each case, the C atom linking the rings is the flap atom. In all three structures, weak intramolecular C—H...O interactions are present. The crystal packing is stabilized through a number of intermolecular C—H...O and C—H...X interactions, where X = Cl in (I) and F or S in (II), and C—H...O interactions are observed predominantly in (III). In all three structures, molecules are linked through centrosymmetric ring motifs, further tailored through a relay of C—H...X [Cl in (I), Br in (II) and O in (III)] interactions.     

Structural insights into methyl‐ or methoxy‐substituted 1‐(α‐aminobenzyl)‐2‐naphthol structures: the role of C—H…π interactions

Aminobenzylnaphthols are a class of compounds containing a large aromatic molecular surface which makes them suitable candidates to study the role of C—H…π interactions. We have investigated the effect of methyl or methoxy substituents on the assembling of aromatic units by preparing and determining the crystal structures of (S,S)‐1‐{(4‐methylphenyl)[(1‐phenylethyl)amino]methyl}naphthalen‐2‐ol, C₂₆H₂₅NO, and (S,S)‐1‐{(4‐methoxyphenyl)[(1‐phenylethyl)amino]methyl}naphthalen‐2‐ol, C₂₆H₂₅NO₂. The methyl group influenced the overall crystal packing even if the H atoms of the methyl group did not participate directly either in hydrogen bonding or C—H…π interactions. The introduction of the methoxy moiety caused the formation of new hydrogen bonds, in which the O atom of the methoxy group was directly involved. Moreover, the methoxy group promoted the formation of an interesting C—H…π interaction which altered the orientation of an aromatic unit.     

Metal‐ and Oxidant‐Free Alkenyl C−H/Aromatic C−H Cross‐Coupling Using Electrochemically Generated Iodosulfonium Ions

A three‐step transformation consisting of 1) addition of electrochemically generated iodosulfonium ions to vinylarenes to give (1‐aryl‐2‐iodoethoxy)sulfonium ions, 2) nucleophilic substitution by subsequently added aromatic compounds to give 1,1‐diaryl‐2‐iodoethane, and 3) elimination of HI with a base to give 1,1‐diarylethenes was developed. The transformation serves as a powerful metal‐ and chemical‐oxidant‐free method for alkenyl C?H/aromatic C?H cross‐coupling.     

Electrochemical Intramolecular C—H/O—H Cross‐Coupling of 2‐Arylbenzoic Acids

A synthetic protocol to lactones by electro‐oxidative induced C—H activation of 2‐arylbenzoic acids has been developed. By using Na₂SO₄ aqueous solution as a cheap and green supporting electrolyte, different 2‐arylbenzoic acids could provide the corresponding lactones in 30%—90% yields. This reaction could be conducted on a gram scale with a good efficiency as well as a high utility for natural product synthesis.     

Palladium‐Catalyzed Formal [4+2] Cycloaddition of Benzoic and Acrylic Acids with 1,3‐Dienes via C—H Bond Activation: Efficient Access to 3,4‐Dihydroisocoumarin and 5,6‐Dihydrocoumalins

We report a palladium‐catalyzed formal intermolecular [4+2] cycloaddition of benzoic and acrylic acids with 1,3‐dienes including the stock chemicals 1,3‐butadiene and isoprene leading to synthetically useful 3,4‐dihydroisocoumarins and 5,6‐dihydrocoumalins. Stepwise C—H bond cleavage and annulation are likely involved in the reaction pathway. The synthetic potential of the methodology was demonstrated by two short derivatizations and total synthesis of natural product Clausamine B.     

Novel Chiral Ligands‐Enabled Transition‐Metal‐Catalyzed Asymmetric C—H Borylation

Although C—H borylation has been recognized as an efficient approach to organoboron compounds, the asymmetric variants have emerged only very recently. These results pointed out that the development of novel chiral ligands was pivotal to the success of asymmetric C—H borylation. Herein, a brief summary and comments on the key progresses are presented.     

Metal‐Free Direct C−H Cyanation of Alkenes

A metal‐free and direct alkene C?H cyanation is described. Directing groups are not required and the mechanism involves electrophilic activation of the alkene by a cyano iodine(III) species generated in situ from a [bis(trifluoroacetoxy)iodo]arene and trimethylsilyl cyanide as the cyanide source. This C?H functionalization can be conducted on gram scale, and for noncyclic 1,1‐ and 1,2‐disubstuted alkenes high stereoselectivity is achieved, thus rendering the method highly valuable.     

Rh‐catalyzed Transient Directing Group Promoted C—H Amidation of Benzaldehydes Utilizing Dioxazolones

Transition‐metal catalyzed C—H functionalization of benzaldehydes is of great interest in organic synthesis. Herein, we developed a transient directing group assisted amidation of benzaldehydes catalyzed by rhodium catalyst. With the employment of 10 mol% of 4‐trifluoromethyl aniline, the in situ generated imine groups as the directing group efficiently enable this transformation. By using this protocol, a wide range of benzaldehydes were efficiently converted into the corresponding N‐(2‐formylphenyl)benzamides utilizing dioxazolones as the nitrogen source.     

Cobalt‐Catalyzed Cyclization of N‐Methoxy Benzamides with Alkynes using an Internal Oxidant through C−H/N−O Bond Activation

The cyclization of substituted N‐methoxy benzamides with alkynes in the presence of an easily affordable cobalt complex and NaOAc provides isoquinolone derivatives in good to excellent yields. The cyclization reaction is compatible with a range of functional group‐substituted benzamides, as well as ester‐ and alcohol‐substituted alkynes. The cobalt complex [Co^IIICp*(OR)₂] (R=Me or Ac) serves as an efficient catalyst for the cyclization reaction. Later, isoquinolone derivatives were converted into 1‐chloro and 1‐bromo substituted isoquinoline derivatives in excellent yields in the presence of POCl₃ or PBr₃.     

Dimers linked by type‐I C—F...F—C contacts in (Z)‐3‐methyl‐4‐[2‐(4‐methylphenyl)hydrazinylidene]‐1‐(pentafluorophenyl)‐1H‐pyrazol‐5(4H)‐one

The title compound, C₁₇H₁₁F₅N₄O, is described and compared with two closely related analogues in the literature. There are two independent molecules in the asymmetric unit, linked by N—H...O hydrogen bonds and π–π interactions into dimeric entities, presenting a noticeable noncrystallographic C₂ symmetry. These dimers are in turn linked by a medium‐strength type‐I C—F...F—C interaction into elongated tetramers. Much weaker C—H...F contacts link the tetramers into broad two‐dimensional substructures parallel to (101).     

Metallierung und C‐C‐Kupplung von 2‐Pyridylmethylamin: Synthese und Strukturen von Methylzink‐2‐pyridylmethylamid,Tris(trimethylsilyl)methylzink‐2‐pyridylmethylamid und (Z)‐1‐Amino‐1,2‐bis(2‐pyridyl)ethen

Metalation and C‐C Coupling Reaction of 2‐Pyridylmethylamine: Synthesis and Structures of Methylzinc‐2‐pyridylmethylamide, Tris(trimethylsilyl)methylzinc‐2‐pyridylmethylamide and (Z)‐1‐Amino‐1,2‐bis(2‐pyridyl)ethene The metalation of 2‐pyridylmethylamine with dimethylzinc yields methylzinc‐2‐pyridylmethylamide ( 1 ), which shows a dimer‐trimer equilibrium in solution. Compound 1 crystallizes trimeric with a Zn₃N₃‐cycle in boat conformation. The endocyclic Zn‐N distances vary between 202 and 206 pm. Heating of this compound in toluene in the presence of dimethylzinc leads to the precipitation of zinc metal and to the formation of a few crystals of bis—[methylzinc‐2‐pyridylmethylamido]‐N, N′‐bis(methylzinc)‐2,3,5,6—tetrakis(2‐pyridyl)‐1,4‐diazacyclohexane ( 2 ). The protolysis of this solution with acetamide gives yellowish (Z)‐1‐amino‐1,2‐dipyridylethene ( 3 ) in a rather poor yield. The enamine tautomer is stabilized by N‐H···N hydrogen bridges. The demanding tris(trimethylsilyl)methyl group at the zinc atom allows the isolation of the dimeric tris(trimethylsilyl)methylzinc‐2‐pyridylmethylamide (4) ₂ in good yield. A C‐C coupling reaction of this compound with dimethylzinc is not possible.     

Three closely related 1‐(naphthalen‐2‐yl)prop‐2‐en‐1‐ones: pseudosymmetry,disorder and supramoleular assembly mediated by C—H…π and C—Br…π interactions

It has been observed that when electron‐rich naphthyl rings are present in chalcones they can participate in π–π stacking interactions, and this can play an important role in orientating inhibitors within the active sites of enzymes, while chalcones containing heterocyclic substituents additionally exhibit fungistatic and fungicidal properties. With these considerations in mind, three new chalcones containing 2‐naphthyl substituents were prepared. 3‐(4‐Fluorophenyl)‐1‐(naphthalen‐2‐yl)prop‐2‐en‐1‐one, C₁₉H₁₃FO, (I), crystallizes with Z ′ = 2 in the space group P and the four molecules in the unit cell adopt an arrangement which resembles that in the space group P 2₁/a . Although 3‐(4‐bromophenyl)‐1‐(naphthalen‐2‐yl)prop‐2‐en‐1‐one, C₁₉H₁₃BrO, (II), with Z ′ = 1, is not isostructural with (I), the molecules of (I) and (II) adopt very similar conformations. In 1‐(naphthalen‐2‐yl)‐3‐(thiophen‐2‐yl)prop‐2‐en‐1‐one, C₁₇H₁₂OS, (III), the thiophene unit is disordered over two sets of atomic sites, with occupancies of 0.780 (3) and 0.220 (3), which are related by a near 180° rotation of the thiophene unit about its exocyclic C—C bond. The molecules of compound (I) are linked by three independent C—H…π(arene) hydrogen bonds to form centrosymmetric octamolecular aggregates, whereas the molecules of compound (II) are linked into molecular ladders by a combination of C—H…π(arene) and C—Br…π(arene) interactions, and those of compound (III) are linked into centrosymmetric dimers by C—H…π(thiophene) interactions.     

Adsorption behaviour of a CdII–triazole MOF for butan‐2‐one in a single‐crystal‐to‐single‐crystal (SCSC) fashion: the role of hydrogen bonding and C—H…π interactions

The adsorption behaviour of the Cd^II–MOF {[Cd(L)₂(ClO₄)₂]·H₂O ( 1 ), where L is 4‐amino‐3,5‐bis[3‐(pyridin‐4‐yl)phenyl]‐1,2,4‐triazole, for butan‐2‐one was investigated in a single‐crystal‐to‐single‐crystal (SCSC) fashion. A new host–guest system that encapsulated butan‐2‐one molecules, namely poly[[bis{μ₃‐4‐amino‐3,5‐bis[3‐(pyridin‐4‐yl)phenyl]‐1,2,4‐triazole}cadmium(II)] bis(perchlorate) butanone sesquisolvate], {[Cd(C₂₄H₁₈N₆)₂](ClO₄)₂·1.5C₄H₈O}_n, denoted C₄H₈O@Cd‐MOF ( 2 ), was obtained via an SCSC transformation. MOF 2 crystallizes in the tetragonal space group P4₃2₁2. The specific binding sites for butan‐2‐one in the host were determined by single‐crystal X‐ray diffraction studies. N—H…O and C—H…O hydrogen‐bonding interactions and C—H…π interactions between the framework, ClO₄^? anions and guest molecules co‐operatively bind 1.5 butan‐2‐one molecules within the channels. The adsorption behaviour was further evidenced by ¹H NMR, IR, TGA and powder X‐ray diffraction experiments, which are consistent with the single‐crystal X‐ray analysis. A ¹H NMR experiment demonstrates that the supramolecular interactions between the framework, ClO₄^? anions and guest molecules in MOF 2 lead to a high butan‐2‐one uptake in the channel.