Sequential cross-metathesis/cyclopropanation: short syntheses of (+/−)-cascarillic acid and (+/−)-grenadamide

The total synthesis of (+/−)-cascarillic acid has been achieved by a sequential cross-metathesis/Simmons–Smith cyclopropanation between, respectively, 1-octene with an appropriate unsaturated carboxylic acid. In parallel, a direct access to grenadamide was developed from 1-nonene with a readily available unsaturated amide. In both cases, the chemical yields were high (up to 98%) and the E/Z ratio was near 80/20. The synthesis of a dibromocyclopropane analogue has also been considered.