Reactivities of electron-deficient arenes

点击翻译按钮获取中文摘要

This project will use quantitative information about the electrophilic and nucleophilic reactivity of organic molecules to develop unprecedented approaches to organic syntheses through dearomative reactions of electron-deficient arenes (EDAs). To unravel the individual steps of EDA/nucleophile reactions at the molecular level, strategies in molecular chemistry and quantum-chemical molecular modeling will be applied and beneficially synergized with kinetic and thermodynamic studies. The combined expertise of the French and German researchers in this joint proposal will generate new mechanistic insights and innovative synthetic routes, including high pressure and flow chemistry, for the assembly of new complex three-dimensional heterocyclic molecular architectures in a predictable and controlled manner. The majority of reactions used in organic synthesis can be considered as combinations of electrophiles with nucleophiles and the application of the Mayr-Patz equation (MPE), lg k(20 °C) = sN(N + E), provides a classification to predict the reaction rates for a given electrophile-nucleophile couple. In this project, we will calibrate the electrophilicity (E) of EDAs capable of performing additions and (x+2) cycloadditions with electron-rich entities. Studies will include Michael additions, in which a single new sigma bond is formed, as well as concerted processes. The nucleophiles studied will cover stable molecules, such as dienamines or azomethine imines, and will extend to short-lived "photo-enols" generated by laser-flash induced photoenolizations. The application of the MPE defines the lower limit of rates for EDA-nucleophilic reactions involving the formation of a new single bond in the rate-determining step. Cycloadditions whose transition states benefit from interactions between more than two reaction centers proceed more rapidly. Such concerted cycloadditions will be further investigated by high-level DFT methods and under high-pressure to exploit their synthetic potential.