Fused isoindoles

A synthesis of highly-substituted tetracenes was developed starting from isoindole (benzo[c]pyrrole) <06OL273>. For example, treatment of dibromonaphthalene 87 with phenyllithium in the presence of isoindole 86 followed by deamination of the intermediate cycloadduct provided tetracene 88. Separately, the synthesis and cycloaddition chemistry of oxadisilole-fused isoindoles was investigated <06SL2510>. 

The high-pressure carbonylation of dimeric palladium derivatives 183 (R = Me or cyclopropyl) in ethanol or methanol/ chloroform leads in moderate yields to fused isoindoles 184 as mixtures with their alkoxy derivatives 185, easily separated by flash chromatography (Equation (25) a991JOM371)). 

Using a phosphazene base allows unreactive nitroaromatic compounds to condense with ethyl isocyanoacetate to give C-annelated pyrroles. Stable 2H-isoindoles with electron-withdrawing groups have been prepared using the reaction of dinitrobenzene derivatives with isocyanoacetate in the presence of a phosphazene base (BTPP). The structure of an isoindole was confirmed by X-ray crystallographic analysis, and this substance existed in the solid phase only as the 2H-isomer. The reaction of 6-nitroquinoline gave a pyridine fused isoindole [20] (Scheme 5.5). 

Despite its obvious attractiveness as a potential route to isoindoles and benz-fused isoindoles, no new examples of the dipolar cycloaddition of munchnones and arynes have been reported since the first report by Kato and co-workers. This area is ripe for further exploration, particularly because many new mild methods for generating arynes and hetarynes have been developed since 1976. 

Scheme 45 Synthesis of benzo-fused isoindoles from dinitronaphthalenes...

Recent developments in the synthesis of heterocycle-fused isoindoles 12COC1005. 

Indole is a heteroaromatic compound consisting of a fused benzene and pyrrole ring, specifically ben2o[ ]pyrrole. The systematic name, IJT-indole (1) distinguishes it from the less stable tautomer 3JT-indole [271-26-1] (2). Iff-Indole [120-72-9] is also more stable than the isomeric ben2o[ ] pyrrole, which is called isoindole, (2H, (3) and IH (4)). A third isomer ben2o[i ]pyrrole is a stable compound called indoli2idine [274-40-8] (5). 

In summary, all estimates of resonance energies indicate a decrease in aromaticity in the sequence benzene > thiophene > pyrrole > furan. Similar sequences are also found for the benzo[6] and dibenzo analogues. A somewhat different sequence is found for the benzo[c] fused heterocycles with isoindole > benzo[c]thiophene > benzo[c]furan. As would be anticipated, the resonance energies for the benzo[c] heterocycles are substantially lower than those for their benzo[6] isomers. 

The major internal comparisons to be made within this chapter are between (13) pyrrole (1), furan (2), thiophene (3), selenophene (4) and tellurophene (5) b) pyrrole (1) and indole (6) (c) indole (6), benzo[6 Jfuran (7) and benzo[6]thiophene (8) d) indole (6), isoindole (9) and indolizine (10) and (e) benzo[6] and benzo[c] fused systems. The names of relevant heterocyclic radicals are given with the structures of the parent heterocycle. 

The five-membered ring heterocycles possess Diels-Alder reactivity of varying degree. This is most pronounced in the case of furan and benzo[c] fused heterocycles such as isoindole. In this capacity they are functioning as heterocyclic analogues of cyclopentadiene, and high Diels-Alder reactivity can be correlated with low aromaticity. 

It is of interest to compare the stability of the protonated forms of benzo[u], benzo[Z>] and benzo[c] fused pyrroles, i.e. the cations derived from indolizines, indoles and isoindoles. Indolizine gives a stable pyridinium ion and does not polymerize in the presence of acid. 

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). 

The often inaccessible and labile isoindoles can be accessed by the BZ reaction, as can be heteroisoindoles, such as 32. " Novel pyrroles fused to rigid bicyclic skeleta are readily crafted via a BZ reaction. Certain nitroheterocycles undergo the BZ... 

The combination of the Diels-Alder reaction of fi-sulfonylnitroethylene and the Barton-Zard reaction provides a new synthesis of pyrroles fused with polycyclic skeletons fEq 10 31 Pyrroles fused with bicycle [3 3 3 Qctodiene are important precursors for synthesis of isoindoles via the retro Diels-Alder reaction fEq 10 33 ... 

Subsequently, other publications have appeared involving the DA reactions of porphyrins with other dienes. For instance, the reaction of meso-tetrakis(pentafluorophenyl)porphyrin Id with the diene generated from pyrrole-fused 3-sulfolene gave rise to the isoindole-fused chlorin derivative 8 accompanied by a mixture of stereoisomeric bacteriochlorins 9 (Scheme 2) <98CC2355>. 

The benzo[a] (19), benzo[/t (15) and benzo[c] (16) fused heterocycles are heterocyclic analogues of naphthalene, with the dibenzo heterocycles (17) bearing a similar electronic relationship to phenanthrene. Some of these compounds are still known by their trivial names indole (15 Z = NH), isoindole (16 Z = NH), carbazole (18) and indolizine (19). The names thianaphthene and pyrrocoline for (15 Z = S) and (19) respectively are now little used. Particular confusion can arise in consulting... 

The 7r-electron excessive character of pyrrole and indole renders both systems extremely susceptible to electrophilic attack and the fused benzene rings of carbazole also undergo electrophilic substitution more readily than does an unsubstituted benzene ring. In contrast, the 2/7-isoindole system only survives intact during electrophilic substitution reactions under the mildest of conditions and the system is more susceptible to [ 4 + 2] cycloaddition reactions than is pyrrole. 1,1-Disubstituted IH-isoindoles generally undergo nucleophilic addition-elimination reactions across the 2,3-bond or yield products derived from an initial electrophilic attack at the 2-position. 

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