Cycloaddition reactions pyrroles

Furan has the greater reactivity in cycloaddition reactions compared with pyrrole and thiophene the latter is the least reactive diene. However, A -substituted pyrroles show enhanced dienic character compared with the parent heterocycle. 

Benzo[Z)]furans and indoles do not take part in Diels-Alder reactions but 2-vinyl-benzo[Z)]furan and 2- and 3-vinylindoles give adducts involving the exocyclic double bond. In contrast, the benzo[c]-fused heterocycles function as highly reactive dienes in [4 + 2] cycloaddition reactions. Thus benzo[c]furan, isoindole (benzo[c]pyrrole) and benzo[c]thiophene all yield Diels-Alder adducts (137) with maleic anhydride. Adducts of this type are used to characterize these unstable molecules and in a similar way benzo[c]selenophene, which polymerizes on attempted isolation, was characterized by formation of an adduct with tetracyanoethylene (76JA867). 

A-Substituted pyrroles, furans and dialkylthiophenes undergo photosensitized [2 + 2] cycloaddition reactions with carbonyl compounds to give oxetanes. This is illustrated by the addition of furan and benzophenone to give the oxetane (138). The photochemical reaction of pyrroles with aliphatic aldehydes and ketones results in the regiospecific formation of 3-(l-hydroxyalkyl)pyrroles (e.g. 139). The intermediate oxetane undergoes rearrangement under the reaction conditions (79JOC2949). 

H-pyran synthesis from, 3, 759 bis(trimethylsiloxy) in pyrrole synthesis, 4, 333 chromene synthesis from, 3, 750 cycloaddition reactions with isocyanates, azetidin-2-ones from, 7, 261 dihydropyran synthesis from, 3, 771 fuiyl... 

N-alkylation, 4, 236 Pyrrole, 2-formyl-3,4-diiodo-synthesis, 4, 216 Pyrrole, 2-formyl-1-methyl-conformation, 4, 193 Pyrrole, 2-formyl-5-nitro-conformation, 4, 193 Pyrrole, furyl-rotamers, 4, 546 Pyrrole, 2-(2-furyl)-conformation, 4, 32 Pyrrole, 2-halo-reactions, 4, 78 Pyrrole, 3-halo-reactions, 4, 78 Pyrrole, 2-halomethyl-nucleophilic substitution, 4, 274 reactions, 4, 275 Pyrrole, hydroxy-synthesis, 4, 97 Pyrrole, 1-hydroxy-cycloaddition reactions, 4, 303 deoxygenation, 4, 304 synthesis, 4, 126, 363 tautomerism, 4, 35, 197 Pyrrole, 2-hydroxy-reactions, 4, 76 tautomerism, 4, 36, 198... 

The regioselectivity observed in these reactions can be correlated with the resonance structure shown in Fig. 2. The reaction with electron-rich or electron-poor alkynes leads to intermediates which are the expected on the basis of polarity matching. In Fig. 2 is represented the reaction with an ynone leading to a metalacycle intermediate (formal [4C+2S] cycloadduct) which produces the final products after a reductive elimination and subsequent isomerisation. Also, these reactions can proceed under photochemical conditions. Thus, Campos, Rodriguez et al. reported the cycloaddition reactions of iminocarbene complexes and alkynes [57,58], alkenes [57] and heteroatom-containing double bonds to give 2Ff-pyrrole, 1-pyrroline and triazoline derivatives, respectively [59]. 

Scheme 2.17 reports some cycloaddition reactions of pyrano-[4,3-b]-pyrrole 40 (R = Me, Ri = CO2-FBU). 

Dipolar cycloaddition reaction of azomethine ylides to alkynes or alkenes followed by oxidation is one of the standard methods for the preparation of pyrroles.54 Recently, this strategy has been used for the preparation of pyrroles with CF3 or Me3Si groups at the (3-positions.55 Addition of azomethine ylides to nitroalkenes followed by elimination of HN02 with base gives pyrroles in 96% yield (Eq. 10.48).56... 

The same strategy provides a useful tool to derivatize corrole 22 and sapphyrin 25 (Scheme 7). In the case of corrole 22, the reaction with pentacene (after 6 h at 200 °C) afforded mainly the dehydrogenated adduct 23 this is formed from the selective addition of pentacene to the befa-pyrrolic double bond near to the direct pyrrole-pyrrole link and subsequent dehydrogenation <04S 1291>. In minor amount, the reaction also gave rise to the dehydrogenated adduct 24 resulting from an unexpected thermal [4+4] cycloaddition reaction. 

Azomethine ylide cycloadditions have been utilized to prepare a number of novel fused pyrroles including pyrrolo[2,1 -a isoquinolincs <06CHJC279, 06TL1469> and pyrrolo[l,2-Zdpyridazines <06SL804>. Fused hydroxypyrroles were obtained in cycloaddition reactions with trimethylsilylketenes (TMS ketene) <06TL1469>. 

Cycloaddition reactions involving dithione intermediates derived by the reductive extrusion of sulfur atoms from [1,2,3,4,51pen tathi enopino[6,7-i>]pyrroles provided access to 1,4-dithin-fused pyrroles (i.e., 89) <06OL4529>. 

DihydroindolesA novel synthesis of fused dihydroindoles involves [2 + 2 + 2]cycloaddition of alkynes with the 2,3-double bond of N-alkynoylated pyrroles. The reaction of 1 with bis(trimethylsilyl)ethyne results in two diaster-... 

A [4 + 2]-cycloaddition reaction of 1,3,4-oxadiazole 195 was followed by isomerization and elimination of dinitrogen to provide a pyrrole [160]. 

FIGURE 8.20 Peptides activated at an IV-methylamino-acid residue are postulated to epimer-ize because of the formation of the oxazolonium ion. Evidence for the latter resides in spectroscopic studies,96 and the isolation of a substituted pyrrole that was formed when methyl propiolate was added to a solution of Z-Ala-MeLeu-OH in tetrahydrofuran 10 minutes after dicyclohexylcarbodiimide had been added.95 The acetylenic compound effected a 1,3-dipolar cycloaddition reaction (B), with release of carbon dioxide, with the zwitter-ion that was generated (A) by loss of a proton by the oxazolonium ion. 

NICS(O) value (—11.0) is lower than that for the corresponding azadiphosphole (—12.8 see section III.C.2.1), similar to the differences in the furan and pyrrole NICS values (—12.3 and —14.7, respectively, at the same level of theory).The high reactivity of the oxadiphosphole in cycloaddition reactions is in accord with its low aromaticity. 

Although pyrroles do not generally participate in Diels-Alder reactions with olefinic dienophiles, the very reactive hexafluoro-Dewar benzene with pyrrole gives the 1 1 and 1 2 adducts, 27 and 28, both of which probably have all-ea o stereochemistry. Some other 7-azabicyclo-heptene derivatives have been obtained via cycloaddition reactions of 7-azaquadricyclanes (see Section II, F). 

That in the case of pyrrole the formation of the pyrrole anion and the nature of its reactions is of importance, and for furan the reason why cycloaddition reactions occur readily... 

As a result of its reduced aromaticity, relative to pyrrole, furan undergoes [4 + 2] cycloaddition reactions much more readily. It combines as a diene with electron-poor dienophiles to yield Diels-Alder-type adducts. Maleic [(Z)-butenedioic acid] anhydride, for example, reacts at room temperature, and the only isolated adduct is the exo isomer (the more thermodynamically favoured adduct) (Scheme 6.27a). 

Thiophene is present in the benzene fraction from the distillation of coal tar. As with pyrrole and furan, the same type of resonance forms contribute to its overall molecular constitution, and the compound is aromatic in character. There is a difference between thiophene and furan, however, because sulfur is less electronegative than oxygen. Thus, the chemistry of thiophene tends to be closer to that of pyrrole than to that of furan. For example, thiophene does not enter easily into [4 + 2] cycloaddition reactions and quite severe conditions, high pressure (15 bar) and a temperature of 100 C, are necessary in order to force a cycloaddition between it and maleic anhydride. 

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