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.

本研究开发了二芳基乙酮的化学选择性转化策略：通过好氧氧化裂解路径可生成芳基甲酸，或通过串联好氧氧化/苯偶酸重排/脱羧路径生成二芳基甲酮。该转化具有可控性，适用于宽泛的底物范围，目标产物产率可达良好至优异水平。通过控制实验、1H核磁共振（1H NMR）跟踪与单晶X射线衍射（single-crystal X-ray diffraction）开展的机理研究，揭示了一套复杂的反应机理网络：其中两种关键中间体α-酮氢过氧化物与二芳基乙二酮，以及三条可行的反应路径均被提出并验证。这些反应路径相互关联，可通过调控反应条件实现合理切换。该方法可实现规模化合成，能够制备多种高价值化合物，包括维生素B3、联苯二甲酸以及非甾体抗炎药酮洛芬（ketoprofen）。本实验方案在利用复杂机理网络调控反应路径、从同一类起始原料实现发散合成方面取得了实质性进展。