Asymmetric Transfer Hydrogenation of Aryl Heteroaryl Ketones using Noyori-Ikariya Catalysts

A range of ketones flanked by a combination of an aromatic and a heterocyclic ring (furan, thiophene, N -methylimidazole) were reduced under asymmetric transfer hydrogenation (ATH) conditions. Using a range of [(arene)Ru(TsDPEN)Cl] precatalysts, including tethered derivatives, the reduction enantioselectivity was high (up to 99% ee) in cases where the aromatic ring contained an ortho -substituent. The enantioselectivity is influenced by a combination of steric and electronic factors which for the furan and thiophene series, follow literature precedents. In the case of the N -methylimidazole-containing ketones, an unexpected switch in enantioselectivity took place upon variation of the opposing aromatic group. Pyrrole- containing ketones were resistant to reduction. This study demonstrates the asymmetric transfer hydrogenation (ATH) of a range of hindered heterocyclic ketones, in high conversion and ee, using Noyori-Ikariya catalysts.