N-heterocyclic carbene ligands for iridium-catalysed asymmetric hydrogenation

The general objective of this research work was to investigate the potential of N-heterocyclic carbenes as ligands for the asymmetric iridium-catalysed hydrogenation of olefins and imines. In this context, efficient synthetic routes were developed to access three new classes of NHC-based ligands. The first class consists of chiral monodentate C2-symmetric NHCs which are combined with two different co-ligands, pyridine or triphenylphosphine, in order to give rise to direct analogues of Crabtree's catalyst. In the second class, the NHC is tethered to a chiral oxazoline unit and forms a six-membered-chelate ring upon complexation. Finally, the third class of ligands consists of bidentate ligands, in which the NHC is linked to either a phosphine or a phosphinite moiety.
Analogues of Crabtree’s catalyst bearing a chiral C2-symmetric NHC:
Six iridium complexes, analogues of Crabtree's catalyst bearing monodentate NHCs, were synthesised starting from readily available enantiopure C2-symmetric imidazolium salts (Figure 5.1).
Characterisation by crystallographic studies and 2D NMR gave insight into the geometry of the complexes and their dynamic behaviour. The catalytic activity of these new iridium complexes was tested in the enantioselective hydrogenation of a range of unfunctionalised
olefins. Full conversion of trisubstituted olefins was only obtained under forcing conditions (50 bar H2, 100C°, 16h). Higher activities were measured for terminal olefin 73, which was fully hydrogenated in 2 hours at room temperature and 50 bar H2. The low enantioselectivities observed overall (up to 44%) are probably due to the lack of rigidity of such compounds compared to chelate complexes.
Oxazoline-NHC ligands:
Two sets of oxazoline-NHC iridium complexes 81a-f and 90a-o were synthesised (Figure 5.2).
Simple and efficient syntheses, which enable easy variation of the ligand substituents, were developed for both classes. X-ray data analysis of one compound from each library confirmed that the electronic properties of the iridium are similar to those observed in Ir-P,N complexes. Complexes 81a-f and 90a-o were successfully tested in the asymmetric hydrogenation of unfunctionalised olefins. The high asymmetric inductions obtained (ee value up to 90% with trans-α-methylstilbene) were attributed to the rigidity generated by the six-membered chelate ring. Despite the wide range of catalysts investigated, the enantiomeric excesses measured with our two families did not compete with the most efficient Ir-P,N complexes.
Phosphine/phosphinite-NHC ligands:
Three new iridium phosphine-NHC complexes 121a-c (R1 = Me, iPr and mesityl) were synthesised and fully characterised by X-ray diffraction studies and 2D NMR analysis (Figure 5.3).
An efficient four step synthesis was developed from 2-phenyl oxirane, giving access to iridium complex 131. The electronic properties of the two types of iridium complexes were investigated by X-ray analyses and NMR studies. In contrast to Ir-P,N and oxazoline-NHC complexes, almost no difference of the trans influence exerted on the two cod double bonds was observed.
The four complexes were tested in the enantioselective hydrogenation of olefins. Low conversion values were measured in the hydrogenation of unfunctionalised olefins. However, promising activities (approximate TOF value of 400 h-1) were found when functionalised substrates such as allylic alcohol and imines were hydrogenated. The moderate enantioselectivities measured throughout the screen are thought to originate from the lack of rigidity of the two types of complexes, which display conformers at room temperature as shown by 2D NMR analyses.