Selective γ-Substitution of α,β-Unsaturated Esters via α-Trimethylsilyl β,γ-Unsaturated Esters

In order to achieve selective γ-substitution of α,β-unsaturated esters, we investigated the directive effect of silicon in the reaction of various electrophiles with a-trimethylsilyl ß, -unsaturated esters. These esters were prepared by nickel-catalyzed vinylation reactions of the lithium enolate of ethyl a-(trimethylsilyl)acetate. The α-silyl β,γ-unsaturated esters reacted with a variety of electrophiles (aldehydes, ketones, acetals, ketals, acid chlorides, and chloro thioethers) in the presence of Lewis acids (titanium tetrachloride and trimethylsilyl trifluoromethanesulfonate) to give exclusively the γ-substituted product in moderate to good yields. In some cases, the primary substitution products underwent additional conversions under the reaction conditions, such as the cyclization of the 5-hydroxyl or 5-keto enoates to dihydropyrones or pyrones, respectively. These α-silyl β,y-unsaturated esters are effective reagents for achieving complete 7-selective substitution of αβ-unsaturated ester systems.