Lewis Acid-Enhanced Reactivity of α,β-Unsaturated Ester and Amide toward Radical Addition

摘要

Since alkyl radicals which are most frequently utilized in organic synthesis are generally of a nucleophilic character, their addition to olefinic substrates is enhanced by electron-withdrawing substituent(s) on the olefinic linkage. Thus, a syntheticdesign to improve reactivity of the substrates (hence, to increase the product yields) is usually made by placing an effective electron-withdrawing group in the substrate or by increasing the number of such substituents. Among olefinic compounds havingan electron-withdrawing group, α,β-unsaturated esters and amides belong to a group of relatively unre-active substrates in radical reactions. In fact, we encountered a low product yield in performing alkyl radical addition to certain α,β-unsaturatedesters (vide infra). We conceived that prior complexation of a Lewis acid (LA) to the carbonyl group of an unsaturated ester would decrease the electron density of its olefinic moiety and thus function to increase the electron-withdrawing properties of this substituent. Although this methodology for activation of α,β-unsaturated carbonyl compounds is well established in Diels-Alder reactions and in ionic reactions such as 1,4-addition of nucleophiles, to our knowledge, radical acceptor activation by LA has not been investigated in organic-synthesis. Herein we would like to disclose our findings on the use of LA for the above purpose.