Lewis Base-catalyzed Aldol Reactions of Trimethylsilyl Enolates

Lewis Base-catalyzed Aldol Reactions of Trimethylsilyl Enolates 

Since 1973, many Lewis acid-catalyzed aldol reactions have been studied, as described above. There have, however, been few examples of Lewis base-catalyzed aldol reaction using special silyl enolates, e.g. phosphoramide-catalyzed aldol reactions of trichlorosilyl enolates 69 (Eq. (36)) [47] and CaCh-catalyzed reactions of dimethylsilyl enolates 72 in aqueous DMF (Eq. (37)) [56]. 

New challenges were then made to develop useful Lewis base-catalyzed aldol reactions of trimethylsilyl enolates, simple and the most popular silicon enolates. It has recently been found that aldol reactions of trimethylsilyl enolates with aldehydes proceed smoothly under the action of a catalytic amount of lithium diphenylamide or lithium 2-pyrrilidone in DMF or pyridine (Eq. (38)) [57]. This Lewis base-catalyzed aldol reaction of trimethylsilyl enolates [58] has an advantage over acid-catalyzed reactions in that aldol reaction of carbonyl compounds with highly-coordinative functional groups with Lewis acid catalysts are smoothly catalyzed by Lewis bases to afford the desired aldol adducts in high yields. 

Typical Experimental Procedure for Lithium 2-Pyrrolidone-catalyzed Aldol Reaction (Eq. (39)) [57b,c] 

A solution of ketene silyl acetal 74 (146 mg, 0.84 mmol) in DMF (0.8 mL) was added to a solution of lithium pyrrolidone in DMF (0.1 m, 0.6 mL, 0.06 mmol) at —45 °C and a solution of aldehyde (89.5 mg, 0.60 mmol) in DMF (1.6 mL) was then added. The reaction mixture was stirred at the same temperature for 1 h and the reaction was then quenched by adding saturated NH4CI. The mixture was extracted with diethyl ether, and the combined organic extracts were washed with brine, dried over Na2S04, filtered, and concentrated. The crude product was purified by preparative TLC (hexane-ethylacetate, 3 1) to give the silylated aldol adduct 75 (187 mg, 96%). 

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