Palladium-catalysed direct arylations of NH-free pyrrole and N-tosylpyrrole with aryl bromides

The palladium-catalysed direct coupling of aryl halides with pyrroles provides a greener access to arylated pyrroles than more classical couplings such as Suzuki, Stille or Negishi reactions. However, so far, NH-free pyrrole and N-tosylpyrrole gave disappointing results for such couplings either in terms of regioselectivity of the arylation, catalyst loading or substrate scope. The reactivity of both NH-free pyrrole and N-tosylpyrrole was studied, and the tosylated pyrrole led to higher yields of coupling products due to better conversions of the aryl bromides. A range of aryl bromides undergo regioselective coupling at C2 of N-tosylpyrrole in moderate to good yields using 1 mol % [Pd(Cl(C₃H₅)]₂ as the catalyst, KOAc as the base in DMAc.     

Influence of the solvent and of the reaction concentration for palladium-catalysed direct arylation of heteroaromatics with 4-bromoacetophenone

The solvent is certainly one of the main sources of wastes during palladium-catalysed direct arylation reactions. We found that such direct arylations of heteroaromatics can be performed using very high concentrations of reactants (0.5 M–5 M). However, the Pd catalyst precursor used must be adapted to both the solvent nature and the concentration of reactants. The reactions performed in DMA, NMP or DMF can be carried out in very concentrated reaction mixtures using 0.1 mol% Pd(OAc)₂ catalyst without phosphine ligand. On the other hand, the reactions in CPME, pentan-1-ol or diethylcarbonate should be performed with a palladium catalyst associated with a phosphine ligand. These reaction conditions allow us to reduce the amount of wastes formed in the course of these couplings.     

Some recent applications of Fischer carbenemetal complexes in organic synthesis

{[2-(Dialkylamino)ethenyl]ethoxycarbene}chromium complexes 4 have been made available from lithiated terminal alkynes, hexacarbonylchromium, triethyloxonium tetrafluoroborate and secondary amines in a one-pot operation, in good to excellent yields. Reactions of these complexes with alkynes afford 5-dialkylamino-3-ethoxycyclopentadienes 8 with excellent chemoselectivity. From cyclopentadienes of type 8, angular and linear triquinanes, di- and triannelated benzene derivatives 24/25, steroid-like skeletons 30/31, and hexacycles 32/33 can be obtained with great facility. In addition, otherwise not easily accessible cyclopenta[b]pyrans 42/43 and novel spiro[4.4]nonatrienes 52/53 can be prepared in single operational steps from complexes 4 and terminal alkynes via [3 + 2 + 2 + 1] and [3 + 2 + 2 + 2] cocyclizations incorporating two and three alkyne units, respectively. Upon heating simple Fischer carbene complexes of type 2 with methylenecyclopropanes 64, cyclopentenones 65 are formed by formal [4 + 1] cycloadditions. New carbenemetal complexes which have different chemical reactivities can be formed in situ by transmetallation from the corresponding carbenechromium complexes. Various cyclopentenone, cyclopentene and cycloheptanone derivatives are easily accessible from these new carbenemetal (nickel and rhodium) complexes and an alkyne or an allene.     

Catalyst and base controlled site-selective sp and sp direct arylation of azine N-oxides

Site-selective direct arylation of both sp² and sp³ sites on azine N-oxide substrates is described. The arylation reactions are carried out in either a divergent manner or a sequential manner. The sp³ arylation reaction is applied to the synthesis of the natural products, papaverine and crykonisine, and a rationale for low reactivity of electron-deficient aryl halides is provided. Mechanistic investigations point toward the intimate involvement of the base in the mechanism of these reactions.     

Expanded scope of heterocyclic biaryl synthesis via a palladium-catalysed thermal decarboxylative cross-coupling reaction

The palladium-catalysed decarboxylative cross-coupling of heterocyclic aromatic carboxylates and aryl halides is described. The cross-coupling proceeds under relatively mild conditions using catalytic Pd(0) and tetrabutylammonium bromide (TBAB). Utilizing a mixed solvent system consisting of N,N-dimethylformamide (DMF) and N-methyl-2-pyrrolidone (NMP), the cross-coupling system operated at temperatures ranging from 80 to 140 °C.     

Synthesis of aryl alkynyl carboxylic acids and aryl alkynes from propiolic acid and aryl halides by site selective coupling and decarboxylation

The coupling of propiolic acid with aryl iodides afforded the aryl alkynyl carboxylic acids and aryl alkynes in generally good yields. Aryl alkynyl carboxylic acids were obtained when the reaction was performed in the presence of Pd(PPh₃)₂Cl₂ (2.5 mol %), dppb (5.0 mol %) and DBU (5 equiv) at 50 °C. For the synthesis of the terminal aryl alkynes, the reaction was conducted in the presence of Pd(PPh₃)₂Cl₂ (2.5 mol %), dppb (5.0 mol %), DBU (5.0 equiv), and Cu(acac)₂ (10 mol %) at 25 °C for 5 h, and further reacted at 60 °C for 6 h.     

Synthesis of unsymmetrically disubstituted ethynes by the palladium/copper(I)-cocatalyzed sila-Sonogashira–Hagihara coupling reactions of alkynylsilanes with aryl iodides,bromides, and chlorides through a direct activation of a carbon–silicon bond

In this paper, we explore the copper/palladium-cocatalyzed cross-coupling reactions of 1-aryl-2-trimethylsilylethynes with aryl iodides, bromides, and chlorides as coupling partners, to furnish unsymmetrically disubstituted ethynes in moderate to excellent yields. Various aryl iodides were subjected to reaction under the optimized conditions with 5 mol % of Pd(PPh₃)₂ and 50 mol % of CuCl. The steric properties of the aryl iodide proved more influential to the outcome of the cross-coupling reaction than electronic factors. In addition, we succeeded in synthesizing unsymmetrical diarylethynes using two different aryl iodides in one-pot. Furthermore, under the same reaction conditions with 10 mol % of PdCl₂, 40 mol % of P(4-FC₆H₄)₃, and 50 mol % of CuCl as catalyst, we succeeded in synthesizing unsymmetrical diarylethynes from various aryl bromides. Finally, we explored reactions with aryl chlorides and duly discovered that unsymmetrical diarylethynes were obtainable in moderate to good yields when 10 mol % of Pd(OAc)₂, 10 mol % of (?)-DIOP, and 10 mol % of CuCl were used. These reactions proceed through a direct activation of a carbon–silicon bond in alkynylsilanes by CuCl to generate the corresponding alkynylcopper species via transmetalation from silicon to copper. Mechanistic investigations on the reaction of alkynylsilanes with aryl bromides confirmed that the trimethylsilyl bromide generated in situ retarded both transmetalation steps between CuCl and alkynylsilane, and between palladium(II) species formed by oxidative addition and alkynylcopper species.     

Ruthenium hydride catalyzed silylvinylation of terminal alkynes under ethylene atmosphere at 80 psi

The development of methods for the stereoselective synthesis of polysubstituted 1,3-dienes is a challenge to synthetic chemistry. Herein is reported a selective approach for the synthesis of polysubstituted 1,3-dienes using the ruthenium hydride catalyzed intramolecular silylvinylation of alkynes under 80 psi of ethylene gas. This strategy affords a single diene isomer, is applicable to substrates with aryl and alkyl substitution at the propargyl and homopropargyl positions, and has been utilized in the synthesis of 5- and 6-membered oxasilacycles.     

Palladium-based catalytic systems for the synthesis of conjugated enynes by sonogashira reactions and related alkynylations

Conjugated alkynes are recurring building blocks in natural products, a wide range of industrial intermediates, pharmaceuticals and agrochemicals, and molecular materials for optics and electronics. The palladium-catalyzed cross-coupling between sp(2)-hybridized carbon atoms of aryl, heteroaryl, and vinyl halides with sp-hybridized carbon atoms of terminal acetylenes is one of the most important developments in the field of alkyne chemistry over the past 50 years. The seminal work of the 1970s has initiated an intense search for more general and reliable reaction conditions. The interest in the catalytic activation of demanding substrates, the need to minimize the consumption of depletive resources, and the search for easy access to an increased variety of functionalized enynes has led to the current generations of high-turnover catalysts. This Review gives an overview of the highly efficient palladium catalyst systems for the direct alkynylation of C(sp(2)) halides with terminal alkynes, both in homogeneous and heterogeneous phases.     

Copper/Silver‐Mediated Direct ortho‐Ethynylation of Unactivated (Hetero)aryl CH Bonds with Terminal Alkyne

A copper/silver‐mediated oxidative ortho‐ethynylation of unactivated aryl C?H bonds with terminal alkyne has been developed. The reaction uses the removable PIP directing group and features broad substrate scope, high functional‐group tolerance, and compatibility with a wide range of heterocycles, providing an efficient synthesis of aryl alkynes. This procedure highlights the potential of copper catalysts to promote unique, synthetically enabling C?H functionalization reactions that lie outside of the current scope of precious metal catalysis.     

Copper-catalyzed cross-coupling of amides and potassium alkenyltrifluoroborate salts: a general approach to the synthesis of enamides

Potassium alkenyltrifluoroborate salts undergo coupling with amides to give enamides using a catalytic amount of Cu(OAc)₂ under mild oxidative conditions. The air and water stable alkenyltrifluoroborate salts offer a practical alternative to the use of alkenyl halides and alkenylboronic acids as cross-coupling partners. A range of amides participate in the cross-coupling, including heterocyclic amides, imides, carbamates, benzamides, and acetamides. Optimization studies established two sets of conditions, best suited to either high pK_a or low pK_a amide substrates. Lower pK_a amide substrates worked best using a dichloromethane solvent system in the presence of 4 Å molecular sieves, 10 mol % Cu(OAc)₂, and 20 mol % N-methylimidazole. Higher pK_a amide substrates worked best using a ‘ligandless’ protocol using a 1:1 dichloromethane/DMSO solvent system in the presence of 4 Å molecular sieves and 10 mol % Cu(OAc)₂. The cross-coupling reactions occur stereospecifically with retention of alkene configuration from the alkenyltrifluoroborate salt. The mild reaction conditions employed are tolerant of various functionalities, including nitro, acetals, alkyl and aryl halides, and α,β-unsaturated carbonyls. Finally, the importance of copper sources and the presence of minor impurities were investigated.     

Palladium-catalyzed Mizoroki–Heck type reaction with aryl trialkoxysilanes using hydrazone ligands

Palladium-catalyzed Mizoroki–Heck type reaction of olefines with aryl trialkoxysilanes gave the arylation products using a catalytic amount of hydrazone–Pd(OAc)₂ system with AgF at 60 °C in good yields.     

Fe-catalyzed three-component dicarbofunctionalization of unactivated alkenes with alkyl halides and Grignard reagents

A highly chemoselective iron-catalyzed three-component dicarbofunctionalization of unactivated olefins with alkyl halides (iodides and bromides) and sp²-hybridized Grignard reagents is reported. The reaction operates under fast turnover frequency and tolerates a diverse range of sp²-hybridized nucleophiles (electron-rich and electron-deficient (hetero)aryl and alkenyl Grignard reagents), alkyl halides (tertiary alkyl iodides/bromides and perfluorinated bromides), and unactivated olefins bearing diverse functional groups including tethered alkenes, ethers, protected alcohols, aldehydes, and amines to yield the desired 1,2-alkylarylated products with high regiocontrol. Further, we demonstrate that this protocol is amenable for the synthesis of new (hetero)carbocycles including tetrahydrofurans and pyrrolidines via a three-component radical cascade cyclization/arylation that forges three new C–C bonds.

A highly selective iron-catalyzed three-component dicarbofunctionalization of unactivated alkenes with alkyl halides and sp²-hybridized Grignard reagents is reported.     

Insertion of the p-complex structure of silylenoid H2SiLiF into X–H bonds (X = C,Si, N,P, O,S, and F)

The insertion reactions of the p-complex structure (A) of silylenoid H₂SiLiF into XH_n molecules (X = C, Si, N, P, O, S, and F; n = 1–4) have been studied by ab initio calculations at the G3(MP2) level. The results indicate that the insertion reactions of A into X–H bonds proceed via three reaction paths, I, II, and III, forming the same products, substituted silanes H₃SiXH_n − 1 with dissociation of LiF, respectively, and all insertion reactions are exothermic. All the seven X–H bonds can undergo insertion reactions with A via path I and II, but only four of them, C–H, Si–H, P–H, and S–H, undergo insertion reactions via path III. The following conclusions emerge from this work: (i) the X–H insertion reactions of A occur in a concerted manner via a three-membered ring transition state; (ii) for path I and II, the stabilization energies of the A–XH_n complexes decrease in the order HF > H₂O > H₂S > NH₃ > SiH₄ > CH₄; (iii) for path I and II, the greater the atomic number of heteroatom (X) in a given row, the easier the insertion reaction of XH_n hydrides and the larger the exothermicity, and for the second-row hydrides, the reaction barriers are lower than for the first-row hydrides; (iv) The barriers of path I are lowest in those of three pathways with the exception of A + SiH₄ system, which barrier of path III is lowest. Moreover, the present study demonstrates that both electronic and steric effects play major roles in the course of insertion reactions of A into X–H bonds.     

Synthesis,crystal structures,metal-atom distribution and magnetic properties of Cr5−xTixSe8 (x ≈ 2, 3, 4)

The non-stoichiometric chromium titanium selenides Cr_5−xTi_xSe₈ (x ≈ 2, 3, 4) were prepared applying high-temperature solid-state reactions. The crystal structures have been refined with X-ray and neutron powder diffraction data applying the Rietveld method. The compounds crystallize in the space group F2/m (monoclinic, non-standard setting of C2/m) with four formula units per unit cell. The structures of all phases are related to the NiAs-type structure with ordered metal vacancies in every second metal-atom layer. Among the four different metal-atom sites two are fully occupied and the remaining two are only partially occupied. The MSe₆ octahedra share edges within layers and faces between layers. Consequently, long M–M separations occur in the layers whereas short M–M contacts result between M atoms of face-sharing octahedra. The lattice parameters of the samples and the M–M/M–Se bonds exhibit a remarkable deviation from Végard's rule which is caused by the distribution of Ti and Cr atoms over the independent crystallographic sites. The refinement of neutron diffraction data reveals that for x ≈ 2, 3, Ti atoms are located on three metal sites and only for x ≈ 4 the fourth position is also occupied by Ti. For all compositions a pronounced preference of Ti for sites within the full metal-atom layers is observed. Furthermore, a significant depletion of one partially occupied metal-atom site is accompanied by an increase of occupancy of the other partially occupied metal-atom site. The magnetic properties in the high-temperature range show Curie–Weiss behavior with negative paramagnetic Curie temperatures θ indicating strong antiferromagnetic exchange interactions which get weaker with increasing Ti content. The zero-field-cooled and field-cooled susceptibility curves diverge at low temperatures suggesting spin-glass behavior. The freezing temperature is lowered with increasing Ti content.     

Determination of copper,lead, cadmium and zinc content in commercially valuable fish species from the Persian Gulf using derivative potentiometric stripping analysis

This study was performed to determine the concentrations of cadmium, lead, copper and zinc in the edible muscle of pelagic (Scomberomorus commerson, Chirocentrus dorab, Sphyraena jello, Rachycentron conadum, Thunus tonggol, and Tenualosa ilisha) and demersal (Nemipterus japonicas, Epinephelus coioides, Platycephalus indicus, Psettodes erumei, Pomadasys argenteus, and Acanthopagrus latus) fish species from the Persian Gulf during winter and summer. The samples were analyzed by the derivative potentiometric stripping technique; and the results were expressed as μg/g of wet weight. The obtained range of metals in fish species was 0.024–0.111 μg/g for cadmium, 0.057–0.471 μg/g for lead, 0.799–4.790 μg/g for copper and 3.226–11.390 μg/g for zinc. The study revealed that seasonal variation influenced the concentration of metals in the samples. The highest concentration of cadmium, lead, copper and zinc was found in Platycephalus indicus (0.147 μg/g), Acanthopagrus latus (0.534 μg/g), Psettodes erumei (5.294 μg/g) and Psettodes erumei (13.528 μg/g) in winter, respectively. Moreover, demersal fish species had higher cadmium, lead and zinc concentrations, but lower copper content than pelagic ones. Our study demonstrated that the estimated daily and weekly intakes of lead, copper and zinc, and estimated monthly intake of cadmium via consumption of fish flesh were below the PTDI, PTWI and PTMI values established by FAO/WHO.     

Investigation of Alkyne Regioselectivity in the Ni‐Catalyzed Benzannulation of Cyclobutenones

A Ni‐catalyzed benzannulation reaction of cyclobutenones and alkynes provides a rapid synthesis of heavily substituted phenols. The regioselectivity of this reaction can be modulated by variation of substituents on the alkyne. Though the incorporation of Lewis basic donors provides modest selectivities, the use of aryl substituents can provide high levels of regiocontrol. Finally, alkynylboronates derived from alkyl‐substituted acetylenes provide both high yields and regioselectivities. This study suggests that alkynes bearing one sp²‐ and one sp³‐based substituent can undergo benzannulation with high levels of regiocontrol whereby the sp³‐based group is incorporated ortho‐to the phenolic OH.     

Theoretical study of Au/SAPO-11 catalyst and its potential use in thiophene HDS

Quantum chemistry calculations were carried out, using ONIOM2 methodology, in order to investigate the thiophene interaction with gold supported on silicoaluminophospates molecular sieves (Au/SAPO-11) catalysts. Two models were studied, one containing one Au atom per site, and the other with two Au atoms per site. Thiophene adsorption was found to be η¹ type. This adsorption presents a ΔH of ?13.2 and ?9.7 kcal/mol, for the models with one Au atom (Au/SAPO-11), and two Au atoms (Au₂/SAPO-11), respectively. The partial hydrogenation of the thiophene–Au/SAPO-11 and thiophene–Au₂/SAPO-11 complexes gives 2,5-dihydrothiophene (DHT), with a ΔH of ?23.0 and ?36.8 kcal/mol, respectively. 2-Butene production was found in both models with further hydrogenation. Likewise the direct butadiene elimination is achieved, but only with the separated Au dimer (ΔH = ?17.5 kcal/mol).     

Nickel-catalyzed decarboxylative coupling of an alkynyl carboxylic acid with aryl iodides

A decarboxylative coupling reaction with an alkynyl carboxylic acid and aryl iodides in the presence of a nickel catalyst was developed. When the reaction was conducted with NiCl₂ (10 mol%), Xantphos (15 mol%), Mn (1.0 equiv), and Cs₂CO₃ (1.5 equiv), the desired diaryl alkynes were formed in moderated to good yields. Furthermore, this method does not produce the diyne, which is formed in the homocoupling of alkynyl carboxylic acids.     

Activated sterically strained C=N bond in N-substituted p-quinone mono- and diimines: XIII. Reactions of N-alkyl(aryl, trifluoromethyl)sulfonyl-, N-arylsulfinyl- and N-arylsulfanyl-1,4-benzoquinone monoimines with alcohols

Steric strains arising between the substituent atoms at nitrogen (S, SO, or SO₂) and the methyl group located in positions 3 or 5 of the quinoid ring of 3,5-dimethyl-substituted quinone monoimines lead to the increased angle C=N-S. As a result in these quinone monoimines the reactions of 1,2-addition become thermodynamically possible since the formation of quinolide structures with the sp³-hybridized carbon atom removes the steric strain.