Palladium‐Catalyzed C?S Activation/Aryne Insertion/Coupling Sequence: Synthesis of Functionalized 2‐Quinolinones

The insertion of an aryne into a C S bond can suppress the addition of an S nucleophile to the aryne in the presence of palladium. Catalyzed by Pd(OAc)₂, a wide range of α‐carbamoyl ketene dithioacetals readily react with arynes to selectively afford functionalized 2‐quinolinones in high yields under neutral reaction conditions by a C S activation/aryne insertion/intramolecular coupling sequence. The attractive feature of the new strategy also lies in the versatile transformations of the alkythio‐substituted quinolinone products.     

Palladium‐Catalyzed CS Activation/Aryne Insertion/Coupling Sequence: Synthesis of Functionalized 2‐Quinolinones

The insertion of an aryne into a C? S bond can suppress the addition of an S nucleophile to the aryne in the presence of palladium. Catalyzed by Pd(OAc)₂, a wide range of α‐carbamoyl ketene dithioacetals readily react with arynes to selectively afford functionalized 2‐quinolinones in high yields under neutral reaction conditions by a C? S activation/aryne insertion/intramolecular coupling sequence. The attractive feature of the new strategy also lies in the versatile transformations of the alkythio‐substituted quinolinone products.     

ortho-Difunctionalization of arynes by LiZnEt2(TMP)-mediated deprotonative zincation/elimination of aryl triflates

Generation of arynes from aryl triflates has been achieved using lithium diethyl(tetramethylpiperidyl)-zincate base LiZnEt₂(TMP), via a directed ortho-deprotonative zincation and subsequent elimination of the triflate group. The aryne formation has been demonstrated by the cycloaddition reaction with diene and insertion reactions with ureas. Furthermore, the nucleophilic addition of LiZnEt₂(TMP) to arynes was observed in the absence of external aryne partners, offering a new cascade strategy for diverse difunctionalization of arynes.     

Synthesis of benzo-annulated 1,3-oxazine derivatives through the multi-component reaction of arynes with N-heteroaromatics and aldehydes or ketones

A multi-component reaction involving arynes, N-heteroaromatic compounds (including pyridine, quinoline, and isoquinoline), and aldehydes or ketones for the synthesis of benzo-annulated 1,3-oxazine derivatives has been described. The whole process is carried out under mild conditions and furnishes the desired products in 35–85% yields. Furthermore, regioselectivity and diastereoselectivity can be observed when using 3-OMe aryne precursor in this reaction.     

Synthesis of haloconduritols from an endo-cycloadduct of furan and vinylene carbonate

A method for preparing haloconduritols having a conduritol-A construction is described. A mixture of endo- and exo-cycloadduct derivatives prepared from the Diels-Alder reaction of furan and vinylene carbonate was converted into diacetate derivatives by hydrolysis (K₂CO₃/MeOH) followed by acetylation (Ac₂O/pyridine). Boron trihalide (BBr₃ or BCl₃)-assisted ring-opening of the endo-diacetate in CH₂Cl₂ at −78°C gave (1α,2α,3β,6β)-6-halogeno-4-cyclohexene-1,2,3-triol 1,2-diacetate from which the corresponding triacetate was prepared by acetylation (AcCl). trans-Esterification of the triacetate (MeOH/HCl) afforded (1α,2α,3β,6β)-6-halogeno-4-cyclohexene-1,2,3-triol (X=Br or Cl). BF₃-Assisted ring-opening of the endo-diacetate in CH₂Cl₂ gave (1α,2α,3β,6β)-6-chloro-4-cyclohexene-1,2,3-triol 1,2-diacetate by means of halogen exchange.     

Synthesis of tripeptides containing a very crowded α,α-disubstituted glycine with pyridine rings by solid-phase Ugi reaction

Tripeptides containing a novel α,α-disubstituted glycine with two pyridine rings, α,α-di(2-pyridyl)glycine (2Dpy), were synthesized by the solid-phase Ugi reaction using di(2-pyridyl)methanimine attached directly to a Rink amide resin. Thereby, yields of the tripeptides, Z-AA₁-2Dpy-AA₃-OMe (AA₁ and AA₃ = Gly or Aib), were markedly improved, compared with yields by the solution method.     

Highly selective insertion of arynes into a C(sp)-O(sp3) σ bond

Arynes react with ethoxyacetylene to afford 2-ethoxyethynylaryl derivatives through a highly chemo- and regioselective formal insertion of the aryne into the C(sp)-O(sp(3)) bond of the alkyne. Computational studies suggest that the reaction does not proceed through a mechanism initiated by the nucleophilic addition of the oxygen atom to the aryne as previously proposed but by the addition of the triple bond of the alkyne to the aryne.     

Aryne [3 + 2] cycloaddition with N-sulfonylpyridinium imides and in situ generated N-sulfonylisoquinolinium imides: a potential route to pyrido[1,2-b]indazoles and indazolo[3,2-a]isoquinolines

The aryne [3 + 2] cycloaddition process with pyridinium imides breaks the aromaticity of the pyridine ring. By equipping the imide nitrogen with a sulfonyl group, the intermediate readily eliminates a sulfinate anion to restore the aromaticity, leading to the formation of pyrido[1,2-b]indazoles. The scope and limitation of this reaction are discussed. As an extension of this chemistry, N-tosylisoquinolinium imides, generated in situ from N'-(2-alkynylbenzylidene)-tosylhydrazides via an AgOTf-catalyzed 6-endo-dig electrophilic cyclization, readily undergo aryne [3 + 2] cycloaddition to afford indazolo[3,2-a]-isoquinolines in the same pot, offering a highly efficient route to these potential anticancer agents.     

Sol–gel derived Si/C/O/N‐materials: molecular model compounds,xerogels and porous ceramics

Polymeric Si/C/O/N xerogels, with the idealized polymer network structure comprising [Si O Si(NCN)₃]_n moieties, were prepared by reactions of hexachlorodisiloxane (Cl₃Si O SiCl₃) with bis(trimethylsilyl)carbodiimide (Me₃Si NCN SiMe₃, BTSC). NMR and FTIR spectra indicate the existence of ‐NCN‐ and Si O Si‐ units in the xerogels and also in the ceramic materials obtained upon pyrolysis. The feasibility of this reaction protocol was confirmed on the molecular level by the deliberate synthesis of the macrocyclic compound [SiPh₂ O SiPh₂(NCN)]₂, the crystal structure and spectroscopic data of which are reported. The influence of pyridine as a catalyst for the cross‐linking reaction was studied. The degree of cross‐linking increased within the polymers with the addition of pyridine. It was shown by the reaction of hexachlorodisiloxane with excess pyridine that the latter appears to activate only one out of the two ‐SiCl₃ moieties under formation of hexacoordinated silicon compounds. The crystal structure of Cl₃Si O SiCl₃(pyridine)₂ is presented. Quantum chemical calculations are in support of this adduct being a potential intermediate in the pyridine catalyzed sol–gel process. The ceramic yield after pyrolysis of the Si/C/O/N‐xerogels at 1000 °C, which reaches values up to 50%, was found to depend on the aging protocol (time, temperature), whereas no correlation was found with the amount of pyridine added for xerogel synthesis. The Si/C/N/O‐ceramics obtained after pyrolysis at 1000 °C under NH₃ are completely amorphous. Chemically they have to be considered as hybrids between an ideal [SiOSi(NCN)₃]_n network and glass‐like Si₂N₂O. The products are mesoporous with closed pores and a broad pore size distribution. Copyright © 2011 John Wiley & Sons, Ltd.     

Oxofluorovanadates(V). I. Monooxopentafluorovanadates and monooxotetrafluorovanadates

The preparation of potassium, ammonium and ethylenediamine monooxopentafluorovanadates and of pyridine, α-picoline, quinoline, guanidine, ethylenediamine, α,α′-dipyridyl, o-phenanthroline and sodium monooxotetrafluorovanadates are reported. Infrared spectra of NaVOF₄ · 0.7 H_aO, (quinoline · H)(VOF₄) and (α-α′-dipyridyl · H₂) (VOF₄)₂ have been recorded (700–4000 cm^?1). Thermogravimetric study up to 450°C of (pyridine · H)(VOF₄), (quinoline H)(VOF₄) and (α,α′-dipyridyl · H₂)(VOP₄)₂ show that in all cases impure V₂O₅ is the ultimate product on heating.     

Synthesis and X-ray structure of a highlyhindered N-functionalized alkyl-cobalt(II) complex trans-[Co{[C(SiMe3)2C5H4N-2}2]

The thermally-stable cobalt(II) dialkyl compound CoR₂ [R = C(SiMe₃)₂C₅H₄N-2] (1) has been prepared by reaction of [{LiR}₂] with cobalt(II) chloride in ether. An X-ray structural study has revealed a centrosymmetric molecular skeleton (for two nearly identical independent molecules) in which a pair of sterically-hindered, functionalized pyridine ligands R⁻ are trans-chelated to the central planar four-coordinate cobalt(II) atom, with mean CoC_α and CoN distances of 2.094(6)Å and 1.919(4) Å respectively, and a C_αCoN angle of 69.6(2)°.     

Arene Trifunctionalization with Highly Fused Ring Systems through a Domino Aryne Nucleophilic and Diels–Alder Cascade

A convenient and efficient domino aryne process was developed under transition‐metal‐free conditions to generate a range of tetra‐ and pentacyclic ring systems. This transformation was realized via a 1,2‐benzdiyne through a nucleophilic and Diels–Alder reaction cascade using styrene as the diene moiety. Three new chemical bonds, namely one C?N and two C?C bonds, and two benzofused rings could be constructed concomitantly, which was made possible by distinct chemoselective control at both the 1,2‐aryne and 2,3‐aryne stages. Moreover, in‐depth studies were carried out on the domino aryne precursors and controlling the diastereoselectivity.     

One-pot synthesis of imidazo[1,2-α]pyridine thioethers using imidazo[1,2-α]pyridines,arylsulfonyl chlorides and hydrazine

Abstract

A one-pot reaction of making RS-substituted imidazo[1,2-α]pyridine derivatives by directly using aryl or alkylsulfonyl chloride and hydrazine was developed, selectively giving good yields of the expected products. Compared with previously reported methods of using ArSO₂NHNH₂ as a sulfur source, this method is much cheaper, more practical and convenient and enriches current methods to make thioether-containing compounds, providing a good example of green chemistry.     

Selective fluorination of substituted trichloromethyl benzenes by HF in liquid phase: Preparation of fluorinated building blocks

The selective fluorination by successive Cl/F exchanges of α,α,α-trichlorotoluene, substituted or not by a chlorine atom, was studied in the presence of HF as the fluorinating agent. The influence of the presence of a catalyst or a basic solvent (such as dioxane, pyridine, tributylphosphate) in order to control the fluorination was also investigated. In mild conditions (50 °C and after 1 h of reaction), HF in excess was required in order to obtained the trifluoromethylation by Cl/F exchanges. The presence of SbCl₅ in small amount activated the Cl/F exchanges and only a stoichiometric amount of HF was required whatever the chlorinated molecules. Selective mono and difluorination could be obtained by using basic solvents.     

Synthesis and properties of α-substituted benzylpyridinium salts as cationic initiators

α-Methylbenzylpyridinium SbF₆ (1a) and α,α-dimethylbenzylpyridinium SbF₆ (1b) were prepared and the effect of α-methyl groups on the active species and the activity of 1a, 1b during the cationic polymerization of glycidyl phenyl ether (GPE) was evaluated. 1b was prepared by the reaction of α,α-dimethylbenzyl alcohol with pyridinium hexafluoroantimonate (2) in several solvents, and the yield depended on the dipole moment of the solvents, although it was poor for the reaction of α,α-dimethylbenzyl chloride with pyridine for the steric hindrance of the α-methyl groups followed by exchange with NaSbF₆. Both 1a and 1b acted as a latent thermal initiator during the cationic polymerization of GPE and 1b showed higher activity during cationic polymerization with the higher steric effect of the α-methyl groups than 1a. The ¹H-NMR analysis of the obtained poly GPE indicated that the active species of 1b changed from the benzyl cation to H⁺, depending on the reaction temperature, although 1a released benzyl cations as active species in the cationic polymerization of GPE. © 1996 John Wiley & Sons, Inc.     

Microwave-assisted benzyne-click chemistry: preparation of 1H-benzo[d][1,2,3]triazoles

The benzotriazoles were prepared by three-component and two-component microwave-assisted [3+2] cycloadditions of various azides to benzyne, 3-methoxybenzyne, and 4,5-difluorobenzyne. In the three-component reaction, the aryne is generated, in the presence of an azide prepared in situ, by the reaction of an o-(trimethylsilylaryl) triflate with either CsF or KF/18-Crown-6. However, in the two-component reactions, a freshly prepared azide is added to the reaction vessel prior to aryne generation. Good to excellent yields of benzotriazoles were obtained in 15-20 min when the microwave-assisted reactions were carried out at 125 °C. These reaction times are significantly faster than similar reactions carried out using conventional heating.     

Ring-opening copolymerization of α-chloromethyl-α-methyl-β-propionolactone with ε-caprolactone

α-Chloromethyl-α-methyl-β-propionolactone (CMMPL) has been copolymerized with ε-caprolactone (CL) using a wide range of feed compositions and aluminium triisopropoxide [Al(OⁱPr)₃] as an initiator. Random copolymers of CMMPL with CL were obtained. The pendant chloromethyl groups of the copolymer were converted to quaternary ammonium salts by reaction with pyridine, resulting in an increased hydrophilicity of the copolymers.     

Pd(OAc)2-catalyzed domino reactions of 1,2-dihaloarenes and 2-haloaryl arenesulfonates with Grignard reagents: efficient synthesis of substituted fluorenes

Pd(OAc)₂-catalyzed domino reactions of 1,2-dihalobenzenes and 2-haloaryl arenesulfonates with hindered Grignard reagents to form substituted fluorenes, which are believed to occur through palladium associated aryne intermediates, are described. Such palladium associated aryne reaction pathway was found to be favored by omitting the use of phosphine and N-heterocyclic carbene ligands for palladium catalysts and with better leaving groups. Our study suggested that Pd(leaving group)X associated arynes should be formed first and the sp³ C-H activation preferentially occurred at benzylic C-(1°)H bonds. The work described here provides a high yield, one-step access to substituted fluorenes from readily available 1,2-dihalobenzenes and 2-haloaryl arenesulfonates and hindered Grignard reagents, and this substituted fluorene-making method may find applications in the preparation of substituted fluorene-containing molecules including polymers.     

Dual activity of electrocatalytic activated CO2 toward pyridine for synthesis of isonicotinic acid: An EC′C′C mechanism

The present study demonstrates the indirect electrocatalytic synthesis of isonicotinic acid using a Ni complex, [Ni^II(Me₄-(NO₂Bzo)₂[14]tetraeneN₄)], in an acetonitrile solution at room temperature. The complex was used as an excellent electrocatalyst for the reduction of carbon dioxide. The results indicate that the electrocatalytic reduction product of CO₂ (CO₂⁻) has a dual role in the electrosynthesis of isonicotinic acid. The dual activity of CO₂⁻ involved indirect electrocatalytic reduction of pyridine as well as its radical reaction with pyridine radical anion to form isonicotinic acid. Finally, EC′C′C mechanism was proposed for the synthesis of isonicotinic acid. In contrast, the reaction of pyridine with CO₂ in the absence of the complex follows an EC′C mechanism, and the final product is 4,4′-bipyridine.     

C–F Bond Cleavage Reactions with Beryllium,Magnesium, Gallium,Hafnium, and Thorium Halides

The work describes unexpected stoichiometric C–F bond cleavage reactions of beryllium, magnesium, gallium, hafnium and thorium halides with α,α,α-trifluorotoluene. The reaction of BeBr₂ / GaBr₃ or MgBr₂ / GaBr₃ mixtures as well as neat GaI₃ with α,α,α-trifluorotoluene in the presence of (OSi₂Me₄)₂ ( I ) yields the carbenium ion containing compounds [Ph-C(O₂Si₂Me₄)][GaX₄] (X = Br: 1 , X = I/F: 2 ). Both compounds were successfully characterized and a defluorination type reaction under incorporation of a siloxy unit was observed. Compound 1 was also characterized by single-crystal X-ray diffraction analysis. The conversion of α,α,α-trifluorotoluene with BeI₂, HfI₄ or ThI₄ turned out to be a halodefluorination-type reaction with formation of α,α,α-triiodotoluene ( 3 ). An adequate NMR spectroscopic and the X-ray crystallographic characterization of 3 were performed for the first time.