Lithium Acetate-Catalyzed Aldol Reaction between Aldehyde and Trimethylsilyl Enolate in Anhydrous or Water-Containing N,N-Dimethylformamide

Abstract

Abstract Lithium acetate (AcOLi)-catalyzed aldol reactions between trimethylsilyl enolates and aldehydes proceed smoothly in anhydrous DMF or pyridine to afford the corresponding aldols in good to high yields under weakly-basic conditions (Tables 1–5). This catalytic aldol reaction is performed smoothly also by using other metal carboxylates that are easily prepared in situ by treating carboxylic acids with lithium carbonate (Li2CO3) (Table 2, Scheme 5). In order to show the effect of mild and readily-available AcOLi catalyst, the aldol reaction in water-containing DMF was studied in detail. AcOLi and various metal carboxylates behaved as effective Lewis base catalysts in aldol reactions between trimethylsilyl enolate and aldehydes in DMF–H2O (50:1) (Tables 6, 7). One of the most characteristic points of the above reaction that took place in water-containing DMF is that the aldehydes having a free amide and a hydroxy or even a carboxyl group reacted smoothly and afforded the desired aldols 29–31 in moderate to high yields (Table 8, Entries 12–15). Trimethylsilyl enolates derived from carboxylic esters behaved similarly as excellent nucleophiles in the above reaction. This is the first example of Lewis base-catalyzed aldol reactions to afford the desired aldol adducts even when silyl enolates derived from carboxylic esters were used in a water-containing organic solvent.