Enantioselective protonation of prochiral enolates with chiral imides

Abstract

New chiral proton sources possessing an asymmetric 2-oxazoline ring, ( S, S)-imide 1 and related imides, were synthesized from Kemp's triacid and optically active 2-amino alcohols. With these chiral imides, various lithium enolates of α-monoalkylated cycloalkanones were effectively protonated with excellent to moderate enantioselectivity. An increase in enantioselectivity was observed in the asymmetric protonation of prochiral enolates with ( S, S)-imide 1 using lithium salt as an additive. For example, ( R)-enriched 2- n-pentylcyclopentanone 35 was obtained in high yield with 90% ee when the silyl enol ether 33 was treated with n-BuLi in the presence of 5 equiv of LiBr in Et 2O, and the resulting lithium enolate 34 was then protonated by a solution of ( S, S)-imide 1 in THF. In contrast, the product 35 obtained without LiBr exhibited a lower enantiomeric excess (74% ee).