The Development of the Asymmetric Morita—Baylis—Hillman Reaction Catalyzed by Chiral Brønsted Acids

Abstract

AbstractThis report describes the development of a chiral Brønsted acid‐catalyzed asymmetric Morita–BaylisHillman (MBH) reaction of cyclohexenone with aldehydes. During the course of our studies on chiral Lewis acid‐promoted MBH reactions, we discovered that chiral binaphthol‐derived Brønsted acids serve as promoters of the asymmetric MBH reaction. We propose that the phosphonium enolate of cyclohexenone is stabilized via hydrogen‐bonding with the binaphthol‐derived Brønsted acid, creating a chiral nucleophile. A practical and efficient set of conditions was developed using stoichiometric PEt3 as the nucleophilic promoter and catalytic amounts of a binaphthol‐derived Brønsted acid to effect the reaction of cyclohexenone with various aliphatic and aromatic aldehydes in good yields and enantiomeric excesses (up to 96% ee).