Pyrrole ring closure synthesis

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. 

There are numerous studies on the synthesis of pyrrolizines from enam-ines. In these reactions, one of the step is the closure to a new hydrogenated pyrrole ring. In polar solvents, the reaction of enamines with dimethyl acetylenedicarboxylate follows two different pathways, the formation of cycloadducts (18) and Michael adducts (19) (81T3525). Subsequent studies of this reaction have demonstrated (by low-temperature NMR) that compounds of the type 20 are intermediates in this cyclization (83JA4775). On the basis of this information (83JA4775), the authors then studied this type of cyclization using dienamines (21). The reaction follows the scheme shown, with a [1,6] antarafacial hydrogen shift and the formation of a dipo-... 

The introduction of substituents at the 3-position of pyrrole has been actively pursued in recent years due to the importance of this class of compound in natural product synthesis. In contrast to the significant number of preparations of polysubstituted 3-arylpyrroles, there have been relatively few syntheses of simple 3-arylpyrroles. A literature survey on the preparation of 3-arylpyrroles showed that the methods reported include the reductive cycliza-tion of 2-arylsuccinonitriles, the base-induced ring-closure of arylvinamidinium salts, and... 

The synthons of porphyrin syntheses are the pyrroles, which in turn must be made from 1,4-difunctional synthons. These carbon skeletons are available by an aldol-type condensation of the enol of a 1,3-diketone with an a-nitrosylated acetoacetate (Knorr pyrrole synthesis. Scheme 1.3.4). The final reductive ring closure by Schiff base formation is again a reversible condensation reaction. After dehydration, however, a stable 7i-electron sextet is formed, which gives the resulting pyrrole aromatic stability. Hydrolysis of this enamine can now only occur in very strong acid. In water of modest acidity or basicity it is perfectly stable. 

In the 1980s, Boris A. Trofimov published several manuscripts describing the synthesis of pyrroles and vinylpyrroles from ketones, hydroxylamine and acetylene. The reaction was believed to occur via hydroxylimine formation, followed by O-vinylation, rearrangement, then ring closure. The Trofimov reaction has been studied in limited detail but has been shown to have application to the synthesis of a variety of pyrroles. 

Texier-Boullet, F., Klein, B., and Hamehn, J. (1986). Pyrrole and pyrazole ring closure in heterogeneous media. Synthesis, 409 11. 

According to the data in Table 3.1, of the 12 possible methods for the synthesis of pyrrolo[l,2-a]quinoxalines the most successful are the methods based on the QAl, QBl, QCl, QC2, and QE2 approaches. Methods based on QA2, QA3, QA4, and QB2 can only be realized after effective methods have been developed for the synthesis of Al-alkylated derivatives of quinoxalines with alkyl fragments of various lengths and with various functional groups at the terminal atoms of the alkyl fragment that promote closure of the pyrrole ring, or with participation of the C(2) atom of the quinoxahne system, or with participation of the substituent at position 2 of the quinoxahne system. 

Roy and coworkers reported that Ir-Sn bimetallic complex serves as efficient catalyst for the synthesis of furans and pyrroles from 1,3-dicarbonyl compounds. This reaction proceeds initial alkylation of 1,3-dicarbonyl compounds with propargyUc alcohol to form propargylated 1,3-dicarbonyl intermediate, followed by ring closure which led to the cyclization products [167]. 

Feist pyrrole ring synthesis Fischer-type ring closure Pschorr — diketone —... 

Often, in the synthesis of natural products containing the indolizidine substructure, it is necessary to modify a preformed indolizidine ring. This is the case in the synthesis of (+)-myrmicarin 217 191 where the key step is the closure of the third ring through an electrophilic substitution on the pyrrole nucleus (Scheme 45) <2000JOC2824>. 

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