Pyrroles ring closure reactions

A variety of pyrrole ring closure reactions are conveniently formulated as proceeding via nitrene intermediates, although it is doubtful whether a free nitrene is involved. Pyrolysis of o-nitrobiphenyls with iron(II) oxalate (61T(16)80), or reduction under milder conditions with triethyl phosphite (65JCS4831) or tris(trimethylsilyl) phosphite (79TL375), leads to the carbazole, as does the pyrolysis or photolysis of 2-azidobiphenyls (Scheme 3) (75JA6193). 

Pyrrole can be reduced catalyticaHy to pyrroHdine over a variety of metal catalysts, ie, Pt, Pd, Rh, and Ni. Of these, rhodium on alumina is one of the most active. Less active reducing agents have been used to produce the intermediate 3-pyrroline (36). The 2-pyrrolines are ordinarily obtained by ring-closure reactions. Nonaromatic pyrrolines can be reduced easily with to pyrroHdines. 

The Michael addition /ring-closure reaction of the imines 68 and 69 with the ester nitrostyrene 67 proceeded smoothly in refluxing anhydrous acetonitrile in the presence of NaHCOs to give pyrroles 70 and 71. The syntheses were completed by subjecting pyrroles 70 and 71 to hydrogenolysis to give compounds 72 and 73 quantitatively, followed by base-mediated lactonization with sodium hydride in dry THF to produce lamellarin K in 93% and lamellarin L in 87% yield over two steps. Lamellarins K and L were successfully prepared in three steps in 65% and 61% overall yields, respeetively. 

A further example of an azo coupling reaction with an activated methylene compound (12.91), followed by ring closure to give a pyridazine derivative (12.92) in good yield (66%) was decribed by Gewald and Hain (1984). The reductive treatments of 12.92 give the pyrrole compounds 12.93 and 12.94 in 70% yield (Scheme 12-45). 

Petrillo reports that the reaction of l,4-diaryl-2,3-dinitrobutadienes 42 with representative primary amines leads to //-alkyl-3-alkylamino-2,5-diaryl-4-nitropyrrolidines 43 presumably via a disfavored 5-endo-trig ring closure <00EJOC903>. Acid catalyzed elimination of the amine led to the corresponding trans-2,5-diaryl-3-nitro-3-pyrrolines 44 which could be dehydrogenated to the corresponding pyrroles 45. 

Alder/retrograde Diels-Alder reaction sequence of a diaryl alkyne with a 3,6-dicarbomethoxy tetrazine. The resulting diazine (14) is then reduced, cleaved and cyclized with Zn/acetic acid to the 2,3,4,5-tetrasubstituted pyrrole (15), which is then N-alkylated with a-bromo-4-methoxyacetophenone to give a pentasubstituted pyrrole (16). The synthesis of lukianol A is completed by ester hydrolysis, decarboxylation, ring closure and deprotection. 

Examples of the coupling of enam-ines are rare [60]. In most cases, the enamines undergo methanolysis to form electroinactive aminoacetals prior to the coupling reaction. Enamino ketones or enamino esters, however, yield via dimerization of the radical cations and subsequent ring closure pyrrole derivatives... 

N-Alkyl isoindolo[2,l-fc][2,4]benzodiazepines 190 (R = alkyl. Scheme 38, Section 3.1.1.2) are synthesized by an intramolecular N-acyliminium ion-amide reaction (1997TL2985, 1998T1497). Isothiocyanates 23 undergo under basic conditions in DMF ring closure by an intramolecular substitution between N1 of the pyrrole ring and isothiocyanate group to afford benzo[/]pyrrolo[l,2-c] [l,3]diazepine-5-thiones 25 (Scheme 2, Section 2.1.1.1 (2005BMCL3220)). 

Pyrroles are found in the volatiles of most heated foods [29], although they have received less attention than some other classes of aroma volatiles. Some pyrroles may contribute desirable aromas, e.g. 2-acetylpyrrole has a caramel-like aroma, and pyrrole-2-carboxaldehyde is sweet and corn-like, but alkylpyrroles and ac-ylpyrroles have been reported to have unfavourable odours [22]. Many more volatile pyrroles have been found in coffee than in other foods [30], and they are common products of amino acid-sugar model systems. Pyrroles are closely related in structure to the furans, and they are probably formed in a related manner from the reaction of a 3-deoxyketose with ammonia or an amino compound followed by dehydration and ring closure (cf Scheme 12.2). 

Not only acetylene derivatives do undergo palladium catalysed intarmolecular carbon-nitrogen bond formation with amines. The similar reaction of olefins in a Wacker-type process also leads to ring closure. (0-Aminopentenes bearing a suitable leaving group in the 4-position were converted to pyrroles in a cyclization-isomerisation-elimination sequence (3.65.),82... 

This synthetic route is based on ring closure by Dieckmann condensation of 1,2-bis-carbalkoxyalkylpyrrolidines. It has gained special importance during the last few years, after application to several total syntheses of naturally occurring pyrrol izidine bases. The usual starting compounds employed in this route are esters of a-pyrrolidineacetic acid, proline, and their homologues, which are converted into N-substituted dialkyl dicarboxylates. The esters of the dicarboxylic acids are subjected to Dieckmann condensation and subsequent ketonic hydrolysis the resultant ketones are used in further reactions. 

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