Furfuryl intramolecular Diels-Alder reaction

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]... 

Table 18. Intramolecular Diels-Alder reactions under high pressure of furfuryl-substituted alkylidenecyclopropanes 195...

The use of isopropylidine acetals (112) as tethers in the intramolecular Diels-Alder reactions of dienes with alkenes facilitates the formation of civ-fused cycloadducts (113) from an endo transition state (Scheme 41).218 The intramolecular Diels-Alder reaction of 4-[tris-(2-mcthylcthyl)silyl]oxy-2//-thiopyran derivatives with potential dienophiles tethered at C(2), C(3), C(5), and C(6) positions yielded cycloadducts when the dienophiles were activated with a carbomethoxy group.219 By the substitution of a phenylsulfonyl group on the dienophile of 2-benzopyran-3-ones, it is possible to enhance exo addition during intramolecular Diels-Alder cyclizations to yield a predominance of trans-fused hexaphenanthrenes related to natural products.220 The intramolecular Diels-Alder reaction of 2-furfuryl fumarates has been investigated by molecular mechanics (SIBFA)/continuum reaction field computations.221 The intramolecular 4 + 2-photo-cycloaddition of A-benzylcinnamamides (114) in the presence of C(,H6 gives 3-azatricyclo[5.2.2.01,5]undeca-8,10-dien-4-ones (115) with high stereoselectivity (Scheme 42).222... 

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]. 

Under high pressure, intramolecular [2 + 4] cycloadditions of a methylenecyclopropane moiety without being activated by an electron-withdrawing group - can be achieved. Thus, furfuryl derivatives 3, with an allyl ether or allylamine type linkage to a methylenecyclopropane, undergo intramolecular Diels-Alder reactions at 10-12 kbar to yield interesting new spirocyclo-propane-annulated tricyclic compounds 4 diastereoselectively in excellent yields. 

Butz and Sauer investigated the intramolecular Diels-Alder reaction of furfuryl fumarates 148 to synthesize oxabicyclo[2.2.1]heptene derivatives 149 and 150 (Scheme 8.37) [69]. Four new stereocenters of defined configuration are generated in this transformation under the induction of the stereogenic center in the side arm with remarkable selectivity. The cycloaddition of 148 with various substituents R at the stereogenic center was investigated and it was found that the diastereo-... 

Jung ME, Gervay J. gem-Dialkyl effect in the intramolecular Diels-Alder reaction of 2-furfuryl methyl fumarates the reactive rotamer effect, the enthalpic basis for acceleration, and evidence for a polar transition state. //lm Chem Soc. 1991 13(1) 224—232. 

Other Applications. Indium(III) triflate catalyzes the intramolecular Diels-Alder reaction of furans in aqueous media under microwave irradiation. In a one-pot procedure, allyl bromide reacts with (2-furfuryl)anilines affording the intramolecular Diels-Alder products in good to excellent yields, in very short reaction times (eq 19). Under thermal conditions, yields of40-45% are obtained. Such products allow access to indole derivatives through cleavage of the epoxy bridge and aromatization. 

The Diels-Alder reaction of ester-tethered trienes is also known as a powerful methodology to construct polycylic Y lactones [68]. Romo et al. [69] surveyed effective organic nucleophilic catalysts for tandem intermolecular Diels-Alder reaction/lactonization reaction of achiral a, 3-unsaturated acid chlorides with dienyl alcohol 100 (Scheme 45). In this case, when chiral Lewis base 102 was used as a nucleophilic catalyst, excellent enantioselectivity was realized. Lipase-catalyzed domino kinetic resolution/intramolecular Diels-Alder reaction of furfuryl alcohols with acrylic acids was also carried out by Akai and Kita [70]. 

When furfuryl diester 15 was reacted with an equimolar amount of DMAD under high pressure (Skbar, 7days), the product 18 was isolated in 25% yield (Scheme 4) [10]. Interestingly, product 18 was isolated even in the presence of an excess of DMAD in the reachon. This result was explained that bo intramolecular and intermolecular reactions had been promoted under the high-pressure conditions. Thus, intramolecular Diels-Alder (IMDA) reaction of one of the tethered furans occurred inihally with the cyclobutene Jt-bond of 15 and led to the formation of the adduct 16. The remaining furan enhty in product 16 was then free to react with DMAD to form the oxanorbomadiene adduct 17 and reaction stopped at that stage. However, product 18 was finally isolated rather than 17 as a result of secondary retro-DAof 17. 

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