Siegel ’97 Invents Mild Route to Phenols

Phenols, ArOH, are ubiquitous in nature, chemical testimony to the oxidizing power of the air we breathe. But chemists have always stumbled over the laboratory oxidation of arenes, ArH -> ArOH. The phenol products are easier to oxidize than the starting arenes so overoxidation rules the day.

Prof. Dionicio (“Dio”) Siegel ’97 and his collaborators have reported a breakthrough in arene oxidation in “Metal-free oxidation of aromatic carbon–hydrogen bonds through a reverse-rebound mechanism,” Nature 2013 (DOI 10.1038/nature12284). As Dio et al. put it:

“Here we demonstrate that phthaloyl peroxide functions as a selective oxidant for the transformation of arenes to phenols under mild conditions. Although the reaction proceeds through a radical mechanism, aromatic C–H bonds are selectively oxidized in preference to activated Csp3–H bonds. Notably, a wide array of functional groups are compatible with this reaction, and this method is therefore well suited for late-stage transformations of advanced synthetic intermediates.”

The research, which combines experimental work from the Siegel lab at U Texas-Austin with computational studies from the Houk lab at UCLA, is also covered in “Easy access to phenols,” C&E News (News of the Week, July 15, 2013, paywall).