Lanthanide triflate-promoted palladium-catalyzed cyclization of alkenyl beta-keto esters and amides

[reaction: see text] Lanthanide triflates were found to promote the palladium-catalyzed cyclization of alkenyl beta-keto esters and amides. In the presence of catalytic amounts of PdCl(2)(MeCN)(2) and Ln(OTf)(3), various alkenyl beta-keto esters and amides underwent regioselective cyclization reactions to give six-, seven-, or eight-membered-ring carbocycles in moderate to excellent yields.     

Recyclable and reusable Pd(OAc)2/DABCO/PEG-400 system for Suzuki-Miyaura cross-coupling reaction

[reaction: see text] A stable and efficient Pd(OAc)2/DABCO (triethylenediamine) catalytic system for Suzuki-Miyaura cross-coupling reaction has been developed. In the presence of Pd(OAc)2 and DABCO, coupling of aryl halides with arylboronic acids was carried out smoothly to afford good to excellent yields and high turnover numbers (TONs) (the maximal TONs were up to 960,000 for the reaction of 1-iodo-4-nitrobenzene with phenylboronic acid) using PEG-400 as the solvent. Moreover, the Pd(OAc)2/DABCO/PEG-400 system could be recycled and reused five times without any loss of catalytic activity for aryl iodides and bromides.     

Metal-induced cyclization of thiosemicarbazones derived from beta-keto amides and beta-keto esters: open-chain and cyclized ligands in zinc(II) complexes

The reactions of Zn(OAc)(2) with acetoacetanilide, methyl acetoacetate, o-acetoacetanisidide, and ethyl 2-methylacetoacetate thiosemicarbazones (HTSC(1), HTSC(2), HTSC(3), and HTSC(4), respectively) were explored in methanol. With HTSC(1), HTSC(2), and HTSC(3), following isolation of the corresponding zinc(II) thiosemicarbazonates [Zn(TSC(x))(2)] (x = 1, 2, 3), the mother liquors afforded pyrazolonate complexes [ZnL(1)(2)(H(2)O)] (HL(1) = 2,5-dihydro-3-methyl-5-oxo-1H-pyrazole-1-carbothioamide) that had been formed by cyclization of the corresponding TSC(-). The reaction of HTSC(4) with zinc(II) acetate gave only the pyrazolonate complex [ZnL(2)(2)(H(2)O)] (HL(2) = 2,5-dihydro-3,4-dimethyl-5-oxo-1H-pyrazole-1-carbothioamide). All compounds were studied by IR and NMR spectroscopy, and HTSC(3), [Zn(TSC(3))(2)] x DMSO, [ZnL(1)(2)(H(2)O)] x 2DMSO, and [ZnL(2)(2)(H(2)O)] x 2DMSO were also studied by X-ray diffractometry, giving a thorough picture of the cyclization process. In preliminary tests of the effects of HL(1) and [ZnL(1)(2)(H(2)O)] on rat paw inflammatory edema induced by carrageenan, HL(1) showed antiinflammatory activity.     

Rhenium(I)-induced cyclization of thiosemicarbazones derived from beta-keto esters

The reactions of methylacetoacetate and ethyl 2-methylacetoacetate thiosemicarbazones (H(2)L(A) and H(2)L(B), respectively) with [ReX(CO)(5)] and [ReX(CO)(3)(CH(3)CN)(2)] (X = Cl, Br) were explored under various experimental conditions. Besides the adducts fac-[ReX(CO)(3)(H(2)L)], in which the rhenium is coordinated to three carbonyl groups, the X anion, and the N,S-bidentate thiosemicarbazone ligand, the following complexes were also isolated: fac-[ReBr(CO)(3)(Hpyz(B))], the tetrameric complexes fac-[Re(pyz(A))(CO)(3)](4) and fac-[Re(pyz(B))(CO)(3)](4), and fac-[Re(pyz(B))(CO)(3)(H(2)O)] (where Hpyz(A) and Hpyz(B) are pyrazolones derived by cyclization of H(2)L(A) and H(2)L(B), respectively). The cyclization reactions were monitored by (1)H NMR spectroscopy and the complexes isolated were identified by elemental analysis, mass spectrometry, IR and (1)H NMR spectroscopy, and in some cases by X-ray diffractometry. The isolation and the full structural identification of the rather unusual fac-[ReBr(CO)(3)(Hpyz(B))], which contains the enol form of the pyrazolone ligand, affords new insight into the cyclization of thiosemicarbazones derived from beta-keto esters.     

Manganese(III) acetate-mediated alkylation of beta-keto esters and beta-keto amides: an enantio- and diastereo-selective approach to substituted pyrrolidinones

beta-Keto esters and beta-keto amides can be efficiently alkylated on reaction with enol ethers and manganese(III) acetate in the presence of copper(II) acetate. These intermolecular radical addition reactions can be used to construct quaternary carbon centres in excellent yield and this method has been utilised in a diastereoselective approach to substituted pyrrolidinones.     

Reactions of thiosemicarbazones derived from beta-keto amides and beta-keto esters with Zn(II) and Cd(II) acetates: influence of metal, substitution, reagent ratio and temperature on metal-induced cyclization

Zinc(II) and cadmium(II) acetates were reacted in methanol under various experimental conditions with thiosemicarbazones derived from beta-keto amides or beta-keto esters (HTSC). Some of these reactions afforded thiosemicarbazonate complexes [M(TSC)2] with IR and NMR spectra compatible with N,S-coordination, but most gave complexes [ML2], where HL is a substituted 2,5-dihydro-5-oxo-1H-pyrazole-1-carbothioamide resulting from cyclization of the HTSC. Some of these pyrazolonates and two of the HL ligands were studied by X-ray diffractometry, and their structures are discussed. Surprisingly, the reactions of zinc(II) acetate with HTSC in 1:1 mol ratio usually gave a third, previously unreported type of complex with a dideprotonated ligand, [Zn(L-H)], which was also formed when [ZnL2] and Zn(OAc)2 interacted at room temperature in 1:1 mol ratio. These L-H complexes are highly insoluble in all common solvents, which hinders their characterization but suggests that they are polymeric in nature.     

Copper(I)-catalyzed chlorine atom transfer radical cyclization reactions of unsaturated alpha-chloro beta-keto esters

Copper(I) chloride catalyzed chlorine atom transfer radical cyclization reactions of a series of olefinic alpha-chloro beta-keto esters were investigated. It was found that alpha-dichlorinated beta-keto esters were suitable substrates; the chlorine transfer mono or tandem radical cyclization reactions catalyzed by CuCl complex with bis(oxazoline) or bipyridine proceeded smoothly in dichloroethane at room temperature or 80 degrees C, providing cyclic and bicyclic compounds in moderate to high yield. [reaction: see text]     

PdCl2(MeCN)2-catalyzed carbonylation of diethylamine with carbon dioxide: Selective synthesis of tetraethylurea and diethylformamide

The reaction of diethylamine with carbon dioxide (CO₂) with PdCl₂(MeCN)₂ as a catalyst gives tetraethylurea(1) or diethylformamide(2) selectively under mild reaction conditions by employing the PPh₃/CCl₄/MeCN and the HCOONa/methyl cellosolve systems, respectively.     

Synthesis of 2-oxazolines via boron esters of N-(2-hydroxyethyl) amides

A new, convenient, one-pot process is presented for the synthesis of 2-oxazolines in high yields (75-94%) via boron esters of N-(2-hydroxyethyl) amides. The procedure involves thermolysis of the boron esters at 240-260 °C, in the presence of solid CaO as an acid scavenger and allows the preparation of oxazolines from hydroxyethyl amides of aliphatic and aromatic monocarboxylic acids.     

PEG-400 promoted Pd(OAc)2/DABCO-catalyzed cross-coupling reactions in aqueous media

PEG-400 [poly(ethylene glycol-400)] was found to improve the Pd(OAc)₂/DABCO-catalyzed aqueous Suzuki-Miyaura and Stille cross-coupling reactions. In the presence of Pd(OAc)₂, DABCO, and PEG-400, a variety of aryl halides were coupled with arylboronic acids or organotin compounds efficiently to afford the corresponding cross-coupled products in moderate to excellent yields. The turnover numbers was up to 900,000 for the Suzuki-Miyaura reaction and up to 9800 for the Stille reaction. The catalyst system was also effective for Heck and Sonogashira cross-coupling reactions to some extent.     

Novel copper/PEG-400 catalyst systems for chemoselective S- and N-arylation of 2-mercaptobenzothiazole

A novel approach for chemoselective S- and N-arylation of 2-mercaptobenzothiazole was developed by copper/PEG-400 catalyst systems. Copper source and reaction temperature play an important role in this protocol, selective S-arylation of 2-mercaptobenzothiazole was achieved by using CuI/PEG-400/50 °C catalyst system, while selective N-arylation was achieved with CuO/PEG-400/140 °C catalyst system. Both are compatible with a variety of aryl halides and selectively give the desired S- and N-arylation products in good to excellent yields, respectively.     

Simple and efficient CuI/PEG-400 system for amination of aryl halides with aqueous ammonia

The cross-coupling reaction between aryl halides with aqueous ammonia was efficiently catalyzed in CuI/PEG-400 System with high yield. A range of electron-withdrawing or electron-donating aryl iodides and bromides were found to be applicable to the environmentally benign system. The process allows assembly of primary arylamines in great diversity which bear a wide range of functional groups including cyano, nitro, acetyl, ether, or amino moiety.     

Recyclable and reusable NiCl2(PPh3)2/CuI/PEG‐400/H2O system for the sonogashira coupling reaction of aryl iodides with alkynes

A stable and highly efficient NiCl2(PPh₃)₂/CuI/PEG‐400/H₂O catalytic system for the Sonogashira reaction has been developed. In the presence of NiCl₂(PPh₃)₂ and CuI, the coupling reaction of aryl iodides with terminal alkynes was carried out smoothly in a mixture of poly(ethylene glycol) (PEG‐400) and water at 100°C with K₂CO₃ as base to afford a variety of arylacetylenes in good to excellent yields. The isolation of the products was readily performed by extraction with petroleum ether, and the NiCl₂(PPh₃)₂/CuI/PEG‐400/H₂O system could be easily recycled and reused six times without significant loss of catalytic activity. Our system not only avoids the use of easily volatile organic solvents but also solves the basic problem of catalyst reuse. Copyright © 2015 John Wiley & Sons, Ltd.     

Efficient synthesis of di- and trisubstituted 2-aryloxazoles via ytterbium(III) triflate catalyzed cyclization of tertiary propargylic alcohols with aryl amides

An efficient synthetic method to prepare di- and trisubstituted 2-aryloxazoles based on Yb(OTf)₃ catalyzed cyclization of trisubstituted propargylic alcohols with aryl amides is described. The reaction was accomplished in moderate to excellent product yields and with complete regioselective control. The mechanism is suggested to involve activation of the starting alcohol by the metal catalyst that results in its ionization. Subsequent cyclization of this newly generated carbocationic species with the aryl amide then affords the oxazole. In view of the mild conditions along with the low cost, commercially availability of Yb(OTf)₃ and its high tolerance to air and moisture, the present synthetic approach offers an operationally simplistic and convenient route to this important aromatic heterocycle.     

Synthesis of 2-(N-formyl)-5-aryl/aryloxymethyl-1,3,4-thiadiazoles with potential bioactivity in PEG-400

<正>An environmental benign procedure for synthesis of 2-(N-formyl)-5-aryl/aryloxymethyl-1,3,4-thiadiazoles has been developed by reaction of 2-amino-5-aryl/aryloxymethyl-1,3,4-thiadiazoles with formic acid in PEG-400.The key advantages of this protocol are the shorter reaction time,higher yields,lower cost,simple workup,and environment-friendly compared to conventional organic solvent reaction.The present method does not involve any hazardous organic solvent or catalyst.     

Palladium-catalyzed tandem dimerization and cyclization of acetylenic ketones: a convenient method for 3,3'-bifurans using PdCl2(PPh3)2

Alkynones undergo tandem dimerization and cyclization in the presence of PdCl2(PPh3)2 and triethylamine in tetrahydrofuran at room temperature to give 3,3'-bifurans predominantly. Other palladium catalysts while under similar conditions, by rearrangement, lead to 2,5-disubstituted furans. This distinguished property of PdCl2(PPh3)2 has been attributed to the involvement of hydridopalladium halide. This method provides a simpler route to a variety of furans and a regioselective synthesis of polysubstituted 3,3'-bifurans using easily accessible acetylenic ketones.     

Stereocomplex Mediated Gelation of PEG-(PLA)2 and PEG-(PLA)8 Block Copolymers

Stereocomplex mediated hydrogels have been prepared by mixing solutions of polymers of opposite chirality of either PEG-(PLA)₂ triblock copolymers or PEG-(PLA)₈ star block copolymers. The critical gel concentrations of the mixed enantiomer solutions were considerably lower compared to polymer solutions containing only the single enantiomer. Moreover, gel-sol transition temperatures were increased and gel regions were expanded due to stereocomplexation. Rheology measurements showed that stereocomplexed hydrogels based on PEG-(PLA)₈ have higher storage moduli compared to those based on PEG-(PLA)₂. Stereocomplexed hydrogels prepared from 13 wt% PEG-(PLA)₂ solutions in PBS showed a storage modulus of 0.9 kPa at 37 °C, while at similar conditions stereocomplexed hydrogels of PEG-(PLA)₈ showed a storage modulus of 1.9 kPa at 10 wt%.     

Synthesis of some esters and amides of 2-substituted 4,6-bis(p-carboxyphenoxy)-sym-triazine

A number of corresponding esters and amides were obtained by the reaction of the chlorides of 2-substituted 4,6-bis(p-carboxyphenoxy)-sym-triazines (CPT) with ethanol and some primary amines in the presence of a hydrogen chloride acceptor. It was observed that hydrazine and hydrazine hydrate have a cleavage effect on the C-O bond of chloride of CPT in the 4 and 6 positions even at 0 °C. Dihydrazides of CPT were synthesized at –40 °C.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1406–1411, October, 1981.     

A highly efficient and recyclable NiCl2(dppp)/PEG-400 system for Suzuki-Miyaura reaction of aryl chlorides with arylboronic acids

Abstract

NiCl₂(dppp) in PEG-400 is shown to be a highly efficient catalyst for Suzuki-Miyaura coupling of aryl chlorides with arylboronic acids. The reaction could be conducted at 100?°C using K₃PO₄ as base, yielding a variety of biaryls in good to excellent yields. The isolation of the products was readily performed by extraction with petroleum ether and NiCl₂(dppp)/PEG-400 system could be easily recycled and reused up to five times without significant loss of activity. Our system not only avoids the use of easily volatile and toxic dioxane or toluene as a solvent but also solves the basic problem of nickel catalyst reuse.