The past decade has seen kinder, gentler oxidations emerge in rapid succession. Cobalt. P-450s. Iron. Now, two recent papers bring new wrinkles to the oxygenation of organic molecules in unexpected ways.
The first, from the Concellon / del Amo group in Org. Lett., relates a neat trick performed by Oxone, usually a reagent reserved to make other oxidants.
"This work was not originally intended..[but]...was worth studying. [We] remark that Oxone is a crystalline solid oxidant, easy to handle, non-toxic...and, above all, stable and cheap."All great reasons to run these reactions, which are formally derivatives of the classic Baeyer-Villiger reaction. They blast through a brief substrate table (26 entries, 33-95% yields), and seem pretty excited about investigating the mechanism.
The second reaction, hot off the Nature presses, involves another legacy reagent: phthaloyl peroxide. I suspect the Siegel group was looking for sp3 C-H activation conditions, but instead discovered a serendipitous site-selective arene activation, reliably producing phenols.
The reaction works across a broad functional group palette - azides, silyl groups, boronate esters, primary halogens - that other oxidants would tear apart. They ultimately do about 50 substrates, including 3 natural product-like scaffolds, with yields ranging from 45-95%.
Deciphering the mechanism requires Ken Houk's computational super-powers. The researchers discover a "reverse-rebound" mechanism operates, meaning an oxygen radical from phthaloyl peroxide adds into the ring, the electron bounces around in the pi cloud, and then ejects the ipso hydrogen in a two-step process. Interestingly, other radical oxygen oxidants (di-benzoyl peroxide) led to primarily sp3 oxidation, showing that the structure of the radical precursor plays a big role here.