Pyrrole 2, 3-quinodimethane

CATEGORY llegf CYCLIZATIONS - CYCLOADDITIONS INVOLVING PYRROLE-2,3-QUINODIMETHANE INTERMEDIATES AND EQUIVALENTS... 

This category corresponds to the construction of the carbocyclic ring by 2 + 4 cycloaddition with pyrrole-2,3-quinodimethane intermediates. Such reactions can be particularly useful in the synthesis of 5,6-disubstituted indoles. Although there are a few cases where a pyrrolequinodimethane intermediate is generated, the most useful procedures involve more stable surrogates. Both 1,5-di-hydropyrano[3,4-b]pyrrol-5(lf/)-ones[l] and l,6-dihyropyrano[4,3-b]pyrrol-6-(in)-ones[2] can serve as pyrrole-2,3-quinodimethane equivalents. The adducts undergo elimination of CO2. 

Indoles by cycloaddition with pyrrole-2,3-quinodimethane equivalents... 

Pyrano-[4,2-b]-pyrrol-5-ones (40) and pyrano-[4,3-b]-pyrrol-6-ones (41) (Figure 2.4) are stable cyclic analogs of pyrrole 2,3-quinodimethane and undergo Diels Alder reaction [40, 41] with various dienophiles to afford indole derivatives after loss of carbon dioxide. 

Diels-Alder reaction of indole-2,3-quinodimethanes, 164-169 of pyrrole-2,3-quinodimethanes, 85-87 of vinylindoles, 159 -164 of vinylpyrroles, 79, 84-85 N.N-dihexyl 2-phenylindole-3-acetamide, procedure for. 62... 

Pyrano[3,4-6]pyrrol-5-ones function as pyrrole-2,3-quinodimethane equivalents. These compounds can be obtained by Bp3-mediated cyclization of l-(phenylsulfonyl)pyrrole-3-acetic acid with carboxylic acids. Use of a-substituted pyrrole-3-acetic acids can introduce a 4-substituent (Equation (146)) <90JCS(P1)2156>. 

From the spectroscopic data of Sections II,A-C it can be concluded that partially saturated heterocyclic /J-enamino esters possess a specific push-pull stabilization owing to the conjugation of electron-donating amino group and electron-withdrawing ester function.67 Push-pull stabilization is responsible for the remarkable stability of this class of compounds similar stabilization allows isolation of certain antiaromatic cyclobutadienes or nonaromatic o-quinodimethanes.68 2-Aminofurans, -pyrroles, and -thiophenes, because of their extremely large electron density, are generally unstable and sensitive... 

Mixed Oxygen-Nitrogen Systems.- The benzocyclobutane (532) opens on heating to the quinodimethane (533) which undergoes a spontaneous intramolecular Diels-Alder reaction to yield the [2]pyrano 3,4- ]pyrrole (534). The photochemical rearrangement (535)— (536) has been reported.The conjugate base of the... 

Chou used an alternative route to a number of pyrazole sulfones starting from the dihydrothiophene 31 (Scheme 26) <93JOC493 93H(35)2839>. The same dihydrothiophene was also used as the starting point for isoxazole <92TL8121> and pyrrole <92CC549> fused sulfones as precursors for the respective o-quinodimethanes (Scheme 26). 

The dihydrothiophene dioxide 32 is a common precursor to thiophene <91CC1287> (Scheme 27), pyrrole <93MI1> and furan <92H(34)663> sulfones. Other simple dihydrothiophenes that have been converted to heterocyclic sulfones and hence to o-quinodimethanes are shown in Scheme 28. 

Many examples of Diels-Alder reactions have been carried out on quinodimethanes derived in a variety of ways from pyrrole and indole precursors. This area continues to be widely investigated because of its generality and its synthetic utility. In the case of pyrrole derivatives, this methodology leads to the synthesis of indoles, and particularly those substituted in the benzene ring. 

The thieno[3,4-6]pyrrole-l,1-dioxide (289) reacts with DMAD at 200°C to give the cycloadduct (291), presumably by trapping a pyrroIe-2,3-quinodimethane (290). The cycloadduct can then be dehydrogenated to the indole (292) (Scheme 85) <92CC549>. Formation of a quinodimethane structure (294) is also postulated to result from the Cope rearrangement of the phenylbutadienylpyrrole... 

The pyranoindolone strategy has also been applied to the analogous pyrrole systems. Similar quinodimethane structures (311) and (312) can be generated from pyrrole acetic acids and undergo cycloadditions to indoles (Scheme 95) <90JCS(P1)2156,92T7447,93T7353). 

Another strategy for annelation of pyrroles and indoles involves cycloaddition reactions. Because the heteroaromatic rings have substantial aromatic stabilization, the C2—C3 bond is not very reactive toward cycloaddition and there are only a few examples of the heterocycles acting as dienophiles. The carbocyclic ring of indole, like benzene, is unreactive toward cycloaddition. However, vinylpyrroles and indoles are quite reactive and react as electron-rich dienes because of the electron-donating nature of the ring. Other cycloaddition reactions involve the 2,3-dimethylene derivatives of pyrrole and indole, the so-called quinodimethanes, which are very reactive dienes. These intermediates, and more stable synthetic equivalents, are useful in cycloadditions with a variety of dienophiles. 27/-Isoindole, which itself can be thought of as a quinodimethane, is a very reactive diene. 

Thieno[2,3-c]furan and thieno[2,3-c]pyrrole also behave as thiophene-2,3-quinodimethane equivalents. Thus, intramolecular Diels-Alder reaction of the furan (588) followed by acid-catalyzed dehydration affords the benzo[6]thiophene (589) in good overall yield (Scheme 122) <88TLI 137>. The Diels-Alder reaction of the pyrrole (590) with DMAD followed by oxidation of the resulting adduct (591) affords the benzo[ft]thiophene (592) with loss of nitrosomethane (Scheme 123) <90JOC2446>. 

With the knowledge that furans are generally better partners in Diels-Alder reactions than pyrroles [91], Gribble and Saulnier in 1983 were the first to synthesize the 4H-fiiro-3,4-fc]indole (4 f-furano[3,4-b]indole) ring system (44) and evaluate its potential as an indole-2,3-quinodimethane... 

Catalytical activities have been claimed for copolymers arising from pyrrole and bithiophene with a small amount of dispersed platinum to be effective in the electrochemical oxidation of hydrogen, formic acid and methanol [245] the same catalytic effect was found for electrodes of 3-methyIPT with electrochemically deposited platinum and tin [246]. The reduction of tetracyano-p-quinodimethane and chloranil can be achieved at a glassy carbon electrode coated with 3-methylPT [247]. Phenol derivatives and carbon dioxide can be converted to salicylic acid derivatives on 3-hexylPT electrodes under irradiation in ethanolic solution [248]. This electrode material acts as a photocatalyst on irradiation with visible light, the luminescence is quenched by carbon dioxide as well as phenol. 

---