Dr Simon Doherty
The unifying them in the Doherty group is ligand synthesis directed towards efficient synthesis of target molecules. In one well-established and highly successful project the Doherty group is addressing the increasing demand for more efficient, inexpensive and highly versatile diphosphines for use in asymmetric catalysis. As a result a number of entirely new and potentially powerful synthetic approaches have been developed including the use of zirconium-mediated reductive coupling to prepare conformationally flexible NUPHOS (Newcastle University) diphosphines. An exhaustive and comprehensive catalyst testing programme has demonstrated that platinum group metal complexes of these diphosphines exhibit metastable atropos character and can be resolved and the derived Lewis acid complexes used as catalysts for a host of asymmetric C-C and C-heteroatom bond forming reactions, in the majority of cases giving ee's that either rival or exceed those obtained with their BINAP counterpart. Having established the efficiency of NUPHOS diphosphines, future efforts will focus on the synthesis of chiral versions in order to eliminate the need for a resolution step and which will broaden their application potential.
In a more recent and exciting development rhodium-catalysed [2+2+2] cycloaddition has been used to construct an entirely new class of biaryl diphosphine (NU-BIPHEP) in an operationally straightforward manner under extremely mild conditions and in exceptionally high yield. This methodology represents a significant improvement on existing multi-step procedures and provides access to diphosphines with highly substituted and functional architectures which would otherwise be difficult to prepare. Preliminary studies have firmly demonstrated that these NU-BIPHEP diphosphines form highly efficient catalysts for a host of asymmetric transformations. The group is currently developing an asymmetric version of this cycloaddition in order to prepare chiral NU-BIPHEP diphosphines in order to exploit their commercial potential.
In an entirely different approach, Diels-Alder cycloaddition has been applied to the synthesis of bis(bicyclic) biaryl-like CATPHOS diphosphines. Preliminary studies have established CATPHOS as a highly efficient ligand for palladium-catalysed C-C and C-heteroatom bond formation, in the majority of cases outperforming its BINAP counterpart. Future studies will develop the synthesis of chiral versions for use in asymmetric catalysis and explore the range of alkynylphosphines that undergo this Diels-Alder cycloaddition with the aim of preparing electron-rich monodentate derivatives for use in palladium-catalyzed cross-couplings.
Efficient asymmetric hydrogenation of ketones is a rapidly evolving as a highly efficient strategy for the synthesis of non racemic alcohols. However, catalysts are often relatively expensive and substrate specific and there is a need for an inexpensive and more versatile class of catalysis. The Doherty group has shown that ruthenium complexes based on inexpensive and readily available conformationally flexible diphosphines (CYCLOPHOS) form highly efficient catalysts for the asymmetric hydrogenation of a range of aryl-alkyl ketones, giving ee's up to 96%. After optimization the same phosphines form highly efficient catalysts for the asymmetric hydrogenation of β-keto phosphonates giving the corresponding β-hydroxy ketones in excellent ee. The group is currently exploring the asymmetric hydrogenation of enamino-phosphonates as a route to non-racemic β-amino acids as part of a larger project that is exploring asymmetric synthesis directed towards the synthesis of α-and β-amino phosphonates and other biologically important small molecules.
Other projects in the Doherty group are using ionic liquids to address the need to improve existing processes. In one approach oxazoline ligands have been tagged with an immidazolium fragment to improve retention of catalyst in the reaction phase. As a result, cooper catalysts based on immidazolium-tagged oxazoline have been recycled 10 times with no loss in activity or selectivity. Additional benefits associated with the use of ionic liquids have been discovered including significant and substantial enhancement in rate and enantioselectivity compared to organic solvent. The group is currently exploring the use of ionic liquids to engineer a continuous process for the palladium-catalyzed methoxycarbonylation of ethylene. This will be achieved by immobilizing the catalyst in a thin film of ionic liquid which itself will be immobilized on a high surface area mesoporous material to form a supported ionic liquid phase catalyst (SILP).