过渡金属催化的醛直接转化为酮的自由基反应研究

酮是基本的有机结构单元之一，在天然产物、药物和新材料中广泛存在，因此，它们的合成非常重要。本项目计划探索两类过渡金属催化的醛直接转化为酮的自由基反应，包括：1、以金属自由基（•MX）捕获酰基自由基生成酰基金属中间体，再经金属交换、还原消除等步骤制备酮；2、以碳自由基对醛基加成产生烷氧自由基，再经1,2-氢迁移、单电子转移和脱质子步骤合成酮；然后，以上述反应为关键步骤开展阿尔茨海默病药物多奈哌齐等药物或具有生理活性的天然产物合成研究，完善所发展的酮合成方法。相比传统的多步合成法，本项目拟发展的酮催化合成法仅需要一步，是一种高效、绿色和原子经济的方法。

Ketones are ubiquitous chemical entities in a wide range of natural products, drugs, and materials. As such, the development of novel as well as efficient methods for their construction is of significant importance. This project focuses on the exploration of transition-metal-catalyzed radical protocols for the aldehyde→ketone conversion. First, the type II reaction (Scheme 1b), involving the cross-coupling of acyl radicals with metal radicals (•MX), transmetallation, and a subsequent reductive elimination, has been proposed for the direct production of ketones from readily available aldehydes. Second, the addition of carbon-centered radicals to aldehydes, followed by a formal 1,2-hydrogen atom shift, single electron transfer, and deprotonation domino process, has been designed as another effective and complementary approach to ketones (type III) (Scheme 1c). In the meantime, investigations regarding the synthetic utility of these two types of reactions will also be conducted, including total synthesis of the antitumor active marine natural product hamigeran B, and drugs like donepezil, with the aim to improve the scope and limitations of developed methods. Compared with the traditional step by step method, the catalytic methodology described here can provide a straightforward, highly efficient, atom-economic, and green method for the access of ketones, which may be valuable for organic synthesis.