Cao Guang-Mei, Hu Xin-Long, Liao Li-Li, Yan Si-Shun, Song Lei, Chruma Jason J, Gong Li, Yu Da-Gang
Key Laboratory of Green Chemistry and Technology of Ministry of Education, College of Chemistry, Sichuan University, Chengdu, China.
Department of Chemistry, University of Virginia, Charlottesville, VA, USA.
Nat Commun. 2021 Jun 3;12(1):3306. doi: 10.1038/s41467-021-23447-8.
Photoredox-mediated umpolung strategy provides an alternative pattern for functionalization of carbonyl compounds. However, general approaches towards carboxylation of carbonyl compounds with CO remain scarce. Herein, we report a strategy for visible-light photoredox-catalyzed umpolung carboxylation of diverse carbonyl compounds with CO by using Lewis acidic chlorosilanes as activating/protecting groups. This strategy is general and practical to generate valuable α-hydroxycarboxylic acids. It works well for challenging alkyl aryl ketones and aryl aldehydes, as well as for α-ketoamides and α-ketoesters, the latter two of which have never been successfully applied in umpolung carboxylations with CO (to the best of our knowledge). This reaction features high selectivity, broad substrate scope, good functional group tolerance, mild reaction conditions and facile derivations of products to bioactive compounds, including oxypheonium, mepenzolate bromide, benactyzine, and tiotropium. Moreover, the formation of carbon radicals and carbanions as well as the key role of chlorosilanes are supported by control experiments.
光氧化还原介导的极性反转策略为羰基化合物的官能团化提供了一种替代模式。然而，使用一氧化碳对羰基化合物进行羧基化的通用方法仍然很少。在此，我们报道了一种策略，通过使用路易斯酸性氯硅烷作为活化/保护基团，以可见光光氧化还原催化多种羰基化合物与一氧化碳进行极性反转羧基化反应。该策略对于生成有价值的α-羟基羧酸具有通用性和实用性。它对具有挑战性的烷基芳基酮和芳醛，以及α-酮酰胺和α-酮酯都有效，据我们所知，后两者从未成功应用于与一氧化碳的极性反转羧基化反应。该反应具有高选择性、广泛的底物范围、良好的官能团耐受性、温和的反应条件以及易于将产物衍生为生物活性化合物，包括奥芬溴铵、甲哌卡因溴化物、苯那辛和噻托溴铵。此外，对照实验支持了碳自由基和碳负离子的形成以及氯硅烷的关键作用。
