Indole Grignard reagents with ketones

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). 

Kutney s approach started with isophorone 84, which was converted into the dibenzoate 85, and thence to the acid 86 on treatment with indolyhnagnesium iodide. Conversion to the acid chloride followed by treatment with indolylmagnesium iodide, induced cyclization to the trans-taseA tetracycle 87. Base-catalyzed epimerization to the cM-fused tetracyclic ketone 88, followed successively by hydride reduction, conversion into the benzoate, treatment with the indole Grignard reagent, and deprotection, gave YCK (73) (Scheme 4). The overall yield was however low (4%), but the method allows access to 6a-c z-YCK via the ketone 87 (57,55). 

The diketoindoles 777 were prepared in three steps starting from indol-3-ylacetic acid (680) and 5-chloro indol-3-ylacetic acid (774) in 75% and 66% overall yield, respectively. The indole acids 680 and 774 were converted into Weinreb amides 775, followed by reaction with ethyl Grignard reagent to afford the corresponding indol-3-yl ketones 776. In order to introduce the second carbonyl moiety, the 3-substituted... 

The Fischer indole synthesis has also been employed. The nitrile (XXXVIII) reacts with the Grignard reagent prepared from y-ethoxy-propyl bromide to give an intermediate (XXXIX) which in the presence of acid generates the cyclic ketone XL. The phenylhydrazone of the last can be cyclized to sempervirine (XXXV) (24). 

Conversion of isatins into oxindoles can be achieved by catalytic reduction in acid, or by the Wolff-Kischner process.3-Substituted indoles result from Grignard addition at the ketone carbonyl, followed by lithium aluminium hydride reduction of the residual amide, then dehydration. The reaction of isatin with triphenylphosphine provides an easy synthesis of 3-(triphenylphosphorylidene)oxindole, a Wittig reagent. ... 

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