Pyrroles Trofimov pyrrole synthesis

Trofimov s pyrrole synthesis reacts ketoximes with alkynes under strongly basic conditions (Scheme 53) (90AHC178, 94H(37)1193). A key sigmatropic rearrangement of an O-vinyloxime is followed by a typical imine-carbonyl condensation. Frequently an IV-vinylpyrrole formed from the initial pyrrole is a major by-product (92CHE510). 

An important advantage of the Trofimov pyrrole synthesis is its technological feasibility, that is, the opportunity of applying it for the commercial production of difficultly accessible, though pharmaceutically and technically useful pyrroles. This was convincingly demonstrated and proved by N-vinyl-4,5,6,7-tetrahydroindole piloting (84M17). 

Trofimov and co-workers have developed a pyrrole synthesis which involves reactions of ketox-imes with alkynes under strongly basic conditions (Scheme 51) <90AHC178,94H(37)l 193>. The key step in the reaction is a sigmatropic rearrangement of an 0-vinyloxime which is followed by a typical... 

The Trofimov pyrrole synthesis (the Trofimov Reaction) refers to the conversion of ketones to pyrroles in the presence of NH2OH, KOH and DMSO at elevated temperatures. The reaction was shown to occur via hydroxylamine and 0-vinylhydroxylamine intermediates. 

One of the weaknesses of the Trofimov reaction is the requirement for using acetylene under high pressure. To obviate this requirement, acetylene analogs (vinyl halides and 1,2-dihaloethanes) were examined for the utility as components in the Trofimov reaction. The results are promising and indicated that further development of this variation in the Trofimov reaction could lead to a more practical and attractive method for pyrrole synthesis. 

Trofimov Pyrrole Synthesis under a Flow of Acetylene Gas ... 

Over the last decades, a novel branch of the pyrrole chemistry, based on the reaction of ketones (ketoximes) with acetylenes in the superbase catalytic systems (the Trofimov reaction), has emerged and keeps progressing rapidly. New facile and highly efficient approaches to the diverse compounds of the pyrrole series have been developed. The investigations in this line are gathering momentum. Not only the discoverers and developers of novel pyrrole synthesis (the authors of this monograph) but many other research teams both in Russia and abroad are engaged in these studies. 

Trofimov, B.A., L.N. Sobenina, and A.I. Mikhaleva. 1987. Advances in Pyrrole Synthesis. Moscow, Russia VINTTI. 

Sobenina, L.N., A.I. Mikhaleva, and B.A. Trofimov. 1989. Synthesis of pyrroles fiom heterocyclic componnds. Khim Geterocicl 3 291-308. 

Trofimov has extended his previously reported heterocyclization of ketoximes 39 with acetylene to propyne or its isomer allene in superbase systems (MOR/DMSO M = K, Cs, R = H, t-Bu) to afford a facile synthesis of substituted pyrroles 40 and 41 . Due to a fast propyne to allene protropic isomerization under the reaction conditions, the product is the same regardless of which species is employed. 

General synthesis of pyrroles and 1-vinylpyrroles by the reaction of ketoximes with acetylenes and their synthetic equivalents (vinyl halides and dihaloethanes) in the presence of the strongly basic KOH/DMSO system (Trofimov reaction) has been reviewed ° in recent years. Therefore, in the present work this reaction will be described very shortly. In principle, pyrrole (51) synthesis can be carried out as a one-pot procedure by treating ketones (49) with hydroxylamine and then reacting the ketoximes (50) formed with acetylenes (equation 22). 

Extention of the reaction of ketoximes with acetylene to oximes of hydroxyalkyl ketones can lead to the synthesis of inaccessible, functionally substituted pyrroles and A-vinyl derivatives. However, the methyl a- and /3-hydroxyalkyl ketoximes used by Trofimov et al. (80ZOR410) appeared to react with acetylene in the KOH/DMSO system in an abnormal way. 

In brief communications concerning the use of dialkyl ketoximes (79IZV2840 81MI7, 81MI8) in this reaction, no comprehensive synthetic procedures are described. The experimental details for the synthesis of 2,3-dialkyl-substituted pyrroles from symmetrical and unsymmetrical dialkyl ketoximes and dichloroethane in the KOH/DMSO system (Scheme 63) were first discussed by Trofimov et al. (85KGS59). 

Volume 51 of Advances consists of three chapters, V. V. Mezheritskii and V. V. Tkachenko (Rostov-on-Don, U.S.S.R.) review the synthesis of peri-annelated heterocycles, a large and interesting class which has not previously been treated in a systematic fashion. R. M. Acheson (Oxford, U.K.) provides the first detailed survey of 1-hydroxypyrroles and their benzo derivatives, compounds which show an interesting and unusual chemistry. Finally, B. A. Trofimov (Irkutsk, U.S.S.R.) describes the minifold preparative possibility for pyrroles from ketoximes and acetylenes, a reaction discovered by Trofimov and developed by him into a most important entry into pyrrole chemistry. 

Two-step synthesis of pyrroles from ketones and acetylenes via the Trofimov reaction 03MI20. 

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