Projektbeschreibung
Neue Strategie zur selektiven Funktionalisierung von Kohlenstoff-Wasserstoff-Bindungen
Die Funktionalisierung von Kohlenstoff-Wasserstoff-Bindungen (C-H) – der häufigsten chemischen Bindung in der Welt der Lebewesen – hat Wege zur Synthese einer Vielzahl neuer organischer Moleküle eröffnet. Es war bislang jedoch schwierig, die C-H-Bindungen eines Alkans selektiv zu funktionalisieren. Das EU-finanzierte Projekt FlowHAT wird ein leistungsstarkes und vielseitiges chemisches Verfahren namens Wasserstoff-Atom-Transfer zum Einsatz bringen – bei dem einfach ein Wasserstoffatom von einem Molekül auf ein anderes übertragen wird. Dieses Verfahren verwendet kostengünstigere Katalysatoren, um eine breite Palette neuer Bindungen wie Kohlenstoff-Sauerstoff- und Kohlenstoff-Stickstoff zu schaffen, die wichtige Schritte beim Aufbau komplexer Moleküle darstellen.
Ziel
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.
Wissenschaftliches Gebiet
Programm/Programme
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Thema/Themen
Finanzierungsplan
HORIZON-AG - HORIZON Action Grant Budget-BasedGastgebende Einrichtung
1012WX Amsterdam
Niederlande