涉及环状二酰基过氧化物的新型反应及其合成方法研究

Compared to open-chain peroxides, cyclic diacyl peroxides have the nature of operational safety, and the ability to generate various reactive diradical, distonic radical anion and dianion intermediates, which exhibit diverse and unique chemical reactivities. However, the topic about these reactivities has not been studied extensively and systematically around the world. Starting from the design and preparation of a series of cyclic diacyl peroxides in this proposal, we will focus on intersection and discovery of new reactions and new synthetic methodologies, and exploration of new strategies based on the possibility to carry out the total synthesis of natural products and the construction of their core skeletons. The main research contents include: 1) structural strain-promoted cycloaddition via diradicalization/decarboxylation; 2) C-H bond activation/functionalization by transition-metal catalysts; 3) reactivity investigation and synthetic application of Brønsted base-tethered bifunctional reagents; 4) ultimately, kinetic, isotope labelling and computational analysis of the above-mentioned reactions are used to reveal the reaction mechanisms. Moreover, we will seek to demonstrate the exceptional synthetic utility of our innovative methodologies for total synthesis of natural products and biologically significant molecules (such as cycloprodigiosin, 1,2,3,4-tetrahydronaphthalene-derived natural products, carbazole alkaloids and polyhalogenated natural products). Our research programs will largely enrich and expand the new reactivities, new synthetic methods and strategies of cyclic diacyl peroxides, and will be potentially valuable in the development of novel reagents and their synthetically useful applications.

环状二酰基过氧化物与开链过氧化物相比，具有较好的安全性，尤其是它可形成特殊的双自由基、自由基负离子或双负离子活性中间体，因而呈现出独特、多样性的化学反应性，但国内外在这方面研究极少。本项目拟通过设计和合成环状二酰基过氧化物，系统研究其新型反应、合成方法以及在天然产物核心骨架构建和全合成中的应用。主要内容包括：1）张力促进的双自由基/脱二氧化碳环加成反应；2）过渡金属催化氧化的碳氢键官能团化反应；3）布朗斯特碱拴系的双功能试剂的反应性及应用研究；4）基于上述反应和合成方法，结合反应动力学、同位素标记和计算模拟等方法研究反应机理，并设计合成生物活性天然产物或其核心骨架，如环灵菌红素、四氢萘骨架天然产物、咔唑类生物碱、多卤代天然产物。该项目对发展、探索环状二酰基过氧化物的新反应、新方法、新机制具有重要的学术意义，同时对发展新试剂和天然产物合成新策略具有潜在的应用价值。

国内外在环状二酰基过氧化物的反应性能和合成应用方面的研究较少。在项目执行的四年时间里，紧密围绕“涉及环状二酰基过氧化物的新型反应及其合成方法研究”这一核心内容，逐步按照计划开展相关研究，取得了以下重要进展和主要成果：.1）通过不对称Diels-Alder反应，成功构建了手性取代的环己烯基二羧酸衍生物；设计合成了多种环状/非环状二酰基过氧化物。在此基础上，利用环己烯基环状二酰基过氧化物作为高张力环炔前体，开发了光和环张力联合促进的[3+2]和[4+2]环加成反应。2）利用环状二酰基过氧化物作为氧化剂，发展了基于高价钯化学的碳氢键分子内/分子间的选择性官能团化反应。3）将环状二酰基过氧化物与卤盐混合，原位制备了布朗斯特碱拴系的自由基负离子或卤代试剂，分别实现了杂原子中心自由基的可控产生以及多类卤官能团化反应。总之，我们圆满完成了既定的研究内容。..共发表SCI论文11篇，包括Angew. Chem. Int. Ed.（2篇）、Green Chem.（1篇）、Chin. Chem. Lett.（1篇）等。申请或获得授权中国发明专利共6项，共培养了4名硕士及4名博士。