Descripción del proyecto
Nueva estrategia para la funcionalización selectiva de los enlaces carbono-hidrógeno
La funcionalización de los enlaces carbono-hidrógeno (C-H) —el enlace químico más común en el mundo de los seres vivos— ha abierto el camino a la síntesis de una gran variedad de nuevas moléculas orgánicas. Sin embargo, la capacidad de funcionalizar selectivamente los enlaces C-H de un alcano ha sido un desafío hasta ahora. En el proyecto FlowHAT, financiado con fondos europeos, se aprovechará una técnica química potente y versátil denominada transferencia de átomos de hidrógeno (HAT, por sus siglas en inglés), un proceso que simplemente traslada un átomo de hidrógeno de una molécula a otra. La técnica conllevará el uso de catalizadores más baratos para crear una amplia gama de nuevos enlaces, como los de carbono-oxígeno y carbono-nitrógeno, que son pasos importantes en la construcción de moléculas complejas.
Objetivo
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.
Ámbito científico
Programa(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régimen de financiación
HORIZON-AG - HORIZON Action Grant Budget-BasedInstitución de acogida
1012WX Amsterdam
Países Bajos