Leimgruber-Batcho

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. 

Acylation of the Leimgruber Batcho enamines with phosgene followed by methanolysis and reductive cyclization generates methyl indole-3-carb-oxylates[8]... 

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

Carrera and Sheppard improved upon a Leimgruber-Batcho indole synthesis [24] to prepare 6-bromoindole (20) in excellent overall yield from 4-bromo-2-nitrotoluene [29a], and Rapoport utilized this method to synthesize 4-, 5-, 6-, and 7-bromoindole [29b]. 

When indoles unsubstituted in the heterocyclic ring are required, the Leimgruber-Batcho synthesis can be used. In its original form the... 

Indoles from p-dialkylamino-o-nitrostyrenes. The Leimgruber Batcho synthesis 7... 

A procedure for obtaining indole-3-carboxylate ester from the f-pyrrolidino-o-nitrostyrene intermediates in the Leimgruber-Batcho indole synthesis was demonstrated. Although ethyl chloroformate is evidently not reactive enough, phosgene followed by methanolysis effects f) -carbomethoxylation. Reductive cyclization then gives the indole esters. <95SC95>... 

The widely employed Leimgruber-Batcho protocol for indole synthesis comprises two consecutive steps—the formation of enamines followed by a reductive cyclization. The formation of enamines (such as 14, Scheme 7) presumably required an initial deprotonation of the methyl ortho to the aromatic nitro-group by methoxide generated from DMF-DMA under elevated temperatures (overnight heating in DMF) [27]. The use of microwave irradiation at 180 °C allowed the reduction of the time of formation of enamines such as 14 from 22 h (at 110°C) to 4.5 h (and even to 40 min in several... 

Leimgruber-Batcho indole synthesis (from o-nitrotoluene and dimethylformamide dimethyl acetal) 84H(22)195. 

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