Direct conversion of cinnamate esters into β,β-disubstituted ketones mediated by cyano-magnesio cuprates

Abstract

The clean synthesis of unsymmetrical ketones from carboxylic acid derivatives has been a challenge in the organic community dating back over 80 years. Herein we report the conversion of simple alkyl cinnamates to β,β-disubstituted ketones with cyano-magnesio cuprates in high yields with no observation of tertiary alcohol byproduct. The lack of tertiary alcohol is attributed to a putative enolate intermediate that serves as a ketone protecting group. A distinctive steric inhibition trend was observed related to both the size of the R group on the parent ester and the nucleophilic cuprate. Lastly, we demonstrate that this reaction can be coupled with known copper mediated allylic substitution reactions yielding β,γ-disubstituted ketone (8) from parent α-chloro-β,γ-ethylenic ester (7).