Diels-Alder reaction with dimethyl fumarate

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>. 

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. ... 

Toward asymmetric Diels-Alder reaction in industrial chemistry, the use of menthyl group as an inexpensive and recyclable chiral auxiliary was investigated. As a pioneering work in this field, Yamamoto reported aluminum Lewis acid-catalyzed Diels-Alder reaction of dimethyl fumarate with cyclopentadiene (Scheme 6.119) [143]. Later, more suitable reaction conditions for large-scale synthesis was investigated. 

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). 

These examples demonstrate that a selective Heck-Diels-Alder sequence with two different alkenes is only possible either in a stepwise manner, if an alkene reacts much faster in the Heck reaction than in the subsequent cycloaddition so that the 1,3-diene can be isolated, or as a real cascade reaction if one alkene is more reactive and thus selectively reacts as a coupling partner, whereas the other one is a better dienophile. Both concepts have been used by Kollar et al. for the annelation of cyclohexene rings onto the steroidal skeleton 26 (Scheme 4) [28-30]. At 60 °C the cycloaddition was sufficiently suppressed so that the Heck coupling product 29 could be isolated and subsequently subjected to Diels-Alder reactions with different dienophiles. For a domino reaction with both methyl acrylate and dimethyl fumarate (28) present in the reaction mixture, the conditions had to be precisely adjusted so that the mixed products 31 and 32 were formed predominantly along with only small amounts of the products of a twofold reaction of either 27 (R = CC Me) or 28 with 26. These conditions also proved suitable for a cascade reaction of 26 involving allyl alcohol 27 (R = CH2OH) or allyl acetate 27 (R = CH2OAc) and dimethyl fumarate (28). 

The stereochemistry of the adduct obtained in many Diels-Alder reactions can be selected on the basis of two empirical rules formulated by Alder and Stein in 1937. According to the cis principle , the relative stereochentistry of substituents in both the dienophile and the diene is retained in the adduct. That is, a dienophile with trans substituents will give an adduct in which the trans configuration of the substituents is retained, while a cis disubstituted dienophile will form an adduct in which the substituents are cis to each other. This aspect is often referred to as the stereospecific nature of the Diels-Alder reaction. For example, in the reaction of cyclopentadiene with dimethyl maleate, the cis adducts 74 and 75 are formed, while in the reaction with dimethyl fumarate, the trans configuration of the ester groups is retained in the adduct 76 (3.64). 

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. 

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. 

The 18 n-electron system furo[3,4-c]octalene (356) is available by a Wittig reaction starting from cyclooctatetraene-1,2-dicarboxaldehyde it is obtained as an unstable pale yellow liquid, which is rapidly oxidized in air. The electronic spectrum resembles that of 353, showing little extended conjugation. Compound 356 underwent Diels-Alder addition at the terminal cyclooctatetraene ring thus treatment with dimethyl fumarate leads to monoadduct 357. ... 

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). 

Olah et al.902 demonstrated in 1979 that Nafion-H is able to catalyze Diels-Alder reaction of anthracene with a number of dienophile (maleic anhydride [Eq. (5.329)], para-benzoquinone, dimethyl maleate, dimethyl fumarate) in chloroform or benzene... 

Complete stereoselectivity occurs in the Diels-Alder reaction through syn addition of the dienophile to the diene. Hence, the reaction of dimethyl fumarate and dimethyl maleate with cyclopentadiene yields the trans and cis adducts, respectively (Scheme 26.1).29... 

A triplex has been proposed as an intermediate in some photoreactions. Yang and co-workers [54] found that addition of 1,3-dienes to anthracene excimers leads to different products than does its adition to monomeric excited arenes. Lewis and co-workers [55, 56] found that stilbene excimers can be intercepted by dimethyl fumarate to give an oxetane through a presumed triplex. More recently, Schuster and co-workers [57,58] studied the Triplex Diels-Alder reaction of 1,3-dienes with enol, alkene, and acetylenic dienophiles. Take 9,10-dicyanonaphthalene (DCN)/indene (IN)/l,3-cyclohexadiene (CHD) system as an example ... 

Rather large rate enhancements with increasing solvent polarity have also been found for intramolecular Diels-Alder reactions such as the cyclization of 2-furfuryl methyl fumarate shown in Eq. (5-42a) to yield lactone D. This first-order reaction is about 3200 times faster in dimethyl sulfoxide than in toluene as solvent [807]. 

One reported exception is the thermal stereospecific SO2 extrasion of frans-acetoxyphenyl sulfone (613), coupled with Ae Diels-Alder reaction of Ae postulated ( ,Z)-diene (614) to dimethyl fumarate, yielding (615 94%) (Scheme ISS). ... 

The investigation of the Diels-Alder reaction of 2-substituted-a,/5-unsaturated hydrazones in a concentrated solution of LiNTf2 in MeCN revealed a spectacular rate increase when the reaction of 80 with A-phenylmaleimide (81) was run in this media (2.5 M LiNTf2-MeCN) (Sch. 40). These conditions also enable cycloadditions to be performed with less reactive dienophiles such as dimethyl fumarate or malate such cycloadditions result in stereospecific cyclizations [90]. 

Charlton and Alauddin have also reported an asymmetric synthesis of (+)-isolariciresinol dimethyl ether by using a chiral sulfone in an asymmetric Diels Alder reaction (scheme 45) [108]. The key step here involves elimination of sulfur dioxide from the sulfone (123) to yield the o-quinonedimethane which undergoes cycloaddition with dimethyl fumarate to give mainly (124). They have further extended this work to include the synthesis of a series of retrodendrin derivatives [109]. 

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