Aldol reactions of acetone with aromatic aldehyde

The 1,2,3-triazole-linked fluorous proline organocatalyst 32 was introduced by Pericas and coworkers in 2013 for the asymmetric aldol reactions of acetone with aromatic aldehydes, giving higher enantioselectivities than other proline derivatives (Scheme 11.27). ° The fluorous tag and the use of a per-fluorinated solvent allowed the easy recycling and reuse of 32, for at least six times. 

Recently, kinetic and specdoscopic studies gave a mechanistic explanation of the role of water in the aldol reaction with aromatic aldehydes. While the addition of water increases the catalyst concentration by suppression the formation of parasitic species such as the oxazolidinone, decreases the relative concentration of key minimum intermediates by Le Chatelier s principle, shifting the equilibrium towards proline (1). The net effect on the reaction rate of these opposing roles would differ when different substrates are used in the reaction, with the intrinsic rate per active catalysts species within the cycle being suppressed by the added water in the aldol reaction of acetone with aromatic aldehydes [37]. 

Cordova and coworkers demonstrated that simple dipeptides, particularly alanine-containing ones, were effective catalysts for the direct aldol reactions of cyclic ketones with aromatic aldehydes, and the reactions have been explored using either DMSO or water as the reaction medium [40a,b]. Tsogoeva and Wei showed that L-histidine-based dipeptides are good catalysts for the direct aldol reaction of acetone with aromatic aldehydes [41]. 

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