Rh(III)- and Ir(III)-catalyzed asymmetric transfer hydrogenation of ketones in water

Asymmetric transfer hydrogenation (ATH) of ketones by formate in neat water is shown to be viable with Rh-TsDPEN and Ir-TsDPEN catalysts, derived in situ from [CP*MCl(2)](2) (M = Rh, Ir) and TsDPEN. A variety of ketones were reduced, including non-functionalized aryl ketones, heteroaryl ketones, ketoesters, and unsaturated ketones. In comparison with Ir-TsDPEN and the related Ru(II) catalyst, the Rh(III) catalyst is most efficient in water, affording enantioselectivities of up to 99% ee at substrate/catalyst (S/C) ratios of 100-1000 even without working under an inert atmosphere. The aqueous phase reduction is shown to be highly pH-dependent; the optimum pH windows for TOF greater than 50 mol mol(-1)h(-1) for Rh- and Ir-TsDPEN are 5.5-10.0 and 6.5-8.5, respectively. Outside the pH window, the reduction becomes slow or stagnant depending on the pH. However, the enantioselectivities erode only under acidic conditions. At a higher S/C ratio, the aqueous ATH by Rh-TsDPEN is shown to be product- as well as byproduct-inhibited; the product inhibition appears to stem at least partly from the reaction being reversible. The aqueous phase reduction is simple, efficient and environmentally benign, thus presenting a viable alternative for asymmetric reduction.