新型有机小分子催化剂的设计、合成及在不对称光化学反应中的应用研究

In organic synthesis, photochemical reactions are increasingly widely used in the construction of carbon-carbon and carbon-hetero bonds. Asymmetric photochemistry is more environmentally friendly, efficient and convenient tool to synthesize chiral compounds, especially multiple-ring and highly-strained molecules. But in the excited state, organic molecules are short-lived and highly active; they can occur chemical transformation directly, owing to the weak interaction with the chiral source. The asymmetric induction is still challenging in photochemical reactions. . The known organocatalysts for enantioselective photochemical reactions are synthesized difficultly and modified hardly, the application is very limited. In this project, the organocatalyst with a rigid structure that tethers the H-bonding template and the photosensitizer together derived from 1-Amino-2-indanol was designed and synthesized from readily available chiral starting materials in a short sequence for the first time. And the catalyst has proved effective and practical in asymmetric intramolecular [2+2] photocycloaddition reaction. The modular structure makes it straightforward to carry out systematic positional optimization of each unit. The organocatalysts identified in the project will be utilized in asymmetric photocycloaddition reactions and photoinduced electron transfer reactions. The project is intended to expand the types of photoreactions catalyzed by organocatalysts and develop a new class of practical asymmetric photochemical methodology.

在有机合成中，光反应在碳碳键、碳杂键的构筑上发挥着重要作用。不对称光化学是合成手性化合物，特别是具有多环或高张力手性分子的更环保，更高效，更便捷的方法。有机分子在电子激发态时寿命短，活性高，甚至可以不与手性源作用而直接发生化学转化。这为不对称光反应的手性诱导带来了很大挑战。. 现有有机小分子光反应催化剂结构单一，难以修饰，且合成难度大，产率低，应用十分有限。本项目将手性模板和光敏基团相结合，首次设计并合成了基于1-氨基-2-茚醇刚性骨架的有机小分子光反应催化剂。该催化剂合成简单，原料易得，极易修饰。在分子内不对称[2+2]光环化反应中的应用已证实其有效。本项目拟将基于1-氨基-2-茚醇骨架的有机小分子光反应催化剂应用于不对称光环化反应及光诱导电子转移反应，以拓展有机小分子光反应催化剂催化的反应类型，从而开发一类实用的不对称光化学合成新方法。

本项目旨在发展一类简单高效的基于1-氨基-2-茚醇骨架的有机小分子光反应催化剂，将其应用于不对称光环化反应及光诱导电子转移反应，从而发展一类实用的不对称光化学合成方法，并将其应用于天然产物或具有生物活性化合物的合成。按照项目计划，我们设计合成一系列基于1-氨基-2-茚醇骨架的有机小分子光反应催化剂，并将其应用于分子内的[2+2]光环化反应。研究发现：（1）我们设计合成的基于1-氨基-2-茚醇骨架的有机小分子光反应催化剂能有效地催化分子内的[2+2]光环化反应。但是，只能得到中等的产率、中等的对映选择性和较差的区域选择性；（2）催化剂的结构单一，改进困难，难以进一步结构优化，这为催化剂库的建立设置了障碍。（3）项目研究期间，开展了基于异氰化合物的环加成反应，以高产率、高对映选择性和非对映选择性合成了一系列五元杂环化合物；基于氮氧烯丙基阳离子，实现了其与环酮的[3+2]环加成反应。这两类合成方法学有望被应用于天然产物或具有生物活性化合物的合成。