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).