Fumarates. Diels-Alder reactions

Diels-Alder reaction TALEIC ANHYDRIDE, MALEIC ACID AND FUMARIC ACID] (Vol 15) -from waste combustion [FUELS FROM WASTE] (Vol 12)... 

Removal of maleic and fumaric acids from the cmde malononitrile by fractional distillation is impractical because the boiling points differ only slightly. The impurities are therefore converted into high boiling compounds in a conventional reactor by means of a Diels-Alder reaction with a 1,3-diene. The volatile and nonvolatile by-products are finally removed by two vacuum distillations. The by-products are burned. The yield of malononitrile amounts to 66% based on cyanogen chloride or acetonitrile. 

Sorbic acid is oxidized rapidly in the presence of molecular oxygen or peroxide compounds. The decomposition products indicate that the double bond farthest from the carboxyl group is oxidized (11). More complete oxidation leads to acetaldehyde, acetic acid, fumaraldehyde, fumaric acid, and polymeric products. Sorbic acid undergoes Diels-Alder reactions with many dienophiles and undergoes self-dimerization, which leads to eight possible isomeric Diels-Alder stmctures (12). 

The Diels-Alder cycloaddition reaction (Section 14.4) is a pericvclic process that takes place between a diene (four tt electrons) and a dienophile (two tr electrons) to yield a cyclohexene product. Many thousands of examples of Diels-Alder reactions are known. They often take place easily at room temperature or slightly above, and they are stereospecific with respect to substituents. For example, room-temperature reaction between 1,3-butadiene and diethyl maleate (cis) yields exclusively the cis-disubstituted cyclohexene product. A similar reaction between 1,3-butadiene and diethyl fumarate (trans) yields exclusively the trans-disubstituted product. 

The discovery that Lewis acids can promote Diels-Alder reactions has become a powerful tool in synthetic organic chemistry. Yates and Eaton [4] first reported the remarkable acceleration of the reactions of anthracene with maleic anhydride, 1,4-benzoquinone and dimethyl fumarate catalyzed by aluminum chloride. The presence of the Lewis-acid catalyst allows the cycloadditions to be carried out under mild conditions, reactions with low reactive dienes and dienophiles are made possible, and the stereoselectivity, regioselectivity and site selectivity of the cycloaddition reaction can be modified [5]. Consequently, increasing attention has been given to these catalysts in order to develop new regio- and stereoselective synthetic routes based on the Diels-Alder reaction. 

The synthesis of highly substituted rigid tricyclic nitrogen heterocycles via a tandem four-component condensation (the Ugi reaction)/intramolecular Diels-Alder reaction was investigated in both solution and solid phase [24]. The Ugi reaction in MeOH (Scheme 4.2) involves the condensation of furylaldehydes 17, benzylamine 18, benzyl isocyanide 19 and maleic or fumaric acid derivatives 20, and provides the triene 21 which immediately undergoes an intramolecular Diels-Alder reaction, affording the cycloadduct 22 in a diastereoisomeric mixture with high yield. 

Another example of an enzymatic one-pot multiple Diels-Alder reaction is illustrated in Table 4.20 [83]. Racemic furfuryl alcohols 130 in the presence of ethoxy vinyl methyl fumarate 131 and enzyme TOYOBO-LIP undergo enzymatic acylation followed by kinetic enzymatic resolution to give the acyl derivatives 132 which then affords the adducts 133 and 134 by intramolecular Diels-Alder reaction 3-methyl-furfuryl alcohol 130 (R = Me) in acetone gives the best results. 

High-pressure and thermally induced intramolecular Diels-Alder reactions of furfuryl fumarates. Influence of tether substituents on diastereoselectivity [74]... 

The results of Diels-Alder reactions of cyclopentadiene with diethyl fumarate, diethyl maleate and ethyl acrylate carried out in SC-H2O are reported in Scheme 6.32 [79]. The cycloaddition of diethyl fumarate occurred with low yield. 

Diels-Alder reactions are stereospecific with respect to the E- and Z-relationships in both the dienophile and the diene. For example, addition of dimethyl fumarate and dimethyl maleate with cyclopentadiene is completely stereospecific with respect to the cis or trans orientation of the ester substituents. 

Scheme 4.3 Diels—Alder reaction of anthracene with diethyl fumarate.

The success of bis(oxazoline)-copper(II) catalyzed Diels-Alder reactions involving acryloylimides as dienophiles has been extended to the Michael reaction, Eqs. 204 and 205. The observed enantiofacial discrimination in the Diels-Alder reactions was expected to translate well to Michael reactions involving enolsilanes as nucleophiles. Indeed, fumarate-derived imides afford Michael adducts of enolsilanes in high enantioselectivity (240). Diastereoselectivity in these reactions may be regulated by judicious choice of thioester and enolsilane geometry to provide either diastereomer in high selectivity (>99 1 syn or 95 5 anti). 

Uses In organic synthesis (Diels-Alder reactions) manufacturing of agricultural chemicals, dye intermediates, pharmaceuticals, and alkyd-type resins manufacture of fumaric and tartaric acids pesticides preservative for oils and fats. 

Several examples of ring transformation can be found in CHEC-II(1996) <1996CHEC-II(7)921 > and some are referred to earlier in this chapter (see Sections 10.23.9.1.1 and 10.23.9.2.1). The benzobisthietes 114 and 115 can be ring-expanded by Diels-Alder reactions with dimethyl fumarate to afford the corresponding thiopyrans in moderate yield, due to competing oligomerization (Equations 59 and 60) <1998TL9639>. 

Dichlorodibutyl ether, 27 Diels-Alder reaction of butadiene with maleic anhydride, 93 Diene synthesis of cis-A -tetrahydro-phthalic anhydride, 93 Diethyl benzalmalonate, 84 Diethyl carbonate, 44 Diethyl fumarate, 46 Diethyl cis-HEXAiiYDROPiiTHALATE, 29 Diethyl malonate, 70 Diethyl o-nitrobenzoylmalonatc, 71 Diethyl sodium phthalimidomalonate, 7... 

Hydrolase-catalyzed domino reactions incorporating a resolution and a subsequent cycloaddition reaction have been described [95-97]. This constitutes an attractive approach to complex synthetic intermediates. For example, the l-(3-methyl-2-furyl)]propanol roc-93 reacts with ethoxyvinyl methyl fumarate (94) catalyzed by Lipase LIP (from Pseudomonas aeruginosa) to furnish a dienophilic fumarate ester, which spontaneously undergoes an intramolecular Diels-Alder reaction with the furan moiety furnishing exclusively the syn-adduct, the oxabicy-clohexene 95 in excellent along with the remaining alcohol S-96 (Scheme 4.31) [95]. A similar approach has been used for a procedure that includes a series of domino reactions that includes dynamic kinetic resolution of the 3-vinylcyclohex-... 

A benz-analog of 353, namely 360, has been obtained in a Wittig reaction with either o-phthalaldehyde or furan-3,4-dialdehyde as expected, 360 was found to be more stable than 353. Diels-Alder reaction with dimethyl fumarate resulted in cycloaddition to the furan ring. ... 

In the fused compounds (241) and (242) the furan ring fails to react as a diene and Diels-Alder reaction with dienophiles occurs on the terminal carbocyclic rings. However, (243) and (244) afford monoadducts with dimethyl fumarate by addition to the furan rings (70JA972). The rates of reaction (Table 2) of a number of dehydroannuleno[c]furans with maleic anhydride, which yield fully conjugated dehydroannulenes of the exo type (247), have been correlated with the aromaticity or antiaromaticity of the products (76JA6052). It was assumed that the transition state for the reactions resembled products to some extent, and the relative rates therefore are a measure of the resonance energy of the products. The reaction of the open-chain compound (250), which yields the adduct (251), was taken as a model. Hence the dehydro[4 + 2]annulenes from (246) and (249) are stabilized compared to (251), and the dehydro[4 ]annulenes from (245) and (248) are destabilized (Scheme 84). 

The generation of benzo[c]furan as a transient species by retro Diels-Alder reactions has been used for synthetic purposes. When the adduct (414) was decomposed in the presence of dimethyl fumarate the product (415) was obtained decomposition of (414) with dimethyl maleate yielded the adducts (416) and (417) in the ratio 2 1 (Scheme 110) (69TL5231). 

Pyrrolidines and pyrrolidinones can be synthesized on insoluble supports by intramolecular carbometallation of alkenes (Entry 1, Table 15.4) and by Ugi reaction of support-bound isonitriles with amines and 4-oxo acids (Entry 4, Table 15.4). In Entry 5 in Table 15.4, the pyrrolidinone ring is formed by intramolecular Diels-Alder reaction of a furan with a fumaric acid derivative. 2-Pyrrolidinones have also been prepared by treatment of resin-bound O-mesitylenesulfonyl cyclobutanone oximes with... 

Furan [110-00-9] - [BUTADIENE] (Vol 4) - [FURANDERIVATIVES] (Supplement) -from butenediol [ACETYLENE-DERIVED CHEMICALS] (Voll) -Diels-Alder reaction [MALEIC ANHYDRIDE, MALEIC ACID AND FUMARIC ACID] (Vol 15) -from waste combustion [FUELS FROM WASTE] (Vol 12)... 

Recently175 fourteen products were separated chromatographically and identified from the reaction of indole with DMAD in the absence of solvent. All were explained as arising from the fumarate 255, which was isolated, or the maleate 256 which was not. These compounds could undergo Diels-Alder reactions with DMAD to yield 265 and 267, respectively, which were not isolated, but on aromatization both would give the carbazole 266, which was the major product obtained. The main product from the fumarate 255 with DMAD is, in fact, 266,... 

Likewise with the dienophile the maleate and fumarate esters 2.90 and 2,92 react with butadiene to give diastereoisomeric adducts 2.91 and 2.93, in which the substituents retain, as a consequence of the suprafacial nature of the developing overlap, the cis and trans relationships they had in the dienophiles. Diels-Alder reactions are much used in organic synthesis, not only because two new C-C bonds are made in one step, but also because the relative stereochemistry of up to four new stereogenic centres is predictable. 

Chiral Ti complex, derived from hydrobenzoin dilithium salt and TiCl4, can be used for the asymmetric Diels-Alder reaction of several dienes with fumarate [53] (Eq. 8A.30). However, attempted use of acrylate as dienophile resulted in low enantioselectivity. 

Narasaka reported a highly enantioselective Diels-Alder reaction between isoprene and a fumaric acid derivative 17 using a catalytic amount of a chiral titanium reagent prepared from tartrate-derived chiral 1,4-diol 18 and TiCI2(0-/-Pr)2 [27]. When a stoichiometric amount of the partially resolved chiral diol (25% ee) was used, the corresponding cycloadduct 19 with 83% ee was obtained (Scheme 9.12). In this reaction, white precipitate was formed, which proved to... 

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