Multicomponent and Domino Processes for the syntheses of highly functionalized cyclohexanones, piperidinones and their derivatives

用于合成高官能化环己酮、哌啶酮及其衍生物的多组分和多米诺工艺

• 批准号: 194847653
• 负责人: Dr. Stephan Cludius-Brandt
• 金额: --
• 依托单位: École Polytechnique Fédérale de Lausanne (EPFL)
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2011-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/194847653?language=en
• 关键词: Multicomponent; Domino; Processes; syntheses; highly

The usual procedure for the synthesis of organic compounds is the stepwise formation of the individual bonds in the target molecule. Multicomponent reactions (MCRs) and domino processes provide a much more efficient methodology. Several bonds can be formed within one sequence without isolating the respective intermediates, changing the reactions conditions or adding further reagents. Such procedures avoid costly and time-consuming purifications processes, as well as protection and de-protections steps and are therefore inherently environmentally friendly and atom economic. The development of new MCRs is a challenging task in modern organic chemistry since one has to consider not only the reactivity match of the starting materials, but also the reactivity of the intermediate functions generated in situ. The working group of Prof. Zhu at the EPFL in Lausanne is focusing on the substrate design approach in order to develop new MCRs. In this project therefore, the designed and hitherto unknown compound tert-butyl 4-(acetoxymethyl)-3-oxopent-4-enoate (1) is used to perform novel MCRs and domino processes to synthesize highly functionalized cyclohexanones, piperidinones and derivatives thereof. During the project, a convenient synthesis of compound 1 has to be developed and its ability to act as a key compound in palladium-catalyzed MCRs and domino processes has to be investigated. Since two new stereogenic centers are created during the envisaged process, conducting the reactions in an enantioselective fashion is highly desirable and will also be under investigation. Due to the high functionalization of the synthesized products and the consequent many possible transformation reactions, this methodology could be of considerable interest in the total synthesis of natural products and biologically active compounds in which the synthesized compounds can act as chiral building blocks.

合成有机化合物的通常步骤是在目标分子中逐步形成单个键。多组分反应（mcr）和多米诺过程提供了一种更有效的方法。几个键可以在一个序列中形成，而无需分离各自的中间体，改变反应条件或添加进一步的试剂。这种程序避免了昂贵和耗时的净化过程，以及保护和去保护步骤，因此本质上是环境友好和原子经济的。在现代有机化学中，新型mcr的开发是一项具有挑战性的任务，因为人们不仅要考虑起始材料的反应性匹配，还要考虑原位生成的中间功能的反应性。洛桑EPFL朱教授的工作组正专注于基板设计方法，以开发新的mcr。因此，在这个项目中，设计的和迄今未知的化合物叔丁基4-（乙酰氧基甲基）-3-氧opopt -4-enoate(1)被用来进行新的mcr和多米诺工艺来合成高功能化的环己酮、胡椒酮及其衍生物。在该项目中，必须开发一种方便的化合物1的合成方法，并研究其在钯催化的mcr和多米诺反应中作为关键化合物的能力。由于在设想的过程中产生了两个新的立体中心，因此以对映选择性的方式进行反应是非常可取的，并且也将在研究中。由于合成产物的高功能化和随之而来的许多可能的转化反应，该方法在天然产物和生物活性化合物的全合成中具有相当大的兴趣，其中合成的化合物可以作为手性构建块。