Of tetrahydrofuran derivative

The application of 1,3-dipolar cycloaddition processes to the synthesis of substituted tetrahydrofurans has been investigated, starting from epoxides and alkenes under microwave irradiation. The epoxide 85 was rapidly converted into carbonyl ylide 86 that behaved as a 1,3-dipole toward various alkenes, leading to quantitative yields of tetrahydrofuran derivatives 87 (Scheme 30). The reactions were performed in toluene within 40 min instead of 40 h under classical conditions, without significantly altering the selectivi-ties [64]. 

The synthesis of tetrahydrofuran derivatives from unsaturated alcohols via hydroformylation intermediates was developed many years ago. Moderate yields are obtained from but-2-en-l,4-diol (Scheme 54)94 but hydroformylation is not the major pathway when coniferyl alcohol is subjected to the oxo process (Scheme 55).9S A more complicated reaction is involved... 

This kind of reactivity turned out to be particularly attractive when applied to suitably functionalized terminal alkynes. Oxidative monoaminocarbonylation of 4-yn-l-ols led to the formation of tetrahydrofuran derivatives through intramolecular conjugate addition of -OH group to the triple bond of the initially formed 6-hydroxy-2-ynamide intermediates (Scheme 38) [310]. 

Allyloxy and 2-propargyloxy alkyl tellurides as precursors of tetrahydrofuran derivatives... 

An efficient synthesis of tetrahydrofuran-derived spiro-p-lactams has been reported to be performed by a Staudinger-type reaction of either 2- or 3-tetra-hydrofuroyl chloride with imines [66]. The reaction was carried out by adding Et3N... 

Scheme 16 Synthesis of tetrahydrofuran-derived spiro-J3-lactams...

The stereoselectivity of this reaction rises when more bulky nucleophiles are employed (compare entries 7, 3,1, and 5). This is most impressively demonstrated by comparison of the y-lactol reduction with its allylation leading to 205 or 206, respectively (Scheme 10). Formation of tetrahydrofuran derivative 208, dihydrofuran 209, or unsaturated a-methylen-y-butyrolactone 207 illustrate that various modes of straightforward work-up procedures provide two different five membered heterocycles 93 b-96). A second example without the geminal dialkyl substitution at C-3 of the siloxy-cyclopropane depicted in Eq. 86 making available the annulated tetrahydrofuran-3-carboxylate 210 underlines the generality of the C-C-bond forming hydroxyalkylation reaction via ester enolates. 

The selective intramolecular nucleophilic addition of a hydroxy group at Cyof a ruthenium allenylidene generated by activation of propargylic alcohol by RuCl(Cp)(PPh3)2/NH4PF6 provides a ruthenium vinylidene species, which reacts with allylic alcohols as previously described in the section Formation of Unsaturated Ketones (Eq. 11, Scheme 18) [79]. This unprecedented tandem reaction makes possible the construction of tetrahydrofuran derivatives in good yields and has been used as a key step in the synthesis of (-)calyculin A [80]. 

An efficient and operationally simple synthesis of tetrahydrofuran-derived spiro-P-lactams 15 and 16 using the Staudinger reaction of unsymmetrical cyclic ketones has been described <02JCS(P1)571 02SL69>. Similarly, spiro-P-lactams 17 were synthesized via Staudinger reaction of imines derived from 7-oxanorbomenone with alkoxyacetyl chlorides <02TL6405>. 

Ring opening of tetrahydrofuran derivatives has been studied using chlorotrimethylsilane and sodium iodide 2-methyltetrahydrofuran is opened predominantly to give 5-iodopentan-2-ol but the reaction involving 3-methyltetrahy-drofuran is less selective. Lithium 4,4-di-/-butylbiphenylide has also been used to cause the ring opening of tetrahydrofuran at 80 C in the presence of boron trifluoride etherate. 

Although less commonly used, Raney Ni cleavage of the C—S bond of sulfoxides and sulfones is also of interest. For example, the removal of sulfoxides is one of the steps in the synthesis of spiroketals and of tetrahydrofuran derivatives (Scheme 2). Exceptionally, the desulfurization is not accompanied by the hydrogenolysis of a benzyl ether group. 

Now we turn from model systems to the reduction of coal. Detailed mass balance considerations suggest the weight of tetrahydrofuran-derived products on coal after the reduction step to be in the range of 4% (48-hr reduction) to 7% (213-hr reduction). These numbers are consistent with results of Larsen and Hombach, who employed " C-labeled tetrahydrofuran (35). Of direct influence to the application of the Sternberg procedure to coal characterization is Larsen s further observation that 60% of the added tetrahydrofuran is bonded inextricably to the coal (35, 36). 

Nakada, M., Iwata, Y., Takano, M. Reaction of dianions of acetoacetic esters with epibromohydrin derivatives a novel synthesis of tetrahydrofuran derivatives and tetrahydropyran derivatives. Tetrahedron Lett. 1999,40, 9077-9080. 

Both syntheses (see Chapter 5.3.3) and reactions of tetrahydrofuran derivatives have been reported last year e.g., the synthesis of 2 ,3 -dideoxy-3 hydroxymethylcytidine (a unique antiviral nucleoside) <97T8085>, cyclic dinucleotides <97T11033>, 7-... 

A stereoselective synthesis of five- to seven-membered cyclic ethers has been achieved by de-iodonative ring-enlargement of cyclic ethers having an iodoalkyl substituent. For example, the reaction of tetrahydrofuran derivative 360 with (diacetoxyiodo)toluene proceeds under mild conditions to afford ring-expanded product 361 (Scheme 3.144). The use of hexafiuoroisopropanol (HFIP) as solvent in this reaction is critical [462]. 

Cycloaddition of cyclopropanes to aldehydes leads to the formation of tetrahydrofurans derivatives, whose enantiomeric form can be obtained either by using enantioenriched cyclopropane substrates or by a dynamic kinetic asymmetric transformation. In this regard, Johnson et al. reported a dynamic kinetic asymmetric [3 -I- 2] cycloaddition of racemic cyclopropanes 63 for the enantioselective synthesis of tetrahydrofurans 64. In this study, the magnesium catalyst can promote the ring opening of the racemic cyclopropane and catalyses the reaction of one of the ring-opened enantiomers with the aldehydes (Scheme 3.19). 

Intramolecular alkoxymetalation of alkenes is one of the efficient methods to prepare cyclic ethers. He and co workers have reported that silver (I) triflate catalyzes the intramolecular addition of alcohols to olefins [26]. The reaction of 2,2-diphenyl-4-hexen-l-ol (16) under the influence of 5 mol% of the silver(I) catalyst affords a 10 1 mixture of tetrahydrofuran derivative (17) and tetrahydropyran derivative (18) in high combined yield (Scheme 18.6). In the case of terminal disubstituted y-hydroxyl alkenes, 6-endo cyclization products are formed exclusively. This procedure has been successfully expanded to cyclization of pent-4-enoic acid, hex-5-enoic acid, and their derivatives leading to the corresponding lactones [26]. Using similar cyclization methods catalyzed by silver(I) compounds, 1-allenyl isochromenes [27], dihydrobenzofurans [28], and dihydrobenzopyrans [28] have been synthesized. 

Figure 3.41 Formation of tetrahydrofuran derivatives from 1,2-dioxoianes.

Prenylation of Acetals. (a,a-Dimethylallyl)trimethylsilane reacts with acetals in the presence of a Lewis acid to give the corresponding homoallyl alcohols with corr5)lete regioselectivity (eqs 1 and 2). The reaction with carbonyl compounds often leads to the formation of tetrahydrofuran derivatives (eq 3), presumably through the formation of chloride. ... 

Zhao C, Lu J, Yan J et al (2003) One-pot four-component synthesis of tetrahydrofuran derivatives involving an alkyne an ethylene and two aldehydes via CuQ-mediated reactions of oxazireonacyclopentenes with aldehydes. Tetrahedron Lett 44 6895-6898... 

Similar tetrahydropyran synthesis is performed with 2-(trimethylsiloxymethyl)pro-pen-3-ylsilane 33 and two molecules of aldehydes (Scheme 5.9) [16]. For example, 33 reacts with propanal in the presence of BFj-OEtj to give Kxo-methylene tetrahydropyran 36 as a single diastereomer without any [3-t2] formation of tetrahydrofuran derivatives. A proposed mechanism involves an ene-type reaction leading to silyl enol ether 34 followed by formation of oxonium ion 3S and intramolecular cyclization. 

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