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

• Applicant: Dr. Stephan Cludius-Brandt
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2011 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 194847653

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.

• DFG Programme: Research Fellowships
• International Connection: Switzerland
• Host: Jieping Zhu, Ph.D.