Trienes intramolecular Diels-Alder reaction

Aqueous hydrofluoric acid dissolved in acetonitrile is a good catalyst for intramolecular Diels-Alder reactions [9] This reagent promotes highly stereoselective cyclizations of different triene esters (equation 8) The use of other acids, such as hydrochloric, acetic, and trifluoroacetic acid, results in complete polymerization of the starting trienes [9] (equation 8)... 

Brmsted acid-assisted chiral Lewis acid 8 was also applied to the intramolecular Diels-Alder reaction of an a-unsubstituted triene derivative. ( , )-2,7,9-Decatrienal reacts in the presence of 30 mol% of the catalyst to afford the bicyclo compound in high yield and good enantioselectivity [lOd] (Scheme 1.17). 

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. 

In intramolecular Diels-Alder reactions, two rings are formed in one step. The reaction has been used to synthesize a number of interesting ring systems.29 The intramolecular cyclization of ( )-l-nitrodeca-l,6,8-triene at 80 °C affords an endo cycloadduct with the tram ring fusion preferentially, as shown in Eq. 8.18. In contrast, (Z)-nitroalkenes produce a nearly 1 1 mixture of cis- and tra/w-fused cycloadducts.30... 

Isopropyl-4,6-dimethyltricyclo[4.4.05 9]dec-3-en-2-one (40) with unknown absolute configuration was isolated as a putative male pheromone of a Brazilian predatory stink bug (Tynacantha marginata), and its enantiomers were synthesized by Kuwahara as shown in Scheme 58 [88]. The triene A gave B and C by an intramolecular Diels-Alder reaction, and they could be converted to the enantiomers of 40. 

Diels-Alder catalysis.1 This radical cation can increase the endo-selectivity of Diels-Alder reactions when the dienophile is a styrene or electron-rich alkene. This endo-selectivity obtains even in intramolecular Diels-Alder reactions. Thus the triene 2, a mixture of (Z)- and (E)-isomers, cyclizes in the presence of 1 to 0° to the hydroindanes 3 and 4 in the ratio 97 3. Similar cyclization of (E)-2 results in 3 and 4 in the ratio 98 2 therefore, the catalyst can effect isomerization of (Z)-2 to (E)-2. Even higher stereoselectivity is observed when the styrene group of 2 is replaced by a vinyl sulfide group (SC6H5 in place of QHtOCT ). 

The cross-conjugated trienes have potential in many different types of diversification strategies. For example, the triene clearly lends itself to inter- and intramolecular Diels-Alder reactions. Incorporation of the hydroxymethyl group on the tether allows attachment of functionality suitable for reactions subsequent to the Alder-ene reactions. As depicted in Scheme 8.5, propargyl tosylamides A, alkynyl silanes B, acrylate esters C, and propargyl ethers D can all be readily prepared from 39... 

Corey later reported that BLA 59a catalyzes the intramolecular Diels-Alder reaction of several triene aldehydes and esters with high asymmetric induction to yield the corresponding 6/5-trons-fused bicyclic structures (Scheme 5.74) [143]. 

Intramolecular Diels-Alder reactions of trienes. -10 The thermal cycli/ation of the (f ,L)-triene 1 afl ords trans- and ci.v-perhydroindcnes 2 and 3, with a slight preference for the former isomer. The reaction is markedly catalyzed by Lewis acids such as A1C13, C,II5A1C12, and TiCI4, and results in cyclization exclusively to the... 

A. A. Ghini, C. Bumouf, J. C. Lopez, A. Olesker, and G. Lukacs, Intramolecular Diels-Alder reactions on pyranose trienes. Stereoselective access to bis-annulated pyranosides. Tetrahedron Lett. 37 2301 (1990). 

Alkynes are poor dienophiles in the Diels- Alder reaction decomposition occurs by an attempted thermal intramolecular Diels-Alder reaction of dienynes at 160 °C. In contrast, the Ni-catalysed [4+2] cycloaddition of the dienyne 50 proceeded smoothly at room temperature using tri(hexafluoro)isopropyl phosphite to give 51, which was converted to the yohimbine skeleton 52 [15]. The same reaction is catalysed by RhCl(Ph3P)3 in trifluoroethanol [16]. Intramolecular Diels-Alder reactions of the 6,8-dieneyne 53 and the 1,3,8-triene 55, efficiently catalysed by [Rh(dppe)(CH2CH2)2]SbF6 at room temperature, gave 54 and 56 [17],... 

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. 

By reaction of the dienal 701 with the dienyl anion 697 and subsequent hydrolysis, the triene 702 was obtained. This enone 702 underwent intramolecular Diels-Alder reaction to give the traws-fused tetrahydroindanone 7031002 (Scheme 182). 

Intramolecular Diels-Alder reactions resulting in bridgehead alkenes usually require high reaction temperatures. Consequently catalysts that permit use of lower temperatures are useful. Of a number of Lewis acids studied, diethylaluminum chloride was found to be the most efficient for the intramolecular cycloaddition of the triene 7 to 8 at 21°. The... 

This model also predicts that selectivity for the tranr-fused cycloadducts in nonatriene (n = 0) or deca-triene (n = 1) cyclizations should increase as size of the coefficients at C 2)IC S + n) are increased relative to those at C(l)/C(9 + n), that is, as the polarization of the dienophile or diene is increased. Tables 1 and 2 summarize results of intramolecular Diels-Alder reactions that provide a test of this propo-gai.24.25 it ig tiiat an electron-releasing Et N group at C(9) of the nonatrioioate system leads to a substantial increase in selectivity for the trans-fased product (compare entries 4-6, Table 1). Increased trans stereoselectivity also occurs with C(9)-alkoxy-substituted nonatrienes. A similar effect... 

An interesting sequence of two consecutive Heck-type cyclizations and a subsequent Diels-Alder addition was observed when the methoxycarbonyl-substituted 2-bromo-trideca-1,1 l-dien-6-yne ( /Z)-63 was treated with the typical palladium catalyst (Scheme 3-20) [172]. The cyclization of dienyne 63 at 80 °C gave two diastereomeric trienes ( /Z)-64. At higher temperature (130 °C), an intramolecular Diels-Alder reaction of only the ( J)-isomer ( )-64 occurred to give the tetracyclic 65, whereas (Z)-64 remained as such, probably due to steric interference of the methoxy group. 

In order to confirm the structures of solanapyrones, chemical synthesis of these phytotoxins were attempted based on biogenetic consideration [55], The retro synthesis envisaged intramolecular Diels-Alder reaction of the achiral polyketide triene (a), a key intermediate, which is further divided into a pyrone moiety (b) and a diene moiety (c). The moieties a and b were prepared from dehydroacetic acid and hexadienyl acetate, respectively. Aldol condensation of the aldehyde (72) with the dithioacetal (73) gave a dienol, which was further converted to a triene (74). The intramolecular Diels-Alder reaction of 74 in toluene at 170-190 °C for 1 hr in a sealed tube yielded a mixture of the adducts (75) and (76) in a ratio of 1 2. This product ratio depends on the solvents, i.e. in water (1 7), and should be useful in differentiating between artificial and enzymatic reactions in biosynthetic studies. Removal of the thioacetal groups in 75 and 76 yielded solanapyrone A (67) and D (70) in a ratio of 3 5. Though solanapyrone D (70) had not been isolated from the natural resources at this stage, the structure and stereochemistry were confirmed by H NMR spectrum. 

Methyl 2-azabicyclo[3.1 -0]hex-3-ene-2-carboxylate (4) also reacts according to a [4+6] cycloaddition mechanism if tropone (26) is used as the electron-deficient triene. The primary product 27 of this [(27t-l-2ff)-l-(27t-f-27r + 27r)] process, containing a doubly bridged 11-membered ring, could not be isolated and immediately underwent an intramolecular Diels-Alder reaction to form the cage compound 28. ... 

Such a procedure has been exploited for the synthesis of several derivatives for which an anti-inflammatory activity has been claimed [58]. A derivative under study as the Histamine H3 antagonist was prepared by the thermal intramolecular Diels-Alder reaction of a triene derivative of buta-1,3-diene-1-sulfonic acid amide. 1,3-Butadiene sulfonamides 182 (a 67%, b 69%, c 99%, d 51%) were prepared by the base mediated condensation of M-Boc-methanesulfonamides (181) with a series of aldheydes. N-akylation of 182 to give trienes 183 (a 69%, b 76%, c 82%, d 59%) was achieved by reacting the sodium salts with allyl bromide in THF at reflux. The intramolecular Diels-Alder reactions of compounds 183 were performed at 145 °C in toluene in a sealed vessel under argon. Under these conditions compounds 184 and 184 were obtained in good yields (a 76% ratio 6 1, b 71% ratio 6 1, c 92% ratio 3 1, d 87% ratio 3 1). 

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