title: Brønsted acids as additives for the direct asymmetric aldol reaction catalyzed by l-prolinethioamides. direct evidence for enamine-iminium catalysis.
abstract: The use of protonated l-prolinethioamide instead of the free base derivative 1 as the organocatalyst for the direct aldol addition has a profound and appreciable effect on both the yield and the stereochemical course of the reaction. 4-Nitrobenzaldehyde (2) reacts with acetone in the presence of the protonated catalyst 1.TFA, affording aldol product 3 with a yield up to 99% and an ee up to 98%. The catalyst loading can be lowered to 2.5 mol %. More than 20 different acids were investigated as an additive, and its role as cocatalyst has been discussed. Furthermore, reactions of l-prolinethioamide salts with acetone have been monitored using ESI-MS and 1H NMR techniques, giving insight into the mechanism of the direct aldol reaction. The presumed formation of the iminium salt 10 has been unambiguously confirmed.
authors.affiliation: Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, Warsaw, Poland. dgryko@icho.edu.pl
authors.forename: Dorota
authors.initials: D
authors.lastname: Gryko
authors.forename: Magdalena
authors.initials: M
authors.lastname: Zimnicka
authors.forename: Radosław
authors.initials: R
authors.lastname: Lipiński