Iridium Catalysts with Chiral Imidazole‐Phosphine Ligands for Asymmetric Hydrogenation of Vinyl Fluorides and other Olefins

Abstract

New chiral bidentate imidazole-phosphine ligands have been prepared and evaluated for the iridium-catalysed asymmetric hydrogenation of olefins. The imidazole-phosphine-ligated iridium catalysts hydrogenated trisubstituted olefins with the same sense of enantiodiscrimination as known iridium catalysts possessing oxazole and thiazole as N-donors.The imidazole-based catalysts were shown to hydrogenate vinyl fluorides, in some cases with the highest ee values published to date.

Development of iridium-catalyzed asymmetric hydrogenation: New catalysts, new substrate scope

“…Another set of olefins with highly polarized double bonds, the vinyl fluorides, have also been hydrogenated by chiral N,P--ligated iridium complexes, with variable success. 25 As mentioned in Section 2, the electron density at the iridium (i.e. the electron donating nature of the nitrogen substituent of the N,P ligand) has an influence on the chemoselectivity of asymmetric hydrogenation; 26 substrates and conversely electron--withdrawing ligands used for electron--rich substrates.…”

Iridium catalysis: application of asymmetric reductive hydrogenation

“…Conversely, the oxazole is a very weak base, with a lesser donation electron density to the iridium making it a better electron acceptor for a richer alkene. The basicity of the nitrogen 40 in these aza-cycles depends on the second heteroatom as well as on the saturation of the ring ( Figure 4). The importance of the acidity of the solution and the catalyst was probed, and showed that Ir catalysts are significantly more acidic than their Rh counterparts.…”

“…28 As can be seen, most substrates required higher pressure and temperature than commonly used. This in turn require often 40 changing from the normally employed solvent (CH 2 Cl 2 ) to α,α,α-trifluoro-toluene, which exhibits very similar electronic properties to dichloromethane but with a higher boiling point. 29 As part of the screening process it was determined that either an increase in temperature (from 25 to 40°) or pressure (50 to 100 45 bar) was necessary, though when one sufficed an elevation of pressure was preferred over that of temperature (which caused a decrease in ee).…”

“…Vinyl fluorides have a similarly polarised olefinic bond, but when hydrogenated with similar N,Pligated iridium catalysts and conditions, the results remained inferior to those in Table 4. 40 Following the reasoning outlined in 40 the ligand design section, the tuning of the ligand was pivotal to obtaining good results, hence the use of highly similar catalysts. The choice of the N linker atom to the phosphine group combined with the choice of a thiazole heterocycle lead to a highly enantioselective iridium catalyst, which was able to hydrogenate 45 with the electron poor alkenes efficiently.…”

“…Replacing two small mono-dentate ligands by a larger chiral bi-dentate one opens the possibility for asymmetric 40 hydrogenation, as the chirality can be more efficiently transferred to the product from the ligand. Kagan's DIOP ligand 8 and the aforementioned DIPAMP, developed by Knowles for the L-DOPA process (based on Wilkinson's catalyst) are amongst the most famous examples of this.…”