Chiral phosphine lewis bases catalyzed asymmetric aza-Baylis-Hillman reaction of N-sulfonated imines with activated olefins

Min Shi; Lian-Hui Chen; Chao-Qun Li

doi:10.1021/ja0447255

Chiral phosphine lewis bases catalyzed asymmetric aza-Baylis-Hillman reaction of N-sulfonated imines with activated olefins

J Am Chem Soc. 2005 Mar 23;127(11):3790-800. doi: 10.1021/ja0447255.

Authors

Min Shi¹, Lian-Hui Chen, Chao-Qun Li

Affiliation

¹ State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China. mshi@pub.sioc.ac.cn

PMID: 15771513
DOI: 10.1021/ja0447255

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 (approximately -30 to -20 degrees C) or at room temperature in THF, respectively. In CH2Cl2 upon heating at 40 degrees 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 Bronsted acid phosphine Lewis base system has been disclosed in this catalytic, asymmetric aza-Baylis-Hillman reaction.