Lithium Hexamethyldisilazide-Mediated Enolizations: Influence of Triethylamine on E/Z Selectivities and Enolate Reactivities

Lithium hexamethyldisilazide (LiHMDS) in triethylamine (Et 3N)/toluene is shown to enolize acyclic ketones and esters rapidly and with high E/ Z selectivity. Mechanistic studies reveal a dimer-based mechanism consistent with previous studies of LiHMDS/Et 3N. E/ Z equilibration occurs when <2.0 equiv of LiHMDS are used. Studies of the aldol condensation and Ireland-Claisen rearrangement of the resulting Et 3N-solvated enolates show higher and often complementary diastereoselectivities when compared with analogous reactions in THF. The Et 3N-solvated enolates also display a marked (20-fold) acceleration of the Ireland-Claisen rearrangement with evidence of autocatalysis. A possible importance of amine-solvated enolates is discussed.