Recyclable Catalyst Technology for Cross-Coupling Reactions at Manufacturing Scale

Homogeneous Palladium (Pd) cross-couplings, based on Nobel-prize winning methodologies, have become essential for
the production of life-enhancing pharmaceuticals & chemicals (est. worth to sector: >£10 bn). However there are
environmental & sustainability issues, often addressed by heterogeneous Pd catalysts but with reduced performance. This
project combines the advantages of each type of Pd catalysis by development of a broad-spectrum 'Catch & Release'
cross-coupling technology. Novel functionalised silica materials will allow purification of reaction products by temporary
capture of the Pd catalyst in heterogeneous form, capable of release back in it's active form into solution by new reaction
components for further production. The technology is employed in semi-continuous format, with application possible across
multiple process industries. Initial applications towards the manufacture of pharmaceuticals & agrochemicals will be
demonstrated. This project fits rigorously within the TSB competition's headline goal of providing 'Sustainable
manufacturing for the process industry' and describes an innovative 'Novel Catalysis' approach. This is delivered through a
technology which enables change from existing batch to semi-continuous processing and the development of inherently
more sustainable processes, which recover & reuse the active catalysts, both metal and ligand, whilst dramatically reducing subsequent product purification requirements. The overarching objective is the identification and optimisation of an
appropriately functionalised aryl bromide on the silica solid support to effectively catch & then release the active Pd catalyst
and to take this as proven technology into manufacture.
Our consortium links academic and SME expertise in ligand design/immobilisation and understanding of metal-catalysed
couplings together with global industrial product end-users. The widespread application of transition metal (Pd) crosscoupling
reactions in a variety of chemistry-related industries means the chosen subject material is of high and topical
importance as the UK strives for faster production processes to increase it's competitive edge in manufacturing. The
project's combination of the benefits of homogeneous Pd catalysis (fast reaction rates, selectivity and flexible catalyst
choice) with the use of a solid phase to temporarily support the active Pd catalyst (for subsequent reuse) & simultaneously
allow easy product purification will enable high efficiency chemical synthesis with increased throughput by semi-continuous
processing. First development and then fine-tuning of the silica-supported linker to suitably effect the cross-coupling
reaction step is critical to industry adoption of the final commercial product as a broad-spectrum, preferred method for
cross-coupling at process scale; the project's activities and objectives reflect this. The output from this innovative and
improved catalytic route for cross-couplings will be observed by better process economics, through recycling of high cost
synthetic metals, including Pd, and organic ligands, and reduced toxic waste outputs. The endpoint commercial product
would generate international interest and lead to export sales. In summary, our project focuses primarily on catalysis
process innovation, through improvement of the lifetime and recycling of the Pd catalyst for cross-couplings by the
introduction of a heterogeneous stage to the catalytic cycle, which also serves as a reaction purification step.

This project focuses primarily on catalysis process innovation, through improvement of the lifetime & recycling of the Pd
catalyst for cross-couplings by the introduction of a heterogeneous stage to the catalytic cycle, which also serves as a
reaction purification step. The Pd catalyst is retained in the active form then re-released from the solid support by new
reaction components, such as the boronic acid input of Suzuki reactions. This ambitious project therefore has the potential
to make a substantial impact on all of the four companies involved and, in turn, their customers.
For Phosphonics, the key impact will be a new product / technology. For CatSci the impact will be in the form of
demonstrable innovation and collaboration with major agrochemical and pharmaceutical industries; for this newly formed
("micro SME") company the access to new customers for catalyst development via the Phosphonics catch and release
product will be very great indeed.
For the larger partners (AstraZeneca and Syngenta) the development of a robust methodology for efficient catalyst
recycling via capture then controlled reintroduction will provide improved process economics, through recycling of high cost
synthetic metals, including Pd, & organic ligands, & reduced toxic waste outputs. The endpoint commercial product would
generate international interest & lead to export sales, and analogous benifits (cost, efficiency, environmental factors) will be
enjoyed by these new customers of phopshonics.
For Bristol university the project will also have substantial impact as it will provide activity in a new area, strategic new links
with new industrial partners and the opportunity to begin new programmes funded by research councils / industry in the
study of catalysis, an area identified by the EPSRC for expansion.