Synthesis of Pipernonaline: A Catalytic Wittig Approach

Amides are typically poor nucleophiles, and thus their involvement in Wittig reactions has been scarcely researched. However, recent advances in high-activity, low-temperature catalysis have shown promise for Wittig reactions involving tertiary amides. Prior studies have focused on the development of air-stable catalytic phosphines. These advances were utilized in this research to synthesize and characterize pipernonaline, a natural product formed through a Wittig reaction utilizing a cinnamaldehyde derivative and a bromoacetyl tertiary amide. The cinnamaldehyde derivative, (E)-3-(benzo[d][1,3] dioxol-5-yl) acrylaldehyde, was synthesized via a Wittig reaction of piperonal and a Weinreb amide, followed by reduction with lithium aluminum hydride. The bromoacetyl tertiary amide was synthesized via an acyl substitution reaction between bromoacetyl bromide and piperidine. Future research will focus on utilizing this methodology to isolate other members of the piperacase family.