Tetrahedral boronates as basic catalysts in the aldol reaction

Abstract

Abstract β-Hydroxyketones are versatile building blocks in organic synthesis, which can be conveniently synthesized from ketones and aldehydes by aldol reactions. Unfortunately, these reactions often suffer from dehydration of the initially formed β-hydroxyketones. Previously, tetrahedral 3,5-difluorophenylborate was shown to be an efficient and selective catalyst for this reaction. The present investigation concerns the catalytic performance of phenyl borates with different substitution patterns in the aldol reaction. It appears that the dehydration reaction can be suppressed by selecting substituents and substituent positions with reduced electron withdrawing effects on the borate function. Optimal suppression of the dehydration of β-hydroxyketones was obtained for compounds corresponding to phenylboronic acids with a pK a > 7. The reactions between benzaldehyde and butanone or 3-pentanone did not show diastereoselectivity, which suggests that the catalysts merely act as bases rather than as templates for the transition state of the aldol reaction. Sterically more demanding ketones were not converted.