Synthesis of dihydrofurans

Scheme 6.11. Tandem Zr-catalyzed kinetic resolution and Ru-catalyzed conversion of the resulting optically pure ethers in the enantioselective synthesis of dihydrofurans. The efficiency of the catalytic resolution requires the presence of the pendant acyclic alkene and depends on its substitution.

S. Arai, K. Nakayama, Y. Suzuki, K. Hatano, T. Shioiri, Stereoselective Synthesis of Dihydrofurans under Phase-Transfer-Catalyzed Conditions , Tetrahedron Lett. 

An alternative synthesis of dihydrofurans was recently described by Hoppe and co-workers [84], The easily accessible 4-hydroxy-l,2-alkadienyl carbamates 106 were treated with Nal in the presence of NCS, which resulted in the formation of 3-iodo-2,5-dihydrofurans 107 (Scheme 8.28). Syn,syn-106 and syn,anti-106 gave the corresponding enantiopure 3-iodo compounds 107a,b in moderate to good yield. By treatment of syn,syn-106 with iodine in DMSO at 90 °C, the authors obtained the corresponding 3-iodofuran [84]. 

Heterocycles.—The phosphonium salt (59) is an effective three-carbon synthon, as demonstrated by its reaction with enolates of /9-keto-esters (Scheme 20) to give cyclopentenyl sulphides via an intramolecular Wittig reaction.63 Ylides are also intermediates in the synthesis of dihydrofurans (60) from the cyclopropylphos-phonium salt (61) and sodium carboxylates (Scheme 21).64 Cumulated ylides are very useful for the synthesis of heterocyclic compounds, e.g. (62), from molecules which contain both an acidic Y—H bond and a carbonyl or nitroso-function, as shown in Scheme 22.65... 

Synthesis of dihydrofuran derivatives by cyclization of oxime derivatives has been described. Thus, reduction of 2-quinolineacetaldoxime (26) with H2/Pt02 afforded fura-noquinoline 27 as a single product (equation 1. 4-Formy l-3-hydroxy-5-hydroxymethyl-2-methylpyridine oxime (28) in the system NaN02/HCl/H20 cyclized to furopyridine 29 (equation 13). ... 

Some examples that illustrate the scope of this transformation are given in Table 8.3 [for further examples, see (368,369)]. Note that this reaction, in contrast to the synthesis of dihydrofurans and furans, is not limited to a-diazoketones as the a-carbonylcarbene moiety concealed in diazoesters also works. 

Dihydrofuranes. The reaction of dimethylsulfonium methylide (1) with a-keto ketene dilhiouccluls (2) provides a simple synthesis of dihydrofuranes (3), which can lie enlivened into various furuncs ami hulcnolidcs as shown in Scheme (I).2... 

Tetrahydrofurans.1 Co(OAc)2 promotes a reaction between methyl acetoace-tate and terminal alkenes to form tetrahydrofurans. This reaction is similar to a synthesis of dihydrofurans effected with Mn(III) acetate (14, 198), but differs in that oxygen is required with the cobalt catalyst. Of further significance, only a single tetrahydrofiiran is formed and in relatively good yield (68-71 %). A dihydrofuran is also formed, but only in minor amounts. 

Conversion ofpropargyl esters to dihydrofurans1 (11,469-470). The reaction can be used for an enantioselective synthesis of dihydrofurans. Thus reduction of 3-hydroxy-l-alkynyl ketones (2) with Midland s reagent, (+)-l, provides (4S)-2-bu-tyne-l,4-diols (3) in 84-91% ee. Monoacylation (4) followed by treatment with... 

Hwu et al. have examined the dependence of the metal oxidant on the mode of reactivity in silicon-controlled allylation of 1,3-dioxo compounds [95JOC856]. The use of manganese(III) acetate furnished the dihydrofuran product 22 only. On the other hand, use of cerium(IV) nitrate resulted in the formation of both acyclic (23) as well as the cyclized compound, with the product distribution dependent on the nature of the allylsilane. Facile synthesis of dihydrofurans by the cerium(IV) mediated oxidative addition of 1,3-dicarbonyl compounds to cyclic and acyclic alkenes has also been reported [95JCS(P1)187]. 

The synthesis of dihydrofurans from propargyl esters is another reaction in which both gold and silver have been employed. In early work, Shigemasa et al.37 reported the efficient chirality transfer in the cycloisomerization of monoesters of butynediols. They used 8-15 mol% of AgBF4 as catalyst in benzene at 80°C in the dark. 

The synthesis of dihydrofuran derivatives such as 177 has been performed to explore scope and limitations of the Lewis acid promoted hydroxyalkylation of siloxycyclopropanes. Table 6 shows that aromatic as well as aliphatic ketones can efficiently be incorporated. Enolization of ketones does not occur and a 1-methyl group at the cyclopropane is no obstacle for the reaction, which now binds the carbonyl compound to a quartemary center with surprisingly high efficiency (entry 5). Albeit there are some restrictions with regard to the substitution pattern of the cyclopropanes, bicyclic siloxycyclopropanes also give good yields (e.g. entry 6 and Eq. 76). Further examples of the tetrahydrofuran synthesis from intermediate y-lactols with... 

Table 6. Synthesis of Dihydrofuran Derivatives Analogous to 177 (Scheme 7)...

A multicomponent reaction of a species generated from addition of dimethoxycarbene onto the triple bond in DMAD in the presence of aldehydes or quinones has been described, affording a facile synthesis of dihydrofuran derivatives (Equation 70) <2001TL2043>. 

The synthesis of dihydrofurans with an additional ester moiety and one or two quaternary centers are prepared from titanium enolates formed by reactions of 3,4-dienoates with Cp2TiCl2. Titanium enolate derivatives TiCl3[CH2CH2C(=0)0Et] and the Tebbe reagent compound have been applied in the synthesis of pumilio-toxin.1915 Chiral allyl and mono-Gp chloro enolato titanium compounds add with high enantioface discrimination to aldehyde.973... 

LaDS, Alexander JB,CefaloDR,GrafDD,HoveydaAH, SchrockRR(1998) Mo-catalyzed asymmetric synthesis of dihydrofurans. Catalytic kinetic resolution and enantioselec-tive desymmetrization through ring-closing metathesis. J Am Chem Soc 120 9720-9721... 

The similar reaction is used for the synthesis of dihydrofuran derivatives. Photo-lytic cleavage of the Se-CF2 bond of 22 in the presence of 2,3-dihydrofuran, the phenylselenyl group transfer reaction proceeds quickly to provide 24, and further photolysis of 24 results in the formation of the compound 25. ... 

Synthesis of dihydrofurans substituted in position 2 05EJO4929. Synthesis, properties, and application of 5-alkoxy-2,5-dihydrofuran-2-ones 05CJO239. 

Rh(II)-catalyzed reaction of iodonium yhdes with conjugated compounds leading to efficient synthesis of dihydrofurans, oxazoles and dihydrooxepines [ 1068] synthesis of various heterocycles by Rh(II)-catalyzed reactions of iodonium ylides with vinyl ethers, carbon disulfide, alkynes and nitriles [1055] Rh(II)-catalyzed reaction of iodonium ylides with electron-deficient and conjugated alkynes leading to substituted furans... 

Kim, S. and Lee, H. 2008. Cyclization of allenyne-l,6-diols catalyzed by gold and silver salts An efficient selective synthesis of dihydrofuran and furan derivatives. Adv. Synth. Catal. 350 547-551. 

V. Nair, S. Bindu, V. Sreekumar, L. Balagopal, Synthesis 2003, 1446-1456. Novel dipolar cycloaddition reactions of zwitterionic species generated from dimethoxycarbene and dimethyl acetylenedicarhoxylate with carhonyl compounds facile synthesis of dihydrofuran derivatives. 

Schmidt B, Nave S. Synthesis of Dihydrofurans and Dihydropyrans with Unsaturated Side Chains Based on Ring Size-Selective Ring-Closing Metathesis. Adv Syndi Catal. 2007 349(l-2) 215-230. 

Boyer, A. Rhodium(lI)-catalyzed stereocontroUed synthesis of dihydrofuran-3-imines from l-Tosyl-l,2,3-triazoles. Org. Lett. 2014, 16, 1660-1663. 

Shi and coworkers established a highly efficient cascade reaction for the synthesis of dihydrofurans 106, which was developed through a diastereo but not enantiose-lective, proline-catalyzed, one-pot, three-component condensation of nitro alkenes, aldehydes, and 1,3-diketone/p-ketoesters (Scheme 2.27) [42],... 

Methoxyallene has previously been used to prepare acetylenes via its reaction with Grignard reagents, in the presence of copper(i) halides.The use of preformed dialkylcuprates, however, gave the vinyl ethers instead. The E Z ratio varied with the substituent but it is difficult to explain why the difference is observed.Methoxyallene has also been converted into its vinyl anion and used in the synthesis of dihydrofurans and furans in an analogous way to ordinary vinyl ethers.Similarly allenic cuprates have been prepared and used in the synthesis of allenes and allenic pheromonessome examples are outlined in Scheme 58. The addition of lithium dimethylcuprate to allene phosphine oxides and allenic ketones was interpreted in terms of a 1,2- rather than a 1,4-addition process, in contrast to a/3-unsaturated... 

Y.R. Lee, J.Y. Suk, Efficient synthesis of dihydrofurans and furans by rhodiiun(Il)-catalyzed reactions of cyclic diazodicarbonyl compoimds. Tetrahedron 58 (2002) 2359-2367. 

Y.R. Lee, B.S. Kim, D.H. Kim, Ceric ammonium nitrate (CAN)-mediated oxidative cycloaddition of 1,3-dicarbonyls to conjugated compounds. Efficient synthesis of dihydrofurans, dihydrofurocoumarins, dihydrofuroquinolinones, dihydrofurophenalenones, and furonaphthoquinone natural products. Tetrahedron 56 (2000) 8845-8853. 

Scheme 9.29 Synthesis of Dihydrofuran-2(3H)-ones through C(sp )-H Hydyoxylations.

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