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

An efficient double addition of substituted alkenylmagnesium bromides to bis-Weinreb amides has been developed, giving alpha,omega-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 gamma-ketoamides that are core motifs of several pharmaceutical agents and promising drug candidates.