手性磷酰氨基酸配体的设计及其在碳氢键活化反应中的应用研究

C–H activation reactions have been drawing extensive attention in the past decade as converting C–H bonds directly into carbon-carbon and carbon-heteroatom bonds can significantly improve step-economy in synthesis. Due to the high bond dissociation energy of C–H bonds and the presence of multiple similar C–H bonds in a target molecule, the reactivity and selectivity have always been the two main challenges in C–H activation. It has been proved that ligand (such as mono-N-protected amino acid) can not only accelerate the reaction rate, but also control the enantioselectivity of the C–H activation reactions. However, only limited types of ligands and enantioselective C–H activation reactions have been reported. Therefore design and synthesis of new ligands is the key for C–H activation. Chiral BINOL-phosphoric acids have been successfully applied in a large number in asymmetric transformations as Brønsted or Lewis acid catalysts. In this project, we will make full use of the excellent asymmetric induction ability of the chiral phosphoric acids in the enantioselective transformations to design and synthesize a novel type of chiral N-phosphorylamino acid ligands and study their application in C-H activation reactions. We anticipate the development of a novel type of ligands which could accelerate or induce the enantioselectivity of some C-H activation reactions, therefore solve the problem of the reactivity and enantioselectivity in these reactions.

碳氢键活化由于可以直接将碳-氢键转化为碳-碳键和碳-杂原子键从而显著提高合成的步骤经济性，近十几年已受到广泛关注。由于碳氢键有很高的离解能以及目标分子中通常含有多个类似的碳氢键，反应的活性和选择性一直都是碳氢键活化中的两个最具挑战性的问题。研究证明配体在碳氢键活化反应中不仅可以提高反应的速率而且还有可能控制反应的对映选择性。然而目前已报到的配体类型及其可实现的对映选择性碳氢键活化反应仍然很有限，发展可用于碳氢键活化反应新型配体是解决该领域中关键问题的核心。BINOL衍生手性磷酸作为Brønsted酸或者Lewis酸催化剂已经被成功应用在多个不对称反应中。本项目拟充分利用手性磷酸在不对称反应中优秀的对映选择性控制能力，设计合成一类新型的手性磷酰氨基酸配体并探索其在碳氢键活化反应中的应用，旨在发展一类具有加速作用或者手性诱导作用的新型配体并用其解决碳氢键活化反应中的反应活性和对映选择性问题。

设计合成新颖的手性配体对手性合成化学的发展具有重要的促进作用，本项目以含轴手性的BINOL为起始手性源，充分利用该C2对称性的手性分子的优秀手性环境，设计合成了一系列可以与过渡金属配位的新型C1轴手性配体。并且发现这一类配体与铜盐原位生成的催化剂可以高效地催化2-萘酚及其衍生物的不对称氧化偶联反应，生成手性的BINOL衍生物，e.r.值最高达到96:4。该项目不仅为手性BINOL衍生物的合成提供了一种新方法，还为其他不对称催化反应提供了一类新型的手性配体，研究结果具有重要的科学意义，该类新型手性配体在其他不对称催化反应中具有很好的应用前景。