Grignard reagents, indole

The indole Grignard reagents have been widely employed as intermediates in synthetic work, mainly for the introduction of substituents into the 1- or 3-positions of the indole ring system. 

In view of the importance of these compounds in indole chemistry and since there is no adequate modern survey of this field, an attempt has been made to review comprehensively the chemistry of the indole Grignard reagents. 

Oddo reported that the organomagnesium derivatives of p3Trole, indole, skatole, and carbazole could be prepared in a single operation by mixing the parent heterocyclic compound with an alkyl halide and magnesium in anhydrous ether.The product formed was reported to be the same as that obtained by the more conventional procedure. However, this approach to the synthesis of the indole Grignard reagents does not seem to have been exploited in subsequent work. 

In some instances the reactions of the indole Grignard reagents resemble those of simple aryl or alkyl magnesium halides, but in many eases they appear to reaet anomalously. 

A number of synthetic approaches to the pyrrolo[2,3-6]indole ring system, present in tlie physostigmine [i.e., eserine (22)] molecule, which involve indole Grignard reagents as intermediates, have been described. 

It is only in relatively recent years that the interaction of indole Grignard reagents with unsaturated aliphatic halogen compounds has... 

Recently two further examples of the 1-acetylation of indoles by this route have been observed by Heacock and Hutzinger. l-Acetyl-5-benzyloxyindole (216) and l-acetyl-5-benzyloxy-3-methylindole (217) were obtained by the action of ethyl acetate on the relevant indole Grignard reagents at low temperatures. ... 

Majima et al. prepared ethyl y-(3-indolyl)-y-oxobut3rrate (250) in a similar manner by the condensation of the indole Grignard reagent with -ethoxycarboiiylpropionyl chloride.Methyl y-(3-indolyl)-y-oxobutyrate (251) has been obtained by the action of mcthoxycarbonylpropionyl chloride on indole magnesium iodide in ether. Ballantine et al. prepared methyl y-(5-methoxy-3-... 

Sanna reported that l,3-di(3-indolyl)-l,3-dioxo-%-propanc (266) and l,4-di(3-indolyl)-l,4-dioxo-M-butane (267) were formed by the action of malonyl chloride and succinyl chloride, respectively, on the indole Grignard reagent in ether, and analogous products could be obtained from 2-methylindole. 

Recent work by Powers has suggested that in addition to the di-indolylphenylmethane derivatives, 3-aroylindoles are obtained by the action of aromatic aldehydes on the indole Grignard reagents. 

Majiina and Kotake prepared 2,2-di(3-indolyl)propane (336) by the action of acetone on indole magnesium iodide in other or anisole. Recently 1 -indolyl derivatives have been o btained as primary products by interaction of ketones with indole Grignard reagents for example acetone gave a 75% yield of 2-(l-indolyl)propan-2-ol (337). 

A crystalline addition product of indole with picryl chloride (i.e. l-chloro-2,4,6-trinitrobenzene), together with an unidentified amorphous substance, were obtained by the action of picryl chloride on indole magnesium iodide, and analogous products were obtained in the reaction between the indole Grignard reagent and 1-chloro-2,4,5-trinitrobenzene. 

The reaction of ethyl nitrate with the indole Grignard reagent is discussed... 

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