Mechanistic investigation of the 2,5-diphenylpyrrolidine-catalyzed enantioselective α-chlorination of aldehydes

The mechanism for the 2,5diphenylpyrrolidine-catalyzed enantio-selective alpha-chlormation of aldehydes with electrophilic halogenation reagents has been investigated by using experimental and computational methods. These studies have led us to propose a mechanism for the reaction that proceeds through an initial N-chlorination of the chiral catalyst-substrate complex, followed by a 1,3-sigmatropic shift of the chlorine atom to the enamine carbon atom. The sugested reaction course is different from previously proposed mechanisms for organocatalytic enamine reactions, in which the carbon-electrophile bond is formed directlv Furthermore, the rate-determining step in the overall reaction was determined and the presence of nonlinear effects was probed.