THF Derivatives Research Articles

Chiral Bis(8-Quinolyl)Ethane-Derived Diimine: Structure Elucidation and Catalytic Performance in Asymmetric Synthesis of (S)-Warfarin

C2-symmetric diimine generated in situ from (R,R)-HPEN and 8-formylquinoline was readily transformed to novel chiral diimine pre-III bearing 1(S),2(S)-bis(quinolin-8-yl) ethane and salicylic aldehyde fragments via stereoselective diaza-Cope rearrangement. The structure and absolute configuration of the product was established by the X-ray diffraction study of the corresponding Rh(III) complex. In the presence of pre-III, practically important enantioselective reactions of 4-hydroxycoumarin with α,β-enones afforded anticoagulant (S)-warfarin and its derivatives in aqueous THF in high yield (88–92%) with enantioselectivity 85–93% ee.

Diastereoselective Synthesis of THF Derivatives

Key words ketimines - epoxides - tetrahydrofurans - oxazolidines - hydrogen-bond catalysis

Photoprotective properties of new derivatives of kinetin.

The chronic exposure of skin to ultraviolet (UV) radiation causes adverse dermal reactions, such as erythema, sunburn, photoaging, and cancer, by altering several signalling pathways associated with oxidative stress, inflammation, and DNA damage. One of the possible UV light protection strategies is the use of dermal photoprotective preparations. The plant hormone kinetin (N6-furfuryladenine; KIN) exhibits antioxidant and anti-senescent effects in human cells. Topically applied KIN also reduced some of the clinical signs of photodamaged skin. To improve the biological activities of KIN, several derivatives have been recently prepared and their beneficial effects on cell viability of skin cells exposed to UVA and UVB light were screened. Two potent candidates, 6-(tetrahydrofuran-2-yl)methylamino-9-(tetrahydrofuran-2-yl)purine (HEO) and 6-(thiophen-2-yl)methylamino-9-(tetrahydrofuran-2-yl)purine (HEO6), were identified. Here the effects of KIN, its N9-substituted derivatives the tetrahydropyran-2-yl derivative of KIN (THP), tetrahydrofuran-2-yl KIN (THF), HEO and HEO6 (both THF derivatives) on oxidative stress, apoptosis and inflammation in UVA- or UVB-exposed skin cell was investigated. Human primary dermal fibroblasts and human keratinocytes HaCaT pre-treated with the tested compounds were then exposed to UVA/UVB light using a solar simulator. All compounds effectively prevented UVA-induced ROS generation and glutathione depletion in both cells. HEO6 was found to be the most potent. All compounds also reduced UVB-induced caspase-3 activity and interleukin-6 release. THP and THF exhibited the best UVB protection. In conclusion, our results demonstrated the UVA- and UVB-photoprotective potential of KIN and its derivatives. From this point of view, they seem to be useful agents for full UV spectrum protective dermatological preparations.

Trapping Nanostructures on Surfaces through Weak Interactions.

The assembly of imidazole-functionalized phenanthroline-strapped zinc porphyrins (ZnPorphen) with alkyl or polyethylene glycol (PEG) side chains was studied in solution and by AFM after casting on highly oriented pyrolytic graphite (HOPG) or mica. The nature of the solvent and its evaporation time influenced the morphology of the objects observed. On HOPG, short rods of about 100 nm were observed after fast evaporation of solutions of the alkyl derivatives in CHCl3 , THF, or pyridine, whereas islands of aligned rows of longer wires were obtained from methylcyclohexane (MCH). Slow evaporation of MCH led to a three-dimensional assembly. The PEG porphyrin assembled into short wires on HOPG or fibers on mica after slow evaporation of solutions in THF. This study shows the role of surface-molecule interactions in the interfacial assembly of ZnPorphen derivatives and contributes to understanding the parameters that control their noncovalent assembly into molecular wires on a surface.

Flying-seed-like liquid crystals 5: Liquid crystals based on octakisphenylthiophthalocyanine and their optical properties

We have synthesized three novel flying-seed-like liquid crystals based on phthalocyaninato copper(II) (abbreviated as PcCu ) substituted by bulky groups {(o- C1) PhS (i), (m- C1) PhS (j), [m, p-( C1)2] PhS (k)} instead of using long alkyl chains, in order to investigate their mesomorphism. Their phase transition behavior and the mesophase structures have been established by using a polarizing optical microscope, a differential scanning calorimeter, and a temperature-dependent small angle X-ray diffractometer. As the results, [(o-C1)PhS]8PcCu (8i), [(m-C1)PhS]8PcCu (8j) and {[m,p-(C1)2]PhS}8PcCu (8k) show a Coltet.omesophase at 314.9~362.9 °C, a Colro(P2m) mesophase at 287.4~334.2°C and a Colro(P2m) mesophase at 331.8~386.8°C, respectively. Very interestingly, each of the derivatives thus exhibits a columnar mesophase at very high temperatures. The mesomorphism is apparently originated from the novel bulky groups (i~k). It is also noteworthy that the Q-bands of the present PhS-containing Pc derivatives 8i~8k in THF significantly red-shift by about 35 nm in comparison with those of the corresponding PhO-containing derivatives in THF.

Rapid Ether and Alcohol C–O Bond Hydrogenolysis Catalyzed by Tandem High-Valent Metal Triflate + Supported Pd Catalysts

The thermodynamically leveraged conversion of ethers and alcohols to saturated hydrocarbons is achieved efficiently with low loadings of homogeneous M(OTf)n + heterogeneous Pd tandem catalysts (M = transition metal; OTf = triflate; n = 4). For example, Hf(OTf)4 mediates rapid endothermic ether ⇌ alcohol and alcohol ⇌ alkene equilibria, while Pd/C catalyzes the subsequent, exothermic alkene hydrogenation. The relative C-O cleavage rates scale as 3° > 2° > 1°. The reaction scope extends to efficient conversion of biomass-derived ethers, such as THF derivatives, to the corresponding alkanes.

First cupracarborane commo-clusters based on the medium-cage nido-5,6-C2B8H12-carborane and molecular structure of [Ph3PEt][commo-9,9′-Cu(nido-7,8-C2B8H11)2

A reaction of anhydrous CuCl2 with Na salts of the medium-cage carborane [7-X-nido-5,6-C2B8H10]−(X = H or I) derivatives in THF leads to new cupracarborane commo-clusters, [commo-9,9′-Cu(nido-7,8-C2B8H11)2]− and [commo-9,9′-Cu(11-I-nido-7,8-C2B8H10)2]−, in moderate yields. The clusters were isolated as stable [Ph3PEt]+ salts and characterized by 1H, 31P{1H}, and 11B/11B{1H} NMR spectroscopy and X-ray crystallography (for the unsubstituted derivative). The use in this reaction of the reducing agent Na2SO3 considerably increases the yields of both complexes from 25 and 18% to 74 and 68%, respectively.

Grob-type fragmentation of 5-oxabicyclo[2.1.1]hexane system: a strategy for synthesis of annulated and 2,2,5-trisubstituted tetrahydrofurans

Acid mediated, efficient Grob-type fragmentation reaction facilitated by vicinal ketal and ester moieties in variety of 5-oxabicyclo[2.1.1]hexanes leading to the corresponding annulated and 2,2,5-trisubstituted tetrahydrofurans is reported. Among the Brønsted and Lewis acids tested, BF3·OEt2 appears to give the best results, furnishing near quantitative yield (>99%) of tetrahydrofuran tricarboxylate derivatives under mild reaction condition. In case of unsymmetrical monosubstituted 5-oxabicyclo[2.1.1]hexanes two regioisomeric products are obtained. A strategy to transform one of the ester groups of the title compounds to protected hydroxymethyl moiety was evolved, which allows access to differentially protected 2-hydroxymethyl THF derivatives upon fragmentation. Employing TiCl4/R or S-BINOL as chiral Lewis acid, an enantioselective fragmentation (up to 66% ee) was described for the meso bis-furan derivative.

Aryl Grignard Reagents in Chemodivergent N‐ and C‐Arylations: Concise Access to Two Families of Tetracyclic Fused Carbazoles from 6‐Nitroquinolines

AbstractThe reaction between aryl Grignard compounds and 5‐methoxy‐6‐nitroquinoline derivatives in THF was found to proceed in a chemodivergent mode that depended on the functional groups present in the heterocyclic ring. Thus, the reactions that started from carbostyril derivatives afforded 6‐(arylamino)carbostyrils as the major products, whereas those that started with 2‐alkoxyquinolines gave exclusively 5‐arylquinolines. Both types of products were transformed into tetracyclic fused linear or angular carbazole systems by using palladium‐promoted oxidative coupling or Cadogan reactions, respectively. In the course of this work, an unprecedented oxidative demethylation by palladium acetate of 1,4‐dimethoxybenzene systems to the corresponding quinones was discovered.

Lewis Acidity Enhancement of Triarylboranes via Peripheral Decoration with Cationic Groups

The cationic boranes [Ar(N+)BMes(2)](+), [Ar(N+)(2)BMes](2+), and [Ar(N+)(3)B](3+) (Ar(N+) = [4-(Me(3)N)-2,6-Me(2)-C(6)H(2)](+); Mes = mesityl) have been synthesized and studied by cyclic voltammetry. The results obtained in this study show that the reduction potential of these derivatives in THF is increased by 0.36 V upon each substitution of a mesityl by a cationic Ar(N+) anilium group. Remarkably, the trication [3](3+), whose triflate salt is water soluble, complexes cyanide anions in pure water at pH 7. These properties underscore the dramatic effects caused by the increased number of cationic groups.

Carbon-branched δ-tetrahydrofuran sugar amino acids (SAAs) as dipeptide isostere scaffolds

The synthesis of the first branched sugar amino acid (SAA) scaffolds [methyl (3 R,4 R,5 R)-5-azidomethyl-3,4-dihydroxy-tetrahydrofuran-3-carboxylate and methyl (3 R,4 R,5 S)-5-azidomethyl-3,4-dihydroxy-tetrahydrofuran-3-carboxylate] by an efficient intramolecular displacement of a highly hindered neopentyl triflate allows access to enantiopure THF derivatives which have carbon substituents.

Delineating Oxidative Processes of Aqueous C60 Preparations: Role of THF Peroxide

The oxidative reactivity of THF derivatives formed during THF/nC60 synthesis was evaluated with indigo dye as a model compound. The results showed that the formation of previously undetected oxidizing agents during THF/nC60 synthesis accounted for the degradation of indigo dye by THF/nC60 (THF/nC60/unwashed), while THF/nC60 after vigorous washing (THF/nC60/washed) and nC60 prepared without the use of THF were not reactive. gamma-Butyrolactone (GBL) was detected by GC-MS in the THF/nC60/unwashed as one of THF derivatives, but showed no reactivity with indigo dye. An organic peroxide was detected in the THF/nC60/unwashed by HPLC, and was reactive with indigo dye. This compound was found to also account for the elevated antibacterial and bactericidal activities of THF/nC60/unwashed on E. coli. Analysis by LC/(+ESI)MS and 1H NMR showed that the detected THF peroxide was tetrahydro-2-(tetrahydrofuran-2-ylperoxy)furan. The formation of THF peroxide during the preparation of aqueous stable C60 aggregates provides another potential explanation for the reactivity and oxidative stress mechanisms of THF/nC60 system reported in the literature, although it does not exclude the potential reactivity and toxicity of nC60 itself.

Hydride Shift Generated Oxonium Ions: Evidence for Mechanism and Intramolecular Trapping Experiments to Form trans THF Derivatives

Hydride Shift Generated Oxonium Ions: Evidence for Mechanism and Intramolecular Trapping Experiments to Form <i>trans</i> THF Derivatives

Hydride Shift Generated Oxonium Ions: Evidence for Mechanism and Intramolecular Trapping Experiments to Form trans THF Derivatives

Seitenwechsel: cis-substituierte THF-Derivate, die durch oxidative Cyclisierung von Dienen und Diolen erhalten wurden, werden durch eine 1,2-Hydridwanderung und intramolekulare Abfangreaktion mit Hydrid als Nucleophil in die entsprechenden trans-konfigurierten Heterocyclen umgewandelt (siehe Schema). Auch Organometallverbindungen fangen das intermediäre Oxoniumion ab, sodass an C2 verschiedene Gruppen stereoselektiv eingeführt werden können.

Heavy Grignard Reagents: Challenges and Possibilities of Aryl Alkaline Earth Metal Compounds

Compounds of the type aryl--M--X, with M=Ca, Sr, Ba and X as any kind of ligand (such as halide, phosphanide, amide, aryl), are presented. The low reactivity of the heavy alkaline earth metals calcium, strontium, and barium enforces an activation prior to use for the direct synthesis. The insertion of these metals into C--I bonds of aryl iodides (direct synthesis) yields aryl metal iodides and has to be performed at low temperatures and in THF. Aryl alkaline-earth-metal compounds show some characteristics: 1) the ease of ether cleavage enforces low reaction temperatures, 2) for Sr and Ba the Schlenk equilibrium is shifted towards homoleptic MI2 and MPh2, 3) high solubility of diaryl alkaline-earth-metal derivatives in THF even at low temperatures initiated quantum chemical investigations on the aggregation behavior, and 4) a strong low field shift of the 13C resonances of the ipso carbon atoms in NMR spectra was observed. First results from quantum chemical calculations on diaryl dicalcium(I) suggest a long Ca--Ca bond with a considerable Ca--Ca bond dissociation energy. Initial results on a selection of applications such as metallation, metathesis, and addition reactions of aryl calcium compounds are presented as well.

Palladium‐Catalyzed Formation of Cyclic Ethers – Regio‐, Stereo‐ and Enantioselectivity of the Reaction

AbstractAn efficient and stereoselective synthesis of 3‐alkyl‐3‐hydroxymethyl‐5‐vinyltetrahydrofurans is described by the Pd0‐catalyzed cyclization of the methyl carbonates of ω,ω‐bis(hydroxymethyl)‐α,β‐unsaturated alcohols. The use of chiral ligands gave the corresponding THF derivatives in low to moderate enantiomeric ratios. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2007)

Regio- and stereochemical aspects in the synthesis of homoallylic alcohols from benzoins and their iodocyclisation to 2,3-diphenyltetrahydrofurans

Indium mediated allylation, crotylation and cinnamylation of benzoins and its substituted derivatives in THF–H 2O (2/1) provide a range of homoallylic alcohols. In general, the benzoins undergo allylation and crotylation in a sluggish manner compared to those observed earlier in the case of α-hydroxy aldehydes and are significantly affected by the electronic features of both the benzoin and indium organometallic reagent. The reactions exhibit higher order of diastereoselectivities than those observed for α-hydroxy aldehydes. The cinnamylation though proceeds in a highly diastereoselective manner but is restricted to only benzoin and 4,4′-dichlorobenzoin. The homoallylic alcohols undergo I 2 mediated intramolecular diastereoselective cyclization to provide 2,3-diphenyltetrahydrofuran derivatives. The relative stereochemistries in tetrahydrofurans and homoallylic alcohols have been assigned by coupling constants, NOE experiments and in one case by X-ray crystallography.

Cobalt(diamine)-Catalyzed Cross-coupling Reaction of Alkyl Halides with Arylmagnesium Reagents: Stereoselective Constructions of Arylated Asymmetric Carbons and Application to Total Synthesis of AH13205

A cobalt-diamine complex catalyzes the cross-coupling reactions of primary and secondary alkyl halides with aryl Grignard reagents. It is confirmed that oxidative addition of alkyl halide to cobalt proceeds via a radical process. Optically pure Ueno-Stork halo acetals undergo diastereoselective cross-coupling reactions, the products of which are transformed into optically active THF derivatives. A sequential radical cyclization/arylation reaction under cobalt catalysis provides extremely short access to a synthetic prostaglandin AH13205.

Reactions of 2-imino-3-aryl-4-phenyl-4-thiazolines with 2-cyanopyrazine and 4-cyanopyridine : difference in reactivity

The kinetics of the reactions of 2-imino-3-aryl-4-phenyl-4-thiazolines (2-ITZ, 3a-e) with 2-cyanopyrazine (2-CPZ, 1) and 4-cyanopyridine (4-CPY, 2) have been carried out in methanol at various temperatures. Results show that 2-ITZ derivatives (3a-e) reacted faster and more readily at ambient temperature with 2-CPZ than with 4-CPY. 2-CPZ readily reacted with methanol forming an amidate ester, while 4-CPY did not. The amidate ester was prone to nucleophilic substitution (OMe being a good leaving group). Slower reaction rate was observed for the reactions of 2-CPZ with 2-ITZ and its derivatives in THF. On the other hand 4-CPY did not react with 2-ITZ derivatives even under extreme conditions in THF. The order of reactivity of various substituents both in MeOH and in THF is: p-OMe >o-OMe > p-CH 3 > o-CH 3 > H. The isokinetic temperatures, T iso for the reactions of 2-ITZ with 2-CPZ and 4-CPY in MeOH were 352.6 K and 438.3 K respectively.

Valence-Delocalized Diiron(II,III) Cores Supported by Carboxylate-Only Bridging Ligands

Valence-Delocalized Diiron(II,III) Cores Supported by Carboxylate-Only Bridging Ligands