Chemoselective Transformation of Diarylethanones to Arylmethanoic Acids and Diarylmethanones and Mechanistic Insights

The
chemoselective transformation of diarylethanones via either
aerobic oxidative cleavage to give arylmethanoic acids or tandem aerobic
oxidation/benzilic acid rearrangement/decarboxylation to give diarylmethanones
has been developed. The transformation is controllable and applicable
to a broad spectrum of substrates and affords the desired products
in good to excellent yields. Mechanistic insights with control reactions, 1H NMR tracking, and single-crystal X-ray diffraction reveal
a complex mechanistic network in which two common intermediates, α-ketohydroperoxide
and diarylethanedione, and three plausible pathways are proposed and
verified. These pathways are interlinked and can be switched reasonably
by changing the reaction conditions. This method enables scalable
synthesis and access to a number of valuable compounds, including
vitamin B3, diphenic acid, and the nonsteroidal anti-inflammatory
drug ketoprofen. The present protocol represents a step forward in
exploiting complex mechanistic networks to control reaction pathways,
achieving divergent syntheses from the same class of starting materials.