Pyrrolidine, 2,5-dimethylcyclohexanone enamine from alkylation

A valuable feature of the enamine reaction is that it is regioselective. In the alkylation of an unsymmetrical ketone, the product of reaction at the /ess-substituted a-carbon atom is formed in greater amount, in contrast to direct base-mediated alkylation of unsymmetrical ketones, which usually gives a mixture of products. For example, reaction of the pyrrolidine enamine of 2-methylcyclohexanone with iodomethane gives 2,6-dimethylcyclohexanone almost exclusively. This selectivity derives from the fact that the enamine from an unsymmetrical ketone consists mainly of the more-reactive isomer in which the double bond is directed toward the less-substituted carbon atom. In the more-substituted enamine, there is decreased interaction between the nitrogen lone pair and the -ir-system of the double bond because of steric interference between the a-substituent (the methyl group in Scheme 1.33) and the a-methylene group of the amine. 

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