Dispersion Effects on Reactivity and Chemo-, Regio- and Stereoselectivity in Organocatalysed Domino Reactions: A Joint Experimental and Theoretical Study

这个联合实验和理论项目旨在利用这些新系统中的分散相互作用，开发易于和环境友好的有机催化多步多米诺反应。我们计划进行一系列多组分多米诺骨牌反应，涉及易得的硝基烯烃和醛，以及ch -酸性丙二腈，其广泛的应用和作为一种异常反应性的化合物的用途已经广为人知。我们将主要关注以下三种前所未有的反应：(i)三组分两步多米诺骨牌Knoevenagel/vinylogous Michael反应；（ii）三组分五步支化多米诺骨牌Knoevenagel/硝基- michael /硝基烷- michael /分子内缩合/异构化；（iii）双组分六步多米诺骨牌Knoevenagel/二聚化/分子间缩合/分子内aza-Michael/分子内缩合/异构化反应。详细的机理研究将使用传统的密度泛函数方法结合半经验范德华校正以及新颖的高精度密度泛函数方法来阐明这些有机催化的多米诺骨牌转化中化学选择性、区域选择性和立体选择性的有趣差异，特别是理解和利用这些转化中分散相互作用的影响。将设想的多米诺反应作为测试用例，将开发基于密度功能的有机催化描述的计算设置。

This joint experimental and theoretical project aims at the development of facile and environmentally friendly organocatalytic multi-step domino reactions exploiting dispersion interactions in these novel systems. We plan to conduct a series of multi-component domino reactions involving readily available nitroolefins and aldehydes, as well as CH-acidic malononitrile already known for its broad application and its versatile use as an exceptionally reactive compound. We will mainly focus on the following three unprecedented reactions: (i) three-component two-step domino Knoevenagel/vinylogous Michael reaction; (ii) three-component five-step branched domino Knoevenagel/nitro-Michael/nitroalkane-Michael/intramolecular condensation/isomerization; (iii) two-component six-step domino Knoevenagel/dimerisation/ intermolecular condensation/intramolecular aza-Michael/intramolecular condensation/ isomerization reaction. Detailed mechanistic investigations will be performed using conventional density-functional methods in conjunction with semiempirical van der Waals corrections as well as novel highly accurate density-functional methods to shed light on the intriguing differences in chemoselectivity, regioselectivity and stereoselectivity in these organocatalysed domino transformations, and, in particular, to understand and exploit the influence of dispersion interaction in these transformations. Taking the envisioned domino reactions as test cases, computational setups for a density-functional based description of organocatalysis will be developed.