Tetrahydrofuran production

A definitive feature of this highly stereoselective new route to substituted tetrahydrofurans is that both syn and anti allylic diol stereoisomers typically afford identical tetrahydrofuran products. Thus, there is no need for stereoselective... 

In reactions where several different outcomes are possible, the final product distribution reflects the relative free energies of each transition state when the reaction is under kinetic control (Schultz and Lemer, 1993). Baldwin s rules predict that for acid-catalysed ring closure of the hydroxyepoxide [65] the tetrahydrofuran product [66] arising from 5-exo-tet attack will be preferred... 

An interesting example of the apparent dependence of stereoselectivity on the rate of breakdown of the initial cyclization intermediate has been observed in cyclizations with isoxazolines as the nucleophilic functionality (equation 48 and Table 14).141 The stereochemistry of products from cyclizations to form tetrahydrofuran products varies significantly upon changing the 3-substituent of the isoxazoline ring (Table 14, entries 1-3). The exact factors controlling these variations have not been determined, but the stereoselectivity may be synthetically useful. Particularly noteworthy is the high selectivity for the less... 

A tungsten-catalyzed cycloisomerization of the D-ribose-derived alkynyl alcohol 181 provides a 6-endo-dig cyclization route to 3,4-dihydropyrans. Excellent endo-modc selectivity, and hence minimal tetrahydrofuran production is... 

Dipolar cycloaddition of alkenes with carbonyl ylides generated in situ is a versatile method for tetrahydrofuran synthesis. The synthetic potential of such transformations has been reviewed <2005JOM(690)5533, 2003BMI6-253>. In addition, the stereoselective [3 + 2] annulation of allyl silanes has become a reliable protocol for the synthesis of tetrahydrofurans as demonstrated in several total syntheses . Such a [3 + 2] annulation, for example, affords the tetrahydrofuran product 11 as a single stereoisomer (Scheme 15) <2002OL2945>. Lanthanide salts serve as efficient Lewis acid catalysts in similar [3 + 2] cycloaddition reactions . 

Gold also catalyzed a three-component reaction comprising an ( )- or (Z)-2-(arylmethylene)cyclopropylcarbinol, a terminal alkyne and an alcohol to afford a tetrahydrofuran product <07OL4917>. 

Metal-catalyzed cycloisomerization reactions of w-alkynols (4-pentyn-l-ol derivatives) provide a rapid and efficient access to tetrahydrofurans. In general, these reactions may proceed through two different reaction pathways, formally leading to endo- or r-vo-cycloisomerization products. The formation of the rwn-tetrahydrofuran product can be achieved with catalytic amounts of tungsten pentacarbonyl (Equation 85) <2005CEJ5735>. 

The enantioselective total synthesis of the polysubstituted tetrahydrofuran (-)-citreoviral, the unnatural enantiomer, was synthesized by L.E. Overman et al. The Prins-pinacol rearrangement of an allylic 1,2-diol with an unsymmetrical ketone proceeded with high stereoselectivity. The jb/s(trimethylsilyl)-1,2-diol was condensed with the dimethyl acetal of the unsymmetrical ketone in the presence of catalytic amounts of TMSOTf, which yielded a nearly 1 1 mixture of the corresponding acetal and rearrangement product. The acetal was converted to the desired tetrahydrofuran product upon exposure to tin tetrachloride. 

Mitsubishi Kasei Corp., 1,4—Butancdiol/tetrahydrofuran production technology, CHEMTECH, 18 759-763 (1988). 

In further revelation of the strong stereoelectronic requirement for the intramolecular SN2 reaction, the hydroxy ester 156 furnished the lactone 157 only and none of the tetrahydrofuran product 158 on reaction with a base. Whereas the product 157 arises from the 5-exo-trig process involving attack of the oxy anion on the ester carbonyl function, the difficult 5-endo-thg process involving attack of the oxy ion at the olefinic carbon in conjugate fashion is required for the formation of 158 [25, 26]. 

Figure 11 illustrates the process steps in converting propylene oxide to 1,4 butanediol and tetrahydrofuran. Production of 1,4 butanediol is a three-step process. The first step is the isomerization of propylene oxide to allyl alcohol. A trilithium orthophosphate catalyst is used and reactor operating conditions are 250-300 C (480-570°F) and approximately 10 atm pressure (130 psig). The chemistry is shown in Eq. (23) ... 

When the enantiomeric crotyl silane 477 is added to 464 with aluminum chloride catalysis, virtually no tetrahydrofuran products are produced. Instead, octenoic acid derivative 478 (with the syn- diol configuration) is formed as a single diastereomer. 

A type of 1,3-dipole that has received considerable recent interest is the carbonyl ylide. One method for its formation makes use of carbenoid chemistry (see Section 4.2). Cyclization of an electrophiUc rhodium carbenoid onto a nearby carbonyl group provides access to the carbonyl ylide. Cycloaddition with an alkyne or alkene dipolarophile then gives the dihydro- or tetrahydrofuran product. For example, the carbonyl ylide 235, formed from the diazo compound 234 and rhodium(II) acetate, reacts with dimethyl acetylenedicarboxylate to give the bridged dihydrofuran 236 (3.148). 

The generation of alkoxy radicals that can undergo intramolecular hydrogen abstraction can also be achieved by photolysis of hypohahtes. Photolysis of a hypochlorite (RO—Cl) gives a 1,4-chloro-alcohol, formed as expected by abstraction of a hydrogen atom attached to the 8-carbon atom. The 1,4-chloro-alcohol can be converted readily to a tetrahydrofuran product (4.27). The hydrogen abstraction reaction proceeds through a six-membered cyclic transition state as in the photolysis of nitrites. 

A process, which combines distillation with solvent extraction, is presented in Fig. 11.4-3. Such processes are used in the process industiy for the regeneration of solvents (e.g., tetrahydrofuran, THF) diluted by water (Schoemnakers 1984). The system tetrahydrofuran/water forms a minimum azeotrope at approximately 80 mol% THF. Most of the water is removed as bottoms in distillation coluiim C-1. The overhead fraction 1 is fed into the extractor for removal of the residual water by solvent extraction with concentrated Na0H/H20. The diluted sodium fraction is regenerated in the single stage distillation nnit D-1. If the specified concentration of tetrahydrofuran product is veiy high a further purification step has to be per-... 

Scheme 4.9 Aminoalkoxylation reactions to form 3-aminated tetrahydrofurane products.

The ( -y-(silyl) allyl boronates 47 and 48 were subsequently introduced in order to access more highly oxygenated aldehyde addition products. For example, the allylic silane addition products can undergo subsequent oxidation to provide 1,2- and 1,4-diol products. The allylsilane products are also allylmetal reagents Roush and co-workers have demonstrated their ability to undergo addition reactions with Lewis acid activated aldehydes to form tetrahydrofuran products. ... 

The application of d5-2,3-disubstituted cyclopropane 1,1-diesters to [3 + 2]-annulations with aldehydes under the promotion of AICI3 can result in the formation of the desired polysubstituted tetrahydrofuran products... 

It was demonstrated that addition of dimethyl sulfoxide (DMSO) or MeOH to the reaction mixture can improve the conversion of 5. Furthermore, increasing the temperature to 37°C allowed the reaction to proceed to complete conversion and excellent yield using only six units of enzyme [27]. Neither the enzyme nor MeyPAu Cl could, in isolation, produce the tetrahydrofuran product it arose as a product of the system rather than the individual components [28]. 

Interestingly, cyclic products are not found in the 0-5 and 0-6 assisted oxythallation reactions perhaps because of rearrangements during the dethallation step. The finding of the tetrahydrofuran products (235) and (237) after dethallation of the oxidation products of l-buten-4-ol (234)... 

Startg. methylthio compd. refluxed 4 hrs. with methyl iodide in a soln. ofNaHCOg in methanol-tetrahydrofuran product. Y > 80%. C. V. Grudzinskas and M. J. Weiss, Tetrah. Let. 1973, 141. 

The reactivity of the double bond in these hydroxy vinylsilane products is affected by the trimethylsUyl group. The reaction of (3) with iV-bromosuccinimide leads to the formation of a fi-bromooxetane at 0 °C or of a diene product at 40 °C (eq 5). The expected formation of the tetrahydrofuran product has not been observed. ... 

Startg. m. stirred 12 hrs. at room temp, with acetyl chloride in tetrahydrofuran -> product. Y 90%. Also bromo-analog with acetyl bromide s. Y. Fujisawa and O. Mitsunobu, Chem. Commun. 1973, 201 s. a. R. Marumoto and M. Honjo, Chem. Pharm. Bull. 22, 128 (1974). 

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