Bicyclic pyrrole

In a related reaction, heating ketones in the presence of TlClsOTf leads to 1,3,5-trisubstituted arenes. " Nitriles react with 2 mol of acetylene, in the presence of a cobalt catalyst, to give 2-substituted pyridines. " Triketones fix nitrogen gas in the presence of TiCU and lithium metal to form bicyclic pyrrole derivatives. " ... 

An example of the synthetic utility of the oxidative cleavage of the pyrrole C-2 to C-3 bond is the ring expansion of bicyclic pyrroles (127) to lactams (128) (83S390). 

The Rh4(CO)i2-catalyzed reactions of 1,6-diynes at 95 °C and 20 atm of CO in benzene or acetonitrile are less selective than those catalyzed by Rh2Co2(CO)i2 or Rh(acac)(CO)2, and a different type of silylcarbobicyclization product, azabicyclo[3.3.0]octadienone (351), is formed in addition to 349-type product (352) when benzyldipropargylamines (350) are used (equation 142)339. The formation of a small amount (5%) of the bicyclic pyrrole of 351-type with 7V-tosyl group is also observed besides 348-type (18%) and 349-type (51%) products in the reaction of IV-tosyldipropargylamine339. 

Oxidation of pyrrolizines. Reactioa of /-butyl perbenzoate with bicyclic pyrrole derivatives such as 1 results in introduction of the benzoyloxy group at C in 40-45% yield. Lead tetraacetate, selenium dioxide, DDQ, and NBS are not useful for oxidation of 1. ... 

An alternative synthetic route to (bicyclic) pyrroles 41 involves the coupling of a cyclic ketone with an amine and an a,/i-unsaturated nitroalkene on the surface of alumina (Scheme 17.30) [14]. After MW irradiation for 13-15 min the product 41 was obtained in 71-86% yield. In this synthesis, substitution on the a-position of... 

More recently (2004), Joule proposed a novel synthetic route to access the akuammiline scaffold with reports from his group s synthetic efforts toward realizing this plan. Retrosynthetically, they envisioned akuammiline (1) to result from late stage imine formation of ketone 247 (Scheme 32). The functionality at position 16 would then be elaborated from a carbonyl contained in diketone 248, which in turn was planned to be obtained via an intramolecular Claisen condensation and double bond isomerization of enamine 249, the latter the product of an aza-Diels—Alder cycloaddition involving cyclic 1-aza-1,3-diene 250 and an acrylate 251. To access azadiene 250 they planned an oxidative ring opening of bicyclic pyrrole 252. 

In the forward direction, they first focused on accessing a bicyclic pyrrole scaffold such as 252. Toward this end, 2-phenyl-4H-benzoxazin-4-one (254) was treated with the Grignard derivative of pyrrole in THF to provide (pyrrolyl)ketone 255 (Scheme 33). Pyrrole 255 was next acylated at the... 

The light-induced rearrangement of 2-phenyl- to 3-phenyl-thiophene may occur by a similar mechanism an equilibrium between the bicyclic intermediate (26) and the cyclopro-penylthioaldehyde (27) has been suggested (Scheme 2). The formation of IV-substituted pyrroles on irradiation of either furans or thiophenes in the presence of a primary amine supports this suggestion (Scheme 3). Irradiation of 2-phenylselenophene yields, in addition to 3-phenylselenophene, the enyne PhC=C—CH=CH2 and selenium. Photolysis of 2-phenyltellurophene furnishes solely the enyne and tellurium (76JOM(108)183). 

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... 

Chemistry of conjugated heterocycles built from furan pyrrole, or thiophene ring fused with bicyclic (norbomadiene, bomene, or azanorbomene) skeletons 98YGK192. 

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 ... 

In some instances, the azaquadricyclane is nonisolable and photolysis of the pyrrole-dimethyl acetylenedicarboxylate cycloadduct or of analogous cycloadducts gives directly the 1 //-azepine. For example, 3.6-dichloro-l-tosyl-l//-azepine (10) is produced in excellent yield by photolysis of the [4 + 2] cycloadduct 9.22 Interestingly, dichloroazepine 10 is found (by H NMR spectroscopy) to be in equilibrium with a small amount (1 % at — 67 C) of its bicyclic valence tautomer 11. 

The order of aromaticity of these compounds is benzene > thiophene > pyrrole > fiiran, as calculated by an aromaticity index based on bond-distance measurements. This index has been calculated for five- and six-membered monocyclic and bicyclic heterocycles Bird, C.W. Tetrahedron, 1985, 41, 1409 1986, 42, 89 1987, 43, 4725. 

Oxazolium oxides, which can be generated by cyclization of a-amido acids, give pyrroles on reaction with acetylenic dipolarophiles.144 These reactions proceed by formation of oxazolium oxide intermediates. The bicyclic adduct can then undergo a concerted (retro 4 + 2) decarboxylation. 

Electronic factors also influenced the outcomes of these cyclization reactions cyclization of pyrrole 84 to bicyclic amine 85 is catalyzed by the sterically open complex 79a. In this reaction, initial insertion into the Y - H bond occurred in a Markovnikov fashion at the more hindered olefin (Scheme 19) [48]. The authors proposed that the Lewis basic aromatic ring stabilizes the electrophilic catalyst during the hydrometallation step, overriding steric factors. In the case of pyrroles and indenes, the less Lewis basic nitrogen contained in the aromatic systems allowed for the cyclization of 1,1-disubstituted alkenes. 

Halide substituted isoxazolines 371a-f gave bicyclic dihydropyridones 374 after rearrangement. Methoxycarbonyl substituted isoxazolines 371g-k gave the lactams 375, whereas carbonyl substituted isoxazolines 373a-e gave pyrroles 376 (Scheme 51). 

The intramolecular version of the PKR has attracted much more synthetic interest, leading to valuable bicyclic systems and being more general and viable [97]. Particularly, 1,6-enynes have been extensively used for the construction of the bicyclo[3.3.0]octane [105], cyclopenta[c]furan [106], or cyclopenta[c]pyrrole [107] skeletons in a single step. 

Poisoning and sometimes death from eating (unidentified) mushrooms is well known. In particular, Amanita sp. are particularly dangerous, with much emphasis on the death cap fungus , Amanita phalloides.24 The best known toxins are the amatoxins and phallotoxins, which are complex, bicyclic peptides. An unusual feature relates to sulfur a tryptophan (or substituted tryptophan) unit is linked to a cysteine sulfur at the carbon atom next to the NH group of the pyrrole ring, forming the unit, -CH2-S-C(NH)=C, e.g. in... 

Similarly, in a 1,3-dipolar cycloaddition of DMAD to the conformationally locked cyclic a-alkoxycarbonylnitrone (727), bicyclic ring systems, containing a nitrogen atom at the bridgehead position have been synthesized. A mechanistic interpretation of the origin of the fused pyrroles (729) includes the intermediate formation of the aziridine ring in (728) (Scheme 2.303) (820). 

Despite the development of some new methods for this strategy of bicyclic system formation, the intramolecular C-acylation of pyrrole is still frequently employed. This reaction may be performed starting from W/Tcyanoethyl-pyrroles as well as starting from their acid, ester, and even amide analogues. 

FVP of the aza-bicyclic sulfone 236 at 700°C and 8xl0 2mbar resulted in 3//-pyrrolizin-3-one 237 <2004TL3889>. At same temperature and lower pressure, that is, 4 x 10-2 mbar, the same sulfone affords a mixture of 237 and vinyl pyrrole 238 in 44% and 27% yield, respectively. The latter was the only product obtained when the thermolysis of 236 was performed in a sealed tube in sulfolane. This result and others led Pinho e Melo et al. <2005JOC6629> to suggest the plausible eight-step mechanism shown in Scheme 61. 

Highly substituted pyrrolo[l,2- ][l,2,4]triazines were synthesized from pyrrole derivatives, by closure of the triazine ring. Thus, hydrolytic cleavage of some 1,2-diaminopyrroles having a 1-NH-BOC-protected amino function 43 followed by reaction with 1,2-dicarbonyl compounds afforded a one-pot access to the corresponding bicyclic heterocycles 44 (BOC = f-butoxycarbonyl Equation 6) < 1997J(P 1)1829>. 

Triazolines can decompose under various conditions. Compound 93 leads to the corresponding pyrrole 94 under acidic conditions (Equation 4) <2003TL1477>, whereas thermal treatment of bicycle 95 leads to 96 by a cycloreversion pathway (Equation 5) < 1996JP11617>. 

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