Diels-Alder reactions of pyrroles

Paulvannan K (2004) An atom-economical approach to conformationally constrained tricyclic nitrogen heterocycles via sequential and tandem Ugi/intramolecular Diels-Alder reaction of pyrrole. J Org Chem 69 1207-1214... 

The Diels-Alder reaction of pyrrole-3-carboxyhc esters with TV-methyl- and N-phenyl-maleimides yield exclusively endo adducts.243 The Diels-Alder reaction of... 

McCuiloch - Diels-Alder reactions of pyrroles [700JCH72]... 

Kozikowski Diels-Alder reaction of pyrrole with allene [78JOC2083]... 

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. 

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 ... 

The Boger pyrrole synthesis based on a heterocyclic azadiene Diels-Alder strategy (1,2,4,5-tetrazine to 2,2-diazine to pyrrole) was employed by the author for the total synthesis of ningalin B . Thus a Diels-Alder reaction of the electron-rich acetylene 52 with the electron deficient 1,2,4,5-tetrazine 53 proceeded to give the desired diazine 54 which underwent subsequent ring contraction to afford the core pyrrole structure 55. 

Arai and coworkers197 reported the utilization of a chiral pyrrole sulfoxide as a chiral auxiliary in the asymmetric Diels-Alder reactions of its /V-cinnamoyl and /V-crotonyl derivatives 313 with cyclopentadiene which gave 314-317 (equation 87). The results have been summarized in Table 18. The yield as well as the endo/exo selectivity and the de proved to depend on the type and amount of Lewis acid used. 

An unprecedented nitrogen elimination reaction of 4-amino-7-benzylpyrrolo [23- f][133]triazine-5-caibonitrile (72) to give the pyrrole derivative 74 has been described. The following mechanism, presumably via a a retro Diels-Alder reaction of the imino tautomer 73, has been proposed <990L537>. 

The Diels-Alder reaction of furo[2,3-f]pyrrole 135 with either 1 or 2 equiv of DM AD in benzene gave a stable 1 2 cycloadduct 145 in 88% yield <1995T193>. 

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... 

The iV-aminopyrrole - benzene ring methodology has been applied to a synthesis of the 9,10-dihydrophenanthrene juncusol (218) (81TL1775). Condensation of the tetralone (213) with pyrrolidine and reaction of the enamine with ethyl 3-methoxycarbonylazo-2-butenoate gave pyrrole (214). Diels-Alder reaction of (214) with methyl propiolate produced a 3 1 mixture of (215) and its isomer in 70% yield. Pure (215) was reduced selectively with DIBAL to the alcohol, reoxidized to aldehyde, and then treated with MCPBA to generate formate (216). Saponification to the phenol followed by O-methylation and lithium aluminum hydride reduction of the hindered ester afforded (217), an intermediate which had been converted previously to juncusol (Scheme 46). 

A Diels-Alder reaction of N-(carbomethoxy)pyrrole and phenylsulfonyl 6-chloro-3-pyridyI acetylene was used similarly in a total synthesis of epibatidine, an alkaloid heralded for its high analgesic potency [536]. 

Preparation and Diels-Alder Reaction of a Reactive, Electron-Deficient Heterocyclic Azadiene Dimethyl 1,2,4,5-Tetrazine-3,S-Dicarboxylate. 1,2-Diazine and Pyrrole Introduction. 

A new photoreaction is described for the tricyclic triazoline shown in Scheme 44, which upon irradiation in methanol gives a pyrrole methyl ester205 by retro Diels-Alder reaction of an intramolecular pyrrole-ketene Diels-Alder adduct (88) formed from the diradical (Scheme 154).205 In benzene, ketene dimerization occurs. 

Diels-Alder reactions of N-substituted benzo[4,5]thieno[2,3-c]pyrroles 149 [27] and benzo[4,5]furo[2,3-c]pyrroles 150 [26] with Af-phenylmaleimide and DMAD gave the corresponding exo cycloadducts 151-153 (Scheme 28). Oxidative extrusion of the nitrogen bridge in cycloadducts 152 and 153 via intermediates 154, 155 afforded derivatives of dibenzothiophene 156 [27] and diben-zofuran 157 [26],... 

Moskalev, N. V. Gribble, G. W. Synthesis and Diels—Alder reactions of the furo[3,4-b]pyrrole ring system. A new indole ring synthesis. Tetrahedron Lett. 2002, 43, 197—201. 

Extrusion of sulfur dioxide from a ring-fused dihydiothiophene derivative provides an exceptionally easy method for the preparation of heterocyclic o-dimethylene compounds. These compounds are valuable intermediates in intermolecular Diels-Alder reactions. This extrusion method was used to prepare the o-dimethylene compounds 44-46 <95CC1349> as well as quinolinone derivative 47 <95TL5983>. TTie dihydrothiophene dioxide moiety also played an important role in the formation of the intramolecular Diels-Alder reaction of N-substituted pyrrole 48 <95CC807>. 

Zhang, W., Guo, Y., Liu, Z., Jin,X., Yang, L., and Liu, Z.-L. (2005) Photochemically catalysed Diels-Alder reaction of arylimines with Y-vi nyl pyrrol idi none and N-vinylcarbazole by 2,4,6-triphenyl-pyrylium salt synthesis of 4-heterocycle-... 

The syntheses and Diels-Alder reactions of 5//-thieno[2,3-c]pyrrole (17) as well as benzo and Aralkyl derivatives of furo[2,3-c]pyrrole (22) have been described by Sha et al. <86CC310, 88CC1081, 90JOC2446, 95T193). 

As part of a study to explore the Diels-Alder reactions of this ring system, compound (8 R = R1 = H) was reacted with DMAD to give the pyrrole derivative (11) <85JCS(Pi)899>. It appears that this ring cleavage is initiated by nucleophilic reaction with DMAD. Methyl propiolate behaves similarly, whilst DEAD reacts with the pyrrole ring instead <87JCR(S)356>. 

The synthesis of pyrrole and indole [330] derivatives by aza Diels-Alder reactions of appropriate 1,2,4,5-tetrazines is another valuable synthetical option... 

Numerous studies have dealt with different types of sulfur-containing hetero-dienophiles. Thus, hetero Diels-Alder reactions of N -sulfinyl dienophiles have been thoroughly studied by Weinreb et al. [454] the resulting cycloadducts represent useful and versatile intermediates in the synthesis of homoallylic amines [455] or pyrroles [456]. Further work using this type of S = N dienophiles... 

A novel Mannich reaction between A -alkoxycarbonylpyrroles 739, formaldehyde, and primary amine hydrochlorides catalyzed by Y(OTf)3 gave a monoaminoalkylation product 741 some times in good yield (14-81%) in aqueous media (Scheme 146) <2001TL461>. When formaldehyde was replaced by acetaldehyde or benzaldehyde, no reaction occurred. There was no formation of the 2,7-diazabicyclo[2.2.1]hept-5-ene 740 (through the aza-Diels-Alder reaction of an N-protected pyrrole with an aldehyde and amine salts by catalysis with triflate). 

The inverse electron demand Diels-Alder reactions of 5-amino-177-pyrrole-3-carbonitriles 1121 with various 1,3,5-triazines 1122 are suitable for one-pot syntheses of highly substituted and highly functionalized 7/7-pyrrolo[2,3- -pyrimidine-5-carbonitriles 1123 (Scheme 220) <2002JOC8703>. These are the central heterocyclic nuclei of various nucleoside natural products such as Toyocamycin, Sangivamycin, and Tubercidin (Figure 5). 

It was suggested27-288 that all these compounds would be generated from the unstable endoperoxide (20) (originated from a Diels-Alder reaction of singlet oxygen with the dienio pyrrole system) through various paths, as indicated in Scheme I. 

---