C(acyl)–C(sp2) and C(sp2)–C(sp2) Suzuki–Miyaura cross-coupling reactions using nitrile-functionalized NHC palladium complexes

Application of N-heterocyclic carbene (NHC) palladium complexes has been successful for the modulation of C–C coupling reactions. For this purpose, a series of azolium salts (1a–f) including benzothiazolium, benzimidazolium, and imidazolium, bearing a CN-substituted benzyl moiety, and their (NHC)₂PdBr₂ (2a–c) and PEPPSI-type palladium (3b–f) complexes have been systematically prepared to catalyse acylative Suzuki–Miyaura coupling reaction of acyl chlorides with arylboronic acids to form benzophenone derivatives in the presence of potassium carbonate as a base and to catalyse the traditional Suzuki–Miyaura coupling reaction of bromobenzene with arylboronic acids to form biaryls. All the synthesized compounds were fully characterized by Fourier Transform Infrared (FTIR), and ¹H and ¹³C NMR spectroscopies. X-ray diffraction studies on single crystals of 3c, 3e and 3f prove the square planar geometry. Scanning Electron Microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), metal mapping analyses and thermal gravimetric analysis (TGA) were performed to get further insights into the mechanism of the Suzuki–Miyaura cross coupling reactions. Mechanistic studies have revealed that the stability and coordination of the complexes by the CN group are achieved by the removal of pyridine from the complex in catalytic cycles. The presence of the CN group in the (NHC)Pd complexes significantly increased the catalytic activities for both reactions.

Nitrile-functionalized Pd(ii) complexes have evaluated for the Suzuki–Miyaura cross-coupling reactions. The highest TON value was reached for the acylative Suzuki–Miyaura cross-coupling reaction of acyl chlorides with phenylboronic acids.     

Heterogeneous Suzuki–Miyaura coupling of heteroaryl ester via chemoselective C(acyl)–O bond activation

A site-selective supported palladium nanoparticle catalyzed Suzuki–Miyaura cross-coupling reaction with heteroaryl esters and arylboronic acids as coupling partners was developed. This methodology provides a heterogeneous catalytic route for aryl ketone formation via C(acyl)–O bond activation of esters by successful suppression of the undesired decarbonylation phenomenon. The catalyst can be reused and shows high activity after eight cycles. The XPS analysis of the catalyst before and after the reaction suggested that the reaction might be performed via a Pd⁰/Pd^II catalytic cycle that began with Pd⁰.

A site-selective supported palladium nanoparticle catalyzed Suzuki–Miyaura cross-coupling reaction with heteroaryl esters and arylboronic acids as coupling partners was developed.     

Role of C,S, Se and P donor ligands in copper(i) mediated C–N and C–Si bond formation reactions

The first comparative study of C, S, Se and P donor ligands-supported copper(i) complexes for C–N and C–Si bond formation reactions are described. The syntheses and characterization of eight mononuclear copper(i) chalcogenone complexes, two polynuclear copper(i) chalcogenone complexes and one tetranuclear copper(i) phosphine complex are reported. All these new complexes were characterized by CHN analysis, FT-IR, UV-vis, multinuclear NMR and single crystal X-ray diffraction techniques. The single crystal X-ray structures of these complexes depict the existence of a wide range of coordination environments for the copper(i) center. This is the first comparative study of metal–phosphine, metal–NHC and metal–imidazolin-2-chalcogenones in C–N and C–Si bond formation reactions. Among all the catalysts, mononuclear copper(i) thione, mononuclear copper(i) N-heterocyclic carbene and tetranuclear copper(i) phosphine are exceedingly active towards the synthesis of 1,2,3-triazoles as well as for the cross-dehydrogenative coupling of alkynes with silanes. The cross-dehydrogenative coupling of terminal alkynes with silanes represents the first report of a catalytic process mediated by metal–imidazolin-2-chalcogenones.

The first comparative study of C, S, Se and P donor ligands-supported copper(i) complexes for C–N and C–Si bond formation reactions.     

Palladium nanoparticles as efficient catalyst for C–S bond formation reactions

The development of green, economical and sustainable chemical processes is one of the primary challenges in organic synthesis. Herein, we report an efficient and heterogeneous palladium-catalyzed sulfonylation of vinyl cyclic carbonates with sodium sulfinates via decarboxylative cross-coupling. Both aliphatic and aromatic sulfinate salts react with various vinyl cyclic carbonates to deliver the desired allylic sulfones featuring tri- and even tetrasubstituted olefin scaffolds in high yields with excellent selectivity. The process needs only 2 mol% of Pd₂(dba)₃ and the in situ formed palladium nano-particles are found to be the active catalyst.

Heterogenous catalysis: economical and sustainable synthesis of allylic sulfone featuring tri- and even tetrasubstituted olefin scaffold via decarboxylative cross-coupling from vinyl cyclic carbonates with sodium sulfinates using PdNPs as a catalyst.     

Perfluorinated phosphine and hybrid P–O ligands for Pd catalysed C–C bond forming reactions in solution and on Teflon supports

The synthesis of two types of phosphine ligands that feature perfluorinated ponytails is reported. A bidentate (RfCH₂CH₂)₂PCH₂CH₂P(CH₂CH₂Rf)₂ (Rf = CF₃(CF₂)_n; n = 5, 7) and an alkoxyphosphine made by ring opening a fluorous epoxide, RfCH₂CH(OH)CH₂PR₂ (Rf = CF₃(CF₂)₇), have been prepared and spectroscopically characterised. The electronic effects of the fluorous chains have been elucidated from either the ¹J_Pt–P or ¹J_P–Se coupling constants in Pt(ii) or phosphine selenide compounds. Whilst the bidentate phosphines do not give stable or active Pd catalysts, the hybrid ligand does allow Susuki, Heck and Sonogashira catalysis to be demonstrated with low catalyst loadings and good turnovers. Whilst a fluorous extraction methodology does not give good performance, the ligand can be adsorbed onto Teflon tape and for the Suzuki cross coupling reaction the catalytic system can be run 6 times before activity drops and this has been traced to oxidation of the ligand. Additionally the crystal structure of the hybrid phosphine oxide is reported and the non-covalent interactions discussed.

Phosphine ligands containing a perfluorous ponytail can be sorbed onto Teflon tape and used as ligands for C–C cross coupling reactions with little leaching.     

Microflowers formed by complexation-driven self-assembly between palladium(ii) and bis-theophyllines: immortal catalyst for C–C cross-coupling reactions

The Pd catalyst for Suzuki–Miyaura or the other C–C coupling reactions is one of the central tools in organic synthesis related to medicine, agricultural chemicals and advanced materials. However, recycling palladium is a bottleneck for developing the extreme potential of Pd in chemistry. Herein, we established a new heterogeneous Pd catalytic system in which the catalyst is a nanopetal-gathered flower-like microsphere self-assembled from PdCl₂ and alkyl-linked bis-theophyllines. The microflowers catalyzed quantitatively the reaction of aryl bromides and phenylboronic acid in aqueous media at room temperature. It was found that the reaction proceeds better in an air atmosphere than in nitrogen gas even though the Pd(ii) species employed was lowered to 0.001 mol% in the substance. Very interestingly, the microflowers could be recycled 20 times without deactivation in the C–C coupling reaction between bromobenzene and phenylboronic acid in the presence of sodium chloride. We found that the sodium chloride added played an important role in maintaining the morphology of microflowers and preventing the formation of metallic Pd particles.

Bis-theophylline-palladium complex exhibit high catalytic activity in the C–C coupling reaction with excellent recyclability in the presence of NaCl.     

Recent advances in sulfur–nitrogen bond formation via cross-dehydrogenative coupling reactions

This focus-review surveys literature methods for the construction of sulfur–nitrogen bonds through cross-dehydrogenative coupling reactions between thiols and N–H compounds with a particular emphasis on the mechanistic aspects of the reactions. The literature has been surveyed until the end of 2017.

This review surveys the construction of sulfur–nitrogen bonds through cross-dehydrogenative coupling reactions between thiols and N–H compounds.     

Ultrafine Pd nanoparticles loaded benzothiazole-linked covalent organic framework for efficient photocatalytic C–C cross-coupling reactions

We proposed a strategy that a benzothiazole-linked covalent organic framework (TTT-COF) was used as a substrate to prepare metal composite photocatalyst Pd NPs@TTT-COF. Firstly, benzothiazole linked TTT-COF exhibited superior chemical stability and photoresponse. Moreover, a finer particle size (2.01 nm) and more uniform distribution of Pd NPs were observed in Pd NPs@TTT-COF owing to the binding interaction between Pd NPs and S in benzothiazole groups. Pd NPs@TTT-COF exhibited superior efficiency and reusability in photocatalytic C–C cross-coupling reactions. Mechanism study suggested that photogenerated electrons and holes on TTT-COF played important roles in these reactions.

Benzothiazole-linked covalent organic framework with characteristic properties loaded Pd nanoparticles for photocatalytic C–C cross-coupling reactions.     

Pd-catalyzed C–C and C–N cross-coupling reactions in 2-aminothieno[3,2-d]pyrimidin-4(3H)-one series for antiplasmodial pharmacomodulation

In 2015, we identified gamhepathiopine (M1), a 2-tert-butylaminothieno[3,2-d]pyrimidin-4(3H)-one antiplasmodial hit targeting all development stages of the human malarial parasite P. falciparum. However, this hit compound suffers from sensitivity to hepatic oxidative metabolism. Herein, we describe the synthesis of 33 new compounds in the 2-aminothieno[3,2-d]pyrimidin-4(3H)-one series modulated at position 6 of this scaffold. The modulations were performed using three palladium-catalyzed cross coupling reactions, namely Suzuki–Miyaura, Sonogashira, and Buchwald–Hartwig. For the latter, we developed the reaction conditions. Then, we evaluated the synthesized compounds for their antiplasmodial activity on the K₁P. falciparum strain and their cytotoxicity on the human HepG2 cell line. Although we did not obtain a compound better than M1 in terms of the antiplasmodial activity, we identified compound 1g bearing a piperidine at position 6 of the thieno[3,2-d]pyrimidin-4(3H)-one ring with an improved cytotoxicity and metabolic stability. 1g is an interesting new starting point for further pharmacomodulation studies. This study also provides valuable antiplasmodial SAR data regarding the nature of the ring at position 6, the possible substituent on this ring, and the introduction of a spacer between this ring and the thienopyrimidinone moiety.

Pharmacomodulation at position 6 of a thienopyrimidinone antiplasmodial hit using palladium-catalyzed cross-coupling reactions afforded 33 new compounds, among which a new hit was found with enhanced metabolic stability.     

A supported manganese complex with amine-bis(phenol) ligand for catalytic benzylic C(sp3)–H bond oxidation

With regards to the importance of direct and selective activation of C–H bonds in oxidation processes, we develop a supported manganese amine bis(phenol) ligand complex as a novel catalyst with the aim of obtaining valuable products such as carboxylic acids and ketones that have an important role in life, industry and academic laboratories. We further analyzed and characterized the catalyst using the HRTEM, SEM, FTIR, TGA, VSM, XPS, XRD, AAS, and elemental analysis (CHN) techniques. Also, the catalytic evaluation of our system for direct oxidation of benzylic C–H bonds under solvent-free condition demonstrated that the heterogeneous form of our catalyst has high efficiency in comparison with homogeneous ones due to more stability of the supported complex. Furthermore, the structural and morphological stability of our efficient recyclable catalytic system has been investigated and all of the data proved that the complex was firmly anchored to the magnetite nanoparticles.

An environmentally friendly and efficient catalyst containing three interesting parts, Mn, the amine bis(phenolate) ligand (H₃L^GDC) and the magnetic nanoparticles for benzylic C–H bond oxidation.     

Highly efficient Ru(ii)–alkylidene based Hoveyda–Grubbs catalysts for ring-closing metathesis reactions

Three novel phosphine-free Ru-alkylidenes (7a–7c) have been synthesized and utilized as efficient catalysts for ring closing metathesis (RCM) reaction. Spectroscopic data, i.e. NMR and HRMS, along with single crystal X-ray diffraction analysis, were used to confirm their chemical structures. The tosylated carbenoid 7b showed the highest efficiency in cyclizing different acyclic diene substrates. RCM of various (un)substituted N,N-diallylaniline derivatives and stereoselective RCM of different macromolecular dienes were well tolerated using only a catalytic amount (0.5–2.0 mol%) of the additive catalyst (7b) as compared to the well-known Grubbs (II) and Hoveyda–Grubbs (II) catalysts.

Three novel phosphine-free Ru-alkylidenes (7a–7c) have been synthesized and utilized as efficient catalysts for ring closing metathesis (RCM) reaction.     

Cobalt-catalyzed C(sp3)–H/C(sp2)–H oxidative coupling between alkanes and benzamides

A direct cobalt-catalyzed oxidative coupling between C(sp²)–H in unactivated benzamides and C(sp³)–H in simple alkanes, ethers and toluene derivatives was explored. This protocol achieves direct C–C formation without using alkyl or aryl halide surrogates and exhibits high practicality with ample substrate scope. The method provides a new way to construct linear and five- or six-membered ring moieties in bioactive molecules.

A direct cobalt-catalyzed oxidative coupling between C(sp²)–H in unactivated benzamides and C(sp³)–H in simple alkanes, ethers and toluene derivatives was explored.     

CeO2-modified P2–Na–Co–Mn–O cathode with enhanced sodium storage characteristics

To improve the cycling stability and dynamic properties of layered oxide cathodes for sodium-ion batteries, surface modified P2–Na_0.67Co_0.25Mn_0.75O₂ with different levels of CeO₂ was successfully synthesized by the solid-state method. X-ray photoelectron spectra, X-ray diffraction and Raman spectra show that the P2-structure and the oxidation state of cobalt and manganese of the pristine oxide are not affected by CeO₂ surface modification, and a small amount of Ce⁴⁺ ions have been reduced to Ce³⁺ ions, and a few Ce ions have entered the crystal lattice of the P2-oxide surface during modification with CeO₂. In a voltage range of 2.0–4.0 V at a current density of 20 mA g⁻¹, 2.00 wt% CeO₂-modified Na_0.67Co_0.25Mn_0.75O₂ delivers a maximum discharge capacity of 135.93 mA h g⁻¹, and the capacity retentions are 91.96% and 83.38% after 50 and 100 cycles, respectively. However, the pristine oxide presents a low discharge capacity of 116.14 mA h g⁻¹, and very low retentions of 39.83% and 25.96% after 50 and 100 cycles, respectively. It is suggested that the CeO₂ modification enhances not only the maximum discharge capacity, but also the electric conductivity and the sodium ion diffusivity, resulting in a significant enhancement of the cycling stability and the kinetic characteristics of the P2-type oxide cathode.

The CeO₂ modification significantly enhances the maximum discharge capacity and cycling stability of a P2–Na_0.67Co_0.25Mn_0.75O₂ cathode.     

I2-mediated Csp2–P bond formation via tandem cyclization of o-alkynylphenyl isothiocyanates with organophosphorus esters

A novel, I₂-mediated tandem cyclization of o-alkynylphenyl isothiocyanates with organophosphorus esters has been developed under mild conditions. Different kinds of 4H-benzo[d][1,3]thiazin-2-ylphosphonate could be synthesized in moderate to excellent yields. This method has the advantages of easy access to raw materials, free-metal catalyst, simple operation, high yield and high functional group tolerance.

A highly efficient molecular-iodine-catalyzed cascade cyclization reaction has been developed, creating a series of 4H-benzo[d][1,3]thiazin-2-yl phosphonates in moderate to excellent yields. This approach benefits from metal-free catalysts and available raw materials.

As an important class of organic products, organophosphorus compounds have received considerable attention because they have broad application in the field of materials science,¹ medicinal chemistry,² organic synthesis,³ natural products,⁴ and ligand chemistry.⁵ Phosphorus-containing compounds are valuable precursors of many biologically active molecules which can act as antibiotics,⁶ anti-tumor agents⁷ and enzyme inhibitors.⁸ Traditionally, the preparation of organophosphorus compounds relies on a transition-metal-catalyzed cross-coupling of phosphine reagents with electrophilic aryl halides (Ar-X),⁹ aryl boronic acids (Ar-B),¹⁰ aryl diazonium salts (Ar-N),¹¹ and so on.¹² Recently, the construction of a Csp²–P bond on heterocycles is another powerful method to synthesize the organophosphorus compounds.¹³ For instance, the Duan group and the Ackermann group reported a Ag-mediated C–H/P–H functionalization method to construct a Csp²–P bond by using arylphosphine oxides and internal alkynes as the substrates^13a,b (Scheme 1a). In 2014, Studer and co-workers reported a pioneering radical cascade reaction for the synthesis of 6-phosphorylated phenanthridines from 2-isocyanobiphenyls and diphenylphosphine oxides (Scheme 1b).^13c Before long, Ji and Lu''s group described two similar radical process with excess of PhI(OAc)₂ or K₂S₂O₈ as the oxidant (Scheme 1c).^13d,e Recently, Liang and co-works developed two cases of cascade functionalization to construct phosphorylated heterocycles via the ionic pathway (Scheme 1d and 1e).^13f,g Meanwhile, Li and coworkers reported a Mn(ii)-promoted tandem cyclization reaction of 2-biaryl isothiocyanates with phosphine oxides which went through the same mechanism(Scheme 1f).^13h Despite the usefulness of the above methods, common problems, such as complex reaction substrates, relatively high temperature, excess amounts of oxidants, limited their applications. Furthermore, transition metals are required in these reactions, thereby resulting in limitations in reactants. Therefore, the development of a simple and transition-metal-free method for the formation of the Csp²–P bond from easily prepared starting materials is highly desirable.Open in a separate windowScheme 1Synthesis of P-containing heterocycles through Csp²–P bond formation. o-Alkynylphenyl isothiocyanates are easily prepared organic synthons with versatile chemical reactivity,¹⁴ and they could be used as electrophiles,¹⁵ nucleophiles,¹⁶ and radical receptors¹⁷ due to the N C S moiety in the structure. Recently, the rapid development of the transition-metal-catalyzed cascade cycloaddition of o-alkynylphenyl isothiocyanates with various nucleophiles provides a new and powerful synthetic strategy to synthesize different heterocycles. Very recently, we have developed a tandem cyclization process for the synthesis of 4H-benzo[d][1,3]thiazin-2-yl)phosphonates by using this strategy.¹⁸ As part of our continuing interest in the transformation of o-alkynylphenyl isothiocyanates,¹⁹ we describe herein a novel I₂-promotedtandem reaction to construct Csp²–P bond from o-alkynylphenyl isothiocyanates and phosphine oxides(Scheme 1g).The starting o-alkynylphenyl isothiocyanates were prepared via the Sonogashira coupling of 2-iodoanilines with terminal alkynes,²⁰ followed by the treatment with thiophosgene according to the literature procedure.²¹ We commenced our studies with the reaction of o-phenylethynylphenyl isothiocyanate (1a, 0.2 mmol) and diethyl phosphonate (2a, 0.6 mmol) in the presence of I₂ (0.5 equiv.) as the catalyst, 8-diazabicyclo[5,4,0]undec-7-ene (DBU, 3.0 equiv.) as the base, in dichloromethane (DCM, 2 mL) at 0 °C for 12 h in air atmosphere. Gratifyingly, the desired product diethyl (Z)-(4-benzylidene-4H-benzo[d][1,3] thiazin-2-yl)phosphonate 3a was obtained in 75% yield (Schemes 1–4)Optimization of the reaction conditions^a

tBuOK-triggered bond formation reactions

Recently, inexpensive and readily available tBuOK has seen widespread use in transition-metal-free reactions. Herein, we report the use of tBuOK for S–S, S–Se, N N and C N bond formations, which significantly extends the scope of tBuOK in chemical synthesis. Compared with traditional methods, we have realized mild and general methods for disulfide, azobenzenes imine etc. synthesis.

Inexpensive and readily available ^tBuOK can trigger a series of bond formation reactions, including S–S, S–Se, Se–Se, and N N and C N bonds.     

Effect of unmelted lime on the element distribution behavior on a CaO–SiO2–MgO–Al2O3–FeO–CaF2(–Cr2O3) slag

In this study, a CaO–SiO₂–Al₂O₃–MgO–FeO–CaF₂(–Cr₂O₃) slag was chosen according to the compositions of the stainless steel slag for industrial production, and a CaO block was added to the molten slag after the synthetic slag was fully melted. The influences of unmelted lime on the distribution of elements and the structure of product layers at the lime/slag boundary, particularly the existing state of chromium oxide in the chromium-bearing stainless steel slag, were deeply discussed by scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) and FactSage 7.1. The experiment results indicated that when the unmelted lime existed in the CaO–SiO₂–Al₂O₃–MgO–FeO–CaF₂ slag system, two product layers of periclase (MgO) and dicalcium silicate (Ca₂SiO₄) at the boundary of the CaO block were formed. However, when the CaO block was added in the CaO–SiO₂–Al₂O₃–MgO–FeO–CaF₂–Cr₂O₃ stainless steel slag, besides MgO and Ca₂SiO₄ product layers, needle-shaped calcium chromite (CaCr₂O₄) was also precipitated around the CaO block. Moreover, a small amount of Cr dissolved in the periclase phase. Eh–pH diagrams showed that the CaCr₂O₄ and MgO phase unstably existed in a weak acid aqueous solution. Therefore, the existence of unmelted lime in the stainless steel slag could enhance the leachability of chromium.

The effect of unmelted lime on the distribution of elements and structure of product layers in CaO–SiO₂–MgO–Al₂O₃–FeO–CaF₂(–Cr₂O₂) stainless steel slag and the action of unmelted lime phase mechanism in experimental slags was conducted.     

Nickel(ii)-catalyzed tandem C(sp2)–H bond activation and annulation of arenes with gem-dibromoalkenes

A nickel(ii)/silver(i)-catalyzed tandem C(sp²)–H activation and intramolecular annulation of arenes with dibromoalkenes has been successfully achieved, which offers an efficient approach to the 3-methyleneisoindolin-1-one scaffold. Attractive features of this system include its low cost, ease of operation, and its ability to access a wide range of isoindolinones.

A nickel(ii)/silver(i)-catalyzed tandem C(sp²)–H activation and intramolecular annulation of arenes with dibromoalkenes has been successfully achieved, which offers an efficient approach to the 3-methyleneisoindolin-1-one scaffold.

Over the past years, the transition-metal-catalyzed oxidative C–H/C–H cross-coupling reaction has emerged as a useful, atom- and step-economic synthetic protocol to construct a series of important N-heterocycles.¹ In this context, the synthesis of isoindolinones has attracted considerable attention owing to their interesting biological and pharmaceutical properties,² as well as their usefulness as precursors for the synthesis of structurally diverse and complex molecules (Scheme 1).^2c,3 Several methods have successfully been developed toward isoindolinone synthesis based on Pd,⁴ Cu,⁵ Ru,⁶ and Rh⁷ salts. Among these reactions, the oxidative coupling reactions of benzamides with alkenes^4b,6,7a,f,g or alkynes^5a,5d exhibit high atom economy and the application of this strategy to simple arenes is still largely underdeveloped.⁸ For instance, in 2015, Zhang''s group⁹ revealed cobalt-catalyzed oxidative alkynylation and cyclization of simple arenes and terminal alkynes with silver-cocatalyst via 2-fold C–H bond and N–H bond cleavage and C–C bond and C–N bond formation. In 2016, Song''s group¹⁰ developed a method of a cobalt(ii)-catalyzed decarboxylative C–H activation/annulation of benzamides and alkynyl carboxylic acids and nickel(ii)-catalyzed C(sp²)–H alkynylation/annulation cascade with terminal alkynes to synthesize 3-methyleneiso-indolin-1-ones. Zhang also reported a nickel-catalyzed oxidative alkynylation with amides and terminal acetylenes.^10c In addition, from an environmentally point of view, in 2015, wei''s group¹¹ described an operationally simple, Pd-catalyzed C–H functionalization for the synthesis of important and useful isoindolinones from readily available carboxamides and carboxylic acids or anhydrides. The protocol avoided the use of excess oxidants including benzoquinone, Cu(OAc)₂, or Ag₂CO₃ of previous all the reactions, thus generating stoichiometric amounts of undesired wastes.Open in a separate windowScheme 1Representative isoindolinones with biological and pharmaceutical.To our knowledge, the synthesis of alkynes is among the most fundamental and important synthetic transformations due to the unique reactivity of alkynes including addition, oxidation, reduction, and in particular cyclization.¹² However, the lack of reactivity of alkynes, more electron-deficient than the corresponding alkenes, makes it harder to couple them with heteroarenes. As a consequence, terminal alkyne precursors have been developed to facilitate acetylene exchange.¹³ Halogenoalkynes,¹⁴ hypervalent alkynyliodoniums,¹⁵acetylenic sulfones,¹⁶ copper acetylides¹⁷ and α,β-ynoic acids¹⁸ allowed the generation of more activated alkyne moieties thus broadening the applications of direct alkynylation reactions to heterocycles. Among these alternatives, gem-dihaloalkenes emerged as more efficient coupling partners than the corresponding monohalogenated alkynes along with being inexpensive and readily-available.¹⁹ Indeed, the two geminal halogen atoms on the alkenyl carbon enhance the reactivity of metal complexes thus facilitating cross coupling reactions.²⁰ Stable and readily-available 1,1-dibromo-1-alkenes and our interests in the C–H activation²¹ led us to consider using these reagents in the C–H functionalization to construct the valuable isoindolinones. We can envision that the abundance and structural diversity of the aldehydes (used the preparation of gem-dibromoethylenes via wittig reaction) as well as the merits of C–H functionalization would make the synthetic methods desirable and attractive. Herein, we wish to disclose the nickel(ii)/silver(i)-mediated tandem transformation involving sequential C(sp²)–H/C(sp²)–H alkynylation and intramolecular annulation of unactivated arenes with dibromoethylenes with the assistance of 8-aminoquinoline (Scheme 2). These features of this approach operational simplicity, a wide-ranging substrate scope, and tolerance of various synthetically useful functional groups.Open in a separate windowScheme 2Nickel(ii)/silver(i)-catalyzed alkynylation/annulation of arenes with dibromoalkenes.     

Methods for direct C(sp2)–H bonds azidation

Direct functionalization of C–H bonds has attracted great attention in recent years from the perspectives of atom and step economy. In this context, a variety of processes have been developed for the construction of synthetically and biologically important organic azides through the oxidative C–H bonds azidation. In this review, we have summarized recent progress in the direct azidation of C(sp²)–H bonds. The review is divided into three major sections: (i) direct azidation of aromatic C–H bonds; (ii) direct azidation of olefinic C–H bonds; and (iii) direct azidation of aldehydic C–H bonds. Mechanistic aspects of the reactions are considered and discussed in detail.

Direct functionalization of C–H bonds has attracted great attention in recent years from the perspectives of atom and step economy.     

A modified random network model for P2O5–Na2O–Al2O3–SiO2 glass studied by molecular dynamics simulations

We investigated the short- and medium-range structural features of sodium aluminosilicate glasses with various P₂O₅ (0–7 mol%) content and Al/Na ratios ranging from 0.667 to 2.000 by using molecular dynamics simulations. The local environment evolution of network former cations (Si, Al, P) and the extent of clustering behavior of modifiers (Na⁺) is determined through pair distribution function (PDF), total correlation function (TDF), coordination number (CN), Q_xⁿ distribution and oxygen speciation analysis. We show that Al–O–P and Si–O–Al linkage is preferred over other connections as compared to a random model and that Si–O–Si linkage is promoted by the P₂O₅ addition, which is related to structural heterogeneity and generates well-separated silicon-rich and aluminum–phosphorus-rich regions. Meanwhile, due to the relatively high propensity of Al to both Si and P, heterogeneity can be partly overcome with high Al content. A small amount of Si–O–P linkages have been detected at the interface of separated regions. Clustering of Na⁺ is also observed and intensified with the addition of P₂O₅. Based on the simulated structural information, a modified random network model for P₂O₅-bearing sodium aluminosilicate glass has been proposed, which could be useful to optimize the mobility of sodium ions and design novel functional glass compositions.

(A) A modified structural model proposed for P₂O₅-bearing sodium aluminosilicate glasses. (B) Degree of preferred connection (DPC) of different T–O–T network linkage for LAP, MAP and HAP glass compositions with various P₂O₅ content.     

Synthesis of C14–C21 acid fragments of cytochalasin Z8via anti-selective aldol condensation and B-alkyl Suzuki–Miyaura cross-coupling

An efficient synthesis of the C14–C21 acid fragment of cytochalasin Z₈ was accomplished in 10 steps with 14% overall yield. Boron-mediated anti-selective aldol condensation and Pd(OAc)₂–Aphos-Y-catalysed B-alkyl Suzuki–Miyaura cross-coupling were employed to construct the requisite C17 and C18 stereogenic centres and alkene subunit.

An efficient synthesis of the C14–C21 acid fragment of cytochalasin Z₈ was accomplished in 10 steps with 14% overall yield.

Cytochalasins are secondary fungal metabolites with a wide range of biological activities that target cytoskeletal processes.¹ Cytochalasins Z₇–Z₉ (1–3, Chart 1) were isolated from the marine-derived fungus Spicaria elegans, and their structures and absolute configurations were established by Zhu et al.² Cytochalasin Z₈ (2, Chart 1) is structurally related to cytochalasins Z₇ and Z₉ and features highly substituted hydroisoindol-1-one fused with a 12-membered macrolactone ring at the C-8 and C-9 positions. Cytochalasin Z₈ has been reported to exert cytotoxicity against P388 and A-549 cell lines with IC50 values of 56 and 21 μM, respectively, and therefore has significant potential in cell biology and medicine. A number of laboratories have worked towards total synthesis of the cytochalasin family and developed linear³ or convergent⁴ strategies for their total synthesis. Total synthesis of cytochalasin congeners was accomplished by the laboratories of Stork,^3a,4a Thomas,^3b,3c,3e,3f Trost,^4d Vedejs (zygosporin E),^4b,4c,4e Myers,⁵ Liu and Tang (periconiasins A–E)⁶ and Nay (periconiasin G).⁷ To the best of our knowledge, total synthesis of cytochalasin with a 12-membered macrocyclic ring has not been reported. The intriguing molecular architecture and potent biological activity of cytochalasin Z₈ prompted us to pursue its total synthesis and render it to be readily available for biological investigations.Open in a separate windowChart 1Structures of cytochalasin Z₇–Z₉.The retrosynthetic strategy is depicted in Scheme 1. Intramolecular ring-closing metathesis (RCM) strategy⁸ which is a promising tool for constructing macrolactone is often used for synthesising macrolides.⁹ We envisioned an RCM reaction at C13 and C14 positions and an esterification for assembling a 12-membered macrolactone. Thus, acid fragment 4 was required for the total synthesis of 2. Our strategy was flexible and it allowed rapid access to structural analogues. In this study, we report the synthesis of C14–C21 acid fragment 4via a highly anti-selective aldol condensation¹⁰ of aldehyde 6 with Abiko''s chiral norephedrine-derived propionate (1R,2S)-7 (ref. 11) and B-alkyl Suzuki–Miyaura cross-coupling¹² of chiral alkyl iodide 5 with (Z)-1-bromoprop-1-ene.Open in a separate windowScheme 1Retrosynthetic bond disconnections of cytochalasin Z₈ (2) yielding C14–C21 acid fragment 4 and hydroisoindol-1-one fragment.Our first task was to construct C16–C18 syn–anti stereotriad.¹³ The aldehyde functionality in 6 was expected to undergo an anti-selective aldol reaction with the (E)-boron enolate generated from Abiko''s chiral propionate 7 for installing C17–C18 anti stereochemistry according to our synthetic strategy in Scheme 1. We initially prepared crude aldehyde 6 from commercially available (S)-methyl 3-hydroxy-2-methyl propionate (Roche ester)¹⁴ by tosylation and partial ester reduction¹⁵ (Scheme 2). The unstable crude aldehyde 6, without column chromatographic purification, was immediately used with the (E)-boron enolate derived from 7 for anti-selective aldol reaction to secure the syn/anti stereotriad in 8. The key intermediate 8 was prepared in high diastereoselectivity of 98 : 2 (determined by proton nuclear magnetic resonance spectroscopy) and in the desired absolute configuration as predicted by the chiral auxiliary in 7. The influence of the stereogenic centre of aldehyde 6 on the stereochemical course of the aldol reaction was not observed. The hydroxyl group in 8 was then protected as TES ether 9 (TESOTf, 2, 6-lutidine, 98% yield). Iodide replacement of the tosylate group in 9 with LiI–THF furnished alkyl iodide 5 in 95% yield (Scheme 2).Open in a separate windowScheme 2Synthesis of alkyl iodide 6.The cross-coupling reaction of chiral alkyl iodide 5 with (Z)-1-bromoprop-1-ene was performed under the established conditions¹⁶ for the ‘9-MeO-9-BBN variant’ of the B-alkyl Suzuki–Miyaura cross-coupling reaction.^12f,17 Alkyl iodide 5 was treated with t-BuLi in the presence of 9-MeO-9-BBN in Et₂O–THF to form the corresponding borinate species which was subjected to Pd(OAc)₂–Aphos-Y-catalysed^16,18 cross-coupling reaction with (Z)-1-bromoprop-1-ene in the presence of K₃PO₄·3H₂O as the base in THF–H₂O at room temperature to furnish 11 in 15% yield along with cyclopentanol 10 and deiodinated byproduct 12 (entry 1, Scheme 3). These results suggested that the formation of 10 could be suppressed by controlling reaction temperature. The first step reaction was maintained under low temperatures for a long time before warming up. After adding t-BuLi and THF, the reaction temperature was sequentially kept at −78 °C for 30 min, at −40 °C for 30 min, at −20 °C for 30 min and at room temperature for 2 h. The newly formed borinate species was subjected to coupling reaction with (Z)-1-bromoprop-1-ene. The yield was improved to 40% (entry 3,