Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - FluoroCAT (Catalytic C–F Bond Functionalisation with Transition Metal Catalysis)

Teaser

What is the problem being addressed? Fluorinated organic molecules play a pivotal role in chemical manufacture. For example, it has been estimated that approximately 20-40% of pharmaceuticals and agrochemicals contain at least one fluorine atom. Fluorinated organic molecules...

Summary

What is the problem being addressed?

Fluorinated organic molecules play a pivotal role in chemical manufacture. For example, it has been estimated that approximately 20-40% of pharmaceuticals and agrochemicals contain at least one fluorine atom. Fluorinated organic molecules are also widely applied in materials such as those found in liquid crystal displays. Despite the fact that perfluoroarenes - aromatic hydrocarbons in which every hydrogen atom is replaced with a fluorine atom - are an inexpensive abundant chemical feedstock they are rarely used in chemical manufacture. The strong carbon–fluorine bond provides an impasse to further chemical reactions. Here we propose to develop a new catalytic method to transform inert carbon–fluorine bonds in perfluoroarenes to reactive carbon–aluminium bonds. We will transform the aluminium-containing reactive intermediates into useful products through carbon–carbon and carbon–heteroatom bond forming reactions.

Why is it important for society?

The overall process represents an original underpinning technology to transform inert and chemically persistent fluorinated molecules into building blocks that can be used in chemical manufacture. The new chemical methods are important for society as they can be used in the production of pharmaceuticals, agrochemicals and materials.

Objectives:

The overall objectives of this work is to create a fresh paradigm for using perfluoroarenes in pharmaceutical and agrochemical programmes. The long-term benefits will be felt in the areas of health and food sustainability. The proposed programme will provide world-class training in the areas of organometallic chemistry, homogeneous catalysis and mechanistic analysis.

Conclusions:

Over the course of this grant we discovered two new methods to transform inert carbon–fluorine bonds into carbon–aluminium bonds. The first relies on the use of a high energy aluminium(I) complex which readily undergoes oxidative addition of C–F bonds of fluoroarenes, fluoroolefins and fluoroalkanes. The second method originates from a structurally related aluminium(III) dihydride and requires a palladium bis(phosphine) complex to catalyse C–F bond activation. As part of these studies we have also investigate the interaction of aluminium(III) hydrides, and related zinc(II) and magnesium(II), species with transition metal complexes. These detailed investigations into the organometallic chemistry have led to an understanding of the trajectory of approach of a zinc hydride bonds to transition metal fragments and the solution dynamics of new types of complexes containing three metal atoms bridged by two hydrogen atoms.

Work performed

An aluminium(I) complex originally reported by Roesky and coworkers (ref) was prepared and showed that it undergoes extremely facile oxidative addition reactions with fluorocarbons. These reactions proceed quantitatively and cleanly at room temperature or below and result in breaking the carbon–fluorine bond by oxidative addition to the Al(I) centre. The aforementioned reaction does not require a catalyst and is highly selective for C–Al bond formation (>99:1). To date we have applied it to 8 substrates including fluoroarenes, fluoroolefins and fluoroalkanes. Our initial results have been published in a communication (Chem. Commun. 2015, 51, 15994).

In parallel we have developed catalytic methods that originate from a structurally related aluminium(III) dihydride. While inefficient catalysts based on zirconium (Angew. Chem., Int. Ed. 2012, 51, 12599) and rhodium (Organometallics 2014, 33, 7027) formed the basis of our proposal. Over the course of our study we discovered a new palladium catalyst that was highly effective and selective. This catalyst operates at 1 mol% loading or less with TOFs ~10 h-1 and has been applied to 12 substrates. Again the catalyst is selective for the formation of C–Al bonds, but in this case C–H bond formation is competitive and selectivity for C–Al versus C–H bond formation ranges from 4.4:1 to 27:1.

During our original investigation of the Zr-catalysed method we discovered that the aluminium reagent coordinates to the zirconium complex. This new heterobimetallic contains two distinct metals that are bridged by a hydrogen atoms and is capable of breaking carbon–fluorine bonds and acting as a catalyst for the process described above. As an extension of these studies we investigated new types of coordination complexes in which main group metal hydrides (M = Zn, Mg, Al) act as ligands for transition metals. As part of our preliminary results we described coordination and bond breaking in a series of Rh-complexes (Chem. Sci. 2015, 6, 5617). During the grant period we discovered a whole host of new complexes, including 10 crystallographically characterised heterobimetallics and through a combination of experiment and theory (DFT calculations) described the trajectory of approach of zinc hydrides to transition metals (Angew. Chem., Int. Ed. 2016, 55, 16031) and the solution dynamics of new types of complexes containing three metal atoms bridged by two hydrogen atoms (Chem. Eur. J. 2017, 23, 5682).

Exploitation and Dissemination:
The majority of the work carried out during this fellowship has been published in top quality journals within the chemistry community. A final manuscript is being prepared on the Pd-catalysed methods for C–F bond activation. Key findings have formed the basis of new grant applications and this includes successful funding applications to horizon2020. These include, an ERC starting grant for the host group (FluoroFix) which centers on extension of the development of the catalytic methods but applied to remediation of environmentally persistent HFCs and HFOs, and a Marie Curie Fellowship (FluoroCross) which aims to develop related synthetic methods but based entirely on magnesium reagents recently reported by the host group (J. Am. Chem. Soc., 2016, 138, 12763). The groups work on heterobimetallic complexes was recently recognised by award of the Harrison-Meldola Memorial Prize from the RCS and our findings will be used to form the basis of a further grant application to the UK funding body the EPSRC developing new types of catalysts based on two metals held in close proximity.

Final results

The host research group recently reviewed new methods to transform C–F bonds into reactive C–B, C–Al, C–Mg and C–Si bondsdefined the state-of-the-art as of 2016 (Synthesis, 2017, 49, 810). The methods that were discovered in this project are now the state of the art for transforming C–F bonds to C–Al bonds and represent some of the most efficient and broadly applicable methods to break a number of different types of carbon–fluorine bonds.The long-term impact of these methods and wider societal implications will rely on further development by the host research group. Several challenges remain such as developing diverse applications of the new fluorinated building blocks and extending the scope of the reaction beyond fluoroarenes to the remediation of environmentally persistent fluorohydrocarbons. These challenges are being addressed as part of ongoing work in the host group. There is the potential for impact both in the production of pharmaceuticals and agrochemicals and the remediation of environmentally damaging gases, but it is likely any societal implications will become apparent on a 10-20 year timescale beyond the end of this grant.

Website & more info

More info: http://crimmingroup.org/publications/publications.html.