Isomerization dihydrofurans

From the copper-catalyzed reaction of methyl 2-diazo-3-oxobutyrate 57 a with Z-3-methoxystyrene, dihydrofuran 59 (formed with retention of olefin configuration) and butadienol 60 result130). Such an acyclic by-product also occurs when benzofuran is the cycloaddition partner. In that case, however, regioisomers 61 and 62, arising from the connection of the former diazo carbon with either the 2- or 3-position of the heterocycle, are obtained similarly, two isomeric dihydrofurans 63 and 64 are formed under Cu(hfacac)2 catalysis130). 

The combination of one donor substituent and two acceptor groups also enhances the cyclopropane activity. Although compounds 57 can be synthesized without special precautions, they readily expand at room temperature to the isomeric dihydrofuran... 

Taskinen E, Alanko T, LiebmanJP. Relative thermodynamic stabilities of the isomeric dihydrofurans and isomeric dihydropyrans. An experimental and DFT study. Struct Chem. 2006 17 323-326. 

The isomerization of vinyl- or ethynyl-oxiranes provides a frequently exploited source of dihydrofurans or furans, but analogous conversions of vinylaziridines have not been applied so often. While most of the examples in Scheme 87 entail cleavage of the carbon-heteroatom bond of the original heterocycle, the last two cases exemplify a growing number of such rearrangements in which initial carbon-carbon bond cleavage occurs. 

Pd complexes 9-12 were tested for their catalytic behavior in the asymmetric Heck reaction involving the phenylation of 2,3-dihydrofuran (Scheme 3). The results are summarized in Table 2. The two isomeric products of 2-phenyl-2,5-dihydrofuran are formed with varying yields from 80% to 0%. The obtained ee s are high. Complex 12 is shown to be catalytically inactive. The lack of catalysis in complex 12 is rationalized by differences in the steric requirements between the diphenylphosphinites 1-3 (cone angle >140°) and the more sterically hindered cyclohexyl-phosphinite 4 (cone angle >170°) and the resulting stereochemistry on the Pd center. The ligands in complex 12 adopt a... 

Reacting with the methylene dihydrofuran derivative 192 as trapping reagent, 34d gave rise to a mixture of [4 + 2] cycloadduct 193 and furan 194, which could be separated and obtained in 25% and 37% yields, respectively. Upon further heating, 193, whose configuration has not been determined, isomerized completely to the more stable 194 (Scheme 31) [47]. 

One exception to the preservation of selectivity in microwave reactions was the C2 arylation of 2,3-dihydrofuran, which yielded an isomeric byproduct under the action of microwaves (2-phenyl-2,3-dihydrofuran/byproduct = 71/29), in contrast with the reported procedure using conventional heating (Eq. 11.4). The desired product could be isolated in 58% yield. Attempts to reduce the reaction time by using oil baths (125 °C or 150 °C) did not result in similar yields, but instead furnished complicated reaction mixtures, in definite contrast with the microwave procedure [17]. 

In 1985, Tsuji s group carried out a Pd-catalyzed reaction of propargyl carbonate with methyl acetoacetate as a soft carbonucleophile under neutral conditions to afford 4,5-dihydrofuran 109 [89-91]. The resulting unstable 109 readily isomerized to furan 110 under acidic conditions. In addition, they also reported formation of disubstituted furan 112 via a Pd-catalyzed heteroannulation of hydroxy propargylic carbonate 111 [92], Presumably, an allenylpalladium complex (c/. 114) was the key intermediate. 

Allenyl alcohols have been used as starting materials for a different kind of dihydrofuran synthesis. This is a process with great generality and utility in total synthesis. An example of the process is shown in Eq. 13.43 [42]. Treatment of allenyl alcohol 133 with silver nitrate in aqueous acetone at room temperature leads stereospe-cifically to dihydrofuran 134 in excellent yield. A similar reaction occurs with allenyl ketones, leading to furans. The isomerization is known to take place with Rh(I) [43], Ag(I) [44, 45] Pd(II) [46], Au(III) [47, 48] Cu(I) [49] or Hg(II) [50, 51],... 

Starting from the metallated methoxyallene, the amide 157 was obtained easily, as Brandsma et al. showed [104], The latter selectively delivered the dihydrofurans 158 no isomeric dihydropyrroles were detected (Scheme 15.50). 

However, considerable amounts of 2,3-dihydrofuran 50 and tetrahydro-furan-2-carbaldehyde 53 were present because of an isomerization process. The isomerization takes place simultaneously with the hydroformylation reaction. When the 2,5-dihydrofuran 46 reacts with the rhodium hydride complex, the 3-alkyl intermediate 48 is formed. This can evolve to the 2,3-dihydrofuran 50 via /3-hydride elimination reaction. This new substrate can also give both 2- and 3-alkyl intermediates 52 and 48, respectively. Although the formation of the 3-alkyl intermediate 48 is thermodynamically favored, the acylation occurs faster in the 2-alkyl intermediates 52. Regio-selectivity is therefore dominated by the rate of formation of the acyl complexes. The modification of the phosphorus ligand and the conditions of the reaction make it possible to control the regioselectivity and prepare the 2- or 3-substituted aldehyde as the major product [78]. As far as we know, only two... 

Scheme 7 Mechanism for the hydroformylation-isomerization process of dihydrofurans 46 and 50...

Dibromoethane normally reacts with activated methylene groups to produce cyclopropyl derivatives [e.g. 25, 27], but not with 1,3-diphenylpropanone. Unlike the corresponding reaction of 1,3-dibromopropane with the ketone to form 2,6-diphenylcyclohexanone, 1,2-dibromoethane produces 2-benzylidene-3-phenyl-tetrahydrofuran and the isomeric 2-benzyl-3-phenyl-4,5-dihydrofuran via initial C-alkylation followed by ring closure onto the carbonyl oxygen atom (Scheme 6.2) [28],... 

Rats exposed to a fteptone-containing atmosphere excreted a variety of metabolites resulting from oxidative pathways [176]. The major metabolites were isomeric mono-alcohols and ketones, but small amounts of 2-ethyl-5-methyl-2,3-dihydrofuran (11.171, R = Et, R = Me, Fig. 11.22,a) and 5-ethyl-2-methyl-2,3-dihydrofuran (11.171, R = Me, R = Et) were also detected. These metabolites are believed to arise from 6-hydroxyheptan-3-one (11.170, R = Et, R = Me) and 5-hydroxyheptan-2-one (11.170, R = Me, R = Et). The postulated mechanism of formation of 2,3-dihydrofurans involves their equilibrium with the corresponding linear y-hydroxy ketones, as shown in Fig. 11.22,a. Such a reaction has been documented for linear y-hydroxy aldehydes [177],... 

Epoxy-l-butene (1) is a versatile intermediate for the production of commodity, specialty and fine chemicals (2). An important derivative of 1 is 2,5-dihydrofuran (2,5-DHF). This heterocycle is useful in the production of tetrahydrofuran (3), 2,3-dihydrofuran (4), 1,4-butanediol (5), and many fine chemicals (e.g., 3-formyltetrahydrofuran (6) and cyclopropanes (7)). The homogeneous, Lewis acid and iodide salt-catalyzed rearrangement (isomerization) of 1 to 2,5-DHF has been known since 1976 (8) and is the only practical method for 2,5-DHF synthesis. 

Dihydrofurans are known to polymerize readily by cationic means but not by free radical initiation (77MI11102). 2,3-Dihydro-5-methylfuran (40), for example, has been polymerized to a stereoregular, optically active polymer (Scheme 9) by the appropriate choice of a catalyst system. Interestingly, the double bond isomer 2-methylenetetrahydrofuran (41) can be cationically polymerized (74CL499) to the isomeric polymer (42 Scheme 10). Under the polymerization conditions, no isomerization of (41) to (40) occurred, and the resultant polymer was shown to be isotactic and crystalline by NMR and X-ray analysis, respectively. 

The allenyl epoxide (69) has been converted into the methoxyfuran (70) (76TL2387). A detailed discussion of the vinyloxirane-dihydrofuran isomerization as exemplified by the conversion of the vinyloxirane (71) to the dihydrofuran (72) has been presented (Scheme 14) (78CB3665). 

Mono- and di-alkylated furans were synthesized in a one-pot preparation from 2-propynyl-2-tetrahydropyranyl ether (106), butyllithium and formaldehyde. The intermediate allenyl ether (107) presumably cyclizes via a 2-(2-tetrapyranyloxy)-2,5-dihydrofuran (108) to afford the heterocycle (109) (79AG(E)875). In a similar manner, singly and doubly branched tetrahydropyranyloxybutynolates afforded the substituted furans (110) (Scheme 20). The thermocatalytic isomerization of ethyl l-methyl-2-phenylcyclopropene-3-carboxylate yielded the furan, possibly by a 1,3-sigmatropic displacement step or by a non-concerted biradical intermediate (75T2495). 

The major reaction in the thermal decomposition of 2,3-dihydrofuran (9) is a unimolecular isomerization to cyclopropanecarboxaldehyde (89JPC-1139). In an analogous [1,3] sigmatropic reaction, the isomerization of 2-methyl-4,5-dihydrofuran (10) leads to acetylcyclopropane, which can rearrange to 3-penten-2-one (94JPC2341). The latter product may also be formed directly from 10. 

Simple ring-opening reactions ([5 -> 5] isomerizations), which might be considered as the reversal of well-known cyclization reactions, are rather uncommon in five-membered ring compounds, and only few examples are known for unsaturated heterocycles such as pyrrole (8), dihydrofurans (9, 10), and isoxazoles (11). 

These compounds are very interesting because the corresponding alcohols are not stable. The most striking result is the extreme weakness of their reactivity, even at high temperature (Table 3) at 140°C, ethyl 1-propenyl ether, (IV), leads to 1% of conversion and 2,3-dihydrofuran (VI) is only just more reactive. In both cases, the hydrogenated compound is the main product. The HYD/I+HDO ratio reaches 2.3 for the first reactant and 5.2 for the second one (Table 2). It is also interesting to note that these molecules are not isomerized. 

Direct irradiation of 2,5-dihydrofuran (175) results in the formation of furan, tetrahydrofuran, and the isomeric oxiran (176).146 Certain 2,5-dihydrothiophen derivatives are similarly converted to the corresponding vinylthiirans,147 whereas 5,5-diaryl-2,5-dihydrofurans are reported to undergo di-7i-methane rearrangement.148 An unexpected transannular phototransformation has been observed on irradiation of the l,3-dioxolen-2-one (177)... 

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