A DFT Analysis of Asymmetric Transfer Hydrogenation with Chiral-at-Metal (Rh, Ir) Catalysts

Asymmetric transfer hydrogenation of acetophenone with ammonium formate and chiral-at-metal (Rh, Ir) complexes with 2-phenyloxazole, 2-phenylbenzoxazole, and 2-phenyl-7-t-butylbenzothiazole ligands was studied at ωb98x-D/LANL2DZ(Rh,Ir)/6-31G(d)(N,C,O, H) and single points using 6-311G(2d,p), metal f-functions, and inclusion of the effect of solvation. The results corroborate reported experimental findings and support in situ generation of metal-hydride catalysts (Ir–H > Rh–H) by concerted asynchronous transfer hydrogenation, in which the hydride transfer slightly trails proton transfer from NH₄⁺. The calculated enantioselectivities indicate liberated CO₂ does not play a role. Instead, the vacant metal-hydride coordination site is likely occupied by a formate anion to preset it for the next cycle. Adding 3,5-dimethyl-1H-pyrazole as a coligand increases the enantioselectivities (>66% ee) based on the free energy difference between the transition structures for prochiral re and si approaches of acetophenone. Even better selectivities result with 2-phenylbenzoxazole (92–98% ee) and 2-phenyl-7-t-butylbenzothiazole (99%) with a large 1H-pyrazole as the coligand. The methodology appears to be suited for screening chiral-at-metal catalysts for enantioselectivity.