Phenylmaleimide

Most examples of Diels-Alder reactions reported for both 2-vinyl and 3-vinylindoles involve typical electrophilic dienophiles such as benzoquinone, A"-phenylmaleimide and dimethyl acetylenedicarboxylate (see Table 16.1). T hese symmetrical dienophiles raise no issues of rcgiosclectivity. While there arc fewer examples of use of mono-substituted dienophiles, they appear to react... 

More recently, Cheeseman and coworkers have investigated cycloaddition reactions of 2,6-dioxypyrazines (80jCS(Pl)1603). 2,6-Dihydroxy-3,5-diphenylpyrazine (77) reacts with electron deficient dienophiles such as iV-phenylmaleimide, diethyl maleate and diethyl fumarate (Scheme 26) to yield adducts of the 3,8-diazabicyclo[3.2.1]octane class such as (78). This reaction is believed to proceed by way of the betaine (79) and has precedent (69AG(E)604) in that photolysis of the bicyclic aziridine (80) generates analogous betaines which have been trapped in cycloaddition reactions. 

Pyrrole 1-oxides are known they undergo 1,3-dipolar cycloaddition with DMAD and with A-phenylmaleimide (80TL1833). 

Like benzocyclobutadiene, benzazetes are reactive dienophiles, but fail to react as dienes except in the special case of dimerization. Thus 2-phenylbenzazete is inert to cyclopentene, but-2-yne, iV-phenylmaleimide and iV,iV-dimethylaminopropyne. 

Isoindole itself gives normal Diels-Alder addition products, (107 and 108), with maleic anhydride and A-phcnylmaleimide, these derivatives constituting the main evidence for forma,tion of the parent substance. 2-Alkyl- and 2-arylisoindoles also give normal addition products with these two dienophiles.Although only one product is generally isolated, it seems likely, in view of the known tendency of several Diels-Alder adducts of isoindoles to dissociate to their components (see below), that both exo and endo stereoisomers might be formed in certain cases. The reaction between 2-p-tolyl-isoindole and A-phenylmaleimide has been shown to give both e,xo (109) and endo (110) addition products. ... 

Benz[/]isoindole (125), recently prepared from the p-toluene-sulfonyl derivative (124), proved to be too unstable for isolation, but eould be trapped in solution as the Diels-Alder adduct (127). The corresponding 1-phenyl derivative (126) was also prepared and, aecording to spectral measurements, reacts with maleic anhydride to give the product (128) derived by additive substitution. This subsequently rearranged to the adduct (129). The same behavior is observed in the reaction of (126) with V-phenylmaleimide. This provides the first clear indication that substitution products from isoindole derivatives and dienophiles can be converted into the normal addition products. 

Benz[/]isoindole 10 exists, on the basis of spectroscopic examination, predominantly in the benzenoid tautomeric form 10b, although the formation of the Diels-Alder adduct with N-phenylmaleimide suggests the presence of a small amount of the o-quinoid tautomer 10a (78JOC4469). 

For instance, in the reaetion of a diene 327 with iV-phenylmaleimide, whieh proeeeds by the [4+2]-eyeloaddition route at -70°C in toluene, the endo-adduet 328 is formed in 96% yield (99JOC3039). 

The validity of the model was demonstrated by reacting 35 under the same reaction conditions as expected, only one diastereoisomer 41 was formed, the structure of which was confirmed by X-ray analysis. When the vinylation was carried out on the isothiazolinone 42 followed by oxidation to 40, the dimeric compound 43 was obtained, showing that the endo-anti transition state is the preferred one. To confirm the result, the vinyl derivative 42 was oxidized and the intermediate 40 trapped in situ with N-phenylmaleimide. The reaction appeared to be completely diastereoselective and a single diastereomer endo-anti 44 was obtained. In addition, calculations modelling the reactivity of the dienes indicated that the stereochemistry of the cycloaddition may be altered by variation of the reaction solvent. 

Dimethylquinoxaline undergoes reaction with typical dienophiles such as maleic anhydride, p-benzoquinone, and AT-phenylmaleimide. The products were formulated as Diels-Alder adducts primarily since analogous products were not isolated from reactions with other quin-... 

The benzoquinone adduct is a 2 1 molecular complex of 2,3-dimethylquinoxaline and quinol, and is readily prepared by crystallizing quinol from toluene in the presence of excess of 2,3-dimethyl-quinoxaline. 2,3-Dimethylquinoxaline and A -phenylmaleimide undergo Michael addition to form the quinoxalinylmethyl-A -phenylsuccinimide... 

Mention must also be made of an interesting reaction (103 —> 104) that makes use of the isoxazole nucleus of anthranil as a diene in the reaction with A-phenylmaleimide. This instance is of considerable interest, for it has proved impossible to introduce into the diene synthesis other derivatives with a noncondensed isoxazole ring. ... 

C ( propyl) N phenylmtrone to N phenylmaleimide, 46, 96 semicarbazide hydrochloride to ami noacetone hydiochlonde, 46,1 tetraphenylcyclopentadienone to diphenyl acetylene, 46, 44 Alcohols, synthesis of equatorial, 47, 19 Aldehydes, aromatic, synthesis of, 47, 1 /3-chloro a,0 unsaturated, from ke tones and dimethylformamide-phosphorus oxy chloride, 46, 20 from alky 1 halides, 47, 97 from oxidation of alcohols with dimethyl sulfoxide, dicyclohexyl carbodumide, and pyndimum tnfluoroacetate, 47, 27 Alkylation, of 2 carbomethoxycyclo pentanone with benzyl chloride 45,7... 

N Phenylhydroxylamine condensation, with benzaldehyde to form N,a-diphenylmtronc, 46,127 with n-butyraldehyde, 46, 96 Phenyl lsothiocyanate, 46, 21 Phenylhthium, 46, 109 N-Phenylmaleimide, conversion to 3-phenyl-3 -propylisoxazolidinc-... 

In the same way, furanothiepin 6 is obtained by esterification of the corresponding diacid, then converted with methylmagnesium bromide to the highly reactive diol 7, which gives a eycloadduct with iV-phenylmaleimide in 65% overall yield67 (see Section 2.2.5.). 

The thieno unit of thienothiepin 1 reacts with iV-phenylmaleimide at 150 C to give the Diels-Alder exo-product 2, with the loss of sulfur.71 Furanothiepin 3 (X = S) and its corresponding 5-oxide or 5,5-dioxide react readily with the same dienophile at room temperature, but in different ways. While the parent compound 3 and its oxide (X = S, SO) form the cycloadduct 4 with loss of sulfur, the dioxide gives a stable Diels-Alder adduct 5 (mixture of endojexo-isomers) which, upon heating above 100 C, loses sulfur dioxide to provide the sulfur-free adduct.70... 

Bulky substituents make it possible to prepare a stable 8n-electron thiepin. For that purpose, the methoxycarbonyl groups of furanothiepin 6 (R = C02Me) are converted with methylmagne-sium bromide to the corresponding diol (R = CMe2OH) which reacts spontaneously with N-phenylmaleimide to give the thermally stable endo-thiepin 8.67 Quantitative desulfurization is achieved in the presence of triphenylphosphane. 

Dibenz[c,e]azepine 6-oxide, a cyclic nitrone (see Section 3.2.1.5.1.), yields crystalline 1,3-dipolar cycloadducts with phenylisocyanate (adduct yield 98 % mp 190-191 C) and with N-phenylmaleimide (adduct yield 86% mp 235-236°C).6... 

During investigation of the synthesis of benzocyclobutane 193, Cava and coworkers118 found that o-quinodimethane 192, generated in the pyrolysis of 1,3-dihydrobenzo[c]thiophene 2,2-dioxide (191), can be trapped by Af-phenylmaleimide to give N-phenyl-1,2,3,4-tetrahydronaphthalene 2,3-dicarboimide (194) (equation 125). 

MA = maleic anhydride NPM = N-phenylmaleimide NQ = 1,4-naphthoquinone TONE = tetracyanoethylene... 

The cycloaddition of chiral, racemic and non-racemic alkoxybutadienes 109 with phenyltriazolinedione led to aza compounds [110] in high yield, with good facial selectivity (diastereomeric excess 87-92%) (Equation 2.31). The cycloadditions of the same dienes with N-phenylmaleimide require Lewis acid catalysis. 

Tetraene 141 has been converted into various complex polycondensed adducts by reacting with a variety of dienophiles such as maleic anhydride, N-phenylmaleimide, N-phenyltriazolinedione,p-benzoquinone and tetracyano-ethylene carried out under thermal conditions. All cycloadditions occurred facial-diastereoselectively from an outside attack and provided monocycloadducts which had an exceptionally close relationship between diene and dieno-phile and then underwent intramolecular cycloaddition [125]. The reaction between 141 and p-benzoquinone is illustrated in Scheme 2.53. 

A broad study on the MW-assisted Diels Alder reactions of 2H-pyran-2-ones 50 and 51 with 1,4-naphthoquinone 52 and N-phenylmaleimide 53 (Equations 4.3) supported on silica-gel, K-10 montmorillonite, fitrol and alumina was carried out by Samant and colleagues [41]. 

The Diels-Alder reaction of 2H-pyran-2-ones part IV - Microwave catalyzed Diels-Alder reaction of 4,6-disubstituted-2H-pyran-2-ones with 1,4-naphthoquinone and N-phenylmaleimide [41a]... 

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. 

Tropone (125) and tropolone (130) reacted [44] with N-phenylmaleimide at high pressure (lOkbar) and gave a mixture of exo- and ewJo-adducts, 131 and 132, respectively (Equation 5.16). 

High-pressure organic chemistry. Part 17. Diels-Alder reaction of methyl palustrate with maleic anhydride and N-phenylmaleimide [87]... 

High-pressure Diels-Alder reaction of 1-methyl-2-(1H)-pyridones having a phenyl group with N-phenylmaleimide [94]... 

Interestingly, the cycloaddition of 2-azadiene 44 with N-methylmaleimide in 2.5m LT-DE gave predominantly exo-adduct in contrast to the thermal cycloaddition that is mainly enJo-selective (Scheme 6.27). A similar but not so dramatic increase in cxo-selectivity was also observed [47] for the cycloaddition of 44 with N-phenylmaleimide. The reaction is kinetically controlled, but the origin of the high cxo-selectivity observed in LT-DE is unclear the polar medium probably favors the more polar exo transition state. 

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