Sterically hindered enamines alkylation

A significant improvement in the alkylation of ketone and aldehyde enamines involves the use of sterically hindered amines63. N-Alkylation is prevented with consequent increase in C-alkylation. For example, reaction of the w-butylisobutylamine enamine of cyclohexanone (29) with methyl iodide in boiling acetonitrile (Scheme 16), or trimethy-loxonium tetrafluoroborate at room temperature gave 2-methylcyclohexanone in increased yields of 56% and 74%, respectively63 (compare Scheme 10). 

A comparison of the results of the methylation of the pyrrolidine enamine of cyclohexanone (81 Scheme 42) with those shown in Scheme 43 for the methylation of the n-butylisobutylamine derivative (86) shows that yields are improved with the latter compound. Presumably, the more sterically hindered amine reduces the amount of iV-alkylation and retards the rate of proton transfer between the C-al-kylated iminium salt and the unreacted enamine. 

With anionic allylic sources, highly polar aprotic solvents increase the amount of lone pair alkylation because poor solvent stabilization of the anion leaves the heteroatom end less hindered by solvent. Conversely, groups bound to the heteroatom increase the steric hindrance about it, and therefore decrease the tendency toward heteroatom alkylation. For example, enamines (R2N-C=C) tend to alkylate on carbon rather than nitrogen (as shown in Section 8.4.5). 

This promoted Pt catalyst catalyzes the alkylation of various stericalfy hindered anilines with both primary and secondary alcohols with high selectivities and acceptable conversions. [7]. It is remarkable that increasing steric demand either of the aniline or of the alcohol part, only marginally affects conversion or selectivity. It seems quite reasonable to assume that enamines are involved also in this gas phase reactioa... 

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