温和条件下稀土金属催化的简单开链二级脂肪胺的氢转移反应研究

The hydrogen transfer reactions represent an important subject in organic synthesis. Despite great advances in development of new hydrogen donors and application of the hydrogen transfer reactions in organic synthesis, no substantial breakthrough has yet been achieved in utilization of simple noncyclic secondary amine as a hydrogen donor for reduction of unsaturated functional groups under mild conditions. The project will explore new activation models of amines by rare earth metal complexes and establish a new pathway for the hydrogen transfer from organic amines to hydrogen acceptors. Some basic rules of tandem activation of N-H and C-H bonds of noncyclic aliphatic amines will be revealed and some methods for controlling selectivity of amine transformations will be developed. Based on the hydrogen transfer reaction of noncyclic secondary amines as a key step, we expect to develop some new reactions with potential application and high academic values, such as amino-directed new models of C-H bond activation and transformation of amines, tandem hydrogen transfer reduction/cross coupling/cyclization reactions of amines with alkenes and polar unsaturated groups, olefin isomerization catalyzed synergistically by rare earth metal and amine, regioselective reduction of di- and polyenes using mixed hydrogen donor system consisted of amine and other hydrogen donor. Furthermore, some new reactivity patterns and catalytic properties of rare earth complexes will be revealed, and new strategies for controlling reactivity of rare earth complexes and movement of reaction equilibrium will also be developed. In addition, some similarity and difference between the present rare earth catalysts and the known catalytic systems in promoting the hydrogen transfer of amines will be demonstrated.

氢转移是有机合成中最重要的反应之一。虽然在氢供体开发和氢转移反应的应用等方面取得了巨大进步，但是温和条件下简单非环二级脂肪胺作为不饱和官能团还原的氢供体目前还未获得实质性的突破。本项目拟通过稀土配合物催化剂的设计合成，建立胺活化的新模型和有机胺发生氢转移反应的新途径，揭示普通开链脂肪胺发生连续N-H和C-H键选择性活化与可控性重组的基本规律；以温和条件下开链二级脂肪胺的氢转移反应为突破口，发展一些有应用前景和学术价值的新反应和新方法，如氨基导向的CH键活化新方法，胺与极性和非极性不饱和官能团的可控有序氢转移还原/交叉偶联/环化反应，稀土金属和胺协同催化的烯烃异构化反应，胺与其它氢给体组成的双氢供体体系对双烯和多烯烃的区域选择性还原等。揭示稀土配合物的新反应特性和催化特性，发展调控稀土配合物的反应选择性和控制反应平衡移动的新策略；阐明稀土金属与现有催化体系促进胺发生氢转移反应时的异同点。

发展胺及其衍生物的新活化方法和新转化模式是有机化学领域的重要课题。虽然这方面已经取得巨大进展，但是一些重要的反应模式仍有待实现，部分反应的选择性和条件需要进一步优化。项目以稀土催化为手段，探索了解决胺氢转移反应、胺及其衍生物的C-H键和C-N键形成和转化中一些挑战性科学问题的方法，取得了突破性成果。主要成果包括：开发了温和条件下能使简单开链脂肪胺发生氢转移反应的稀土催化体系，并利用该策略实现了分子内亚胺与烯（炔）的还原偶联/环化模式由常见的碳碳偶联反转为碳氮偶联反应；发展了基于胺与氢硅烷脱氢偶联构建的氢源体系，为双（多）烯胺的区域选择性还原和N-Si键的形成提供了新方法；突破了简单二级酰胺的alpha-C-H键和C-N键接力活化，使二级酰胺与炔酮的环化模式从形成内酰胺转变为形成挑战性的内酯产物；实现了无添加剂协助的金属催化甲酰胺脱羰反应，这也是首例稀土催化脱羰反应；开创了利用氢转移反应还原惰性碳氮键；揭示了稀土配合物的新反应特性和催化特性等。上述大部分反应是其它金属不能或难以促进的转化，具有重要互补性和潜在应用价值。我们预计，这些成果将为开发胺和酰胺在有机合成中的应用和设计稀土催化反应提供新思路，开辟新的前景。发表标注该项目资助的研究论文8篇，获得授权中国发明专利2件。毕业博士4人，毕业硕士1人，博士后1人。受邀在全国性学术会议上做主题及邀请报告5次。