Proline-based organocatalyst-mediated asymmetric aldol reaction of acetone with substituted aromatic aldehydes: an experimental and theoretical study

Abstract

This work involves a facile synthesis of three (S)-proline-based organocatalysts with C2 symmetry and theireffects in enantioselective aldol reaction of acetone with substituted aromatic aldehydes. Moderate enantioselectivities(up to 61% ee) were obtained depending on the nature of the substituents on the aryl ring. Computational calculationsat HF/6-31 + G(d) level were employed to underline the enantioselectivity imposed by all the organocatalysts. Highercalculations at B3LYP/6-311 ++ G(d,p) scrf=(solvent=dichloromethane)//B3LYP/6-31 + G(d) levels of theory werealso performed for the aldol reaction of acetone with benzaldehyde and 4-nitrobenzaldehyde catalyzed by 1. Thecomputational outcomes were consistent with those produced by experimental results and they were valuable to elucidatethe mechanism for the observed stereoselectivity.