Organocatalytic Regioselective Aldol Reaction of Hydroxyacetone with Aliphatic Aldehydes for the Synthesis of Linear Products

Herein, we present an organocatalyst that addresses the reactivity issue of aliphatic aldehydes with hydroxyacetone, leading to the formation of a linear product. Previous proline-based catalysts required a significant excess of hydroxyacetone and could only be applied to aromatic aldehydes. The proposed sulphonamide containing a proline moiety effectively controls the reaction, generating a new stereogenic center dependent on the catalyst's configuration and does not require a large excess of the ketone. We demonstrated that this methodology can be effectively utilized in the synthesis of natural compounds, as confirmed by obtaining the 2-keto-3-deoxy-D-gluconic acid (KDG) methyl ester from optically pure glyceraldehyde and protected hydroxyacetone. image