SYNTHESIS OF POLYARENES BY SEQUENTIAL OXIDATIVE CROSS-COUPLING OF PHENOLS WITH ARENES

Polyphenols are important class of materials found in many bioactive natural products, drugs, natural and unnatural polymers and other man-made materials that are essential to modern society¹. The known synthetic protocols require multistep synthesis involving pre activation of the coupling arens, thus being not effective regarding atom economy considerations². Herein we propose a novel Iron-catalyzed regio selective oxidative sequential cross coupling reaction between different phenols and arenes, providing a direct entry to polyphenolic compounds. New C-C and C-O bonds are constructed in a simple procedure by coupling phenols and arenes while applying catalytic amount of iron salt in the presence of terminal oxidant^3,4.

In order to predict the selectivity of the reactions at different possible reactive sites within the selected phenols (ortho, para, meta), intermediates, and products radicals were measured by EPR spectroscopy. Also the oxidative potential of several phenols and the intermediates was measured by cyclic voltammetry to assess the stability of the phenoxyls radicals.

References:

1. Augustin Scalbert, Polyphenols: antioxidants and beyond. American Society for Clinical Nutrition, 2005, 81, p. 215S-217S
2. Ito M., Kubo H.,.Itani I,. Kita Y, Total synthesis of natural products using hypervalent iodine reagents, J. Am. Chem. Soc. 2013, 135, 14078−14081
3. Parnes R., Kshirsagar, U.A., et al., Iron-Catalyzed Oxidative Cross-Coupling of Phenols and Alkenes. Organic Letters, 2013. 15(12): p. 3174-3177
4. Gaster, E., et al., Significant Enhancement in the Efficiency and Selectivity of Iron‐Catalyzed Oxidative Cross‐Coupling of Phenols by Fluoroalcohols. Angewandte Chemie International Edition, 2015