Batcho-Leimgruber reaction

Siu J, Baxendale IR, Ley SV (2004) Microwave assisted Leimgruber-Batcho reaction for the preparation of indoles, azaindoles and pyrroylquinolines. Org Biomol Chem 160... 

Another approach to 3-(trifluoromethyl)quinolines is based on cychzations of trifluoromethyl-containing intermediates, as illustrated, for instance, by the synthesis of 2-amino-3-(trifluoromethyl)quinoline 103 by means of the Leimgruber-Batcho reaction (Scheme 50) [77],... 

The Leimgruber-Batcho synthesis is a two-step method which provides indoles that arc substituted only in the benzene ring. The method was initially disclosed in a patent[l] and a representative procedure is available in Organic Syntheses[2]. A review of the reaction is available[3]. The reaction involves... 

One route to o-nitrobenzyl ketones is by acylation of carbon nucleophiles by o-nitrophenylacetyl chloride. This reaction has been applied to such nucleophiles as diethyl malonatc[l], methyl acetoacetate[2], Meldrum s acid[3] and enamines[4]. The procedure given below for ethyl indole-2-acetate is a good example of this methodology. Acylation of u-nitrobenzyl anions, as illustrated by the reaction with diethyl oxalate in the classic Reissert procedure for preparing indolc-2-carboxylate esters[5], is another route to o-nitrobenzyl ketones. The o-nitrophenyl enamines generated in the first step of the Leimgruber-Batcho synthesis (see Section 2.1) are also potential substrates for C-acylation[6,7], Deformylation and reduction leads to 2-sub-stituted indoles. 

As for many reductions of the nitro group, the reaction often stops at an intermediate stage (NO, NHOH). Somei was the first to observe this in the Leimgruber-Batcho indole synthesis [60-62]. Although 1-hydroxyindole itself is very unstable, Somei and his coworkers were able to isolate 1-hydroxyindoles bearing an electron-withdrawing... 

There are no detailed reports on the mechanism of the Batcho-Leimgruber process. The mechanism proposed here is based on similar types of reactions reported in the literature. ... 

Several types of substituted formamide acetals have been utilized in the Batcho-Leimgruber reaction, including N,N-dimethylformamide dimethyl and diethyl acetals, N-... 

Li, J. Cook, J. M. Batcho—Leimgruber Indole Synthesis in Name Reactions in Heterocyclic Chemistry, Li, J. J. Corey, E. J. Eds. Wiley Sons Hoboken, NJ, 2005, 104—109. (Review). 

A valuable modification of the Batcho-Leimgruber reaction (p. 239), in which the a-carbon of the enamine is substituted, enables tryptophan derivatives to be synthesized in very good yields. 

Indoles are obtained by specific cyclizations (Fischer synthesis, Reissert synthesis, Batcho-Leimgruber synthesis, Nenitzescu synthesis), as are carbazoles from biphenylene or diphenyl-amines and pyrrolidines (Hofmann-Loffler reaction). 

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