Walter Alexandra, Eisenreich Wolfgang, Storch Golo
School of Natural Sciences and Catalysis Research Center (CRC), Technical University of Munich (TUM), Lichtenbergstr. 4, 85747, Garching, Germany.
Angew Chem Int Ed Engl. 2023 Oct 16;62(42):e202310634. doi: 10.1002/anie.202310634. Epub 2023 Sep 12.
Catalytic desaturations are important strategies for the functionalization of organic molecules. In nature, flavoenzymes mediate the formation of α,β-unsaturated carbonyl compounds by concomitant cofactor reduction. Contrary to many laboratory methods for these reactions, such as the Saegusa-Ito oxidation, no transition metal reagents or catalysts are required. However, a molecular flavin-mediated variant has not been reported so far. We disclose a photochemical approach for silyl enol ether oxidation, which leads to α,β-unsaturated ketones (13 examples) in very good yields. The flavin catalysts are stable throughout the desaturation reaction, and we successfully applied them in a subsequent aerobic epoxidation by simply changing the reaction conditions. This protocol allowed us to directly convert silyl enol ethers into α,β-epoxyketones in a one-pot fashion (12 examples). Sequential flavin catalysis is not limited to one specific reactivity combination and can, inter alia, couple the photochemical oxidation with radical additions. We anticipate that flavin-catalyzed desaturation will be applicable to other substrate classes and that its sequential catalytic activity will enable rapid substrate diversification.
催化脱氢是有机分子功能化的重要策略。在自然界中，黄素酶通过伴随的辅因子还原介导α,β-不饱和羰基化合物的形成。与许多用于这些反应的实验室方法（如Saegusa-Ito氧化）不同，该反应无需过渡金属试剂或催化剂。然而，迄今为止尚未报道分子黄素介导的变体。我们公开了一种用于硅烯醇醚氧化的光化学方法，该方法能以非常高的产率生成α,β-不饱和酮（13个实例）。黄素催化剂在整个脱氢反应过程中保持稳定，并且通过简单改变反应条件，我们成功地将它们应用于随后的需氧环氧化反应中。该方案使我们能够以一锅法将硅烯醇醚直接转化为α,β-环氧酮（12个实例）。连续的黄素催化不限于一种特定的反应性组合，尤其可以将光化学氧化与自由基加成反应相结合。我们预计黄素催化的脱氢反应将适用于其他底物类别，并且其连续催化活性将实现底物的快速多样化转化。
