Acetic Acid Aldol Reactions in the Presence of Trimethylsilyl Trifluoromethanesulfonate

In the presence of TMSOTf and a trialkylamine base, acetic acid undergoes aldol addition to non-enolizable aldehydes under exceptionally mild conditions. Acidic workup yields the beta-hydroxy carboxylic acid. The reaction appears to proceed via a three-step, one-pot process, including in situ trimethylsilyl ester formation, bis-silyl ketene acetal formation, and TMSOTf-catalyzed Mukaiyama aldol addition. Independently synthesized TMSOAc also undergoes aldol additions under similar conditions.