Lithium Ephedrinate Mediated Aldol Reaction of Arylacetonitriles: Thermodynamic Control of Enantioselectivity

Abstract

Deracemization, the conversion of a racemic mixture into an enantiomerically enriched material, is achieved with the retro-aldol reaction of rac-1 in the presence of lithium (-)-ephedrinate [Eq. (1)]. Remarkably, two stereogenic centers are simultaneously deracemized. This reaction shows that efficient thermodynamic control of the enantioselectivity of aldol reactions is possible.

Dynamic Thermodynamic Resolution: Control of Enantioselectivity through Diastereomeric Equilibration

“…A recent report of lithium ephedrinate mediated aldol reactions of arylacetonitriles to aldehydes by Carlier also illustrates dynamic thermodynamic resolution . When 45 is sequentially exposed to (1 R ,2 S )−(−)-ephedrine, n -BuLi, t -BuCHO, and NH 4 Cl, the pure anti aldol product 46 is obtained with enantioselectivities which depend on reac-tion time.…”

“…Dynamic Thermodynamic Resolution Beak et A recent report of lithium ephedrinate mediated aldol reactions of arylacetonitriles to aldehydes by Carlier also illustrates dynamic thermodynamic resolution. 37 When 45 is sequentially exposed to (1R,2S)-(-)-ephedrine, n-BuLi, t-BuCHO, and NH 4 Cl, the pure anti aldol product 46 is obtained with enantioselectivities which depend on reaction time. The authors note that the enantiomeric ratio, but not yield, changes with time and propose that the enantiomeric products are initially formed in a kinetic ratio.…”