手性双功能叔膦催化的不对称[4+n]环加成反应研究

The bifunctional chiral catalysts, which combine two functional groups within one molecule to cooperatively activate nucleophilic and electrophilic reacting partners, provide good-to-excellent reactivities and stereoselectivities in asymmetric reactions. In the project, the chiral cyclohexane-based bifunctional phosphines containing different Lewis basic and Br?nsted acidic sites within one molecule will be prepared. And they will be applied as chiral organocatalysts in the enantioselective reactions, such as [4+1] cycloadditions and [4+2] cycloadditions, to construct highly functionalized chiral cyclic compounds, involving cyclopentenes, cyclohexenes, dihydropyrans, tetrahydropyrans, and tetrahydropyridines. The reactivities and stereoselectivies of these bifunctional chiral organocatalysts can be adjusted by varying the tertiary phosphine and the hydrogen-bonding donors, their relationship will be investigated to design highly effective organocatalysts for the above-mentioned enantioselective reactions. The goal of the project is to develop efficient bifunctional chiral organocatalysts, new enantioselective reactions and useful synthetic methods.

双功能手性催化剂可同时活化亲核试剂和亲电试剂，不仅能进一步提高其催化活性，而且能在反应中更有效地进行立体控制，从而实现高对映选择性合成。本项目拟设计合成基于环己基手性骨架、含不同Br?nsted酸性基团（即氢键供体）和不同亲核性叔膦的双功能手性有机催化剂，研究它们不对称催化的[4+1]环加成和[4+2]环加成等反应。通过对双功能叔膦类手性有机催化剂的结构调控，实现不对称催化反应的高反应活性、高对映选择性以及非对映选择性等。从而认识双功能叔膦类手性有机催化剂的结构与这些不对称反应的立体选择性之间的关系，开发新型高效的手性双功能有机催化剂，发展新的不对称催化反应，为不对称合成手性多官能团环戊烯、环己烯、二氢吡喃、四氢吡喃以及四氢吡啶等环状化合物提供有效的新方法。

本项目设计合成了含不同Brønsted酸性基团的双功能叔膦类手性有机催化剂，研究了它们在不对称催化联烯羧酸酯与活泼亚甲基化合物的[4+1]环加成反应中的应用，并初步探索了不对称催化α,β-不饱和羰基化合物与不饱和烃的[4+2]环加成反应、联烯羧酸酯与芳基三氟甲基酮的[4+2]环加成反应以及α,β-不饱和亚胺化合物与丁烯酮的[4+2]环加成反应。.为发展不对称催化合成手性多官能团杂环化合物的有效方法，将所设计合成的双功能叔膦类手性有机催化剂成功地应用于不对称催化丙烯酸酯与靛红亚胺的aza-Morita-Baylis-Hillman反应，高收率和高对映选择性地获得了手性的3-取代-3-氨基-2-氧化吲哚类化合物。同时，研究了手性多功能叔胺催化的以靛红或其亚胺为反应底物的不对称加成反应和串联反应，高收率和高立体选择性地获得了手性3,3-二取代-2-氧化吲哚和螺吲哚类化合物。