Diastereoselective synthesis of strained spiro-cyclopropanooxindoles from cyclic diazoamides

Reaction of cyclic diazoamides and cyclic olefins or heteroaromatic systems using copper(I) triflate as a catalyst furnished a variety of strained spiro-cyclopropanooxindoles in a diastereoselective manner under mild reaction conditions. The effect of copper(I) triflate and rhodium(II) acetate catalysts on the cyclopropanation was also studied.     

Highly stereoselective cyclopropanation of glycals with cyclic diazoamides: a facile synthesis of spirooxindolyl sugar derivatives

Rhodium(II) acetate catalyzed intermolecular cyclopropanation of glycals with cyclic carbenoids generated from 3-diazo-2-oxindole has been achieved to produce a novel series of spirooxindolyl sugar derivatives in good yields under mild experimental conditions.     

非金属催化剂在催化环氧化物和CO2合成环状碳酸酯中的研究进展

随着科学技术的进步和工业化的发展,大量化石燃料被消耗,大气中二氧化碳浓度急剧增加,导致温室效应加剧,严重威胁到人类的生存和发展。基于可持续发展的思想,利用储量丰富且廉价的二氧化碳作为 C1资源替代有毒的气体(如一氧化碳和光气等)制备具有广泛应用的环状碳酸酯,不仅满足“绿色化学”的要求,而且符合“原子经济性”的原则。迄今为止,大量用于催化二氧化碳和环氧化物环加成反应合成环状碳酸酯的催化剂,包括均相催化剂(如金属卤化物、有机碱、离子液体和金属配合物),多相催化剂(如金属氧化物、负载型催化剂、有机聚合物、金属有机框架材料和碳材料等)被报道。其中金属催化剂占主导地位,大多表现出优异的催化活性。然而,目前可供开采的金属矿越来越少,大多数金属的回收再利用率较低,重金属污染日趋严重。因此,开发新型、廉价、绿色、高效、循环性和稳定性好的非金属催化剂具有重要意义。
　　本文主要介绍了近3年以来用于催化二氧化碳和环氧化物环加成反应合成环状碳酸酯的非金属催化剂,主要包括有机碱、离子液体、固载型催化剂、有机聚合物和碳材料等。概括了不同种类催化剂的设计思想及其催化反应机理,重点阐述了分子内以及分子间各种功能基团的协同作用对环加成反应的影响。通过比较发现,具有“C–N=C”结构的有机碱活性相对较高,氢键给体和亲核物质都能与有机碱协同作用提高其催化活性;传统离子液体的活性一般不理想,氢键给体如羟基和羧基的引入有利于促进环加成反应,且多阳离子和多氢键给体功能化的离子液体表现出更高的催化活性;负载型催化剂中,载体和活性组分之间的协同作用有利于加速环加成反应的进行,多种功能基团负载和以共价键方式多层固载能更好地提高催化剂稳定性和催化活性;利用非烯烃化合物制得的活性组分位于主链的多孔有机聚合物,催化活性和稳定性大多高于活性组分位于侧链的烯烃聚合物;碳材料催化剂中,引入不饱和的 N物种(如伯胺和吡啶氮),有利于 CO2的吸附和活化,能促进环加成反应。此外,利用密度泛函的方法,计算模拟催化反应过程,能更好地揭示反应机理,并为设计和制备高效的催化剂提供理论指导。
　　该领域目前面临的重要挑战是研发可以同时实现二氧化碳捕获和转化的新型、环保和高效非金属催化剂,终极目标是利用多孔催化材料在常温和常压下直接捕获工业废气中的二氧化碳,并利用捕获的二氧化碳实现环状碳酸酯的连续生产。基于协同催化的设计思想,利用多种基团功能化的策略合成高效吸附和活化二氧化碳以及开环活化环氧化物的非金属催化剂,有望实现上述目标。     

Solvent- and metal-free selective oxidation of thiols to disulfides using I2/DMSO catalytic system

We describe herein a simple, fast and inexpensive protocol for the oxidative coupling of thiols employing a stoichiometric amount of DMSO and iodine as the catalyst. Various aromatic disulfides were obtained in good to excellent yields in short reaction times at room temperature, while aliphatic disulfides were achieved in good yields when the reactions were conducted under microwave irradiation.     

Highly diastereoselective synthesis of spiro[cyclopropane-1,3′-indolin]-2′-ones via catalyst-free cyclopropanation using ethyl diazoacetate

Substituted 3-methyleneindolin-2-ones were efficiently cyclopropanated with ethyl diazoacetate to yield spiro[cyclopropane-1,3′-indolin]-2′-ones in a catalyst-free and highly diastereoselective reaction in a mixture of ethanol–acetonitrile (1:1 v/v) as solvent.     

Chemo- and diastereoselective synthesis of spiro-dioxolanes from intermolecular carbonyl ylide cycloaddition with aryl aldehyde

Reaction of cyclic diazoamides and aromatic aldehydes having electron-donating or -withdrawing groups in the presence of rhodium(II) acetate catalyst at room temperature afforded the spiro-indolodioxolanes. A novel three-component reaction involving intermolecular carbonyl ylides has been demonstrated in a chemo- and diastereoselective manner.     

Reduction of substituted spiro[cyclopropane-3-(1-pyrazolines)] to spiro[cyclopropane-3-pyrazolidines] and 1-(2-aminoethyl)cyclopropylamine derivatives

Raney nickel-catalyzed hydrogenation of 5-substituted spiro[cyclopropane-3-(1-pyrazoline)]-5-carboxylates occurs with N—N bond cleavage with simultaneous cyclocondensation to give 3-aminopyrrolidin-2-ones containing a spirocyclopropane fragment. The presence of the second ester group in the pyrazoline side chain, in the position ensuring the formation of a five-membered ring results in 6,11-diazadispiro[2.1.4.2]undecane-7,10-dione, the product of double cyclocondensation of the intermediate diamine. Hydrogenation of the aryl-substituted spiro[cyclopropane-3-(1-pyrazolines)] in the presence of acetone affords hexahydrospiro[cyclopropane-4-pyrimidines], which can be converted into the cyclopropane-containing 1,3-diamines in the individual state or as salts. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2482–2490, November, 2005.     

Acylation of fluorine-containing spiro[cyclopropane-1-pyrazolines] and dehydrohalogenation of the resulting adducts

Acylation of 6-(1-fluorovinyl)-6-methyl- and 6-(2,2,3,3-tetrafluorocyclobutyl)-4,5-diazaspiro[2.4]hept-4-enes with acetyl chloride proceeds as electrophilic addition to the N(5) atom and is accompanied by opening of the cyclopropane ring to give 1-acetyl-3-(2-chloroethyl)-5-(1-fluorovinyl)-5-methyl- and 1-acetyl-3-(2-chloroethyl)-5-(2,2,3,3-tetrafluorocyclobutyl)-4,5-dihydropyrazoles, respectively. Under the same conditions, acylation of 6-(2,3,3-trifluorocyclobut-1-enyl)-4,5-diazaspiro[2.4]hept-4-ene is not regioselective. The (2-chloroethyl) pyrazolines obtained undergo dehydrochlorination into vinylpyrazolines in the presence of an excess of MeONa in MeOH. The reaction of 4-acetyl-6-(2,3,3-trifluorocyclobut-1-enyl)-4,5-diazaspiro[2.4]hept-5-ene with MeONa results in selective replacement of the F atom at the double bond by a methoxy group.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 419–422, February, 2005.     

Syntheses of spiro[cyclopropane-1,3′-oxindole]-2-carboxylic acid and cyclopropa[c]quinoline-7b-carboxylic acid and their derivatives

The synthesis of spiro[cyclopropane-1,3′-oxindole]-2-carboxylic acid, including novel 3-(2- and 3-pyridyl)-substituted analogues and the novel cyclopropa[c]quinoline-7b-carboxylic acid and their ester and amide derivatives is described. These syntheses involve diastereoselective cyclopropanation reactions of methyl 2-(2-nitrophenyl)acrylate and (3E)-(pyridin-2-ylmethylene)- and (3E)-(pyridin-3-ylmethylene)-1,3-dihydro-2H-indol-2-one with ethyl (dimethyl sulfuranylidene) acetate (EDSA). The synthesis of methyl cyclopropa[c]quinoline-7b-carboxylate involves a regioselective reductive cyclization of a nitro-diester precursor. The relative stereochemistry of key compounds has been determined by single-crystal X-ray structural analysis.     

1,3-Dipolar cycloaddition for selective synthesis of functionalized spiro[indoline-3,3'-pyrrolizines]

The 1,3-dipolar cycloaddition reaction of dimethyl hex-2-en-4-ynedioate with azomethine ylides derived from reaction of L-proline with various isatins in methanol selectively resulted in the formation of functionalized spiro[indoline-3,3'-pyrrolizine]acrylates as main products and spiro[indoline-3,3'-pyrrolizine]propiolates as minor products.This result indicated that the electron-deficient alkyne has higher reactivity than that of electron-deficient alkene in 1,3-dipolar cycloaddition reaction.     

Dzhemilev reaction for the synthesis of spiro[3.3]heptane and spiro[3.4]octanes

For the first time cycloalumination of methylenecyclobutane with the aid of Et₃Al in the presence of Cp₂ZrCl₂ leading to 6-ethyl-6-aluminaspiro[3.4]octane has been realized. The latter, without isolation, was converted into spiro[3.3]heptane, 6-thiaspiro[3.4]octane and also spiro[3.4]octan-6-ol and 6-spiro[3.4]octyl formate with high yields and selectivity.     

Grindstone chemistry: one-pot synthesis of spiro[diindenopyridine-indoline]triones and spiro[acenaphthylene-diindenopyridine]triones

A one-pot, pseudo four-component, and simple synthesis of spiro[diindenopyridine-indoline]triones and spiro[acenaphthylene-diindenopyridine]triones via the reaction of 1,3-indandione, aromatic amines and isatins or acenaphthylene-1,2-dione using a ‘Grindstone Chemistry’ method is reported.     

Synthesis of [1,3]dithiole and spiro[1,3]dithiole thiopyran derivatives of the [1,2]dithiolo[1,4]thiazine ring system

We report the synthesis of some new polysulfur-nitrogen heterocycles by cycloaddition reactions to readily available tricyclic condensed 1,2-dithiole-3-thiones. Thus, treatment of bis[1,2]dithiolopyrrole ketothione 1 with diacyl acetylenes gave the bis-aducts 2a-d. On the other hand, cycloaddition of bis[1,2]dithiolo[1,4]thiazine ketothione 3 with 1 equiv of acyl or diacyl acetylenes gave [1,3]dithiolylidenyl[1,2]dithiolo[1,4]thiazines 4a-f in fair to high yields. Catalysis by scandium triflate was used in the reactions that implied the less reactive dipolarophiles. Treatment of 3 with 2 equiv of DBA gave the bis-aduct 5a, and reaction of 4c with DMAD gave the mixed bis-adduct 5b. Cyclic voltammetry of selected examples showed irreversible processes that were influenced by the electrochemical activity of peripheral groups bonded to the heterocyclic system.     

Phosphoryl chloride-mediated solvent-free synthesis of N-aryl-substituted azacycles from arylamines and cyclic ethers

A solvent- and metal-free protocol for preparation of N-aryl substituted azacycles from arylamines and cyclic ethers is described. In this method, the combination of POCl₃ and DBU is crucial for conversion of arylamines and cyclic ethers to five- and six-membered azacycles. Without solvent, a variety of N-aryl-substituted, five-membered azacycles (pyrrolidines, 2-methylpyrrolidines, and piperidine) and six-membered azacycles (isoindolines and tetrahydroisoquinolines) are synthesized in high yields. This green method provides a sustainable and efficient approach for the preparation of azacycles from various cyclic ethers.     

TFA-catalysed tandem double cyclisation: A one-pot,metal-free routes for novel indolo-imidazo[1,2-a]pyridine derivatives

A transition-metal free, one-pot tandem synthetic routes for novel indole and imidazo[1,2-a]pyridine derivative hybrids have been established. An efficient three-component reaction was designed with incorporation of two sequential Groebke–Blackburn–Bienayme (GBB) and cyclization reaction in one-pot under mild acidic condition. The salient feature of this protocol is atom economy, good yield and operational simplicity. A molecular prospective library of 32 compounds was synthesized by utilizing the various substituted aryl aldehydes and 2-aminopyridine.     

Palladium-catalyzed allylation and deacylative allylation of 3-acetyl-2-oxindoles with allylic alcohols

The Pd-catalyzed allylation of 3-acetyl-2-oxindoles with allyl alcohol is performed using 3 mol% of Pd(dba)₂, rac-BINAP and BINOL phosphoric acid as catalytic mixture. This procedure allows the in situ synthesis of 3-allyl-2-oxindole by adding Triton B to the reaction mixture. The deacylative allylation of 3-acetyl-3-methyl-2-oxindoles with allylic alcohols is carried out with 3 mol% of Pd(OAc)₂, dppp and 1.5 equiv. of LiOtBu as base affording the corresponding 3,3-disubstituted 2-oxindoles in good yields. Both methodologies can be combined for the preparation of unsymmetrical 3,3-diallylated 2-oxindoles such as compound 7. The DaA must be carried out in the absence of oxygen in order to avoid the competitive formation of 3-alkyl-3-hydroxy-2-indoles. The later compounds can be easily obtained by deacylative oxidation of 3-alkylated 3-acetyl-2-oxindoles with LiOEt at rt under air.     

Oxidative dual C–H sulfenylation: A strategy for the synthesis of bis(imidazo[1,2-a]pyridin-3-yl)sulfanes under metal-free conditions using sulfur powder

An efficient approach to sulfur-bridged imidazopyridines has been developed under metal-free conditions using inexpensive sulfur powder as the sulfur source. Most appealingly, the reaction can proceed smoothly without addition of any additives, ultimately decreasing the production of chemical waste. The inexpensive and green method should provide a useful strategy for constructing a library of novel and biological interesting heteroaromatic sulfides.     

Convenient synthesis of spiro[indoline-3,4'-pyrano[2,3-c]pyrazole] and spiro[acenaphthyl-3,4'-pyrano[2,3-c]pyrazoles] via fourcomponent reaction

The base promoted four-component reaction of hydrated hydrazine, dimethyl acetylenedicarboxylate, isatines and malononitrile (ethyl cycanoacetate) in ethanol afforded polysubstituted spiro[indoline-3,4‘-pyrano[2,3-c]pyrazoles] and spiro[acenaphthyl-3,4-pyrano[2,3-c]pyrazoles]