Project description
New strategy for selective functionalisation of carbon-hydrogen bonds
The functionalisation of carbon-hydrogen (C-H) bonds – the most common chemical bond in the living world – has opened the way to the synthesis of a large range of novel organic molecules. However, the ability to selectively functionalise the C-H bonds of an alkane has been challenging so far. The EU-funded FlowHAT project will leverage a powerful and versatile chemical technique called hydrogen atom transfer (HAT) – a process that simply moves a hydrogen atom from one molecule to another. The technique will involve the use of cheaper catalysts for creating a wide array of new bonds such as carbon-oxygen and carbon-nitrogen bonds, which are important steps in building complex molecules.
Objective
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.
Fields of science
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Funding Scheme
HORIZON-AG - HORIZON Action Grant Budget-BasedHost institution
1012WX Amsterdam
Netherlands