Descrizione del progetto
Nuova strategia per la funzionalizzazione selettiva di legami carbonio-idrogeno
La funzionalizzazione di legami carbonio-idrogeno (C-H), il legame chimico più comune del mondo, ha aperto la strada alla sintesi di una vasta gamma di nuove molecole organiche. Tuttavia, la capacità di funzionalizzare selettivamente i legami C-H di un alcano è stata finora impegnativa. Il progetto FlowHAT, finanziato dall’UE, sfrutterà una tecnica chimica potente e versatile chiamata trasferimento di atomo di idrogeno (HAT), un processo che sposta semplicemente un atomo di idrogeno da una molecola all’altra. La tecnica comporterà l’uso di catalizzatori più economici per creare una vasta gamma di nuovi legami quali i legami carbonio-ossigeno e carbonio-azoto, che sono passaggi importanti nella costruzione di molecole complesse.
Obiettivo
An essential part of synthetic organic chemistry is the conversion of raw materials into highly complex molecules. While traditionally this has been achieved through conversion of functional groups, Nature has developed strategies to deliberately functionalize C–H bonds in organic molecules. Mimicking Nature’s machinery, chemists have developed a diverse set of powerful C–H bond functionalization strategies. However, undirected and selective C–H bond functionalization is still very challenging and it remains “a dream reaction” for the community. Herein, I propose a novel approach that combines both chemical and technological tools and is based on a continuous-flow photocatalytic Hydrogen Atom Transfer (HAT) that uses cheap decatungstate to activate these C(sp3)–H bonds selectively. Four different reaction classes will be developed which forge C=O, C–NO, C–SO2X and C–CO2H bonds using respectively O2, NO, SO2 and CO2 as cheap and atom-efficient reagents. All these methods provide useful functional handles which can be seamlessly engaged in other transformations. I will show that our methodology can be used to enable the late-stage diversification of bioactive molecules, establishing a new way of retrosynthetic thinking. Furthermore, I propose to exploit the intrinsic ability of HAT to abstract a hydrogen from volatile alkanes, such as methane, to generate the corresponding carbon-centered radicals. These nucleophilic radicals will be engaged in various cross-coupling transformations, including enantioselective variants. Moreover, I envision that a combination of continuous-flow, automation technology and machine learning will provide a much-needed technological impact, enabling the development of unique screening tools for the reproducible functionalization of organic molecules. The synthetic methods and technological tools will provide a breakthrough in the selective functionalization of strong C(sp3)–H bonds in both gaseous alkanes and biologically active molecules.
Campo scientifico
Programma(i)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Argomento(i)
Meccanismo di finanziamento
HORIZON-AG - HORIZON Action Grant Budget-BasedIstituzione ospitante
1012WX Amsterdam
Paesi Bassi