Synthesis of α,ω‐Bis‐Enones by the Double Addition of Alkenyl Grignard Reagents to Diacid Weinreb Amides

Abstract

An efficient double addition of substituted alkenylmagnesium bromides to bis‐Weinreb amides has been developed, giving α,ω‐bis‐enones that are building blocks for certain drugs and polymers. Furthermore, reliable protocols for the preparation of the required substituted alkenylmagnesium reagents from substituted non‐activated alkenyl bromides are reported. The double addition is demonstrated on 25 examples, including enantiopure as well as conjugated and cross‐conjugated bis‐enones. The addition to a cyclohexane‐1,2‐dicarboxamide was found to lead to a selective mono addition, giving access to cyclohexyl γ‐ketoamides that are core motifs of several pharmaceutical agents and promising drug candidates.