Synthesis of 2,3-di- and 2,3,4-trisubstituted furans from 1,2-dioxines generated by an enyne-RCM/Diels-Alder reaction sequence

An efficient method for the synthesis of 2,3- and 2,3,4-substituted furans starting from acyclic enynes was developed using an enyne-RCM/Diels-Alder reaction sequence. The reaction conditions for the transformation of 1,2-dioxines having an adjacent 1,2-oxazine ring into furans and the cleavage of N-O bonds are discussed.     

A versatile synthesis of meyers' bicyclic lactams from furans: singlet-oxygen-initiated reaction cascade

All in one: Meyers' bicyclic lactams were synthesized in high yield from furans using a new and powerful method that involves a one-pot singlet-oxygen-initiated reaction cascade (see scheme; TFA=trifluoroacetic acid). This method has broad synthetic potential because of the ease of access to a wide range of furans with a variety of substituents.     

2,3,4- or 2,3,5-trisubstituted furans: catalyst-controlled highly regioselective ring-opening cycloisomerization reaction of cyclopropenyl ketones

2,3,4- or 2,3,5-trisubstituted furans were highly regioselectively formed from the cycloisomerization reaction of the same starting cyclopropenes 1 via the subtle choice of the transition metal halides. Under the catalysis of 5 mol % PdCl2(CH3CN)2, 2,3,5-trisubstituted furans 2 were given in 50-88% yields with 95-99% regioselectivities, while 2,3,4-trisubstituted furans 3 were formed in 78-96% yields with 99% regioselectivities under the catalysis of 5 mol % CuI.     

Ruthenium-catalyzed coupling reaction of 2,3,5-trisubstituted furans with aryl halides through C-H bond cleavages

A variety of functionalized furans were synthesized by way of a ruthenium-catalyzed coupling reaction of 2,3,5-trisubstituted furans with aryl halides through C-H bond cleavages. The feature of the reaction was facilitative preparation of furan derivatives good functional group tolerance. All reactions gave the desired products in moderate to good yields (56-89%) in the presences of [RuCl₂(p-cymene)] and K₂CO₃ in NMP at 120 °C.     

Palladium-catalyzed one-pot synthesis of highly substituted furans by a three-component annulation reaction

A new three-component cyclization-coupling reaction catalyzed by palladium was developed, producing polysubstituted furans in good yields from readily available substrates. The reaction conditions and the scope of the process were examined, and a possible mechanism is proposed.     

Microwave promoted diastereoselective synthesis of dihydroindeno[1,2-b]furans via one-pot three-component reaction in solvent-free conditions

An efficient method was developed for the synthesis of fused dihydroindeno[1,2-b]furans. One-pot three-component reaction of 1,3-indanedione, aromatic aldehyde and pyridinium ylide in the presence of triethylamine under microwave-irradiation in solvent-free conditions afforded dihydroindeno[1,2-b]furans in a diastereoselective manner in excellent yields.     

Studies on the Diels-Alder reaction of annulated furans: application to the synthesis of substituted phenanthrenes

In an attempt to utilize the synthetic power of the furan nucleus in the synthesis of complex natural products, we have developed an entry into annulated furan intermediates that involves an electrochemical annulation protocol. An approach to the eunicellin diterpenes based on this methodology required the use of an intermolecular Diels-Alder reaction on an annulated furan. Although well known for simple furans, there is a paucity of related examples on annulated furans. To examine the feasibility of such an approach to these diterpenes, we have studied this key cycloaddition reaction. Our studies indicate that the process can be hampered by a facile retro-Diels-Alder that is highly dependent on the dienophile employed.     

Palladium-catalyzed cyclization reaction of allylic bromides with 1,2-dienyl ketones. An efficient synthesis of 3-allylic polysubstituted furans

3-Allylic polysubstituted furans were synthesized via a palladium-catalyzed cyclization reaction of allylic bromides with differently substituted 1,2-allenyl ketones. This process may occur via the reaction of a furanyl palladium intermediate with allylic bromide.     

Reactions of electron-withdrawing thiophene 1,1-dioxides with furans. A novel reaction pathway

Reactions of thiophene dioxides containing electron-withdrawing substituents with furans were studied. The reactions with unsubstituted furan followed the inverse-electron-demand Diels-Alder mechanism. Subsequent elimination of sulfur dioxide from the adduct afforded products of the tetrahydrobenzofuran series. The reactions with substituted furans gave benzylcarbonyl compounds in high yields. The observed regiochemistry of the reaction was explained in terms of the frontier orbital theory using the calculated orbital coefficients. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 687–692, April, 2006.     

Highly diastereoselective Friedel-Crafts reaction of furans with 8-phenylmenthyl glyoxylate

The Friedel-Crafts reaction of (1R)-8-phenylmenthyl glyoxylate with variously substituted furans was found to be efficiently promoted by SnCl(4) or magnesium salts with high diastereoselectivities. MgBr(2) performs especially well under simple, undemanding conditions, giving both high yields and high diastereoselectivities (>90%). The reaction afforded chiral substituted furan-2-yl-hydroxyacetic acid esters, compounds of potentially high synthetic interest. [reaction: see text]     

A surprising steric effect on a tandem cycloaddition/ring-opening reaction: rapid syntheses of difluorinated analogues of (hydroxymethyl)conduritols

Difluorinated analogues of (hydroxymethyl)conduritols can be synthesised from selected furans and a difluorinated dienophile in two reaction steps.     

Highly enantioselective synthesis of 2-furanyl-hydroxyacetates from furans via the Friedel-Crafts reaction

The Friedel-Crafts reaction of alkyl glyoxylates with variously substituted furans was found to be efficiently catalyzed under simple, undemanding conditions by a 6,6'-dibromo-BINOL/Ti(IV) complex with high enantioselectivity. The reaction afforded chiral substituted 2-furanyl-hydroxyacetic acid esters, compounds of high synthetic interest, in good yield and enantiomeric excess, in most examples in the range of 90-97%.     

Cu(I)-catalyzed reaction of diazo compounds with terminal alkynes: a direct synthesis of trisubstituted furans

A method for the synthesis of tri-substituted furans has been developed based on Cu(I)-catalyzed reaction of terminal alkynes with β-keto α-diazoesters. This method for the synthesis of 2,3,5-trisubstituted furans is operationally simple and applicable to wide substrate scope. Moreover, this synthesis employs cheap Cu(MeCN)₄PF₆ as the catalyst and no additional ligand is needed. Similar reaction has also been applied to ethyl (E)-2-diazo-3-(methoxyimino)butanoate for the synthesis of 2,3,5-trisubstituted N-methoxypyrroles with limited success.     

Highly substituted furans from 2-propynyl-1,3-dicarbonyls and organic halides or triflates via the oxypalladation-reductive elimination domino reaction

The palladium-catalysed reaction of 2-propynyl-1,3-dicarbonyls with organic halides or triflates provides an efficient straightforward entry into highly substituted furans. The best results have been obtained by using an excess of the alkyne. The process can tolerate a wide variety of important functional groups both on the alkyne and the organic halide or triflate. Under an atmosphere of carbon monoxide, the reaction affords furan derivatives incorporating carbon monoxide. Depending on the alkyne to organic halide or triflate ratio, acyl furans (incorporating one molecule of carbon monoxide) or enol esters (incorporating two molecules of carbon monoxide) can be isolated as the main products.     

The reaction of cyclic carbinol amides with triflic anhydride as a method to prepare alpha-trifluoromethyl-sulfonamido furans

[reaction: see text] A novel synthesis of alpha-trifluoromethyl-sulfonamido furans via the reaction of cyclic carbinol amides with triflic anhydride has been developed. The reaction proceeds under very mild conditions with a wide set of representative lactams to provide the alpha-trifluoromethyl-sulfonamido-substituted furan in high yield. Rapid access to a 5-substituted indoline can be achieved by thermolysis of the N-but-3-enyl-substituted sulfonamido furan.     

Bis-furyl alditols via SnCl4- or ZnCl2-catalysed reaction of furans with sugars

Alditols have been obtained in very high yield using an excess of electron-rich furans with respect to the protected sugars. The scope and limitation of the reaction have been explored.     

Highly regioselective nucleophilic carbon-carbon bond formation on furans and thiophenes initiated by pummerer-type reaction

[reaction: see text] The reactions of (phenylsulfinyl)furans or -thiophenes with carbon nucleophiles in the presence of trifluoroacetic anhydride allowed the nucleophilic installation of carbon functional groups on the furan and thiophene nuclei with complete regioselectivity.     

Solvent controlled mechanistic dichotomy in a Au(III)-catalyzed, heterocyclization triggered, Nazarov reaction

Tandem Au(III)-catalyzed heterocyclization/Nazarov cyclizations leading to substituted carbocycle fused furans are described. An interesting dichotomy of reaction pathways as a function of solvent, confirmed by the isolation and trapping of reaction intermediates, provided a basis for computational studies that supported the experimental findings.     

A novel cyclization reaction between 2,3-bis(trimethylsilyl)buta-1,3-diene and acyl chlorides with straightforward formation of polysubstituted furans

A novel cyclization process of 2,3-bis(trimethylsilyl)buta-1,3-diene with various acyl chlorides in the presence of aluminium trichloride affords 2,5-disubstituted or 2,3,5-trisubstituted furans in short reaction time; a subsequent acylation process of the furan ring occurs if the reaction time is prolonged.     

3-Chloroalkylfurans in the reaction with sodium diethyl phosphite

Reduction of 3-acylfurans with lithium alumohydride in ether yields stable secondary alcohols. By treatment with thionyl chloride in the presence of pyridine, they are converted to the corresponding chlorides. 3-(1-Chloroethyl)furan and 5-methyl-3-(1-chloroethyl)furan react with sodium diethyl phosphite to give two products: 3-(1-diethoxyphosphorylethyl)furans and 3-ethyl-2-(diethoxyphosphoryloxy)furans. The methyl group in position 5 of the furan ring increases the relative phosphate content of the mixture by a factor of approximately 2.5. Blocking of position 2 or both positions 2 and 5 of the ring with methyl groups leads to phosphoate formation only. The reaction of 2,5-dimethyl-3-(1-chloro-2-methylpropyl)furan also occurs according to the Michaelis-Becker scheme. The products of the side chain dehydrohalogenation with sodium diethyl phosphite were not found.