Mechanistic insights into dioxygen activation by a manganese corrole complex: a broken-symmetry DFT study

The Mn–oxygen species have been implicated as key intermediates in various Mn-mediated oxidation reactions. However, artificial oxidants were often used for the synthesis of the Mn–oxygen intermediates. Remarkably, the Mn(v)–oxo and Mn(iv)–peroxo species have been observed in the activation of O₂ by Mn(iii) corroles in the presence of base (OH⁻) and hydrogen donors. In this work, density functional theory methods were used to get insight into the mechanism of dioxygen activation and formation of Mn(v)–oxo. The results demonstrated that the dioxygen cannot bind to Mn without the axial OH⁻ ligand. Upon the addition of the axial OH⁻ ligand, the dioxygen can bind to Mn in an end-on fashion to give the Mn(iv)–superoxo species. The hydrogen atom transfer from the hydrogen donor (substrate) to the Mn(iv)–superoxo species is the rate-limiting step, having a high reaction barrier and a large endothermicity. Subsequently, the O–C bond formation is concerted with an electron transfer from the substrate radical to the Mn and a proton transfer from the hydroperoxo moiety to the nearby N atom of the corrole ring, generating an alkylperoxo Mn(iii) complex. The alkylperoxo O–O bond cleavage affords a Mn(v)–oxo complex and a hydroxylated substrate. This novel mechanism for the Mn(v)–oxo formation via an alkylperoxo Mn(iii) intermediate gives insight into the O–O bond activation by manganese complexes.

DFT calculations revealed a novel mechanism for the formation of Mn(v)–oxo in the dioxygen activation by a Mn(iii) corrole complex involving a Mn(iii)–alkylperoxo intermediate.     

Mechanistic insights into rare-earth-catalysed C–H alkylation of sulfides: sulfide facilitating alkene insertion and beyond

The catalytic C–H alkylation with alkenes is of much interest and importance, as it offers a 100% atom efficient route for C–C bond construction. In the past decade, great progress in rare-earth catalysed C–H alkylation of various heteroatom-containing substrates with alkenes has been made. However, whether or how a heteroatom-containing substrate would influence the coordination or insertion of an alkene at the catalyst metal center remained elusive. In this work, the mechanism of Sc-catalysed C–H alkylation of sulfides with alkenes and dienes has been carefully examined by DFT calculations, which revealed that the alkene insertion could proceed via a sulfide-facilitated mechanism. It has been found that a similar mechanism may also work for the C–H alkylation of other heteroatom-containing substrates such as pyridine and anisole. Moreover, the substrate-facilitated alkene insertion mechanism and a substrate-free one could be switched by fine-tuning the sterics of catalysts and substrates. This work provides new insights into the role of heteroatom-containing substrates in alkene-insertion-involved reactions, and may help guide designing new catalysis systems.

The alkene insertion via the heteroatom-containing substrate facilitated mechanism were computationally revealed in rare-earth-catalyzed C–H alkylation of sulfides and other heteroatom-containing substrates such as pyridines and anisoles.     

Reactions of triosmium and triruthenium clusters with 2-ethynylpyridine: new modes for alkyne C–C bond coupling and C–H bond activation

The reaction of the trimetallic clusters [H₂Os₃(CO)₁₀] and [Ru₃(CO)₁₀L₂] (L = CO, MeCN) with 2-ethynylpyridine has been investigated. Treatment of [H₂Os₃(CO)₁₀] with excess 2-ethynylpyridine affords [HOs₃(CO)₁₀(μ-C₅H₄NCH=CH)] (1), [HOs₃(CO)₉(μ₃-C₅H₄NC CH₂)] (2), [HOs₃(CO)₉(μ₃-C₅H₄NC CCO₂)] (3), and [HOs₃(CO)₁₀(μ-CH CHC₅H₄N)] (4) formed through either the direct addition of the Os–H bond across the C C bond or acetylenic C–H bond activation of the 2-ethynylpyridine substrate. In contrast, the dominant pathway for the reaction between [Ru₃(CO)₁₂] and 2-ethynylpyridine is C–C bond coupling of the alkyne moiety to furnish the triruthenium clusters [Ru₃(CO)₇(μ-CO){μ₃-C₅H₄NC CHC(C₅H₄N) CH}] (5) and [Ru₃(CO)₇(μ-CO){μ₃-C₅H₄NCCHC(C₅H₄N)CHCHC(C₅H₄N)}] (6). Cluster 5 contains a metalated 2-pyridyl-substituted diene while 6 exhibits a metalated 2-pyridyl-substituted triene moiety. The functionalized pyridyl ligands in 5 and 6 derive via the formal C–C bond coupling of two and three 2-ethynylpyridine molecules, respectively, and 5 and 6 provide evidence for facile alkyne insertion at ruthenium clusters. The solid-state structures of 1–3, 5, and 6 have been determined by single-crystal X-ray diffraction analyses, and the bonding in the product clusters has been investigated by DFT. In the case of 1, the computational results reveal a rare thermodynamic preference for a terminal hydride ligand as opposed to a hydride-bridged Os–Os bond (3c,2e Os–Os–H bond).

The reactivity of 2-ethynylpyridine at low-valent triosmium and triruthenium centers has been investigated.     

Solvent-free and room temperature microwave-assisted direct C7 allylation of indolines via sequential C–H and C–C activation

A Ru or Rh-catalyzed efficient and atom-economic C7 allylation of indolines with vinylcyclopropanes was developed via sequential C–H and C–C activation. A wide range of substrates were well tolerated to afford the corresponding allylated indolines in high yields and E/Z selectivities under microwave irradiation. The obtained allylated indolines could further undergo transformations to afford various value-added chemicals. Importantly, this reaction proceeded at room temperature under solvent-free conditions.

A Ru or Rh-catalyzed direct C7 allylation of indolines with vinylcyclopropanes via sequential C–H/C–C activation under microwave irradiation has been disclosed.

The development of sustainable methodologies is attractive for access to complex molecular architectures in organic chemistry.¹ In recent years, various non-conventional techniques, such as microwave irradiation, sonochemistry, mechanical grinding and photochemistry, have achieved remarkable success.² In particular, microwaves have shown unique advantages with regards to reaction times, energy efficiency, temperature, and reaction media.³ On the other hand, transition-metal-catalyzed activation of C–H⁴ and C–C⁵ bonds has been considered as an ideal method for the formation of C–C and C–X bonds. Nevertheless, transition-metal-catalyzed C–H or C–C bond activation under the above non-conventional techniques remains to be explored. It is thus highly imperative to develop a practical strategy in combination of C–H or C–C activation and microwave irradiation.⁶Recently, there have significant advances in C–H activation technology by merging C–H functionalization with challenging C–C cleavage strategies.⁷ Since the pioneering work by Bergman and co-workers⁸ on the sequential C–H and C–C bond activation, many research groups, including Dong,⁹ Ackermann,¹⁰ Li,¹¹ Cramer,¹² and others¹³ have contributed to C–H/C–C activation. In this content, certain small strained rings are often utilized as an effective synthons to undergo ring-opening reactions driven by strain-release energy.¹⁴ Very recently, VCPs (vinylcyclopanes) have been reported as allyl reagents to access various (hetero)aromatic derivatives through sequential C–H and C–C activation (Scheme 1a–d).¹⁵Open in a separate windowScheme 1Sequential C–H/C–C activations using VCPs.As a continuation of our interest in chelation-directed reactions and novel methods for C–H functionalization,¹⁶ we herein report a Ru or Rh-catalyzed C-7 allylation of indolines under microwave irradiation using VCPs as the allylating agents (Scheme 1e). This transformation possesses great synthetic potential from the viewpoint of green and sustainable chemistry. Notable features of our protocol include (1) C–H/C–C activation with VCPs by microwave irradiation, (2) broad substrate scope with good regio- and E/Z selectivities, (3) high atom economy, and (4) high efficiency (2 h) at room temperature under solvent-free conditions.We initiated our investigation by choosing indoline 1a and VCP 2a as model substrates under microwave irradiation conditions (

A theoretical study based on DFT calculations on the different influence of functional groups on the C–H activation process via Pd-catalysed β-X elimination

We have performed a series of theoretical calculations for palladium-catalyzed β-X elimination reactions. The DFT calculation combined with energy decomposition analysis shows the determining factors of reactivity. Such as, the elemental composition, the structure of different functional groups and the stronger steric repulsions contribution.

The energy decomposition analysis (EDA) results show the quantitative contribution of nucleophile groups in intramolecular interactions.     

Comparative DFT study of metal-free Lewis acid-catalyzed C–H and N–H silylation of (hetero)arenes: mechanistic studies and expansion of catalyst and substrate scope

Direct selective dehydrogenative silylation of thiophenes, pyridines, indoles and anilines to synthesize silyl-substituted aromatic compounds catalyzed by metal-free Lewis acids was achieved recently. However, there is still insufficient mechanistic data for these transformations. Using density functional theory calculations, we conducted a detailed investigation of the mechanism of the B(C₆F₅)₃-catalyzed dehydrogenative silylation of N-methylindole, N,N-dimethylaniline and N-methylaniline. We successfully located the most favourable reaction pathways that can explain the experimental observations notably well. The most favourable pathway for B(C₆F₅)₃-catalyzed C–H silylation of N-methylindole includes nucleophilic attack, proton abstraction and hydride migration. The C–H silylation of N,N-dimethylaniline follows a similar pathway to N-methylindole rather than that proposed by Hou''s group. Our mechanism successfully explains that the transformations of N-methylindoline to N-methylindole produce different products at different temperatures. For N-methylaniline bearing both N–H and para-phenyl C–H bonds, the N–H silylation reaction is more facile than the C–H silylation reaction. Our proposed mechanism of N–H silylation of N-methylaniline is different from that proposed by the groups of Paradies and Stephan. Lewis acids Al(C₆F₅)₃, Ga(C₆F₅)₃ and B(2,6-Cl₂C₆H₃)(p-HC₆F₄)₂ can also catalyze the C–H silylation of N-methylindole like B(C₆F₅)₃, but the most favourable pathways are those promoted by N-methylindoline. Furthermore, we also found several other types of substrates that would undergo C–H or N–H silylation reactions under moderate conditions. These findings may facilitate the design of new catalysts for the dehydrogenative silylation of inactivated (hetero)arenes.

We investigated the mechanism of the dehydrosilylation of (hetero)arenes and extended the scope of the silylation catalysts and substrates.     

One-pot regioselective C–H activation iodination–cyanation of 2,4-diarylquinazolines using malononitrile as a cyano source

A one-pot cyanation of 2,4-arylquinazoline with NIS and malononitrile has been developed. The one-pot reaction includes two steps. The Rh-catalyzed selective C–H activation/iodization of 2,4-diarylquinazoline with NIS, and then Cu-catalyzed cyanation of the corresponding iodinated intermediate with malononitrile to selectively give 2-(2-cyanoaryl)-4-arylquinazolines or 2-(2,6-dicyanoaryl)-4-arylquinazolines in good to excellent yields.

A one-pot cyanation of 2,4-arylquinazoline with NIS and malononitrile has been developed.     

Palladium-catalyzed intramolecular C–H arylation of 2-halo-N-Boc-N-arylbenzamides for the synthesis of N–H phenanthridinones

A palladium catalyzed synthesis of N–H phenanthridinones was developed via C–H arylation. The protocol gives phenanthridinones regioselectively by one-pot reaction without deprotection. It exhibits broad substrate scope and affords targets in up to 95% yields. Importantly, it could be applied for the less reactive o-chlorobenzamides.

Pd(t-Bu₃P)₂/KOAc proved to be a good combination for one-pot synthesis of N–H phenanthridinones with up to 95% yield.     

Ruthenium-catalyzed,site-selective C–H activation: access to C5-substituted azaflavanone

A site-selective ruthenium-catalyzed keto group assisted C–H bond activation of 2-aryl tetrahydroquinoline (azaflavanone) derivatives has been achieved with a variety of alkenes for the first time. A wide range of substrates was utilized for the synthesis of a wide variety of alkenylated azaflavanones. This simple and efficient protocol provides the C5-substituted azaflavanone derivatives in high yields with a broad range of functional group tolerance. Further, the C5-alkenylated products were converted into substituted 2-aryl quinoline derivatives in good yields.

A site-selective ruthenium-catalyzed keto group assisted C–H bond activation of 2-aryl tetrahydroquinoline (azaflavanone) derivatives has been achieved with a variety of alkenes for the first time.     

O2 activation by core–shell Ru13@Pt42 particles in comparison with Pt55 particles: a DFT study

The reaction of O₂ with a Ru₁₃@Pt₄₂ core–shell particle consisting of a Ru₁₃ core and a Pt₄₂ shell was theoretically investigated in comparison with Pt₅₅. The O₂ binding energy with Pt₅₅ is larger than that with Ru₁₃@Pt₄₂, and O–O bond cleavage occurs more easily with a smaller activation barrier (E_a) on Pt₅₅ than on Ru₁₃@Pt₄₂. Protonation to the Pt₄₂ surface followed by one-electron reduction leads to the formation of an H atom on the surface with considerable exothermicity. The H atom reacts with the adsorbed O₂ molecule to afford an OOH species with a larger E_a value on Pt₅₅ than on Ru₁₃@Pt₄₂. An OOH species is also formed by protonation of the adsorbed O₂ molecule, followed by one-electron reduction, with a large exothermicity in both Pt₅₅ and Ru₁₃@Pt₄₂. O–OH bond cleavage occurs with a smaller E_a on Pt₅₅ than on Ru₁₃@Pt₄₂. The lower reactivity of Ru₁₃@Pt₄₂ than that of Pt₅₅ on the O–O and O–OH bond cleavages arises from the presence of lower energy in the d-valence band-top and d-band center in Ru₁₃@Pt₄₂ than in Pt₅₅. The smaller E_a for OOH formation on Ru₁₃@Pt₄₂ than on Pt₅₅ arises from weaker Ru₁₃@Pt₄₂–O₂ and Ru₁₃@Pt₄₂–H bonds than the Pt₅₅–O₂ and Pt₅₅–H bonds, respectively. The low-energy d-valence band-top is responsible for the weak Ru₁₃@Pt₄₂–O and Ru₁₃@Pt₄₂–OH bonds. Thus, the low-energy d-valence band-top and d-band center are important properties of the Ru₁₃@Pt₄₂ particle.

In this theoretical study by DFT computations, characteristic features of the Ru₁₃@Pt₄₂ core–shell particle in O₂ activation are clearly discussed in comparison with Pt₅₅.     

Computational insights into Ir(iii)-catalyzed allylic C–H amination of terminal alkenes: mechanism,regioselectivity, and catalytic activity

Computational studies on Ir(iii)-catalyzed intermolecular branch-selective allylic C–H amination of terminal olefins with methyl dioxazolone have been carried out to investigate the mechanism, including the origins of regioselectivity and catalytic activity difference. The result suggests that the reaction proceeds through generation of active species, alkene coordination, allylic C–H activation, decarboxylation, migratory insertion, and protodemetalation. The presence of AgNTf₂ could thermodynamically promote the formation of catalytically active species [Cp*Ir(OAc)]⁺. Both the weaker Ir–C(internal) bond and the closer interatomic distance of N⋯C(internal) in the key allyl-Ir(v)-nitrenoid intermediate make the migratory insertion into Ir–C(internal) bond easier than into the Ir–C(terminal) bond, leading to branch-selective allylic C–H amidation. The high energy barrier for allylic C–H activation in the Co system could account for the observed sluggishness, which is mainly ascribed to the weaker coordination capacity of alkenes to the triplet Cp*Co(OAc)⁺ and the deficient metal⋯H interaction to assist hydrogen transfer.

DFT studies on Ir(iii)-catalyzed branch-selective allylic C–H amination of terminal olefins with methyl dioxazolone have been carried out to investigate the mechanism, including the origins of regioselectivity and catalytic activity difference.     

Copper-catalyzed one-pot domino reactions via C–H bond activation: synthesis of 3-aroylquinolines from 2-aminobenzylalcohols and propiophenones under metal–organic framework catalysis

A Cu₂(OBA)₂(BPY) metal–organic framework was utilized as a productive heterogeneous catalyst for the synthesis of 3-aroylquinolines via one-pot domino reactions of 2-aminobenzylalcohols with propiophenones. This Cu-MOF was considerably more active towards the one-pot domino reaction than a series of transition metal salts, as well as nano oxide and MOF-based catalysts. The MOF-based catalyst was reusable without a significant decline in catalytic efficiency. To the best of our knowledge, the transformation of 2-aminobenzylalcohols to 3-aroylquinolines was not previously reported in the literature, and this protocol would be complementary to previous strategies for the synthesis of these valuable heterocycles.

Cu₂(OBA)₂(BPY) metal–organic framework was utilized as a productive heterogeneous catalyst for the synthesis of 3-aroylquinolines via one-pot domino reactions of 2-aminobenzylalcohols with propiophenones.     

The concise synthesis and resolution of planar chiral [2.2]paracyclophane oxazolines by C–H activation

Planar chiral [2.2]paracyclophanes are resolved through the direct C–H arylation of enantiopure oxazolines, providing a convenient route to ligands and chiral materials. Preliminary results show that hydrolysis followed by decarboxylative phosphorylation leads to enantiopure [2.2]paracyclophane derivatives that are otherwise challenging to prepare.

Racemic bromo[2.2]paracyclophanes are directly transformed into enantiomerically pure planar chiral oxazolines in one step with simultaneous resolution of planar chirality.

[2.2]Paracyclophane 1 (X = H; Scheme 1) has garnered considerable attention as the core for planar chiral pre-ligands,^1,2 catalysts,^3,4 bioactive entities^5,6 and chiroptical materials.^7,8 The rigidity of the [2.2]paracyclophane provides an almost unrivalled opportunity to control the relative spatial position of various functional groups through a series of regioisomers.^4,9,10 The major roadblock hampering progress in [2.2]paracyclophane chemistry is the resolution of planar chirality, and there are only a limited number of commonly used enantiopure precursors, some of which are hard to obtain on a large scale.^11,12Open in a separate windowScheme 1Previous routes to oxazolines and proposed chemistry.Oxazolines form a host of ‘privileged’ pre-ligands,^13–15 and it is no surprise that numerous oxazoline-substituted [2.2]paracyclophanes 5 have shown potential in asymmetric catalysis.^16–20 The oxazoline moiety aids the synthesis of these compounds, either by permitting resolution of the planar chirality,^{16–19,21,22} or by directing functionalisation of the cyclophane backbone.^16,19,21,23 Every one of these oxazoline-containing [2.2]paracyclophanes 5 was synthesised from a bromo derivative 2via the carboxylic acid 3, then the amide 4, and finally cyclisation (Scheme 1). This adds steps to the synthesis and limits the functionality found in the molecule as the acid is invariably formed by halogen–metal exchange.Direct addition of an oxazoline 6 would allow simultaneous functionalisation and resolution of the planar chirality of [2.2]paracyclophane. Such a strategy would permit a more concise synthesis of [2.2]paracyclophane derivatives with a wider range of substituents. Previously, we have used C–H activation chemistry to synthesise planar chiral N-oxides,^24,25 and believed that the oxazoline C–H activation chemistry of Ackermann^26,27 and Lu²⁸ could be applied to [2.2]paracyclophane. Herein, we report the successful realisation of this strategy. Planar chiral oxazolines are accessed in a single step furnishing molecules that can be used as pre-ligands or as precursors to carboxylic acids that can be further derivatised by traditional means or decarboxylative couplings.The coupling of oxazolines 6 and 4-bromo[2.2]paracyclophane 7 required little optimisation with the chemistry of Ackermann²⁶ transferring to paracyclophane without incident. A range of (heteroatom-substituted) secondary phosphine pre-ligands [(HA)SPO] were screened, and di-tert-butylphosphine oxide (t-Bu₂SPO) gave a catalyst that showed complete conversion of simple [2.2]paracyclophane derivatives, such as 7 (8a 82%; 8c 60% Scheme 2). More complex derivatives required the di-1-adamantylphosphine oxide (Ad₂SPO) otherwise returned unreacted starting material (see below).Open in a separate windowScheme 2Synthesis of 4-oxazolinyl[2.2]paracyclophanes 8a and 8c.Benzyloxazoline 8a was formed as a mixture of diastereoisomers that are separable by column chromatography, but the similarity of the R_f values make resolution extremely challenging, with only the fractions at the beginning and end of a collection containing pure diastereoisomers. This led to screening a range of oxazolines. All coupled but with less satisfactory yields. The phenyloxazoline 6b appears to couple with concomitant aromatisation furnishing oxazole 9. For mono(oxazolines) 8, tert-butyl derivative 6c gave the best results in terms of resolution of planar chirality, with the diastereoisomers 8c being readily separable.²¹Next we established the scope of coupling reaction. Both the pseudo-para- (4,16)- (11a) and pseudo-ortho- (4,12)- bis(oxazolines) 11b were readily prepared from the corresponding dibromo[2.2]paracyclophanes (17,20,29 but only one diastereoisomer of the tert-butyl derivative 11c could be isolated. The other diastereoisomer co-ran with the two diastereomers of the product of protodebromination (8c). The synthesis of pseudo-ortho-bis(benzyloxazoline) 11b has been performed on >1 g scale. The yields are lower but the separation easier. If a single equivalent of 2H-oxazoline 6a is used in the coupling, it is possible to isolate the bromo mono(oxazoline) 11d, but the reaction is non-selective, with a mixture of mono-along and bis(oxazoline) always formed.^16,18,30Scope of oxazoline coupling (only single diastereoisomer of product shown)

Copper-catalyzed C–H acyloxylation of 2-phenylpyridine using oxygen as the oxidant

An efficient copper-catalyzed direct o-acyloxylation of 2-phenylpyridine with carboxylic acids using oxygen as the oxidant has been developed. Various acids including aromatic acids, cinnamic acids and aliphatic acids are effective acyloxylation reagents and provide the desired products in moderate to excellent yields. The reaction proceeds well under an oxygen atmosphere, making this method potentially practical.

A copper catalyzed direct o-acyloxylation of 2-phenylpyridine with various carboxylic acids using oxygen as oxidant has been developed.     

TBAI-assisted direct C–H activation of indoles with β-E-styrene sulfonyl hydrazides: a stereoselective access to 3-styryl thioindoles

The current work describes the challenging introduction of a vinyl sulfide group by simple C–H activation on a variety of substrates. The direct C–H activation of indoles with β-(E)-styrene sulfonyl hydrazides under the sulfenylation conditions, assisted by the iodic catalyst tert-butyl ammonium iodide (TBAI), afforded a series of (E)-styrylthioindoles. Accordingly, β-(E)-styrene sulfonyl hydrazides undergo radical cross-coupling reactions with a variety of substituted indoles to afford structurally diverse indole vinyl thioethers in moderate to high yields with E-stereoselectivity. This method is metal-catalyst-free and is valuable not only because of its novelty, but also for providing a convenient synthetic pathway to a variety of (E)-styrylthioindoles with retention of the configuration. The current study paves the way for the use of β-(E)-styrene sulfonyl hydrazides as a unique styryl mercaptan source in chemical synthesis.

Direct C–H activation of indoles with beta-(E)-styrene sulfonyl hydrazides assisted by TBAI afforded structurally diverse indole vinyl thioethers in moderate to high yields with E-stereoselectivity.     

A DFT study on the C–H oxidation reactivity of Fe(iv)–oxo species with N4/N5 ligands derived from l-proline

The hydroxylation of hexane by two Fe^IVO complexes bearing a pentadentate ligand (N5, Pro3Py) and a tetradentate ligand (N4, Pro2PyBn) derived from l-proline was studied by DFT calculations. Theoretical results predict that both Fe^IVO complexes hold triplet ground states. The hydrogen atom abstraction (HAA) processes by both Fe^IVO species proceed through a two-state reactivity, thus indicating that HAA occurs via a low-barrier quintet surface. Beyond the conventional rebound step, the dissociation path is also calculated and is found to potentially occur after HAA.

The hydroxylation of hexane by two Fe^IVO complexes bearing a pentadentate ligand (N5, Pro3Py) and a tetradentate ligand (N4, Pro2PyBn) derived from l-proline was studied by DFT calculations.     

Auxiliary-directed etherification of sp2 C–H bonds under heterogeneous metal–organic framework catalysis: synthesis of ethenzamide

An efficient protocol for 8-aminoquinoline assisted alkoxylation and phenoxylation of sp² C–H bonds under heterogeneous catalysis was developed. The optimal conditions employed Cu-MOF-74 (20%), K₂CO₃ base, pyridine ligand or dimethyl formamide solvent, and O₂ oxidant at 80 °C or 100 °C for 24 hours. Cu-MOF-74 revealed remarkably higher activity when compared with other previously commonly used Cu-MOFs in cross coupling reactions, supported copper catalysts, and homogeneous copper salts. The reaction scope with respect to coupling partners included a wide range of various substrates. Interestingly, the developed conditions are applicable for the synthesis of high-profile relevant biological agents from easily accessible starting materials. Furthermore, a leaching test confirmed the reaction heterogeneity and the catalyst was reused and recycled at least 8 times with trivial degradation in activity.

An efficient protocol for 8-aminoquinoline assisted alkoxylation and phenoxylation of sp² C–H bonds under heterogeneous catalysis was developed.     

New insights into the surface plasmon resonance (SPR) driven photocatalytic H2 production of Au–TiO2

The Surface Plasmon Resonance (SPR) driven photocatalytic H₂ production upon visible light illumination (≥500 nm) was investigated on gold-loaded TiO₂ (Au–TiO₂). It has been clearly shown that the Au-SPR can directly lead to photocatalytic H₂ evolution under illumination (≥500 nm). However, there are still some open issues about the underlying mechanism for the SPR-driven photocatalytic H₂ production, especially the explanation of the resonance energy transfer (RET) theory and the direct electron transfer (DET) theory. In this contribution, by means of the EPR and laser flash photolysis spectroscopy, we clearly showed the signals for different species formed by trapped electrons and holes in TiO₂ upon visible light illumination (≥500 nm). However, the energy of the Au-SPR is insufficient to overcome the bandgap of TiO₂. The signals of the trapped electrons and holes originate from two distinct processes, rather than the simple electron–hole pair excitation. Results obtained by Laser Flash Photolysis spectroscopy evidenced that, due to the Au-SPR effect, Au NPs can inject electrons to the conduction band of TiO₂ and the Au-SPR can also initiate e⁻/h⁺ pair generation (interfacial charge transfer process) upon visible light illumination (≥500 nm). Moreover, the Density Functional Theory (DFT) calculation provided direct evidence that, due to the Au-SPR, new impurity energy levels occurred, thus further theoretically elaborating the proposed mechanisms.

The Surface Plasmon Resonance (SPR) driven photocatalytic H₂ production upon visible light illumination (≥500 nm) was investigated on gold-loaded TiO₂ (Au–TiO₂).     

DMSO-mediated palladium-catalyzed cyclization of two isothiocyanates via C–H sulfurization: a new route to 2-aminobenzothiazoles

DMSO was found to activate arylisothiocyanates for self-nucleophilic addition. A subsequent intramolecular C–H sulfurization catalyzed by PdBr₂ enables access to a wide range of 2-aminobenzothiazole derivatives in moderate to good yields. This is the first example of a DMSO-mediated Pd-catalyzed synthesis of 2-aminobenzothiazoles through cyclization/C–H sulfurization of two isothiocyanates.

DMSO-initiated coupling of two isothiocyanates; Pd-catalyzed C–H sulfurization.

2-Aminobenzothiazole derivatives are privileged scaffolds which have been widely used in medicine and agricultural chemicals (Scheme 1a).¹ Significant effort has been devoted to the development of synthetic methodologies for the preparation of such species.² Thioureas,^3,4 isothiocyanates,^5,6 and benzothiazoles⁷ are effective reaction partners for the synthesis of 2-aminobenzothiazole derivatives via cross-coupling reactions or C–H functionalization. Intramolecular C–H sulfurization of N-arylthioureas is an effective strategy for the synthesis of 2-aminobenzothiazoles. Such a transformation can be achieved through metal-catalyzed C–H activation³ or via radical reactions.⁶ For example, Doi and coworkers reported a Pd-catalyzed intramolecular C–H sulfurization of arylthiourea using O₂ as an oxidant.^3c Metal-free iodine-catalyzed intramolecular C–H sulfurization also provides an effective pathway to 2-aminobenzothiazoles.^6e Zhu et al. developed an efficient oxidative radical strategy for the synthesis of 2-aminobenzothiazoles via an aminyl radical addition to aryl isothiocyanates followed by C–H sulfurization in the presence of n-Bu₄NI and TBHP.^6c Interestingly, Lei et al. reported a “green” synthesis of 2-aminobenzothiazoles by employing electro-catalysis technology for an external oxidant-free intramolecular C–H sulfurization.^6d In terms of metal-catalyzed C–H sulfurization,⁸ palladium-catalyzed C–H sulfurization has not been widely reported because thioureas are often strong metal-chelating species that may lead to poisoning of palladium catalysts. Thus, only a few examples of Pd-catalyzed protocols have been reported (Scheme 1b).^3b,c,e Therefore, the development of novel palladium-catalyzed C–H sulfurization reaction is of great interest. As a continuation of our interest in sulfur chemistry and C–H sulfurization,⁹ we attempted to transform isothiocyanates into sulfur-containing compounds.¹⁰ Unexpectedly, a newly formed 2-aminobenzothiazole was observed for the reaction of a phenylisothiocyanate. Encouraged by this discovery, we developed a new, facile and efficient DMSO-mediated palladium-catalyzed C–H sulfurization/cyclization of two isothiocyanates for the synthesis of 2-aminobenzothiazoles (Scheme 1c).Open in a separate windowScheme 1Biological application and synthetic methods for the preparation of 2-aminobenzothiazoles.Our study began with the reaction of phenyl isothiocyanate (1a) with PdCl₂ in different solvents ( EntryCatalystSolventYield^b (%)1PdCl₂Toluene02PdCl₂Chlorobenzene03PdCl₂DCE04PdCl₂CH₃CN05PdCl₂DMF126PdCl₂NMP167PdCl₂DMSO728^cPdCl₂DMSO329^dPdCl₂DMSO5810PdBr₂DMSO8211Pd(OAc)₂DMSOTrace12Pd(PPh₃)₂Cl₂DMSOTrace13^ePdBr₂DMSO7014—DMSO015^fPdBr₂DMSO/CH₃CN5516^gPdBr₂DMSO/CH₃CN2317^hPdBr₂DMSO/H₂O6118ⁱPdBr₂DMSO/H₂O75Open in a separate window^aReaction conditions: 1a (0.4 mmol), [Pd] (10 mol%), stirred at 80 °C in solvent (2 mL) for 24 h.^bIsolated yield.^cAt 100 °C.^dAt 60 °C.^ePdBr₂ (5 mol%).^fDMSO/CH₃CN = 1 : 1.^gDMSO/CH₃CN = 1 : 4.^hDMSO/H₂O = 10 : 1.ⁱDMSO/H₂O = 20 : 1.With the optimized reaction conditions in hand, the reaction scope was investigated ( Open in a separate window^aReaction conditions: 1 (0.4 mmol), PdBr₂ (10 mol%), stirred at 80 °C in DMSO (2 mL) for 24 h. Ortho-substituents, such as methyl, methoxy, methylthio, and phenyl, which increase steric hindrance, still performed well to give their corresponding products in moderate to good yields (products 12–20). For reactions involving ortho-substituted substrates, a small amount of brominated by-product similar to compound 19 was observed; however, the majority of these by-products were obtained in far lower yield than 19. To our delight, a naphthyl isothiocyanate also underwent reaction smoothly to give product 22 in 77% yield. 3-Isothiocyanatopyridine was also subjected to the reaction conditions. However, no cyclization/C–H sulfurization occurred; the electron-deficient pyridine ring is not reactive enough for C–H sulfurization. The reaction of meta-substituted methyl phenylisothiocyanates provided two isomers which could not be easily purified.To prove the feasibility of the cyclization of two different aryl isothiocyanates, a cross-reaction between 4-methyl-phenylisothiocyanate and 4-nitro-phenyliso-thiocyanate was conducted. The cross-reaction product 23, was obtained in 27% yield with compound 3 being formed as the main product in 52% yield (Scheme 2). The strong electron-withdrawing nitro group greatly reduces the electron density of the benzene ring, thus C–H sulfurization is disfavored; C–H sulfurization only occurred on the methyl-substituted benzene ring.Open in a separate windowScheme 2PdBr₂-catalyzed cross-reaction of two different isothiocyanates.To gain insight into the reaction mechanism, control experiments were conducted, as shown in Scheme 3. In the absence of PdBr₂, thiourea 24 was obtained in 35% yield for the reaction of 4-methyl phenylisothiocyanate in DMSO at 80 °C over 24 hours (Scheme 3, eqn (1)). This suggested that the thiourea may be the reaction intermediate; however, when thiourea 24 was subjected to reaction with PdBr₂, product 3 was obtained in only 16% yield (Scheme 3, eqn (2)). Aryl isothiocyanate may decompose to aniline, and react with isothiocyanate for C–H sulfurization. However, only a trace amount of product 25 was observed in the reaction between 4-methylphenyl isothiocyanate and aniline (Scheme 3, eqn (3)). None of the target product 26 was observed for the reaction of benzothiazole with 4-methyl phenylisothiocyanate, suggesting that benzothiazole is not a reaction intermediate (Scheme 3, eqn (4)). To our delight, a mass peak corresponding to intermediate 27 was observed with real-time ESI-MS when phenylisothiocyanate was stirred in DMSO at 60 °C (Scheme 3, eqn (5)) (see the ESI, Fig. S1^†). Based on theoretical calculations,¹¹ the dipole moment of the DMSO molecule is 3.9274 debye (gas) or 5.1281 debye in solvent form. Natural bond orbital analysis shows the differences in the charge distribution on the O and S atoms. Obviously, the polarity of the S–O bond increases and a greater distribution of the negative charge on the O atom leads to an improvement in its nucleophilic character. The oxygen atom attacks the carbon atom with the most positive NBO charge in PhNCS (see the ESI, Fig. S2 and S3^†). These results indicate that DMSO acts as a nucleophilic agent for the activation of arylisothiocyanates for C–H sulfurization.Open in a separate windowScheme 3Control experiments.Based on the above results and previous work,³ a possible reaction mechanism has been proposed and is shown in Scheme 4. Firstly, the polarized DMSO undergoes a nucleophilic addition with phenylisothiocyanate to afford the active intermediate A, which then reacts with another equivalent of phenylisothiocyanate to produce an intermediate B. Intermediate B chelates with PdBr₂ to form an intermediate C. Subsequent elimination of HBr leads to the formation of intermediate D, which undergoes reductive elimination to afford the desired product 2. The Pd(0) is oxidized by DMSO to PdBr₂ for the next catalytic cycle.Open in a separate windowScheme 4A possible mechanism.     

Dual C–H activation: Rh(iii)-catalyzed cascade π-extended annulation of 2-arylindole with benzoquinone

A rhodium-catalyzed, N–H free indole directed cyclization reaction of benzoquinone via a dual C–H activation strategy is disclosed. This protocol has a good functional group tolerance and affords useful indole-fused heterocylces. Besides, it is insensitive to moisture, commercially available solvent can be directly used and work quite well for this transformation.

A Rh-catalyzed cascade annulation of N–H free 2-arylindole with benzoquinone via dual C–H activation strategy was reported.

Quinones are widely distributed in nature, and commonly occur in bacteria, flowering plants and arthropods (Fig. 1). They have a wide range of applications, including diverse important pharmacological properties, involvement in redox reactions and development for advanced electrochemical energy storage.¹ Among varied reported quinones, benzoquinone (BQ) is the simplest and most important one. It has been well reported that BQ has a significant and unique role in oxidative palladium(ii)-catalyzed coupling reactions.² The chemistry of benzoquinone has been extensively explored in detail, including nucleophilic addition and cycloaddition reactions, photochemistry and oxidative coupling.^1b,c,2 Although great achievements have been obtained, only a few examples are disclosed about BQ as a reactant applying to transition-metal catalyzed C–H functionalization.^1e Among the examples reported, cyclization or BQ direct functionalization products were mainly afforded (Scheme 1a).Open in a separate windowFig. 1Selected examples of bioactive molecules containing the benzoquinone moiety.Open in a separate windowScheme 1Transition-metal catalyzed C–H functionalization of BQ.Transition-metal catalyzed C–H functionalization has undergone great progresses in the past two decades.³ In order to get a better reactivity and controlled selectivity, a directing group is usually needed for this process. Therefore, various directing groups have been developed.⁴ However, many of them (e.g. various nitrogen-containing heterocycles) remained parts of products after reaction, therefore increasing the procedures and difficulty for structure further modification and manipulation.⁵ As a result, it is highly demanded to explore traceless or easily removable directing groups.⁶ In this context, N–H free indole moiety has gradually emerged as a versatile functionalizable directing group in transition-metal catalyzed cyclization reaction.⁷On the other hand, although the above-mentioned great breakthrough obtained in C–H functionalization, there are few examples reported for dual C–H activation reactions.⁸ During our research program exploring transition-metal catalysis and heterocyclic synthesis,⁹ we intended to prepare the indole-containing heterocycles based on the consideration of their potential biological activity. Herein, we report a rhodium-catalyzed N–H free indole directed annulation reaction with BQ through dual C–H activation strategy (Scheme 1b).Our initial study was carried out by examining 2-phenyl indole 1a and benzoquinone 2a in the presence of [{Cp*RhCl₂}₂] and Cu(OAc)₂·H₂O in commercial available N,N-dimethylformamide under argon atmosphere. To our delight, the desired 9H-dibenzo[a,c]carbazol-3-ol product 3a was isolated in 55% yield ( EntrySolventCatalystAdditiveYield1DMF[Cp*RhCl₂]₂Cu(OAc)₂·H₂O55%2DMF[Cp*RhCl₂]₂—<5%3DMF—Cu(OAc)₂·H₂O—4 t-Amyl-OH[Cp*RhCl₂]₂Cu(OAc)₂·H₂O—5DMAc[Cp*RhCl₂]₂Cu(OAc)₂·H₂O<5%6DMSO[Cp*RhCl₂]₂Cu(OAc)₂·H₂OTrace7DMF[RuCl₂(p-cymene)]₂Cu(OAc)₂·H₂O—8DMFPd(OAc)₂Cu(OAc)₂·H₂O—9DMFRhCl(PPh₃)₃Cu(OAc)₂·H₂O<5%10DMF[Cp*RhCl₂]₂AgOAc—11DMF[Cp*RhCl₂]₂Ag₂O—12DMF[Cp*RhCl₂]₂Cu(acac)₂Trace 13 ^{bb , cc} DMF/DCE[Cp*RhCl₂]₂Cu(OAc)₂·H₂O 84% Open in a separate window^aReaction on a 0.2 mmol scale, using 1a (1.0 equiv.), 2a (1.0 equiv.), additive (2.0 equiv.), CsOAc (2.0 equiv.), [TM] (5 mol%), solvent (1.0 mL), under N₂, isolated yield.^b1a (1.5 equiv.), solvent (0.3 M).^cNaOAc was used instead of CsOAc.With the optimized conditions in hand, we next tend to examine the substrates scope of this reaction. Various 2-aryl indoles with electron-rich substituted groups were tested and worked well for this reaction (10 Finally, an interesting S, N-fused heterocycle 3m was obtained when 2-thienyl indole was employed. Other derivatives of benzoquinone such as 1,4-naphthaquinone or methyl-p-benzoquinone currently failed to produce the related cyclization products with proper yields.Substrates scope^a