Organocatalytic asymmetric aldol reaction using protonated chiral 1,2-diamines

Abstract

Organic-catalyzed stereoselective reactions have gained attention because they avoid the problems associated with metal catalysts, but existing catalysts based on proline have limitations. Therefore, (R,R)-(+)-1,2-diphenylethylenediamine (DPEN) was selectively mono-N-alkylated through reductive alkylation and used as an organic catalyst for the aldol reaction. Using a variety of aldehydes in the catalytic aldol reaction, the N-alkylated DPEN catalyst proceeded from primary amine to enamine and iminium intermediates and achieved both a high yield (80%) and enantioselectivity (90%). It was found that the steric hindrance of the N-alkyl substituent of the chiral diamine and the hydrogen bond between the ammonium moiety and the oxygen of the aromatic aldehyde determine the enantioselectivity. Various aromatic aldehydes were tested, and electron-withdrawing substituents led to good yields, whereas electron-donating substituents led to poor yields via the deactivation of the carbonyl group of the aldehyde. Further, ortho substituents resulted in higher stereoselectivities than para substituents because the stereoscopic effect was enhanced.