Report

Teaser, summary, work performed and final results

Periodic Reporting for period 2 - FluoroFix (Catalytic C–F Bond Functionalization for the Fixation of Environmentally Persistent Fluorocarbons)

Teaser

The rapid expansion of the fluorochemicals market has led to a notable advancement in our quality of life. Fluorinated organic molecules play a pivotal role in chemical manufacture. Among their many uses, they find applications as refrigerants, in polymeric materials and as...

Summary

The rapid expansion of the fluorochemicals market has led to a notable advancement in our quality of life. Fluorinated organic molecules play a pivotal role in chemical manufacture. Among their many uses, they find applications as refrigerants, in polymeric materials and as solvents and surfactants. It has been estimated that approximately 20–25% of pharmaceuticals and 30–40% of agrochemicals contain at least one fluorine atom. For example, Lipitor contains a single fluorine atom and led the market for pharmaceutical sales from 1996–2012 generating €93 billion in revenue over 14.5 years.

The carbon–fluorine bond is the strongest known single carbon–element bond, and it is unsurprising that synthetic fluorocarbons persist in the environment. Hydrofluorocarbons (HFCs) are known to contribute to climate change. For example, HFC-23 has a global warming potential approximately 10,000 times greater than CO2. From the 1st of January 2015, as part of climate change action, the European Union introduced new legislation to control the use of fluorinated gases, including HFCs. This regulation seeks to cut, by containment, reduction and recovery, the emission of fluorinated gases by two-thirds of current levels by 2030. Hydrofluoroolefins (HFOs) are proposed as greener alternatives to HFCs and have been billed as next generation refrigerants. While the global warming potentials of HFOs are lower than HFCs, the long-term effect of these fluorinated gases, and their decomposition products, on the environment is not yet clear. In contrast to mankind, Nature uses fluorine in organic chemistry sparingly. The vast majority of naturally occurring fluorine is in the form of inorganic fluoride, present in mineral forms such as fluorite (CaF2) and cryolite (Na3AlF6).

If new methods could be developed that transform, low-value, environmentally persistent HFCs and HFOs into high-value products, such as pharmaceuticals or agrochemicals, it could re-align the use of these molecules within the fluorochemicals market. Volatile fluorine-containing gases could be used not as end products but as chemical intermediates that never leave the plant. Existing HFCs could be recycled into useful products following recovery at the end of their equipment’s lifetime. If this method also resulted in the formation of inorganic fluoride from fluorinated gases it would represent an environmentally responsible way to return fluorine to the environment and an important step to closing the fluorine cycle.

The decisive objective of this project is to develop new methods to transform environmentally persistent hydrofluorocarbons (HFCs) and hydrofluoroolefins (HFOs), into reactive chemical building blocks that can be used in chemical manufacture.

Work performed

During the 1st work period of the grant, that is from 1st April 2016 to the 30th September 2018 (up to Month 36), significant progress has been made to develop new methods to transform unreactive fluorocarbons into reactive chemical building blocks. The focus of these studies has the design, development and application of new main group reagents to effect reactions that break the strong carbon–fluorine bonds in fluorocarbons. The main group reagents that have been developed are based on some of the most inexpensive and abundant metal and elements in the Earth’s crust. These include simple molecules based on aluminium, boron, magnesium and zinc, in both the more common +3 and +2 oxidation states and the less common +1 oxidation state.



The reaction of these molecules with fluorocarbons – namely fluoroarenes, fluoroolefins (HFOs) and hydrofluorocarbons (HFCs) – has been investigated with the goal of developing processes which selectively transform a C–F bond into a C–Al, C–B, C–Mg or C–Zn bond. Two approaches have been developed, those which rely on the use of a transition metal catalyst to lower the activation energy of the reaction and help break the strong carbon–fluorine bond, and those which do not. A comprehensive understanding of the mode of action of these new reactions has been developed. This includes a detailed understanding of how the main group reagent breaks strong carbon–fluorine bonds. In the cases where a catalyst is present, we have also developed an intimate knowledge of how the transition metal and main group fragments combine to generate reactive species.

In addition to developing methods that transform unreactive fluorocarbons into new fluorinated main group reagents, we have been developing the applications of these reactive fluorinated building blocks. This includes developing new reactions that upgrade organometallic intermediates, containing C–Al or C–Mg, bonds into useful organic molecules by either carbon–carbon or carbon–heteroatom bond formation.

Final results

When we initiated these studies there were no methods known to transform C–F bonds to C–Al or C–Zn bonds, nor where methods to transform C–F bonds into C–Mg bonds that did not rely on specialist methods to generate highly reactive magnesium metal. In addition, general chemical methods to upgrade or recycle HFO-1234ze, HFO-1234yf and HFO-1336-mmz were not reported as were methods that produce reactive chemical building blocks from HFC-23, HFC-152a, HFC-134a or HFC-143a.

During this grant period, we developed the first highly selective catalytic methods that transform C–F bonds to C–Al bonds based on combining an Al reagent in the +3 oxidation state with a palladium-based catalyst and the fluorocarbon (Angew. Chem., Int. Ed. 2017, 56, 12687). Through a detailed mechanistic analysis, we showed that this reaction likely takes place by a sequential transformation of the C–F to C–H to C–Al bond. We identified potentially catalytic species involving a combination of Pd and Al metals and showed that they were competent for the transformation (Chem. Sci. 2018, 9, 5435). Similar methodology is now being developed by combining the same palladium catalysts with magnesium- and zinc-based reagents (see for example, Chem. Commun. 2018, 54, 12326).

We have developed the first non-catalytic methods to transform C–F bonds into C–Al. This work includes a large scope of fluorocarbons including fluoroarenes, fluoroalkanes and fluoroalkenes. For example, reactions of low-valent aluminium(I) reagents with HFO-1234ze, HFO-1234yf and HFO-1336-mmz lead to highly selective methods to generate fluorinated building blocks by cleavage of the carbon–fluorine bonds (preliminary data: Chem. Commun. 2015, 51, 15994; main results: Angew. Chem., Int. Ed. 2018, 57, 6638). This pioneering study represents one of the first methods to upgrade these industrially important olefins and was highlighted in Science magazine (Science, 2018, 360, 871). We studied the mechanism of this transformation by computational methods allowing us to determine that it likely proceeds by two competitive pathways, one involves direct intermolecular attack of the Al-reagent on the C–F bond the other involves reversible coordination of the alkene to the Al-reagent followed by an intramolecular process that cleaves the C–F bond.

In parallel, we developed the first non-catalytic methods to transform C–F bonds into C–Mg bonds. This work includes the report of the reactions of unusual main group reagents containing Mg–Mg and Mg–Zn bonds with fluoroarenes (J. Am. Chem. Soc. 2016, 138, 12763) and fluoroalkanes (Chem. Eur. J. 2018, DOI:10.1002/chem.201804580). We have studying the modes of action of these unusual reagents and shown that they behave somewhat like classic nucleophiles from organic synthesis. For example, through a combination of kinetics and mechanistic probe experiments supported by calculations, we showed that Mg–Mg reagents react with fluoroarenes by a concerted SNAr mechanism in which one Mg centre acts as a nucleophile and the other acts to activate the C–F bond (Chem. Sci. 2018, 9, 2348). Aspects of this work have been highlighted in Chemistry World the flagship science communication periodical of the Royal Society of Chemistry. We are now translating these new methods to HFOs and HFCs.

Website & more info

More info: http://crimmingroup.org.