Skip to main content

A Catalytic Method to Form Carbon–Carbon Bonds by Coupling Two Carbon–Fluorine Bonds.

Periodic Reporting for period 1 - FLUOROCROSS (A Catalytic Method to Form Carbon–Carbon Bonds by Coupling Two Carbon–Fluorine Bonds.)

Reporting period: 2018-01-08 to 2020-01-07

The biaryl motif contains two benzene rings joined by a carbon–carbon bond and is an established chemical building block. In recent years, there has been keen interest in biaryls containing fluorine atoms. The combination of a rigid, potentially planar, biaryl group and electronegative fluorine atom(s) engenders key benefits to organic molecules designed for use in liquid crystal displays or as the active ingredient in pharmaceuticals or agrochemicals. Biaryls are typically synthesized by coupling of an organometallic reagent with an aryl halide, a synthetic method that resulted in the 2010 Nobel Prize in chemistry. Despite wide-spread adoption of this approach, only recently have catalysts been developed that allow the cross-coupling of organometallics with carbon–fluorine bonds; most methods rely on the use of substrates containing weaker carbon–bromine or carbon–iodine bonds.

The direct coupling of two different fluorinated substrates by a reaction which breaks two carbon–fluorine bonds is unknown. If such a reaction could be developed it would open up the use of inexpensive fluorocarbons in synthesis.
In this project we took important steps toward achieving this goal. The main output was the development of a new catalytic reaction that transforms C-F bonds into C-Al bonds. The products of this reaction are useful partners in cross-coupling methodology allowing the synthesis of partially fluorinated biaryls. As part of our studies we developed a deep mechanistic understanding of a series of catalytic transformations including those that transform C-X bonds into C-Al bonds. This includes new transformations that are relevant to the fluorochemicals industry (fluoroarenes) and biomass (furans, anisoles). These new catalytic transformations rely on [Pd---Al] based catalysts. We were able to calculate a series of viable mechanisms for each type of substrate. The advance in our understanding from this comprehensive study will be essential for the long-term development of the project.
In combination the work describes the scope and mechanism of new catalytic reactions that break strong C–F bonds in fluoroarenes and C–O bonds in furans and anisoles. These new reactions are important, not only because they all access to reactive chemical building blocks from readily available and typically unreactive starting materials, but also because we have developed a deep understanding of the mechanism of how the catalysts work. This information will likely transcend individual catalysts and catalytic reactions and form a keystone for developments in the field.
figure-1.png