Pyrrole, intramolecular Diels-Alder reactions

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... 

An intramolecular cycloaddition reaction results in the simultaneous formation of two new rings. Examples include the formation of an octahydroquinoline (Section 4.4.2.3.4) and a tetra-hydrobenzo[c]pyrrole (Section 4.4.3.1) by intramolecular Diels-Alder reactions. 

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>. 

There are a number of examples of substituted pyrroles participating as 4tt components of all-carbon Diels-Alder reactions.63 However, their reported participation as a 1- or 2-azadiene system in [4 + 2] cycloadditions are limited to selected pyrroles.64,65 Pentachloro-2//-pyrrole has been shown to participate in inverse electron demand Diels-Alder reactions with electron-rich dienophiles exclusively in the form of the 2-azadiene system, pentachloro-S/Z-pyrrole,64 and one example of an intramolecular Diels-Alder reaction of a substituted, in situ generated 3//-pyrrole has been described (Chapter 9, Section 2).65... 

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... 

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>. 

A domino sequence comprising a cycloaddition and subsequent cycloreversion step can often find a more general application in organic synthesis, especially in the formation of aromatic compounds such as furans or pyrroles. Oxazole moieties as electron-deficient dienes often serve as the crucial reactive centers which cycloadd to a triple bond and eliminate a nitrile upon cycloreversion. If the first step is intramolecular, the impelling enthalpy preserved in the stability of the formed CN function is additionally accompanied by a positive entropy when the nitrile, sometimes volatile, leaves the substrate. In an older example from 1984 [10], Jacobi and coworkers devised a scheme for the preparation of a highly substituted furan on their synthetic way to paniculide A. An intramolecular Diels-Alder reaction was followed by the critical extrusion of volatile acetonitrile, furnishing the bicycle 8 in 94% yield (Scheme 6.2). 

Eddaif A, Laurent A, Mison P et al (1987) Intramolecular diels-alder reactions of 3H-pyrroles resulting from thermal rearrangements of 2H-pyrroles. J Org Chem 52 5548-5560... 

T. Suzuki, H. Takayama, Intramolecular Diels-Alder reaction of new building blocks, N-substituted 3,5-dihydro-lH-thieno[3,4 c]pyrrole-S, S-dioxides, J. Chem. Soc. Chem. Commun. (1995) 807-808. 

Generally, cycloadditions represent powerful reactions for construction of heterocycles. Tandem intramolecular Diels-Alder/retro-Diels-Alder reaction sequences were applied in the syntheses of many A,B-diheteropentalenes <1996GHEC-II(7)1>. Gribble and co-workers <1998SL1061> reported new syntheses of pyrrolo[3,4-, ]indoles 426, benzo[4,5]furo[2,3-f]pyrroles 429, and benzo[4,5]thieno[2,3-4pyrroles 430 using the 1,3-dipolar cycloaddition... 

An intramolecular oxo-Diels-Alder reaction leads to the synthesis of reduced pyrano[3,4-f]pyrrole esters. When benzene is chosen as reflux solvent, /ra r-substituted products form, whereas air-substituted derivatives are favored in refluxing toluene solvent (see Section 10.06.2.1.2) <2003T8955>. 

Pyrroles, indoles and benzo[ft]thiophene act as good dienophiles in inverse electron demand Diels-Alder reactions with 1,2-diazines, 1,2,4-triazines and sy/n/n-tetrazines. This is examplified by the formation of compounds (189) in excellent yields on interaction of indoles and benzo[c]thiophene with dimethyl l,2,4,5-tetrazine-3,6-dicarboxylate (87JOC4610 90JOC3257). There are also many examples of such intramolecular reactions, e.g. (190 — 191). 

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. 

The use of the An diene participation of vinyinitroso compounds in Diels-Alder reactions in the preparation of aryl pyruvate oximes, amino acids, y-hydroxynitriles,y-lactones, pyridine N-o -ides, and pyrroles is summarized in Scheme 9-III. The intramolecular Diels-AIder reactions of in situ generated and unactivated vinyinitroso compounds have been shown to proceed readily employing electron-rich olefins, and the course of the reaction has been shown to proceed preferentially through an endo transition state [Eq. (36)]. ... 

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