新型手性硫醚催化剂及其衍生物的设计合成与不对称催化应用研究

In recent years, remarkable progress has been achieved in the field of asymmetric catalysis by taking the advantage of various chiral catalysts which are mainly made up of nitrogen, oxygen and phosphorus. However, the development of sulfide, selenium and tellenium based chiral catalysts were rarely reported, although these non-metal elements are considered to have great synthetical potential. Until now, a limited number of thioether、selenide and tellurolane based catalysts have been developed and showed promising reactivity in some reactions , while lots of problems such as low catalytic reactivity and limited substrate scopes have been recognized. In order to exploit diverse catalytic systems, we will design and synthesis a series of multifunctional chiral thioesters based on tetrahydrothiophene framework in this project, as well as new types of selenides and tellurolane based catalysts for preliminary studies. After confirming the basic reactivity of the new catalysts, the study will focus on some interesting or challenging chemical reactions, such as sulfur ylides catalyzed intermolecular asymmetric cyclopropanations, all-carbon based [4+1] cyclization, regioselective conjugate additions of sulfur ylides to electron-deficent dienes and enantioselective electrophilic fluorinations of indoles. In summary, the successful implementation of this project is of great significance to exploring new organocatalytic system, providing novel synthetic tools for asymmetric catalysis and promoting the development of diversity-oriented stereoselective synthesis.

近年来，不对称催化取得了举世瞩目的成就，主要是依赖于氮、磷、氧这三个核心元素构建的手性催化剂体系。而作为具有开发潜力的其他非金属主族元素，诸如硫、硒、碲的手性催化科学研究则相对滞后。目前，已开发的少量手性硫、硒、碲醚类催化剂虽然已经在某些反应中取得较好的催化效果，但仍然存在反应活性低、底物范围窄等许多亟待解决的问题。本项目从不对称催化体系多元化设计开发的角度出发，拟重点合成一系列具有四氢噻吩骨架的手性硫醚多功能催化剂，并对一些结构新颖的手性硒醚和碲醚催化剂进行初步探索。在保证新催化剂基本活性的基础上，我们将在本项目中重点研究诸如：硫叶立德参与的分子间不对称环丙烷化、全碳[4+1]反应构建环戊烷、区域选择性的不对称共轭加成以及不对称亲电氟化反应等具有挑战性、新颖性的反应化学。本项目的成功实施，对于开拓不对称催化体系发展的新方向、建立原创性的手性催化工具、发展有特色的不对称多样合成具有意义。

硫叶立德参与的环化反应是有机合成中重要的反应类型。然而，硫叶立德的反应化学仍存在一些尚未解决的难题，如立体选择性控制问题和环化类型的局限性等。本项目以一系列已有或新改造的硫醚催化剂为工具，探索了各种类型的硫叶立德环化反应。首先，我们在研究中解决了一些经典反应模式的立体选择性控制问题，实现了硫醚催化的不对称环丙烷化和高非对映选择性的[4+1]环化。其次，我们开发了硫叶立德的一些罕见的新颖环化模式，如[4+3]，[6+1]和[3+1]环化反应，成功地发展出一些重要环状骨架的高效合成方法。另外，我们还探索了包括无金属参与的重氮化合物环丙烷化在内的其它一些绿色合成方法。这些成果发表在Angew. Chem. Int. Ed., ACS Catal., Green Chem., Org. Lett.等国内外期刊上。