Diels-Alder cycloaddition vinyl pyrroles

Indoles are usually constructed from aromatic nitrogen compounds by formation of the pyrrole ring as has been the case for all of the synthetic methods discussed in the preceding chapters. Recently, methods for construction of the carbocyclic ring from pyrrole derivatives have received more attention. Scheme 8.1 illustrates some of the potential disconnections. In paths a and b, the syntheses involve construction of a mono-substituted pyrrole with a substituent at C2 or C3 which is capable of cyclization, usually by electrophilic substitution. Paths c and d involve Diels-Alder reactions of 2- or 3-vinyl-pyrroles. While such reactions lead to tetrahydro or dihydroindoles (the latter from acetylenic dienophiles) the adducts can be readily aromatized. Path e represents a category Iley cyclization based on 2 -I- 4 cycloadditions of pyrrole-2,3-quinodimcthane intermediates. 

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 nitrovinyl system has been found to be a better diene than the corresponding vinyl analogs. Condensation of l-methyl-2-(2-nitrovi-nyl)pyrrole 117 with maleic acid yielded ALmethylindole-4,5-dicarboxylic anhydride 118. Failure to isolate the expected diacid 183 is probably due to cyclization to the anhydride in the acidic medium created by the elimination of nitrous acid during the condensation. This process is believed to follow the normal Diels-Alder [4-I-2]-cycloaddition pathway with subsequent loss of nitrous acid [73JCS(P1)2450]. 

The most fully explored synthetic applications of Diels-Alder reaction in annotation of pyrroles and indoles involves use of vinyl derivatives. Because of the donor character of the heteroaromatic ring, vinylpyrroles and vinylindoles react as electron-rich dienes. Various aspects of both the synthesis and cycloaddition reactions of vinylindoles have been reviewed. <85JHC585, 86CZ95, 88H(27)1253>. 

The electrophilicities of the superelectrophiles may also be compared using rate constants for their reactions with indoles, pyrroles, and enamines allowing them to be positioned on Mayr s elec-trophilicity scale [60, 61 ]. Also of interest is the ability of superelectrophiles to take part in Diels-Alder-type cycloaddition reactions to produce adducts with dienes, such as butadiene, and with ethyl vinyl ether [184]. 

Other recent examples of inverse electron-demand Diels-Alder reactions in water are the cycloadditions of ( )-3-diazenylbut-2-enes 72 with a variety of vinyl ethers. The results of cycloaddition of 72 with ethyl vinyl ether (61) are reported in Table 5.5. The reactions were always faster in heterogeneous aqueous medium than in organic solvent and the endo adduct was the prevalent reaction product. Pyrrole derivatives such as ethyl-2-methyl-1-ureido-lH-pyrrole-3-carboxylates, derived from zwitterionic [3 + 2] cycloaddition reactions, were sometimes observed and a reaction mechanism of their formation has been proposed. In water, as well as in DCM, 72 (R = OEt, Ri = H) behaves like an electron-acceptor heterodiene even with a highly reactive diene such as cyclopentadiene, giving quickly, at 15°C, only the endo adduct. The cycloaddition of 72 (R = OEt, Ri = H) with the chiral vinyl ether (-F)-2-(ethenyloxy)-3,7,7-trimethylbicyclo[4.1.0]heptane (62x) was complete in water in 68 h at 15°C and gave a mixture of 83 17 endo/exo adducts with modest enantioselectivity. This is the first example of an asymmetric inverse electron-demand Diels-Alder reaction performed... 

Singlet oxygen reacted stereospecifically with 2-vinyl-thiophens in a 1,4-cycloaddition to give thermally stable 1,4-endoperoxides (147). The previously discovered [2 + 2] photoaddition of benzophenone to 2,5-dimethylthiophen to give oxetans has been extended to other carbonyl derivatives. Mechanisms explaining the formation of pyrroles, obtained by u.v. irradiation of a number of thiophens in the presence of propylamine, have been discussed. Irradiation of (148) led to the Dewar thiophen (149). The structures of dimerization products and Diels-Alder adducts with furans were elucidated. ... 

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