Cyclohexanone → Methyl 3-cyclohexyl-1H-indole-6-carboxylate

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Reaction Steps

Condensation of 1H-indole-6-carboxylic acid with cyclohexanone under basic conditions can generate 3-cyclohexenyl-1H-indole-6-carboxylic acid. This indole ester can be subjected to sequential reduction and esterification to provide methyl 3-cyclohexanyl-1H-indole-6-carboxylate. Treatment of the resultant indole ester with pryridinium tribromide in a mixture of THF and chloroform can generate methyl 2-bromo-3-cyclohexanyl-1H-indole-6-carboxylate. This intermediate can be coupled with a variety of reagents and compounds. For example, 2-formyl-phenyl boronic acids using appropriate palladium catalysts can generate the aromatic aldehyde intermediates shown. These aryl aldehydes are sometimes observed to exist in equilibrium with the related ring-closed hemiaminals, as shown below.

Provenance & Evidence