Selectivity in C-alkylation of dianions of acyclic β-enamino ketones

Abstract

The regioselectivity of dianion formation from 4-(N-alkylamino)pent-3-en-2-one has been probed by deuteriation and alkylation techniques. The results obtained indicate that the regioselectivity can be controlled almost absolutely without resorting to classical conditions used to favour either the kinetic or the thermodynamic products. In fact, the kinetic (α′-dianion) and the thermodynamic dianion (γ-dianion) are preferentially formed in THF at 20 °C with a slight excess of Li-TMP (α′-conditions) or of MeLi/TMEDA (γ-conditions) respectively. While under γ-conditions, alkylation in the γ-position is almost exclusively observed, kinetic preference for the α′-dianion is dependent on the size of the alkyl group linked to the nitrogen atom. The preference for alkylation at the α′-position increases from methyl to the bulky tert-butyl group. Once formed, the α′-dianion very slowly interconverts into the more stable γ-dianion, even in the presence of TMEDA, whereas, when the dianion is formed under γ-conditions, the rate of equilibration is comparable with that of its formation, with the result that γ-dianion is exclusively formed. Theoretical calculations (HF/6–31G//3–21G) on the more stable conformation of the monoanion, both ‘naked’ and as a lithium ion pair, provide convicing explanations of these findings.