IV-Phenylmaleimide

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. 

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. 

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). 

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... 

Abbreviations DEPC, diethylpyrocarbonate DCCD, Af.iV -dicyclohexylcarbodiimide EEDQ, N-ethyoxycarbonyl-2-ethoxy-1,2-dihydroquinoline NEM, A-ethylmaleimide PAO, phenylarsine oxide NPM, IV-phenylmaleimide PLP, pyridoxal phosphate DIDS, diisothiocyanostilbene disulfonate PITC, phenylisothiocyanate. 

Reaction of 2equiv of iV-phenylmaleimide 338 with 1-cyano-fV-methylthioformamide 339 under basic conditions gives rise to the central diazene core 340 in 55% yield (Equation 92) <1999PS(148)117>. 

Alder cycloaddition with iV-phenylmaleimide to afford the colorless 1 1 adduct 110 (Equation 18) <1997T10169>. The adduct reverted to benzobis(thiadiazole) 109 and iV-phenylmaleimide at its decomposition point (>230 °C). 

After treatment of sulfide 383 with iV-chlorobenzotriazole (iV-CBT) in methanol to give sulfoxide 384, followed by reaction with Ac20, the nonclassicaf thiazole 385 was obtained. This highly reactive compound reacted with iV-phenylmaleimide to give a mixture of the corresponding [4+2] cycloadducts 386 (major) and 387 (minor) in good yield. The reaction worked also with activated double bond or triple bonds (Scheme 56) <2000T10011>. 

Symmetrically substituted dienophiles such as p-bcnzoquinone and IV-phenylmaleimide reacted with 4 to give the expected [4 + 2] cycloadducts. No cycloaddition took place, however, in the reaction of l,l-difluoro-2-triphenylsilyloxy-l-propene with 2-chloroacrylo-nitrile, which showed the importance of an additional vinyl group for the reactivity of 4 in... 

In the [2 + 2] cycloadditions of 10 with iV-phenylmaleimide and dimethyl fumarate, the major cycloadducts were formed with a very high degree of ee transfer from 1,3-dimethylallene8. Similar results were obtained in the reaction of 10 with 1,1-dichloro-2,2-difluoroethene. The reaction with less reactive 1,1-diphenylethene did not lead to cycloadduct formation, but resulted in racemization of the chiral 1,3-dimethylallene instead9, which implies reversible formation of the diradical intermediate in this case. Finally, the cycloaddition of 1,3-dimethylallene to methyl propiolate (14) afforded two cycloadducts, 15 and 16, to which >40% of the initial ee had been transferred (equation 5)11. 

Substituted 2-vinylindoles yield the di- and tetra-hydrocarbazoles with JV-methyl-maleimide and maleic anhydride, and with DMAD, respectively (81UP30500, 82CJC419) and the expected cycloadducts are obtained from the reaction of 4-(2-indolyl)-l,2,5,6-tetrahy-dropyridines with iV-phenylmaleimide and with acrylonitrile (68HCA264). Both l-(l-methyl-... 

Several [4rr + 2v] cycloadditions have proved useful. For example, the oxazole (124) and IV-phenylmaleimide give an adduct which can be dehydrated to the pyrrolo[3,4-c]pyridine... 

Other classical synthetic approaches to 2-furanamine have failed, including the Curtius method and Beckmann rearrangement of 2-benzoylfuran oxime. However, hydrazinolysis of AT-(2-furyl)phthalimide, obtained from phthalimide and 2,5-dimethoxy-2,5-dihy-drofuran, gives 2-furanamine which was not isolated but detected by GLC-MS and H NMR spectroscopy. The latter reveals the absence of imino tautomers (75AP713). The chemistry of 2-dialkylamino-5-phenylfurans is typical of enamines protonation occurs on carbon to produce iminium salts. They are stable to base but afford 5-phenylfuran-2(3//)-one on hydrolysis with dilute acid. 2-Morpholino-5-phenylfuran couples with diazonium salts and affords Diels-Alder adducts with maleic anhydride and IV-phenylmaleimide (73JCS(P1)2523). 

Scheme 45 Formation of ortho photocycloadducts from 4-cyanoanisole and ethyl vinyl ether and reaction of the adducts with IV-phenylmaleimide.

Generalization of this result to imines of conjugated aldehydes provides a good synthesis of the A2-pyrroline ring. The intermediacy of an ylid is confirmed by trapping with iV-phenylmaleimide, which takes place with excellent stereocontrol.330... 

Dimethylamino)vinyl)chromones 813 undergo a [2+2] cycloaddition reaction with DMAD to form the intermediate 814, which rearrange to afford xanthones in modest yield (Scheme 229) <1997J(P1)2167, 1999J(P1)3005>. ( )-2-(2-(Dimethylamino)vinyl)chromones 813 can also react with iV-phenylmaleimide 815 and chromone-3-carboxylic acid 816 to afford xanthones in modest yield (Scheme 230) <1997J(P1)2167, 1999J(P1)3005>. 

Cava and Pollack s elegant synthesis of benzo[c]thiophene52 has been extended to the synthesis of, for example, naphtho[l,2-c]thio-phene (47),52 methyl benzo[c]thiophene-5-carboxylate,54 and 1,3-dimethyl- (48)55 and l,3,4,6-tetraphenylthieno[3,4-c]thiophene (49).56 The last compound is of particular interest because it is a remarkably stable (cf. compound 48 which only exists transiently) nonclassical thiophene containing ten n electrons for which the only uncharged resonance structure (49) contains a tetravalent sulfur atom. When the sulfoxide (50) is pyrolyzed over aluminum oxide, it gives the parent cyclic sulfide and 51 by disproportionation.57 However, when 50 is heated in acetic anhydride in the presence of iV-phenylmaleimide,... 

Benzo[c]thiophene 2,2-dioxides, generated in situ, react easily with IV-phenylmaleimide the [4+2] cycloadducts lose S02, and the product so obtained can either add on another molecule of Af-phenylmaleimide, or aromatize (Scheme 198) (75JOC72). 

The diols (266) upon treatment with P4Sio gave the cyclic sulfides (267). Conversion to the sulfoxide, followed by Pummerer dehydration with acetic anhydride, produced the unstable thieno[3,4-c]furan (127), isolated as its IV- phenylmaleimide adduct (268) while the thienopyrroles (12) and (13) were sufficiently stable to permit isolation (Scheme 92) (75ACR139). The thienofuran (127) was also generated under base-catalyzed Pummerer... 

Reaction of the thienofc c ]thiadiazole (133) with iV-phenylmaleimide gave the pyrrolobenzo-thiadiazole (134) <75ACR139>. The thieno[c c ]thiadiazole (133) equilibrates photochemically with the cyclooctabisthiadiazole dimer (135). 

All attempts to isolate the nonclassical 147r-electron tricyclic system (73) resulted only in the formation of dimer (73a), condensed at the benzene ring (Scheme 14). Reaction of (73) with iV-phenylmaleimide, on the other hand, takes place at both the benzene and thiophene rings (69JA6891). 

Wright and co-workers developed a novel entry into spirocyclic, six-membered O-containing heterocycles as they combined oxyallyl cation chemistry profitably with a ROM-RCM process <02AG(E)4560> (Scheme 41). An analogous process, involving the Diels-Alder reaction of 57 with iV-phenylmaleimide followed by ROM-RCM, gave 58 in excellent yield. 

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