Iminium salts reactions with unsymmetrical methyl ketones

In a regiochemical investigation of the reaction of iminium salt (32) with a series of unsymmetrical methyl ketones, Jasor et al. have observed that the site of aminomethylation is solvent dependent (equation 7, Table S). It is found that in MeCN, reaction occurs exclusively at the least-substimted position, while in TFA it occurs mainly at the most-substituted position. Yields are good (70-90%) in TFA but are somewhat reduced in MeCN due to dialkylation, which can be overcome if the more bulky NA -diisopro-pyliminium salt is used. How the solvent influences the two possible rate-determining steps, enolization versus aminomethylation, and the extent of reversibility of the reaction need further investigation in order to determine the basis for the observed dichotomy in regiochemistry. 

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