Diels-Alder reactions of furan

The borane catalyst 4 is also effective in the Diels-Alder reaction of furan (Scheme 1.11). In the presence of a catalytic amount of this reagent a-bromoacro-lein or a-chloroacrolein reacts with furan to give the cycloadduct in very good chemical yield with high optical purity [6d]. 

An example of the Diels Alder reaction of furans is the cycloaddition of 31 with 4,4-diethoxybut-2-ynal (32) which acts as an acetylenedicarbaldehyde synthon to afford 7-oxabicyclo [2.2.1]heptene derivatives [29] which were then converted into substituted cyclohex-l-ene-l,6-dicarbaldehydes by a four-step procedure (Scheme 2.14). 

Diels-Alder reactions of furans are markedly reversible because of the aromatic character of the furan nucleus [la]. The lability of the cycloadducts, even at relatively low temperatures, as well as the sensitivity to acidic conditions of both furans and cycloadducts, preclude the use of strong Lewis acids and have therefore given importance to the high pressure technique. 

Whereas maleic anhydride can react with furan (139a) at ambient pressure, citraconic anhydride (140) reacts only at high pressures due to the strong deactivating effect of the methyl group (Schemes 5.21 and 5.22). The two-step synthesis [53] of the palasonin (141), in an overall yield of 96 %, is a good example of the acceleration of the Diels-Alder by high pressure (Scheme 5.21). Previous synthesis [54] based on the thermal Diels-Alder reaction of furan with methoxy carbonyl maleic anhydride required 12 steps. 

The Diels-Alder reaction can be greatly enhanced by high pressure (Chapter 5) but the effect of pressure is generally weaker in aqueous medium than in organic solvent. Results of high pressure-mediated Diels-Alder reactions of furans and acrylates in water and dichloromethane are reported in Table 6.6 [32]. In aqueous medium the cycloadditions occur with lower yields and less diastereoselectivity than in dichloromethane and, in some cases, addition-substitution reactions were observed. 

Table 6.6 Diels-Alder reactions of furans with acrylates in water and dichloromethane under high pressure...

The reaction of furan with 2,5-dihydrothiophene-3,4-dicarboxylic anhydride is remarkable (Scheme 6.19). Furan is a poor diene and requires high pressure to affect cycloadditions [39]. On the other hand, high temperatures are forbidden because cycloaddition products derived from furan undergo cycloreversion under these conditions. In 5.0m LP-DE, the Diels-Alder reaction of furan with 2,5-dihydrothiophene-3,4-dicarboxylic anhydride proceeds at room temperature and atmospheric pressure in 9.5 h with 70 % yield and with the same diastereos-electivity found when the reaction is carried out under high pressure [40]. 

Keay B. A., Hunt 1. R. Aspects of the Intramolecular Diels-Alder Reaction of Furan Dienes Leading to the Formation of Epoxydecalin Systems Adv. Cycloaddit. 1999 6 173-210... 

A review on fliran and its derivatives in the synthesis of other heterocycles was published <95CHE1034>. Furan decomposes on Pd(lll) at 300 K to form H, CO and CjH, which can dimerize to benzene at 350 K <96JA907>. Again, a considerable number of Diels-Alder reactions with furan and fiiran derivatives was reported. The synthesis of 2-pyridinyl-7-oxabicyclo[2.2.1]heptanes (e.g., 3, 4) was accomphshed via zinc chloride-mediated Diels-Alder reaction of furan with 2-vinylpyridines <96SL703>. 

Although the intramolecular Diels-Alder reaction of furan 40 does not occur with classical heating (Scheme 9.10) [51], the reaction has been performed successfully in 64% yield by using microwaves and absorbing the product on to silica gel-water. 

In another approach to periplanone B by Cauwberghs and De Clercq, an intramolecular Diels-Alder reaction of furan-allene 122 afforded a mixture of two exo adducts 123 and 124 and an endo adduct (not pictured) in 90% yield and a 5 4 1 ratio (Scheme 19.23) [28], Refluxing the mixture in mesitylene (N2, 164 °C) afforded a 2 1 equilibrium mixture of 123-124 through a cydoreversion process. The Diels-Alder adduct 123 was converted to 125 via a series of synthetic manipulations, which constituted a formal total synthesis of periplanone B (126). 

Both enantiomers of the bicyclic enone 78 and their derivatives have been proved to be useful chiral building blocks for the synthesis of natural products [29], among them y-butyrolactones. 78 is readily available in either enantiomeric form by a Diels-Alder reaction of furan with a-acetoxyacry-lonitrile and subsequent hydrolysis, followed by a resolution of the racemate... 

Diels-Alder reaction of furan 90 and 3-acrylol-l,3-oxazolidin-2-one 69 was effectively carried out with Cu(ll)-bu-box 3-derived complex. The corresponding... 

An interesting one-pot, five-component domino process using an intermolecular Diels-Alder reaction of furans with AT-phenylmaleimide as its final step has been used to construct the central core of indolo[2,3- ]carbazoles (Equation 86) <2002AGE4291>. Thus, aminooxazoles produced from an Ugi three-component reaction undergo acylation/intramolecular Diels-Alder/retro-Diels-Alder cycloreversion with pentafluorophenyl arylprop-2-ynoates to give furan derivatives. Subsequent Diels-Alder cycloaddition at elevated temperatures with A -phenylmaleimide produces carbazoles in good yields (Table 5). 

Many Diels-Alder reactions of furan give addition products containing dihydrofuran rings (Section 3.3.1.8). 

Diels-Alder catalyst. Znl2 greatly accelerates Diels-Alder reactions of furane and some dienophiles. The products can be converted into cyclohexadienols by [I-elimination of the oxa bridge.1... 

Diels-Alder reaction of furanes.1 A number of copper and copper(II) salts can catalyze the cycloaddition of a-acetoxy- and a-chloroacrylonitrile to furane at 20-35°. 

Other chemists have also reported that high pressures are not essential for Diels-Alder reactions of furane as originally believed (7, 161 10, 187).2... 

For some other recent applications of the Diels-Alder reaction of furans with ketene equivalents see I. Yamamato and K. Narasaka, Chem. Lett.,... 

The inter- and intramolecular Diels-Alder reactions of furans, and their applications to the synthesis of natural products as well as synthetic materials, were reviewed <1997T14179>. HfCU promoted the endo-seXccuve. inter-molecular Diels-Alder cycloadditions of furans with a,/3-unsaturated esters <2002AGE4079>. The cycloaddition between furan and methacrylate was also achieved under these conditions, providing, however the o-isomer as the major cycloadduct. A catalytic enantioselective Diels-Alder reaction between furan and acryloyl oxazolidinone to provide the < 46i-adduct in 97% ee was achieved by using the cationic bis(4-fer7-butyloxazoline)copper(ll) complex 55, as shown in Equation (41) <1997TL57>. 

Thieno[2,3-c]furan behaves as a thiophene-2,3-quinodimethane equivalent. Diels-Alder reaction of furan 775 with +-phenylmaleimide or maleic anhydride followed by acid-catalyzed dehydration affords benzo [ Jthiophenes 776 (Scheme 123) <1996JOC6166>. 

Privost reaction. A short synthesis of meth shikimate (5) involves base-promoted cleavage of 1, obtained by a Diels-Alder reaction of furane with methyl acrylate (11,... 

Diels-Alder reactions of furans were the subject of a recent review (1986). Their intermolecular versions profit notably from high-pressure conditions (Section 4.1.4.2.1) or the use of benzynes as dienophiles (Section 4.1.7). 

High pressure has been applied successfully to Diels-Alder reactions of furans, which are notoriously troublesome due to low activation barriers and low or even negative AC values. For example, attempts to synthesize the potent vesicant cantharidin (232) via reaction of furan (228) with dimethylmaleic anhydride (234) date back to 1928. The failure of this approach has been attributed to a thermodynamic preference for cycloreversion over cycloaddition. More than SO years later the problem was solved by employing high pressures and either a modified dienophile (229) or diene paitner (233). Interestingly, product (235) reverts to reactants (233) and (234) in solution at atmospheric pressure and room temperature (Scheme S4). 

BF3 Et20 is the most effective catalyst for the Diels-Alder reaction of furan with methyl acrylate, giving high endo selectivity in the 7-oxobicyclo[2.2.1]heptene product (Eq. 59) [105]. 

The intramolecular Diels-Alder reaction of furans, often designated as IMDAF,15 helps to overcome the sluggishness of this heteroaromatic ring system toward [4+21-cycloaddition. Not only do IMDAF reactions allow for the preparation of complex oxygenated polycyclic compounds, but they also often proceed at lower temperatures than their intermolecular counterparts.9 Even more significantly, unactivated rc-bonds are often suitable dienophiles for the internal cycloaddition. Indeed, the submitters discovered that the IMDAF reaction of a series of furanamide derivatives occurred... 

B) Diels-Alder reaction of furan and acentylenedicarboxylic ester, for which aluminium trichloride is known to be useful.[5]... 

Further experiments have shown that MeAlCl2 in catalytic amounts promotes the intramolecular Diels-Alder reaction of furans because the most basic site in the system is fhe reactive site in 13 so fhat the cycloadduct does not inhibit the catalysis (Scheme 6.9). In contrast, increasing the number of equivalents of MeAlCl2 reduces fhe conversion because MeAlCh-lB interaction is the more stable of fhe complexed forms fhis might be partly because of fhe diverse aggregates preferred by MeAlCl2. 

It was first reported in 1996 that indium trichloride catalyzes the Diels-Alder reaction in water [131]. The reaction of acrolein with cyclopentadiene in the presence of 20 mol% InCl proceeds stereoselectively (endo. exo=91 9) (Scheme 8.101). Without catalyst the reaction only goes to 60% completion (endo exo=74 26). The InCh-catalyzed Diels-Alder reaction works with either cyclic or non-cyclic dienes. InCh can be recovered for reuse after the reaction is completed. Indium triflate is also an effective catalyst for intramolecular Diels-Alder reactions of furans under microwave irradiation (Scheme 8.102) [132]. 

Intramolecular Diels-Alder reactions of furan derivatives 86YGK109. Oxidative coupling of furans under the action of transition metal catalysts ... 

---