Efficient Syntheses of New 2,2′-Disubstituted-2,3-dihydrofuran Derivatives and Natural Polyketide Analogues

Efficient syntheses of new 2,2′-disubstituted-2,3-dihydrofuran(5H)-4-one,spiro{benzofuran-2,2′-bicyclo[2.2.1]heptan}-4(5H)-one derivatives, and natural polyketide analogues have been achieved via the oxidative [3 + 2] cycloaddition of 1,3-dicarbonyl compounds with monoterpenes myrcene, camphene, and natural phenyl propenes, namely anethole and safrole respectively. Interestingly, the reaction of isoprene and myrcene with 1,3-dicarbonyl compounds yielded 2,2-disubstituted tetrahydrobenzofuran-4(5H)-one derivatives at room temperature. Thus, several substituted 2,3-dihydrofuran derivatives (3a–3h) with potential biological activity have been synthesized.     

PdI2-catalyzed coupling-cyclization reactions involving two different 2,3-allenols: an efficient synthesis of 4-(1',3'-dien-2'-yl)-2,5-dihydrofuran derivatives

Transition-metal-catalyzed dimeric coupling-cyclization reactions of two different 2,3-allenols afforded 4-(1',3'-dien-2'-yl)-2,5-dihydrofuran derivatives 3. 2-Substituted 2,3-allenols 1 cyclized to form the 2,5-dihydrofuran ring, whereas the 2-unsubstituted 2,3-allenols 2 provided the 1,3-diene unit at the 4-position. The reaction is proposed to proceed through an oxypalladation, insertion, and beta-hydroxide elimination process. The C=C double bond was formed with high E stereoselectivity by beta-hydroxide elimination.     

A cascade process for the synthesis of gem-difluoromethylene compounds

An efficient strategy for the synthesis of 2,2-difluoro-2,3-dihydrofuran derivatives from β-fluoroalkyl-β-enaminoketones is described. The reaction occurred via an intramolecular halophilic attack-initiated cascade process. A series of 2,3-dihydrofurans were prepared in high yields. And an intermolecular domino process achieved providing polysubstituted furans. The mechanism of the reaction is discussed.     

Kishner's reduction of 2-furylhydrazone gives 2-methylene-2,3-dihydrofuran, a highly reactive ene in the ene reaction

[reaction: see text] The Kishner reduction of 2-furylhydrazone gives 2-methylene-2,3-dihydrofuran as the major abnormal reduction product. 2-Methylene-2,3-dihydrofuran is an excellent ene in the carbonyl-ene reaction, reacting with a variety of aldehydes. Most notable was the asymmetric carbonyl-ene reaction of 2-methylene-2,3-dihydrofuran and decanal using Ti(OCH(CH3)2)4/(S)-BINOL to give the corresponding alcohol in 66% yield and 94% ee. The reaction of 2-methylene-2,3-dihydrofuran with 2 equiv of 1,4-benzoquinone unexpectedly gave a monoalkylated 1,4-hydroquinone/1,4-benzoquinone electron donor-acceptor complex.     

Synthesis of 2,3-trans disubstituted tetrahydrofurans through sequential xanthate radical addition-substitution reactions

A two-step preparation of 2,3-trans disubstituted tetrahydrofuran derivatives is reported from S-alkyl dithiocarbonates. The study of the group transfer reaction from xanthates and alkenes afforded intermediate S-alkyl dithiocarbonates. From 2,3-dihydrofuran derivatives, the displacement of the resulting anomeric xanthates with various nucleophiles in the presence of Lewis acid allowed the formation of new carbon-carbon and carbon-heteroatom bonds. This strategy was illustrated by a two-step synthesis of a precursor of modified 2'-beta-C-branched nucleoside analogues.     

Chemistry of sym-tetracyanoethane. 2. Condensation with carbonyl compounds

The reaction of tetracyanoethane with carbonyl compounds proceeds via the scheme of aldol addition with subsequent cyclization of the resulting adducts to give 5-amino-2,3-dihydrofuran derivatives, the structures of which were confirmed by the ¹³C NMR and mass spectra.See [1] for Communication 1.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1605–1610, December, 1982.     

The chemical behavior of 2-methylene-2,3-dihydro-3-furanones

Diphenylketene undergoes regioselective thermal [2+2]-cycloaddition to the heterocyclic C(3)=O carbonyl group of 5-aryl-2-methoxycarbonylmethylene-2,3-dihydrofuran-3-ones and 5-phenyl-2,3-dihydrofuran-2,3-dione to give the corresponding 3-diphenylmethylene derivatives of 2,3-dihydrofuran.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 331–334, February, 1995.     

Synthesis of Perfluoro- and 2-Trifluoromethylpentafluorodihydrofurans and Their Epoxy Derivatives

Perfluorotetrahydrofuran-2-carboxylic acid was converted through a series of transformations into perfluoro-2,3-dihydrofuran and perfluoro-2,5-dihydrofuran; likewise, from (2-perfluorotetrahydrofuryl)difluoroacetic acid 2-trifluoromethylpentafluoro-2,3-dihydrofuran was obtained. Perfluoro-2,3-dihydrofuran and 2-trifluoromethylpentafluoro-2,3-dihydrofuran underwent isomerization into perfluoro-2,5-dihydrofuran and 2-trifluoromethylpentafluoro-2,5-dihydrofuran by the action of cesium fluoride. Treatment of perfluoro-2,5-dihydrofuran with SbF₅ resulted in ring opening and formation of cis-perfluoro-2-butenoyl fluoride, while 2-trifluoromethylpentafluoro-2,3-dihydrofuran was converted into 2-trifluoromethylpentafluoro-2,5-dihydrofuran under the same conditions. Perfluoro-3,4-epoxytetrahydrofuran and 2-trifluoromethyl-3,4-epoxypentafluorotetrahydrofuran containing fused oxirane and tetrahydrofuran rings were synthesized by reactions of perfluoro-2,5-dihydrofuran and 2-trifluoromethylpentafluoro-2,5-dihydrofuran, respectively, with sodium hypochlorite.     

An efficient double 1,2-addition reaction of 2,3-allenoates with allyl magnesium chloride

In this paper, it was reported that double 1,2-addition reaction of 2,3-allenoates with allyl magnesium chloride at room temperature in the absence of any transition metal catalyst provides an efficient method for the synthesis of tertiary alpha-allenols. The optically active allenol could be prepared from the reaction of the optically active 2,3-allenoate without obvious racemization of the axial chirality. Under different reaction conditions, cyclization reactions of alpha-allenol 2i prepared have been studied for the synthesis of different 2,5-dihydrofuran derivatives.     

Catalytic synthesis of dihydrofurans (review)

Various methods for the preparation of 2,3-dihydrofuran, 2,5-dihydrofuran, 2-methylenetetrahydrofuran, and their alkyl and aryl derivatives are examined. The most promising method for the preparation of 2,3-dihydrofuran is the conversion of 1,4-butanediol on cobalt catalysts. 2,5-Dihydrofuran is obtained by dehydration of 2-butene-1,4-diol on Al₂O₃, cobalt-containing and other catalysts, while 2-methylenetetrahydrofuran is obtained by dehydrohalogenation of tetrahydrofurfuryl halides. The various methods for the isomerization of 2,5-dihydrofuran to 2,3-dihydrofuran are discussed. Examples of the application of dihydrofurans in organic synthesis are presented.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1299–1311, October, 1982.     

A highly efficient synthesis of 1,2,3,4-tetrahydroquinolines by molecular iodine-catalyzed domino reaction of anilines with cyclic enol ethers

A highly efficient method for the synthesis of 1,2,3,4-tetrahydroquinoline derivatives via a molecular iodine catalyzed domino reaction of anilines with cyclic enol ethers, such as 2,3-dihydrofuran and 3,4-dihydro-2H-pyran, is described. The reaction may proceed through an aza-Diels-Alder process between an in situ generated 2-azadiene and another equivalent of cyclic enol.     

1,3-Dipolar cycloaddition of β-alkoxyvinyl trifluoromethylketones with aryl (or benzyl) azides: Synthesis of 4-trifluoroacetylated 1H-1,2,3-triazoles

The 1,3-dipolar cycloaddition of aryl (or benzyl) azides with 1,1,1-trifluoro-4-ethoxy-3-butene-2-one proceeded smoothly by heating without solvent. 1-Aryl (or benzyl)-4-trifluoroacetyl-1H-1,2,3-triazoles were formed regiospecifically in good yield. These compounds were readily hydrated when exposed to air. In contrast, the reaction of benzyl azide with 4-trifluoroacetyl-2,3-dihydrofuran only gave minor amounts of 4-trifluoroacetyl-5-benzylamino-2,3-dihydrofuran in addition to an inseparable mixture of other products. 5-Trifluoroacetyl-3,4-dihydro-2H-pyran was inert towards benzyl azide under the same conditions.     

CAN-promoted, diastereoselective synthesis of fused 2,3-dihydrofurans and their transformation into tetrahydroindoles

The reaction between 1,3-cyclohexanediones and chalcones (or their vinilogs) in the presence of 2.5 equiv of cerium(IV) ammonium nitrate afforded trans-2-arylcarbonyl-3-aryl (or styryl)-2,3,6,7-tetrahydrobenzofuran-4(5H)-ones in good to excellent yields and in high diastereoselectivities. The method was also extended to the preparation of derivatives of the 5,6-dihydro-2H-cyclopenta[b]furan-4(3H)-one system. The fused 2,3-dihydrofuran derivatives were transformed into 1-alkyl-2-acyl-3-aryl-6,7-dihydroindole-4(5H)-ones by 2,3-dehydrogenation followed by reaction with primary amines. The direct reaction of the tetrahydrobenzofuran-4(5H)-one compounds derived from dimedone with amines gave 1-alkyl-2-alkylimino-3-aryl-6,7-dihydroindole-4(5H)-ones, while starting materials derived from 1,3-cyclohexanedione underwent an unprecedented 2-deacylation reaction and gave 1-alkyl-3-aryl-6,7-dihydroindole-4(5H)-ones.     

Preparation and reaction of 2-aryl-3-silyl-1,3-butadiene

[reaction: see text] A conjugated pi-electron compound, 2-aryl-3-silyl-1,3-butadiene, was easily prepared from 1-benzyloxy-3-silyl-2-propyne, bis(iodozincio)methane, and an aryl halide in the presence of nickel catalyst. A subsequent cross-coupling reaction of the product with another aryl halide gave an unsymmetrical 2,3-diaryl-1,3-butadiene efficiently.     

胂叶立德与具有对三氟甲基苯基及双吸电子基团烯烃的反应研究

鉮盐1以碳酸钾为碱分别与含对三氟甲基苯基及双吸电子基团的烯烃2或3反应, 高产率、高立体选择性地合成了含对三氟甲基苯基的顺-1,2-环丙烷衍生物4或顺-2,3-二氢呋喃衍生物5, 并对其产物结构进行了确证.     

Iridium complex-catalyzed [2+2+2] cycloaddition of alpha,omega-diynes with monoynes and monoenes

[reaction: see text] [Ir(cod)Cl]2/DPPE was found to be a new catalyst for the cycloaddition of alpha,omega-diynes with monoynes to give polysubstituted benzene derivatives in high yields. Internal monoynes as well as terminal monoynes could be used. The reaction tolerates a broad range of functional groups such as alcohol, amine, alkene, ether, halogen, and nitrile. The reaction of 1,6-octadiyne derivatives with 1-alkynes gives ortho products and meta products. The regioselectivity could be controlled by the choice of ligand. The reaction with DPPE was meta selective, with meta selectivity of up to 82%. The reaction with DPPF was ortho selective, with ortho selectivity of up to 88%. We propose a mechanism to account for this regioselective cycloaddition. [Ir(cod)Cl](2)/DPPE also catalyzed the cycloaddition of alpha,omega-diynes with 2,5-dihydrofuran to give bicyclic cyclohexadiene derivatives. The reaction with 2,3-dihydrofuran and n-butyl vinyl ether gave benzene derivatives instead of cyclohexadiene derivatives. We also propose a mechanism to account for this novel aromatization that includes cleavage of the C-O bond.     

Zirconium-mediated coupling reactions of amines and enol or allyl ethers: synthesis of allyl- and homoallylamines

An easy and efficient zirconium-mediated synthesis of allylamines from simple amines and enol ethers is described. This strategy also allows the synthesis of amino alcohol derivatives containing a Z double bond in their structure when 2,3-dihydrofuran is used. Simple conventional modification of these amino alcohols leads to 2-substituted piperidine derivatives. By applying this approach, a formal total synthesis of the alkaloid coniine is easily achieved from a protected butylamine. Finally, the zirconium-mediated reaction of amines and allyl phenyl ether furnishes homoallylamines or amino ethers depending on the structure of the starting amine.     

PdCl2/NaI-catalyzed homodimeric coupling-cyclization reaction of 2,3-allenols: an efficient synthesis of 4-(1',3'-dien-2'-yl)-2,5-dihydrofuran derivatives

A PdCl2/NaI-catalyzed homodimeric coupling-cyclization reaction of 2,3-allenols was observed to provide an efficient route to 4-(1',3'-dien-2'-yl)-2,5-dihydrofuran derivatives. By using the easily available optically active starting materials, 2,5-dihydrofurans with high enantiopurity may be prepared. A Pd(II)-catalyzed mechanism was also discussed.     

Efficient and mild synthesis of highly substituted 2,5-dihydrofuran and furan derivatives via stepwise reaction

An efficient and mild synthesis of highly substituted 2,5-dihydrofuran and furan derivatives from a variety of alkylidene malonates and 1,4-butyne-diol via one-pot reaction was applied. With various conditions of base amount, temperature and time applied to the reaction, the 2,5-dihydrofuran and the furan derivatives could be selectively obtained. Moreover, the formation of furan derivatives with 2,5-dihydrofuran derivatives as intermediates was also investigated. Some of these 2,5-dihydrofuran derivatives showed potent in vitro anti-tumor activities against HeLa cells.     

Synthesis of optically active 2,3-dihydrobenzofuran derivatives through a combination strategy of iron(III)-catalyzed reaction and enzymatic reaction

Synthesis of optically active 2,3-dihydrofuran derivatives has been accomplished through a combination strategy of ferric ion-catalyzed cycloaddition of styrene derivatives with quinones and following lipase-catalyzed enantioselective acylation.