Substitution 2.3- disubstituted tetrahydrofuran

The Payne rearrangement of the respective epoxy alcohols 79-85 led to the formation of highly substituted 2,3-disubstituted tetrahydrofurans 80-86 stereoselectively. ... 

Starting from substituted allyl bis-(2,4-dimethyl-3-pentyl)-L-tartrate boronic acid, synthesis of a,/l-disubstituted tetrahydrofurans (134, n = 1) or tetrahydropyrans (134, n = 2) can be accomplished with high enantioselectivity (Scheme 3-46).79... 

Alkenyl-substituted -dicarbonyl compounds, upon the same conditions, give rise to 2,5-disubstituted tetrahydrofurans bearing exocyclic double bonds. The products, upon treatment with NaBH, are reduced to the corresponding tellurides which in turn are converted into tellurium-free methyl derivatives by treatment with TBTH. ... 

The allyloxy and propargyloxy compounds are easily prepared by the opening of mono-substituted epoxides with sodium aryl tellurolates, followed by allylation and propargyla-tion of the obtained -hydroxytellurides, submitted to irradiation with a sun lamp in the presence of hexabutylditin, and suffer group-transfer cyclization under 5-exo-mode to give the 2,4-disubstituted tetrahydrofuran derivatives. ... 

Substituted 4-alkenols (1) are converted by Tl(OAc)3 at 0-25° into trans-2,5-disubstituted tetrahydrofurans (2) in 60-80% yield with only traces of the ds-isomer or a tetrahydropyranyl regioisomer.2 The same reaction using Pb(OAc)4 gives 2 in only 31% yield. 

The cyclization of (Z)-l-substituted-5-silyl-4-penten-l-ols 90, shown in equation 50, gave 2,5-disubstituted tetrahydrofurans 91 and 92 with a high trans-selectivity (% tram > 86 for R = Ph, i-Pr, C6Hi3)114. 

Iodolactonization of y, o-unsaturated alcohols results in preferential formation of tram-2, 5-disubstituted tetrahydrofuranes. However, the corresponding benzyl ethers cyclize preferentially to the cis-isomers. The alkyl group must be bulky enough to exert a steric effect, but not to prevent cyclization. Substituted benzyl ethers are particularly useful. Examples of this steric control are illustrated for the preparation of tram- and c/s-linalyl oxide (equations I and II).10... 

A stereoselective synthesis of substituted tetrahydrofurans (69) via Pd-catalysed reactions of aryl and vinyl bromides with y -hydroxy terminal alkenes (68) has been described. This transformation affords trans-2,5- and frara-2,3-disubstituted tetrahydrofurans with up to >20 1 dr. This methodology also provides access to bicyclic and (g) spirocyclic tetrahydrofuran derivatives in good yield with 10-20 1 dr. The effect of... 

A number of complex heterocycles have been assembled using dipolar cycloadditions (Fig. 6). The Affymax group [32] published an approach to the synthesis of tetrasubsti-tuted pyrrolidines by the reaction of azomethine ylids with electron-deficient olefins. A similar approach was described by researchers at Monsanto however, the aldehyde component was bound to the resin instead of the amino acid [33]. Kurth and co-workers [34] described a route to 2,5-disubstituted tetrahydrofurans using a nitrile oxide cycloaddition as the key reaction. Mjalli et al. [35] synthesized highly substituted pyrroles using the dipolar cycloaddition of intermediate 5 with mono- or disubstituted acetylenes. 

The treatment of 4-chlorobutyronitrile, 3-chloropropyl phenyl sulfone, and other related compounds with a base affords 7-halocarbanions which are usually prone to undergo intramolecular substitution to produce substituted cyclopropanes. However, these carbanionic intermediates can be trapped with external electrophilic partners, such as aldehydes, to give alcoholate anions, which then cyclize to produce 2,3-disubstituted tetrahydrofurans in excellent yields (Scheme 78) <2002CEJ4234>. 

Moreover, when methyl ( )-3-hydroxyoct-6-enoate undergoes iodocyclization, a frcm.v-2.5-di-substituted iodotetrahydrofuran is obtained, whereas starting from methyl (Z)-3-hydroxyoct-6-enoate, a 3-hydroxy-2,3-frafw-2,5-c -disubstituted tetrahydrofuran is formed, a key intermediate for a total synthesis of Muscarine132. 

The synthesis of 5-substituted tetrahydro-2-vinylfurans, starting from 4-alkenols, proceeds with a catalytic amount of palladium(II) acetate, in the presence of copper(ll) acetate, under oxygen atmosphere in methanol/water. The resulting 2,5-disubstituted tetrahydrofurans are obtained in moderate yield. When (E)-1 -phenyl-4-hcxcn-1 -ol (1) is used as starting material, traus-tetrahydro-2-phenyl-5-vinylfuran (2) is the sole compound isolated from the reaction mixture, albeit in 40% yield40. 

Cyclization of 2-substituted 4-penten-l-oxyl radicals leads to 2,4-cis-disubstituted tetrahydrofurans. The m-stereoselectivity improves in going from CH3 to C6H5 to C(CH3)3. 

Jean-Baptiste, L. Yemets, S. Legay, R. Lequeux, T. Synthesis of 2,3-trans disubstituted tetrahydrofurans through sequential xanthate radical addition-substitution reactions. J. Org. Chem. 2006, 71, 2352-2359. 

Schmitt A, Reissig H-U (2000) On the stereoselectivity of y — iactoi substitutions with ally and propargyisiianes-synthesis of disubstituted tetrahydrofuran derivatives. J Org Chem 23 3893-3901... 

Pd-catalyzed cyclization was also applied to the stereocontrolled preparation of chiral substituted tetrahydrofurans. The synthesis of optically active tetrahydrofurans was pioneered by Stork and Poirier,who described effective chirality transfer in the Pd-assisted cyclization of y-hydroxy allylic esters. Williams and Meyer deployed a variant of the 0-capture of 7r-allylpalladium complexes in the reactions of substimted trimethylenemethane palladium complexes developed by Trost, using aUylstannane (Scheme 32). A key intermediate 156 in the synthesis of amphidinolide K, a marine nam-ral product, was therefore synthesized starting from enantiopure diastereomer 160. Compound 160 was prepared by in situ transmetallation using the Corey chiral sulfonamide 159 with optically active aUylstannane 157 and then condensation with functionalized aldehyde 158. Formation of the c -2,5-disubstituted tetrahydrofuran 156 occurred with an excellent diastereoselectivity (cis/trans 13 1) and a good yield (88%) from the syn-1,4-precursor 160. 

Zuo and Louie also found that NHC-Ni complexes catalyzed the rearrangement of cyclopropylen-yne derivatives. However, the selectivity of the reaction was strongly dependent on the NHC-Ni catalyst as well as on the substrate substitution. With a SIPr/Ni 1 1 system, a hindered vinylcyclopro-pylene-yne gave the isomerized seven-membered ring as the sole product while the corresponding methyl derivative afforded a disubstituted tetrahydrofuran derivative. The authors then described a successful and general access to the later by using the ItBu/Ni 1 1 system (Scheme 10.6). 

BF3 OEt2 activates the formal substitution reaction of the hydroxyl group of y- or 8-lactols with some organometallic reagents (M = Al, Zn, Sn), so that 2,5-disubstituted tetrahydrofurans or 2,6-disubstituted tetrahydropyrans are formed. ... 

Shibata and co-workers have reported an effective protocol for the cyclization/hydrosilylation of functionalized eneallenes catalyzed by mononuclear rhodium carbonyl complexes.For example, reaction of tosylamide 13 (X = NTs, R = Me) with triethoxysilane catalyzed by Rh(acac)(GO)2 in toluene at 60 °G gave protected pyrrolidine 14 in 82% yield with >20 1 diastereoselectivity and with exclusive delivery of the silane to the G=G bond of the eneallene (Equation (10)). Whereas trimethoxysilane gave results comparable to those obtained with triethoxysilane, employment of dimethylphenylsilane or a trialkylsilane led to significantly diminished yields of 14. Although effective rhodium-catalyzed cyclization/hydrosilylation was restricted to eneallenes that possessed terminal disubstitution of the allene moiety, the protocol tolerated both alkyl and aryl substitution on the terminal alkyne carbon atom and was applicable to the synthesis of cyclopentanes, pyrrolidines, and tetrahydrofurans (Equation (10)). 

Starch can be vinylated with acetylene in the presence of potassium hydroxide in an aqueous tetrahydrofuran medium.1 1 The mechanism possibly involves the addition of the potassio derivative of starch across the carbon-carbon triple bond of acetylene, with subsequent hydrolysis of the organometallic intermediate to give the vinyl ether. Such a mechanism has been postulated for the formation of vinyl ethers from monohydric alcohols and acetylene, in the presence of an alkali metal base as catalyst.1 2 The vinylation of amylose is very similar to the vinylation of amylopectin, except for the relative ratio of mono- to di-substitution. With amylopectin, the proportion of disubstitution is greater. In both starches, the hydroxyl group on C-2 is slightly more reactive than the hydroxyl group on C-6 there is little substitution at the hydroxyl group on C-3. 

When 2-iodoalkyl vinylsilyl ethers 231 (Z=Si) were reacted with 224 in the presence of the Co(dppb)Cl2 catalyst, silatetrahydrofurans 232a (Z=Si) were isolated [294], When substrates 231 with substituted allyl groups (R3 and/or R4=alkyl) were treated with catalytic amounts of Co(dppe)Cl2 and 224 or phenylmagnesium bromide, a 5-exo cyclization proceeded and tetrahydrofurans 232c with exocyclic alkenyl units were isolated in 58-89% yield. For substrates with disubstituted alkene acceptors (R3=alkyl, R4=H), the formation of 18% of reduced tetrahydrofuran 232b was also observed [280, 295],... 

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