Enantioselectivity in the Noyori-Ikariya Asymmetric Transfer Hydrogenation of Ketones

Asymmetric transfer hydrogenation (ATH) is an important catalytic process in the fragrance and pharmaceutical industries. The Noyori-Ikariya chiral molecular ruthenium complex has been the catalyst of choice for this reaction for over 25 years. The mechanism and origin of enantioselectivity have irked chemists ever since the catalyst conception. This work addresses important shortcomings in understanding the origin of enantioselectivity with the Noyori-Ikariya catalysts, traditionally associated with the CH-pi interaction [Angew. Chem., Int. Ed. 2001, 40, 2818]. Here, we show that there are two spatial regions of the catalyst that simultaneously control the enantioselectivity for any arbitrary substrate: the region of the (tethered) eta(6)-arene ligand and the region of the SO2 moiety. Dynamic equilibrium and interplay of attraction and repulsion via CH-pi, C-H center dot center dot center dot H-C, lone pair-pi, lone pair center dot center dot center dot H-C, and other noncovalent interactions in each region lead to stabilization/destabilization of the corresponding diastereomeric transition state and, as such, determine the final percent enantiomeric excess (% ee).

Automated summary

This study reveals that there are two spatial regions of the catalyst that simultaneously control the enantioselectivity for any arbitrary substrate: the region of the (tethered) eta(6)-arene ligand and the region of the SO2 moiety. Noncovalent interactions in each region, such as CH-pi, C-H center dot center dot center dot H-C, lone pair-pi, lone pair center dot center dot center dot H-C, play a crucial role in determining the final percent enantiomeric excess (% ee).