A -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... 

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

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. ... 

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. ... 

In order to smdy the effect of perturbation arising from spiro-conjugation on the chemical reactivities, in particular the facial selectivities, sterically unbiased dienes (96 and 97) based on fluorenes in spiro geometry have been synthesized [165]. These dienes react as Diels-Alder dienes with several dienophiles (maleic anhydride (MA), A-phenylmaleimide (PMI), A-phenyl-l,3,5-triazoUne-2,4-dione (PTD) and iV-methyl-l,3,5-triazoline-2,4-dione (MTD)). 

The cross-hnking efhciency of EP copolymer has been investigated by some workers [368,371] and the yield is found to increase with increasing ethylene content. The value lies closer to PP homopolymer. The amounts of cross-hnking as well as scission have been observed to increase with increasing diene content, the labile point. Cross-linking enhancers like chlorobenzene, nitrous oxide, allylacrylate, and A-phenylmaleimide are reported to promote cross-linking [85,370,371]. 

The generation and trapping of 5,6-bis(trimethylsilyl)benzo[c]furan 126 was reported by Wong utilizing Warrener s s-tetrazine methodology. The trapping of the silylated isobenzofuran with A-phenylmaleimide is illustrated below. A number of other dienophiles such as dimethyl acetylenedicarboxylate, benzoquinone, naphthoquinone and anthra-l,4-quinone have also been used <00TL5957>. 

C, A-diphenyl nitrones (p-XC6H4CHN(0)Ph, X = NO2, Cl, H, Me and MeO) with N-phenylmaleimide to form 2,3,6-triaryl derivatives of l-oxa-2,6-diazabicyclo[3.3.0]octane-5,7-dione. No enthalpy of formation data are available for A-phenylmaleimide or for maleimide itself. However, it is available for the corresponding A-methyhnaleimide along with some other imides. The gas phase enthalpy of hydrogenation of this species (derived as the difference between its enthalpy of formation and that of N-methylsucc-inimide ) is 133.7 2.2 kJmoC. This value is essentially the same as for ethylene (derived as the difference between its enthalpy of formation and that of ethane) of 136.3 0.4 kJmoH. Therefore, let us assume the reaction of the above parent nitrone with ethylene to form the diphenylated isoxazolidine, shown in equation 12, has very much the same exothermicity as with A-phenylmaleimide, namely ca 82 kJmol . If so, the enthalpy of formation of 2,3-diphenylisoxazolidine would be 233 kJmol . Now, is this value plausible ... 

The meso-ionic l,3-dithiol-4-ones (134) participate - in 1,3-dipolar cycloaddition reactions giving adducts of the general type 136. They show a remarkable degree of reactivity toward simple alkenes including tetramethylethylene, cyclopentene, norbomene, and norbor-nadiene as well as toward the more reactive 1,3-dipolarophilic olefins dimethyl maleate, dimethyl fumarate, methyl cinnamate, diben-zoylethylene, A -phenylmaleimide, and acenaphthylene. Alkynes such as dimethyl acetylenedicarboxylate also add to meso-ionic 1,3-dithiol-4-ones (134), but the intermediate cycloadducts are not isolable they eliminate carbonyl sulfide and yield thiophenes (137) directly. - ... 

Furthermore, the synthetic utility of 2,6-divinyl-l,4-dithiin 68 as a reactive diene in Diels-Alder reactions was reported with tetracyanoethylene, maleic anhydride, A -phenylmaleimide, and dimethyl acetylenedicarboxylate (DMAD) and allowed the preparation of various dihydrothianthrene derivatives (Equation 9) <2003S849>. 

Grigg et al. (34) also conducted extensive studies of the thermal 1,2-prototropic generation of azomethine ylides and this can be exemplihed by the diastereofacially selective cycloaddition of 7-aminocephalosprin ylide precursors. Condensation of aryl aldehydes with 120, in refluxing toluene, furnished imines 121, which, in the presence of A -phenylmaleimide, furnished a mixture of cycloadducts 122 and 123 in essentially quantitative yield in a 2 1 ratio. The only observed products... 

The reaction protocol was further developed by alterations to the chiral controlling element of the reaction (49). Use of the precursor 183 under the standard ylide generation and cycloaddition conditions gave a greatly improved diastereomeric excess of >95%, an endo/exo ratio 1 15 and an isolated yield of 62%, with A-phenylmaleimide as the dipolarophile. The improvement in the reaction was rationalized by both endo and exo attack of the dipolarophile to the same diastereomerically favored face of the conformationally restricted U-shaped ylide 184 (Scheme 3.52). 

The chiral dipolarophiles of Garners and Dogan, which were derived from Oppolzer s sultam, have been previously discussed in Section 3.2.1 and, in an extension to these results, the sultam moiety was used as the stereodirecting unit in enantiopure azomethine ylides (56). The ylides were generated either by thermo-lytic opening of N-substituted aziridines or by the condensation of the amine functionality with benzaldehyde followed by tautomerism. These precursors were derived from the known (+)-A-propenoylbornane-2,10-sultam. Subsequent trapping of the ylides with A-phenylmaleimide furnished the cycloaddition products shown in Schemes 3.60 and 3.61. 

Thermolysis of aryl chloro diazirine (18) in the presence of acetone and a trapping agent such as A -phenylmaleimide gave rise to cycloadducts such as 41. The unstable adduct hydrolyzed during purification resulting in synthesis of bicyclic hemiacetals 42 and 43 as a mixture of endo and exo adducts in 37 and 8% yield, respectively. The exclusive generation of the singlet carbene was confirmed by low-temperature electron spin resonance (ESR) study of the irradiated diazirine. 

An interesting preparation of aliphatic diazoalkanes (R R C = N2 R, R = alkyl) involves the photolysis of 2-alkoxy-2,5-dihydro-1,3.4-oxadiazoles (see Scheme 8.49). When the photolysis is carried out in the presence of an appropriate dipolarophUe, the diazo compounds can be intercepted (prior to their further photolysis) by a [3 + 2] cycloaddition reaction (54). As an example, 2-diazopropane was intercepted with A-phenylmaleimide (54) and norbornenes (55) to give the corresponding A -pyrazolines. 

Wilde (9) generated N-acyl mtinchnones for the first time via the acylation and desilylation of 5-siloxyoxazoles. Thus, for example, exposure of 17 to acetyl chloride in the presence of DMAD affords A-acetylpyrrole (19) via A-acetyl-miinchnone 18. Other trapping agents (thiocarbonyls, A-phenylmaleimide) failed and the analogous trimethylsiloxyoxazoles were unusually labile and gave lower yields of pyrroles (13-15%). Ethyl chloroformate was also used in this sequence and gave, for example, pyrroles 20-21. 

Whereas 260 does not react with electron-rich dipolarophiles, the more delocalized isomiinchnone 261 does react with both electron-rich and -deficient dipolarophiles (154). A detailed FMO analysis is consistent with these observations and with the regiochemistry exhibited by diethyl ketene acetal and methyl vinyl ketone as shown in Scheme 10.36. The reaction of 261 with the ketene acetal to give 262 is LUMO-dipole HOMO-dipolarophile controlled (so-called lype III process). In contrast, the reaction of 261 with methyl vinyl ketone to give 263 is HOMO-dipole LUMO-dipolarophile controlled (so-called lype I process). In competition experiments using a mixture of A-phenylmaleimide and ketene acetal only a cycloadduct from the former was isolated. This result is consistent with a smaller energy gap for... 

Wilcox and co-workers (145) reported that the stereoselectivity of 1,3-dipolar cycloaddition reactions can be controlled in a predictable manner when ion pairs are located at a proper position near the reaction site (Scheme 11.40). He has employed an A-phenylmaleimide substrate having a chiral center in the substituent at ortho position of the phenyl group. Due to serious steiic hindrance, this phenyl group suffers hindered rotation around the aryl-nitrogen bond (rotation barrier 22 kcal/mol). Four diastereomeric cycloadducts are possible in the cycloaddition step with a nitrile oxide. When the cycloaddition reaction is carried out in... 

Garner et al. (90,320) used aziridines substituted with Oppolzer s sultam as azomethine ylide precursors. The azomethine ylide generated from 206 added to various electron-dehcient alkenes, such as dimethyl maleate, A-phenylmalei-mide, and methyl acrylate, giving the 1,3-dipolar cycloaddition product in good yields and up to 82% de (for A-phenylmaleimide). They also used familiar azomethine ylides formed by imine tautomerization (320). Aziridines such as 207 have also been used as precursors for the chiral azomethine ylides, but in reactions with vinylene carbonates, relatively low de values were obtained (Scheme 12.59) (92). 

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