Indole Grignard reagents reactions

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 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... 

Oddo and Sessa claimed that 1-carboxyindole (375) was obtained on treatment of indole magnesium iodide with gaseous carbon dioxide. Majima and Kotake later reported that 3-carboxyindole (376) and not 375 was the main product obtained in this reaction improved yields of 376 were obtained when the reaction was carried out in anisole instead of ether.Subsequently, several workers have employed essentially this procedure, for the synthesis of 376. It has recently been shown, however, that both the acids 375 and 376 are formed in approximately equal amounts by the carbonation of the indole Grignard reagent (Kasparek and Hea-cook ). 

The early literature on the reactions of the indole Grignard reagents with the simple diacid chlorides, in particular with carbonyl chloride and oxalyl chloride (see Section III,C,4,b), is both conflicting and confusing and much of the work reported warrants repetition since the evidence presented in support of many of the structural assignments made is not entirel3 convincing. 

In the 19.S0 s a number of workers, including Hoshino, Oddo, and Kubota suggested that indolenine-type intermediates (cf. 431) were formed during the reaction of the indole Grignard reagents [depicted as N—MgX derivatives (cf. 432)] with alkyl and arylalkyl halides. Rather surprisingly these were the last reports dealing with... 

Sebastian also observed that although alkylation of the indole Grignard reagent with methyl iodide in tetrahydrofuran at 23° gave essentially 3-methylindolc, variable amounts of 1- and 3-methyl-indole were obtained on alkylation of the alkali metal salts of indole under similar conditions. Sebastian s results were qualitatively similar to those obtained earlier by Lerner and more recently by Cardillo who studied the reaction of a number of organometalhc... 

Some recent studies have underlined the effect that certain physical properties of the reaction medium have in governing the nature and yields of the products obtained when indole Grignard reagents react with alkyl or alkynyl halides. Such factors include the basicity and dielectric constant of the medium and its ability to solvate any of the reacting species. ... 

They utilized the reaction between indole Grignard reagents and either 3-acetyl-pyridine or nicotinoyl chloride to give the target structures 54 and 365, after the appropriate reduction. None of these compounds displayed antitumor activity anywhere comparable to that of ellipticine. 

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