Dienophiles maleic acid

The reactions of pyrroles with dienophiles generally follow two different pathways involving either a [4 + 2] cycloaddition or a Michael-type addition to a free a-position of the pyrrole ring. Pyrrole itself gives a complex mixture of products with maleic anhydride or maleic acid and with benzyne reacts to give 2-phenylpyrrole rather than a product of cycloaddition (Scheme 47). 

Oxabicyclo[2.2.1]hepta-2,5-dienes are usually obtainable in good yield by addition of acetylenic dienophiles to furans, although 1 2 adducts, e.g., 24, result in some cases since furans also add readily to derivatives of maleic acid. The parent compounds, 7-aza- and 7-oxa-bicyclo[2.2.1]hepta-2,5-diene, are still unknown. 

An interesting paper reports the combined synthesis of 3-vinylindoles from ketones with the vinylindole synthesis of tetrahydrocarbazoles in one flask by using indole (1 equivalent) and excess ketone precursor as the solvent, usually at reflux with maleic acid (1 equivalent), both as the catalyst for 3-vinylindole formation and as the dienophile for the Diels-Alder reaction. These reactions constitute an in situ vinylindole synthesis of tetrahydrocarbazoles (79JOC4402). 

Alkyl-substituted oxazoles have been found to react with maleic acid or its anhydride in a diene synthesis to yield substituted pyridine readily converted to pyridoxine (39). In this route, ethyl d, 1-alaninate hydrochloride is treated with formic-acetic anhydride to yield ethyl N-formyl d,1-alaninate (78%). This compound is refluxed in chloroform with phosphorous pentoxide (40), quenched with aqueous potassium hydroxide, and the organic layer distilled to give 4-methyl-5-ethoxyoxazole (I) (60%). The resulting oxazole (I) is condensed readily with a number of appropriate dienophiles to form 2-methyl-3-hydroxy-4,5-disubstituted-pyridines containing substituents (III, a, b, c) which could be converted to pyridoxine as follows ... 

Alder diene for example it reacts with maleic anhydride in an autoclave at 180° to give the adduct (4). With the less reactive dienophiles acrylic acid and cyclohexene, a small amount of hydroquinone or of trichloroacetic acid is added as catalyst. 

The Diels-Alder reaction of 1,2-dihydrophosphinine oxides with dienophiles, such as acetylenic derivatives and maleic acid derivatives affords 2-phosphabicyclo [2.2.2]octadiene and 2-phosphabicyclo[2.2.2]octene 2-oxides that may be regarded as the precursors of low-coordinate, methylenephosphine oxides that are useful in the phosphorylation of 0- and N-nucleophiles. It was observed that the photo-chemically induced fragmentation-related phosphorylation may follow a novel addition-elimination mechanism instead of the classical elimination-addition protocol. 

One might expect that a D-A reaction of butadiene with any symmetrical dienophile would have a synchronous TS, since the new bonds that are being formed are identical However, that does not seem to be the case, at least for highly electrophilic dienophiles. For example, highly asynchronous TSs are found for maleic acid and 1,2,4-triazoline, as shown in Figure 10.9. ... 

Oxazoles can react as 1,3-dienes, and with dienophiles such as maleic acid derivatives undergo DiELS-Alder reactions (see p 131). With acetylene dienophiles, furans are formed via the corresponding Diels-Alder adducts (see p 60). 

Fumaric and maleic acid derived dienophiles 15.1.8.1 Acyclic dienes... 

The Diels-Alder adducts 2 and 6 retain the anhydride function that was originally present in the dienophile, maleic anhydride. As a rule, this functionality is unstable in the presence of water even at pH 7 and hydrolyzes to a dicarboxylic acid according to the general sequence outlined in Scheme 12.1. This process is initiated by nucleophilic attack of water on the carbonyl function, followed by cleavage of a C-O bond of the anhydride. Because anhydrides are reactive toward water, it is important that the apparatus and reagents you use are dry to maximize the yield of cycloadduct. You may be instructed to prepare the dicarboxylic acids 7 and 8 by intentional hydrolysis of the corresponding anhydrides. Protocols for doing so are included in Part C of the experimental procedures. 

The two cis COOH groups of maleic acid become two cis substituents in a Diels-Alder adduct. The COOH groups can be drawn both above or both below the plane to afford a single achiral meso compound. The trans dienophile fumaric acid yields two enantiomers with trans COOH groups. 

Instead of using a bis(diene), several Diels-Alder polymerizations have been performed with trienes (6). An example is shown in Eq. (III-IO). Initially the reactants form an intermediate that possesses both the diene and dienophile groups. Self-polymerization of this intermediate yields the polymer. The cyclic oligomeric ester from maleic acid and 1,4-butanediol described earlier... 

Conjugation as well as geometric and positional isomerization occur when an alkadienoic acid such as linoleic acid is treated with a strong base at an elevated temperature. CycHc fatty acids result from isomerization of linolenic acid ia strong base at about 250°C (58). Conjugated fatty acids undergo the Diels-Alder reaction with many dienophiles including ethylene, propylene, acryUc acid, and maleic anhydride. 

Dicyclopentadienedicarboxyhc acid can undergo a Diels-Alder reaction in the presence of a stoichiometric amount of a dienophile at 140—190°C to give an adduct of the monomeric acid. The yield of adduct is usually 75—95%. A large number of polyfunctional compounds are easily prepared in this manner. The reaction with maleic anhydride gives a tribasic acid. 

We have also used poly(propynoic acid) in our studies of the photochemical interaction of PCSs with dienophiles, such as maleic anhydride, tetracyanoethylene, and styrene. This photochemical reaction of Diels-Alder type is accompanied by the breakdown of the conjugation system and the formation of slightly colored adducts266. Together with the cycloaddition reaction, photodegradation of PPA and its adducts takes place. A cycloaddition reaction is always preceded by the formation of a donor-acceptor complex of a PCS with a dienophile. 

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. 

An interesting phenomenon has been observed in the high pressure Diels-Alder reactions of the l-oxa[4.4.4]propella-5,7-diene (117) with 1,4-naphthoquinone, maleic anhydride and N-phenylmaleimide, where the diene 117 undergoes a rearrangement to the diene isomer 118 which, although thermodynamically less favored, exhibits a greater reactivity [40]. The reactivities of the three dienophiles differed since maleic anhydride and N-phenylmaleimide reacted only in the presence of diisopropylethylamine (DIEA) and camphorsulfonic acid (CSA), respectively (Scheme 5.15). The distribution of the adduct pairs shows that the oxygen atom does not exert a consistent oriental dominance on TT-facial selectivity. 

The Lewis acid-catalyzed 1,3-migration of divinyl esters allows the formation of 1,3-butadienes, which can undergo cycloaddition. In this respect, Dai and coworkers described a rearrangement of the divinyl alkoxyacetate 1-203 followed by a Diels-Alder reaction with a dienophile such as maleic anhydride 1-204 in the presence of catalytic amounts of Ln(fod)3 to produce 1-205 in up to 61 % yield (Scheme 1.47) [53],... 

The partially hydrogenated phenanthrene derivative 18 (entry 4) is a very moderate diene due to the steric crowding caused by the substituents and the anulated rings, and it reacts even with highly reactive dienophiles such as maleic anhydride (MA) or N-phenylmaleic imide only at high pressure. The minor product 20 in the reaction with MA obviously stems from diene 21. This can be explained by a double-bond isomerization 18 - 21 prior to the cycloaddition, certainly catalyzed by traces of acid present in the MA. In the absence of acid only the Diels-Alder adduct 22 derived from diene 18 was observed. In the reaction of diene 23 with MA (entry 5) a similar sequence of steps was observed. A [1,5] shift of the C—O bond in 23, again certainly acid-catalyzed, produces the diene 26 followed by the Diels-Alder reaction with MA to give 24 and 25. 

As a specific example of the vinylallenes, 294 demonstrates that not only can common dienophiles such as maleic anhydride (MA) be added (to furnish adduct 295 with a rich functionality) [122], but also carbonyl compounds such as propanal to afford 296 when the reaction is carried out in the presence of a Lewis acid catalyst [27]. 

The potential activation of different Lewis acid catalysts and their load effect when used in combination with this solvent were explored, in order to determine the improvement of rates and selectivity to the endo and exo isomers. The list of Lewis acid catalysts included Li(OTf), Li(NTf2), Znl2, AICI3, BF3, HOTf, HNTf2, Ce(0Tf)4 5H20, Y(OTf)3, Sc(OTf)3, Sc(NTf2) and a blank without any Lewis acid. The reaction conditions were as follows 2.2 mmol of cyclopentadiene + 2.0 mmol of dienophile + 0.2 mol% of catalyst in 2 mL [hmim][BF4]. When no catalyst was added, the two ketones (R =Me-C=0 R2 = R3 = H and Ri=Et-C=0 R2 = R3 = H) showed modest activity ( 50% in 1 h) with endojexo selectivity = 85/15. Whereas acrolein showed modest activity (59% conversion in 2 h), methacrolein and crotonaldehyde were inert without a Lewis acid catalyst. Acrylonitrile and methyl acrylate underwent low conversions in 1 h (16-17%) whereas, N-phenylmaleimide, maleic anhydride and 2-methyl-1,4-benzoquinone showed complete reaction in 5 min with high endo isomer yields. 

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