手性双功能催化剂催化多组分反应合成光学活性γ-硝基羰基化合物的研究

Inspired by my early works in asymmetric reactions, in this project, the salen structure has been employed as a base and a series of analogous bifunctional catalysts having acidic and basic moieties in single-component will be designed and fabricated to enhance the reactivity and to regulate the orientation in an asymmetric atmosphere in the multi-component reaction of aldehyde, nitroparaffin and 1,3-dicarbonyl compound to synthesize optically active γ-nitrocarbonyl compounds. The main synthetic approach to prepare these compounds is the asymmetric Michael addition, but this method needs to prepare the Michael acceptor beforehand and increases the workload of work-ups and purifications. The multi-component reaction is one of the best tools available for the preparation of complex and diverse compounds by virtue of efficiency and facility. But the limitation is that multi-component condensation methodology does not have any enantiocontrol during formation of the new stereocenter. This project combines the prominent merits of multi-component reaction with the high enantioselecivity of the asymmetric Michael addition to establish an asymmetric catalytic system for the three component reaction of aldehyde, nitroparaffin and 1,3-dicarbonyl compound to synthesize chiral Michael adduct in one step. Furthermore, this strategy minimizes the number of synthetic operations, Omits the synthetic step of Michael acceptor and improves the ability to control the enantioselective in multi-component reaction.

本项目以高催化活性和高对映选择性的金属salen配合物为依托，以原有研究工作为基础，设计、合成在一个催化剂分子中同时包含酸性和碱性两种功能基团的手性双功能催化剂，构建一种针对醛、硝基烷烃和1,3-二羰基化合物的不对称催化多组分反应体系，简便、高效的合成光学活性γ-硝基羰基化合物。不对称催化Michael加成反应能有效的合成该类化合物，但需要预先合成Michael加成受体，经过多步操作；多组分反应在化合物的构建方式上体现了高效性的特征，步骤简捷、操作方便，但难以实现反应过程中对映选择性的控制，通常得到消旋产物。本项目拟结合多组分反应简便、高效的特性与不对称催化Michael加成反应高对映选择性的特点，开展不对称催化多组分反应一锅法合成光学活性γ-硝基羰基化合物及其它Michael加成终产物的研究，简化操作过程、省略Michael加成受体的合成步骤，改善多组分反应对映选择性难以控制的问题。

多组分反应(multi-component reaction，MCR)是指将3个或3个以上的起始原料加入反应，用一锅煮(one-pot procedure)的方法生成一个终产物，可以实现简便、高效、大量地合成具有结构多样性、复杂性的化合物，在药物发现、农药化学和天然产物全合成等方面应用广泛。本项目的主要研究内容包括：1. 筛选不同的多组分反应，发展新的催化体系，实现简便、高效、大量地合成重要的有机化合物；2. 根据所合成化合物的结构、性质等特点，探索其作为手性配体以及在荧光材料等领域的应用；3. 针对多组分反应，设计、合成手性催化剂，提高反应的立体选择性，实现不对称催化多组分反应。