Tetrahydrofuran Products Research Articles

Rapid assembly of stereochemically rich polycyclic tetrahydrofurans by a conjugate addition-Rh(II) catalysis sequence

An efficient reaction sequence that gives stereochemically rich, polycyclic tetrahydrofurans is described. A highly diastereoselective conjugate addition of enoxy silanes to vinyl diazonium salts gives 2-diazo-1,5‑dicarbonyl compounds in yields up to 99%. The diazo functional group can then be taken advantage of in subsequent Rh catalyzed carbonyl ylide 1,3-dipolar cycloaddition or OH insertion reactions to give tetrahydrofuran products that contain up to 6 contiguous stereocenters in yields up to 89%.

Ring Opening of Epoxides by Pendant Silanols.

We present a new ring-opening reaction of epoxides by pendant silanols, catalyzed by either Ph3C+BF4- or BINOL-phosphoric acid. Silanol epoxides derived from trans-allylic alcohols, cis-allylic alcohols, trans-homoallylic alcohols, and cis-homoallylic alcohols were all compatible and gave products from either endo- or exo-ring opening. With silanol epoxides derived from 4-alkenyl silanols, an unusual rearrangement to tetrahydrofuran products was observed. The utility of this methodology was demonstrated in a short preparation of protected d-arabitol.

Influence of metal ratio on alumina-supported CuPd catalysts for the production of tetrahydrofuran from succinic acid

The present research studies the influence of metal ratio on the construction of γ-Al2O3 supported CuxPdy (x + y = 10 wt%) bimetallic catalysts for the hydrogenation of succinic acid (SA) to tetrahydrofuran (THF). Synergistic effects between Cu and Pd due to alloying formation are responsible for the enhanced activity of the bimetallic catalysts compared to the monometallic ones. The Cu-rich CuPd catalysts, particularly Cu8Pd2/γ-Al2O3 and Cu6Pd4/γ-Al2O3, have emerged as the best catalysts for the production of THF with yields of 85–90%. The key factor that distinguishes them from the rest is the presence of isolated Cu components which holds the potential for further reduction of the intermediate γ-butyrolactone while restraining the hydrogenolysis of SA to butyric acid over the Pd sites.

Critical Switching of Cyclization Modes of Polyepoxides in Acidic Aqueous Media and Neutral Water: Synthesis and Revised Structure of a Nerolidol‐Type Sesquiterpenoid

AbstractBiomimetic epoxide‐opening cascades of polyepoxides enable the efficient and rapid construction of polyether frameworks. Herein, we show that the epoxide‐opening cascade cyclization that affords tetrahydrofuran products in acidic aqueous media produces tetrahydropyran (THP) in neutral water. THP formation proceeded by simply heating polyepoxides in neutral water and followed a different cyclization mode from those observed so far. The novel cascade cyclization in H2O was applied to the synthesis of a new nerolidol‐type sesquiterpenoid, resulting in revision of the proposed structure and determination of the absolute configuration.

Critical Switching of Cyclization Modes of Polyepoxides in Acidic Aqueous Media and Neutral Water: Synthesis and Revised Structure of a Nerolidol-Type Sesquiterpenoid.

Biomimetic epoxide-opening cascades of polyepoxides enable the efficient and rapid construction of polyether frameworks. Herein, we show that the epoxide-opening cascade cyclization that affords tetrahydrofuran products in acidic aqueous media produces tetrahydropyran (THP) in neutral water. THP formation proceeded by simply heating polyepoxides in neutral water and followed a different cyclization mode from those observed so far. The novel cascade cyclization in H2 O was applied to the synthesis of a new nerolidol-type sesquiterpenoid, resulting in revision of the proposed structure and determination of the absolute configuration.

Stereochemistry of Pd(II)-Catalyzed THF Ring Formation of ε-Hydroxy Allylic Alcohols and Synthesis of 2,3,5-Trisubstituted and 2,3,4,5-Tetrasubstituted Tetrahydrofurans.

Pd(II)-catalyzed ring formation of 2,3,5-trisubstituted and 2,3,4,5-tetrasubstituted tetrahydrofurans is described. Oxypalladation of a chiral ε-hydroxy allylic alcohol provides a 5-alkenyltetrahydrofuran ring in excellent yields via a 5-exo-trigonal process. Nine substrates including six secondary allylic alcohols and three primary allylic alcohols with or without an additional secondary hydroxy substituent at the γ-position have been examined. Their structures are restricted by a 2,2,4,4-tetraisopropyl-1,3,5,2,4-trioxadisilocane ring. The stereochemistry of the resulting tetrahydrofuran products was determined by chemical transformation. The reaction mechanism is discussed on the basis of the stereochemical results. The steps in the chiral allylic alcohol directed or the nucleophilic alcohol directed facial selection for the formation of the alkene-Pd(II)-π-complex, the cis-oxypalladation, and a syn-elimination mechanism account for the observed stereochemistry of the reaction.

A New Strategy for Enantioselective Construction of Multisubstituted Five-Membered Oxygen Heterocycles via a Domino Michael/Hemiketalization Reaction.

A new highly enantioselective domino Michael/hemiketalization reaction of α-hydroxyacetophenone with β,γ-unsaturated α-keto esters for the synthesis of 2,2,4,5-tetrasubstituted chiral tetrahydrofurans is reported. With 2 mol % intramolecular dinuclear zinc-AzePhenol complex prepared in situ from the reaction of multidentate semi-azacrown ether ligand with ZnEt2 , the corresponding anti-multisubstituted tetrahydrofuran products were obtained in up to 90 % yields, and 98 % enantiomeric excess (ee) at 0 °C for 45 min. Moreover, the products were easily converted to 2,3,5-trisubstituted 2,3-dihydrofurans without any loss in optical activity.

Production of tetrahydrofuran by dehydration of 1,4-butanediol using Amberlyst-15: Batch kinetics and batch reactive distillation

The production of tetrahydrofuran from 1,4-butanediol has been investigated with the intent of process intensification. Batch kinetic experiments were performed using ion exchange resin catalyst, Amberlyst-15. The presence of water was found to strongly affect the performance of the catalyst. The kinetic experiments were performed to capture the effect of water on the reaction along with other variations in reaction conditions like temperature and catalyst ratio. The obtained kinetic data was then regressed to arrive at a logical rate expression. Detailed theoretical and experimental analysis explains the use of process intensification like reactive separation to improve the conversion. This has been assessed with the help of batch reactive distillation runs.

Structure and reactivity of an isolable seven-membered-ring trans-alkene.

The isolation and characterization of a trans-oxasilacycloheptene is reported. Single-crystal X-ray crystallographic studies indicate a high level of strain and deviation from ideal geometry. Reactions with several electrophiles demonstrated the nucleophilicity of the C=C double bond, affording oxasilacycloheptane and tetrahydrofuran products as single diastereomers.

Structure and Reactivity of an Isolable Seven‐Membered‐Ring trans‐Alkene

AbstractThe isolation and characterization of a trans‐oxasilacycloheptene is reported. Single‐crystal X‐ray crystallographic studies indicate a high level of strain and deviation from ideal geometry. Reactions with several electrophiles demonstrated the nucleophilicity of the CC double bond, affording oxasilacycloheptane and tetrahydrofuran products as single diastereomers.

Vapour phase hydrogenolysis of biomass-derived diethyl succinate to tetrahydrofuran over CuOZnO/solid acid bifunctional catalysts

BACKGROUND: Catalytic upgrading of fermentation-derived succinic acid or its derivates (succinic acid esters and succinic anhydride) to value added chemicals has received great attention recently. The aim of this work is to provide a process for the production of tetrahydrofuran from succinic acid esters. RESULTS: The hydrogenolysis of biomass-derived diethyl succinate was investigated over CuOZnO and CuOZnO/solid acid (HY, HZSM-5, SAPO-11 and Al2O3) catalysts in a fixed-bed reactor. Over CuOZnO, gamma-butyrolactone and 1,4-butanediol can be selectively produced under appropriate reaction conditions, while the selectivity of tetrahydrofuran is relatively low due to the weak acidity of CuOZnO. Over CuOZnO/HZSM, both the formed 1,4-butanediol and ethanol can be further converted to tetrahydrofuran and diethyl ether, while tetrahydrofuran is selectively produced over CuOZnO/HY. CuOZnO/Al2O3 and CuOZnO/SAPO exhibit slight improvements in terms of selectivity to tetrahydrofuran when compared with CuOZnO. CONCLUSION: CuOZnO/HY is an appropriate catalyst to produce tetrahydrofuran from biomass-derived diethyl succinate with high activity, selectivity and stability. Furthermore, Bronsted acid sites with appropriate acid strength are responsible for the selective formation of tetrahydrofuran under the applied reaction conditions. Copyright © 2010 Society of Chemical Industry

Unusually Reactive and Selective Carbonyl Ylides for Three-Component Cycloaddition Reactions

Conditions are described for the Rh-catalyzed formation of highly functionalized dihydro- and tetrahydrofuran products via three-component reactions of aldehydes, alpha-alkyl-alpha-diazoesters, and dipolarophiles. The alkyl-substituted carbonyl ylides that are generated in this fashion are highly reactive in cycloaddition reactions and display a scope of reactivity that is much broader than the three-component reactions of carbonyl ylides derived from ethyl diazoacetate or alpha-aryl-alpha-diazoesters. The reactions of alkyl-substituted carbonyl ylides proceed with high regioselectivity and diastereoselectivity that are rationalized in terms of an asynchronous, endo-selective transition state.

α-(3-Pyridyl)malonates: preparation and synthetic applications

Alkylation of aromatic rings is a major challenge in organic syntheses since more complex carbon skeletons can be constructed. The alkylation of pyridine by nucleophilic aromatic substitution of the nitro group in methyl 3-nitro-4-pyridylcarboxylate ( 1) with malonic ester is reported. The versatility of the α-(3-pyridyl) malonic ester product ( 3) is demonstrated by the formation of a number of new 3-alkylated pyridines and new fused bis-heterocycles. cis 2-Halomethyl-4-(3-pyridyl)tetrahydrofuran products were selectively prepared. Exact 1H and 13C NMR assignments of practically all products were obtained by a series of NMR experiments.

Lead(iv) acetate: intriguing reactivity profile

LTA reaction of homoallyl alcohols derived from norbornyl alpha-diketones exclusively furnished the corresponding alpha-diketones via beta-fragmentation of the allyl group in refluxing benzene while changing the solvent to MeOH resulted in the formation of novel methoxy substituted spirocyclic tetrahydrofuran products.

Evaluation of Zeolites in Production of Tetrahydrofuran from 1,4-Butanediol: Performance Tests and Kinetic Investigations

The liquid-phase dehydration of 1,4-butanediol to tetrahydrofuran was investigated over various materials including synthetic zeolites, namely, ZSM-5, Y, Mordenite, Ferrierite, and Beta as well as silica and alumina. The key characters investigated were the Si/Al ratio and cation exchange. The results showed that the ZSM-5 zeolite exchanged with NH4+ exhibited the highest activity in dehydration of 1,4-butanediol. In all tests, nearly 100% selectivity to tetrahydrofuran was observed. After finding the most active catalyst, the kinetics of dehydration of 1,4-butanediol to tetrahydrofuran was studied over this material. The influence of operating parameters such as temperature, pressure, and substrate concentration on reaction was investigated through the Taguchi analysis of experimental data. A strong dependence of reaction rate on temperature was observed. Pressure, however, was found to have a negligible effect on reaction rate. The contribution of external and intraparticle mass transfer limitations on ...

Synthesis of polysubstituted tetrahydrofurans via Pd-catalyzed carboetherification reactions

Pd-catalyzed carboetherifications of 1-, 2-, or 3-substituted γ-hydroxy internal alkenes afford tetrahydrofuran products bearing three stereocenters in good yield with moderate to good stereoselectivity.

Enantiospecific Sn(II)- and Sn(IV)-Catalyzed Cycloadditions of Aldehydes and Donor−Acceptor Cyclopropanes

A cycloaddition strategy for the synthesis of highly enantioenriched 2,5-cis-disubstituted tetrahydrofurans has been developed. In the presence of catalytic Sn(OTf)2 or SnCl4, a range of aldehydes will undergo formal [3 + 2] cycloadditions with a scalemic donor-acceptor cyclopropane to form optically active heterocycles. Mechanistic studies support an unusual SN2 attack by the aldehyde on the activated cyclopropane. Through this mechanism, stereochemical information contained in the cyclopropane is effectively transferred to the tetrahydrofuran products.

Pyridinium chlorochromate (PCC) oxidation of bishomoallylic tertiary alcohols. A structure–reactivity study

The mechanism of the Cr(VI) oxidation of an alkene C=C is not known for certain. A particularly useful and novel example of this process is the intramolecular oxidative cyclization of bishomoallylic tertiary alcohols by pyridinium chlorochromate (PCC) to yield substituted tetrahydrofuran products via the tethered chromate ester. Several such tertiary alcohols were prepared in this study which varied in the number and position of alkyl groups attached to the C=C. The relative reactivity of these substrates toward PCC under standard conditions is dependent only on the number of R groups on the C=C, not on the degree of substitution on the most highly substituted alkene carbon. This observation suggests a symmetrical transition state in this intramolecular Cr(VI) alkene oxidation.

Palladium catalyzed hydrogenation of furan: optimization of production conditions for tetrahydrofuran

Tetrahydrofuran can be produced from agricultural waste rich in pentosans such as corn stalks. The furan hydrogenation reaction was carried out in the presence of charcoal-supported catalysts, without a solvent, under constant hydrogen pressure. Determination of the principal effects and the effects of interaction of the factors likely to influence the reaction can be achieved through a full two-level factorial design. Interpretation of the results obtained allows the choice of a new experimental mode, corresponding to milder operating conditions. Optimization of the conditions for the production of tetrahydrofuran was carried out with a Doehlert experimental matrix. A study of the corresponding response surfaces shows that high yield can be obtained at low pressure and with a reduced quantity of catalyst.

The stereoselective synthesis of terpene tetrahydrofurans using thallium triacetate

The reaction of diterpenes 1–3 and monoterpenes 9 , 10 with thallium triacetate leads stereoselectively to the tetrahydrofuran products 5–7 and 11 , 12 respectively, by 5-Endo-Trig cyclisation of the 3-alkenol system.