Chiral Phosphine Lewis Bases Catalyzed Asymmetric aza-Baylis−Hillman Reaction of N-Sulfonated Imines with Activated Olefins

Abstract

In the aza-Baylis−Hillman reaction of N-sulfonated imines (N-arylmethylidene-4-methylbenzenesulfonamides and others) with methyl vinyl ketone, ethyl vinyl ketone, and acrolein, we found that, in the presence of a catalytic amount of chiral phosphine Lewis base such as (R)-2‘-diphenylphosphanyl-[1,1‘]binaphthalenyl-2-ol LB1 (10 mol %) and molecular sieve 4A, the corresponding aza-Baylis−Hillman adducts could be obtained in good yields with good to high ee (70−95% ee) at low temperature (∼−30 to −20 °C) or at room temperature in THF, respectively. In CH₂Cl₂ upon heating at 40 °C, the aza-Baylis−Hillman reaction of N-sulfonated imines with phenyl acrylate or naphthyl acrylate gave the adducts in good to high yields (60−97%) with moderate ee (52−77%). The mechanistic insight has been investigated by ³¹P and ¹H NMR spectroscopic measurements. The key enolate intermediate, which has been stabilized by intramolecular hydrogen bonding, has been observed by ³¹P and ¹H NMR spectroscopy. An effective bifunctional Lewis base and Brønsted acid phosphine Lewis base system has been disclosed in this catalytic, asymmetric aza-Baylis−Hillman reaction.