Friedel–Crafts Reaction of Activated Benzene Rings with Captodative and Electron‐Deficient Alkenes. A One‐Step Synthesis of the Natural Product Methyl 3‐(2,4,5‐Trimethoxyphenyl)propionate

Abstract

Electrophilic aromatic substitution of activated benzenes with the captodative olefin 1‐acetylvinyl‐1‐p‐nitrobenzoate (9), and with the electron‐deficient alkenes methyl acrylate (8a), methylvinylketone (8b), and acrolein (8c) were evaluated under Lewis acid catalysis. Olefin 9 proved to be much more reactive than alkenes 8a–8c. We also describe a one‐step synthesis of the antifungal and larvicidal natural product methyl 3‐(2,4,5‐trimethoxyphenyl)propionate (6), by reaction of 1,2,4‐trimethoxybenzene with 8a under microwave irradiation.

Keywords:

• Friedel–Crafts
• Captodative olefins
• Methyl 3‐(2,4,5‐trimethoxyphenyl)propionate

Acknowledgments

We thank Dr. Hugo A. Jiménez‐Vázquez for reviewing the manuscript, and Fernando Labarrios for his help in spectrometric measurements. J. T. acknowledges CGPI/IPN (Grants 200410, 20040123, and 200140) for financial support. R. A. and A. B. thank CONACYT for graduate scholarships. J. T. is a fellow of the EDI/IPN and COFAA/IPN programs.