Intramolecular Diels-Alder reactions high pressure

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 synthesis of the macrocycles 43 (Scheme 9) is an example of repetitive, highly stereoselective Diels-Alder reaction between bis-dienes 41 and bis-dienophiles 42, containing all oxo or methano bridges syn to one another. The consecutive inter- and intramolecular Diels-Alder reactions only succeed at high pressure. Obviously, both reactions are accelerated by pressure. The macrocycles are of interest in supramolecular chemistry (host-guest chemistry) because of their well-defined cavities with different sizes depending on the arene spacer-units. 

A particularly instructive example is the thermolysis of (Z)-l,3,8-nonatriene in which an intramolecular Diels-Alder reaction competes with a sigmatropic [1,5] hydrogen shift (Scheme 24). The use of high pressure here enables a reversal of the selectivity. At 150°C and 1 bar the [1,5] hydrogen shift passing through a monocyclic transition state is preferred. At 7.7 kbar the intramolecular Diels-Alder reaction is preferred due to its bicyclic transition state. 

Diels-Alder reactions have been conducted on solid phase, with either the dieno-phile or the diene linked to the support [156]. The reaction conditions and the regio-and stereoselectivities observed are similar to those in solution [58,157,158]. Illustrative examples of Diels-Alder reactions leading to support-bound cyclohexenes are listed in Table 5.10. Further examples include the cycloaddition of polystyrene-bound 2-sulfonyl-l,3-butadiene and V-phenylmaIcimidc [51], the high-pressure cycloaddition of 1,3-butadienes to resin-bound 1 -nitroacrylates [95], and the intramolecular Diels-Alder reaction of styrenes with acrylates [159]. 

While the syntheses of the acyclic precursors in the examples above each require a couple of steps, symmetrical dienynes with a central triple bond and heteroatoms in the tethers are more easily accessible. They can yield heterotricyclic compounds by the same reaction mode, for example, the diaza- and dioxatricycles 121 are obtained starting from dienynes 119 (Scheme 18) [73]. Yields were best (90%) with N-tosyl linkers, with N-Boc groups the reaction was slower (41% yield), and with N-benzyl linkers only decomposition occurred. This may be due to coordination and blocking of the catalyst by the more Lewis-basic amines. The cis- and frans-diastereomers of 121 were formed in a ratio of 1.8 1, and this ratio did not change in other solvents, at different temperatures, with other catalyst precursors or under high pressure (10 kbar). In view of the apparent influence of the tether, the unsymmetrical oxazaprecursor 122 gave a 7 3 mixture of tricycles 123 and 124. Obviously, the hydridopalladation of the triple bond occurred with some regioselectivity such that intramolecular carbopalladation of the allyl-amine predominated. It is noteworthy that in these cases the intramolecular Diels-Alder reactions of the intermediate trienes 120 already occur under the employed conditions, i.e. at 80 °C. 

An intramolecular Diels-Alder reaction of a furan with a strained and sterically hindered bicyclopropylidene that proceeded under high pressure to provide the acid-labile cycloadduct is shown in Equation (43) <1996T12185>. An apparent increase in the reaction rate was observed with the 5-methoxyfuran 58 compared to the 5-unsubstituted analog 59. 

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. 

A high-pressure technique has also been applied successfully to intramolecular Diels-Alder reactions. 

Furyl derivatives 76, with an allylether or allylamine-type linkage to a methylenecyclopropane framework, readily undergo high pressure-promoted intramolecular cycloaddition" to give spirocyclopropane tricyclic products 77. No cycloaddition reaction occurred at ambient pressure and the products were mostly tar and polymers. Lewis acid catalysis was only marginally successful (Scheme 7.18). At 1.0 GPa and a slightly elevated temperature (60-70 °C) the intramolecular Diels-Alder reaction occurs readily and is exo-diastereo-selective. To quantify the pressure effect on the kinetics the volumes of activation were determined. 

Araki, Y, and Konoike, T, Enantioselective total synthesis of (+)-6- 77i-mevinolin and its analogs. Efficient construction of the hexahydronaphthalene moiety by high pressure-promoted intramolecular Diels-Alder reaction of (7 ,2Z,8 , 10 )-l-[(fert-butyldimethylsilyl)oxy]-6-methyl-2,8,10-dodecatrien-4-one, 7. Org. Chem., 62, 5299, 1997. 

Diels-Alder reactions was measured as -25 cm3 mol l.l 3 Intramolecular Diels-Alder reactions do not always respond to high pressure, although the effects on the intermolecular Diels-Alder can be dramatic. 177,141 There are exceptions, however, and high pressure has been applied to intramolecular Diels-Alder reactions.l In one example, 134 could be cyclized to give a 1 1 mixture of 135/136 in refluxing toluene at ambient pressure.1 13 in order to suppress side reactions, a small amount of the radical scavenger BHT (2,6-Ai-tert-butyl-4-phenylphenol) was used. When this reaction was done at 13 kbar, in dichloromethane at room temperature, an 88% yield of a 1 2.3 mixture of 135/136 was obtained, without the need for added BHT. It is noted that attempts to cyclize 134 using several Lewis acids were not successful. Intramolecular Diels-Alder reactions will be discussed in Section 11.8. 

Keay - High pressure intramolecular Diels-Alder reaction of furan as a diene I89TL1045]... 

The Diels-Alder reactions of -deficient 2//-pyran-2-ones with vinyl moiety containing dienophiles under microwave and high pressures have been extensively reviewed. The microwave-initiated intramolecular Diels-Alder reaction of an alkynol with a furan (80) formed a cycloadduct (81) that readily converted to 3,4-disubstituted 5-hydroxyindoles (82) in 15-74% yields in a one-pot reaction (Scheme 23). ° The treatment of < rt/io-(trifluoromethanesulfonyloxy)aryl boronic acid pinacol ester (83) with t- or i-butyllithium generates arynes (85) via boronate intermediate (84) at... 

Dauben has extended his studies on organic reactions at high pressure to include the Diels-Alder reaction of /7-benzoquinone with achiral and chiral dienoic esters enantiomeric excesses of up to 50% are achieved in the latter case. Unsaturated esters are produced by the EtAlQg-catalysed ene reaction of a-substituted acrylate esters and alkenes. The Lewis-acid-catalysed intramolecular Diels-Alder reaction of the trienecarboxylate ester (127) leads to (128)... 

B. A. Keay, P.W. Dibble, High pressure intramolecular Diels-Alder reactions of the furan diene. Tetrahedron Lett. 30 (1989) 1045-1046. 

S.J. Burrell, A.E. Derome, M.S. Edenborough, L.M. Harwood, S.A. Leeming, N.S. Isaacs, The high pressure mediated intramolecular Diels-Alder reaction of furan dienes a synthetic approach towards daphnanes. Tetrahedron Lett. 26 (1985) 2229-2232. 

At ambient pressure, 195a did not undergo intramolecular [4 + 2] cycloaddition even at temperatures up to 150°C. The use of Lewis acids to promote the Diels-Alder reactions was of marginal success only. In contrast, on exposing the furan derivatives 195 to high pressure (10kbar) in 0.1-0.5 moll-1 solutions at 60-70°C, a clean cycloaddition took place (Table 18). 

Bicyclopropylidene (1) does not undergo an intermolecular Diels-Alder reaction with furan and 2-methoxyfuran even under high pressure. Intramolecular cycloadditions of compounds 160 with a furan tethered to bicyclopropylidene, however, were easily brought about under high pressure (10 kbar) and gave cycloadducts 161 stereoselectively in yields ranging from 32 to 95% (Scheme 35) [58]. 

Intramolecular ionic Diels-Alder reactions were carried out in highly polar media to afford carbocyclic ring systems. The strategy, which obviates the need for high temperatures and pressures, features in situ generation of heteroatom-stabUized allyl cations that undergo subsequent (4 + 2) cycloaddition at ambient temperature. Typically, reactions were complete within 1 hour after addition of substrate. Some cycloadducts were the result of a concerted process, whereas others were formed via a stepwise reaction mechanism (Grieco, 1996). 

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