Diels-Alder reaction with acyclic dienes

The 5-methylene-2(5//)-furanone 216 was found to be a good dienophile in Diels-Alder reactions with acyclic dienes (R = H, 2-Me, 2,3-di-Me, 1-Me, 1,3-di-Me). The reaction took place specifically at the cxo-cyclic double bond to give the corresponding spiro adducts 217 in good yields (Scheme 59) (90JOC3060). 

Yamamoto Y, Yamamoto H. Catalytic asymmetric nitroso Diels-Alder reaction with acyclic dienes. Angew. Chem. Int. Ed. 2005 44 7082-7085. 

Diels-Alder reactions with acyclic and carbocyclic dienes are compiled in Scheme 5. The comparison between the Lewis-acid catalyzed and pressure-induced reaction (entry 1) shows that the application of high pressure, particularly in acid-sensitive systems, can sometimes lead to a better yield. Furthermore, pressure may shift the product ratio, if the activation volumes of the competing reactions are different, so that the application of pressure may also be useful in highly reactive systems, e.g. the reactive indenone 17 as dienophile, provided that a shift in the product ratio is desired. At atmospheric... 

SCHEME 5. Diels-Alder reactions with acyclic and carboxyclic dienes... 

Diels-Alder reactions of 4-heteromethylene-5(4/7)-oxazolones have been described. ( )-4-(Chloromethylene)-5(4//)-oxazolone 737 reacts with 2,3-dunethyl-butadiene in the presence of ethylaluminum dichloride to afford the cycloadduct 738. The cycloaddition reaction is characterized by high diastereoselectivity and occurs without appreciable isomerization of the dienophile. Further synthetic transformations of 738 yield 1-amino-3,4-dimethyl-6-hydroxy-cyclohex-3-enecar-boxylic acid 739 (Scheme 1.121) Examples of Diels-Alder reactions of acyclic dienes and unsaturated 5(4//)-oxazolones are shown in Table 7.50 (Fig. 7.61). 

Vinylbenzofurans also react as dienes in Diels-Alder reactions with acyclic olefins. The 3-vinylbenzofiirans 174,175, and 176 gave the normal adducts resulting from (4ir+27r)-cycloaddition in its reaction with TCNE. A by-product from the reaction of the diene 174 and TCNE was the cyclobutane 177 (91AJC1085). 

More recent developments include the refined catalyst 123 with extra bulk and an extra chiral centre. This catalyses reactions between functionalised dienes such as 120 and acyclic enones such as 121. The very high yields, ees, and endo exo selectivity of the product 122 compensate for the 20% catalyst loading. It is very difficult to get high ees in Diels-Alder reactions with acyclic ketones and you will see in the next section why this catalyst is successful.27... 

Dithioesters bearing a chiral auxiliary have been used in asymmetric thia-Diels-Alder reactions with acyclic 1,3-dienes to produce cycloadducts with a diastereomeric excess of 90%. A Cu(II)bis(oxazoline)/dithioesters complex has been proposed to rationalize the chiral induction ... 

In a Diels-Alder reaction, an acyclic diene will give a product with a cyclohexene ring ... 

The diastereoselectivity of Diels-Alder reactions with acyclic sugar-vinylcarbene complexes depends on the nature of the diene. Whereas the tungsten vinylcar-bene 222 gives all four possible diastereomers of cydoadduct 296 upon reaction with cyclopentadiene, only one pair of diastereomers of 297 is observed with 2,3-dimethylbutadiene (Scheme 11.61) [110]. 

Strained pertrifluoromethyl-substituted valence tautomers of aromatic systems, such as tetrakis(trifiuoromethyl)Dewar thiophene [87] and hexalas(tnfluorQ-methyl)benzvalene [Diels-Alder reactions with various cyclic and acyclic dienes (equations 76 and 77). 

The intermolecular Diels-Alder reaction between the dibromoenone (111) and dienes (112) provides access to bicyclo[5.4.0]undecane systems (113) that are common core structures of many natural products (Scheme 32).118 The alio-threonine-derived O-(/ -biphenyl carbonyl oxy)-/i-phenyloxazaborolidi none catalyses the enan-tioselective Diels-Alder reaction of acyclic enones with dienes.119 The reversal of facial selectivity in the Diels-Alder cycloaddition of a semicyclic diene with a bro-moenone was induced by the presence of the bromo substituent in the dienophile.120 Mixed Lewis acid catalyst (AlBr3/AIMe3) catalyses the Diels-Alder reaction of hindered silyloxydienes with substituted enones to produce highly substituted cyclohexenes.121 Chiral /V-enoyl sultams have been used as chiral auxiliaries in the asymmetric Diels-Alder reactions with cyclopentadiene.122... 

The 4 + 2-cycloaddition of 2-substituted 1,2-dihydropyridines with nitrosoben-zene produces [2.2.2]bicycloadducts, which are readily reduced by alane to trans-2-substituted 3-amino-l,2,3,6-tetrahydropyridines stereospeciflcally.123 The intramolec- (g) ular nitroso-Diels-Alder reaction of a-acetoxynitroso derivatives in aqueous medium produces 3,6-dihydro-l,2-oxazines in high yield.124 The nitroso-Diels-Alder reaction of acyclic OTIPS-dienes (115) and 6-methyl-2-nitrosopyridine (114) in the presence of (g) [Cu(MeCN)4(difluorosegphos)]PF6 yielded the dihydro 1,2-oxazine cycloadduct (116) with high yield and enantioselectivity (Scheme 33). 125 (Fe)... 

When the diene is acyclic, [4+4] cycloaddition remains the primary reaction pathway even when the result is a highly reactive and unstable trans-alkene product, e.g., 150 and 151 (Sch. 35). With 1,3-butadiene, these intermediates are intercepted by an additional equivalent of the diene, to give the 2 1 adducts 152 and 153. When a diene is used that cannot achieve an s-cis conformation such as 154, Diels-Alder reaction with [4+4] adducts 155 and 156 is impossible and these compounds relieve strain via Cope rearrangement to give cyclobutanes 157 and 158, respectively [98]. An intramolecular version of this reaction has been reported [99]. 

Diels-Alder reactions of the type shown in Table 12.1, that is, Diels-Alder reactions between electron-poor dienophiles and electron-rich dienes, are referred to as Diels-Alder reactions with normal electron demand. The overwhelming majority of known Diels-Alder reactions exhibit such a normal electron demand. Typical dienophiles include acrolein, methyl vinyl ketone, acrylic acid esters, acrylonitrile, fumaric acid esters (fnms-butenedioic acid esters), maleic anhydride, and tetra-cyanoethene—all of which are acceptor-substituted alkenes. Typical dienes are cy-clopentadiene and acyclic 1,3-butadienes with alkyl-, aryl-, alkoxy-, and/or trimethyl-silyloxy substituents—all of which are dienes with a donor substituent. 

A plethora of different acyclic and cyclic diaza dienes has been employed in aza Diels-Alder reactions. With regard to acyclic dienes, the main interest has focused on the cycloadditions of 1,3-diaza-1,3-butadienes. A current example of these transformations is the preparation of highly substituted pyrimidine derivatives such as 3-65 by cycloaddition of diaza-1,3-butadienes e.g. 3-64 with electron-deficient acetylenes (Fig. 3-20) [299]. 

Scheme 22. The angular nature of the bisdienophile 74 means that there are two possible constitutionally-different modes for the initial intermolecular Diels-Alder reaction with 76. The first one brings the reactive termini close enough together in 77 to undergo a final intramolecular macropolycyclization to afford 78. The second one, however, places the remaining termini too distant to react in an intramolecular fashion, thus affording the novel acyclic adduct 79 which is terminated at one end by a diene unit and at the other end by a dienophilic unit...

The reactions of p-nitrostyrene (81a) with both acyclic and cyclic enol-ethers have been studied. In general, when electron-rich alkenes interact at 1.5 GPa with p-nitrostyrene (81a), mixtures of bicyclic or tricyclic regioisomers are obtained. For example, the reaction of 81a with enol ether 86 (Scheme 7.21) led to a 7 3 mixture of compounds 87 and 88. p-Nitrostyrene (81a) first reacts as an electron-poor diene in an inverse electron demand Diels-Alder reaction with the enol ether, and then as an electron-poor dipolarophile with the formed monoadduct in a 1,3-dipolar cycloaddition. 

One of the features of Diels-Alder reactions with most alkyl and aryl nitriles as well as cyanamides that has made them rather unattractive as heterodienophiles is the requirement of very high reaction temperatures for cycloaddition.1 Under these extreme conditions the initial 3,6-dihy-dropyridine reaction products of nitriles and simple acyclic 1,3-dienes invariably oxidize to the corresponding pyridines [Eq. (2)]. 

Cationic Lewis acids show improved acidity and hence activity. For instance, even at —94°C, relatively unreactive dienes such as butadiene (8.29) react with bromoacrolein (8.05) with excellent yields and good selectivities in the presence of the oxazaborinane (8.30). The Lewis acidity of oxazoborolidines can also be enhanced by protonation using strong Bronsted acids. The triflate salt (8.32) generated by protonation of the corresponding oxazaborolidine with triflic acid shows high activity and wide scope catalysing the Diels-Alder reaction of acyclic... 

Chiral, optically pure exo-methylene compounds, as for example dioxolanes and 1,3-oxazolidinones B, have been successfully examined as dienophiles in thermal Diels-Alder reactions with 1,3-butadiene or cyclopentadiene. Similarly highly diastereoselective reactions of dioxinones C with cyclopentadiene in benzene at 80°C have been reported in the literature. Non-catalyzed cycloaddition reactions of Meyers bicyclic lactam with acyclic dienes proceed at moderate temperature (60°C) highly stereoselective furnishing the products in excellent yield. Equally high endolexo selectivities and diastereoselectivities were reported for the reactions that have been carried out at low temperature in the presence of Lewis acids, e.g. ZnCL. ... 

The simplest dienes used in the intramolecular Diels-Alder reaction are acyclic. As with the intermolecular cyclization, E dienes are usually more reactive than Z dienes [6], although with highly activated dienophiles or under forcing conditions the latter can be made to participate in the reaction. This topic is addressed in detail in thie next chapter. 

Allenic esters also react with cyclopentadiene in a Diels-Alder reaction endo-selectivity up to 86% was observed in most cases. The unsaturated esters (73) and (74) have been prepared, and their reactions with acyclic dienes studied. The ester (73) undergoes concomitant eliminations of benzenesulphinic acid to give a cyclohexadiene in modest yield, whereas (74) requires a separate treatment with base to bring about its conversion into an aromatic compound. ... 

Pyridazino[4,5-Zi]indole 1268 is another example of aza-diene which was successfully introduced into inverse-electron-demand Diels-Alder reactions with enamines. The reaction proceeds upon prolonged refluxing in 1,4-dioxan (Scheme 293) [792], Notably, reaction of 1268 with acyclic enamine 1270 proceeded in a regioselective manner. 

It was difficult to activate a-branched aldehydes such as acroleins with secondary amines because of the steric effect of poor generation of the corresponding iminium ions. An enantioselective Diels-Alder reaction with a-substituted acroleins 124 was realized by a primary amine organocatalyst 125 (Scheme 1.45) [68]. Acyclic dienes... 

Because the fluorine substituents both inductively and hyperconjugatively withdraw electron density from the C(2)-C(3) tt bond, the LUMO is located there, and Diels-Alder reactions take place exclusively with this bond [25] 1,1 -Difluoro allene and fluoroallene reaet readily with a large selection of cyclic and acyclic dienes, and acyclic dienes, [2+2] cycloadditions compete with the Diels-Alder processes As shown in the example in equation 79, a significantly different regiochemistry is observed for the [2+4] cycloaddition compared with the [2+2]... 

For the construction of oxygen-functionalized Diels-Alder products, Narasaka and coworkers employed the 3-borylpropenoic acid derivative in place of 3-(3-acet-oxypropenoyl)oxazolidinone, which is a poor dienophile in the chiral titanium-catalyzed reaction (Scheme 1.55, Table 1.24). 3-(3-Borylpropenoyl)oxazolidinones react smoothly with acyclic dienes to give the cycloadducts in high optical purity [43]. The boryl group was converted to an hydroxyl group stereospecifically by oxidation, and the alcohol obtained was used as the key intermediate in a total synthesis of (-i-)-paniculide A [44] (Scheme 1.56). 

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