Iron catalysts containing amine(imine)diphosphine P-NH-N-P ligands catalyze both the asymmetric hydrogenation and asymmetric transfer hydrogenation of ketones

Abstract

When activated with base, the iron(II) complexes with tetradentate amine(imine)diphosphine ligands, (S,S)-trans-[FeCl(CO)(PAr2-NH-N-PAr′2)]BF4 (1: Ar, Ar′ = Ph; 2: Ar = Ph, Ar′ = 4-MeC6H4; 3: Ar, Ar′ = 3,5-Me2C6H3), are very active for the asymmetric transfer hydrogenation (ATH) of ketones in KOtBu/2-propanol. For ATH, better enantioselectivity, but lower catalytic activity, was observed in general when using catalyst precursors with the bulkier dixylylphosphino groups compared to those with diphenylphosphino groups. The complexes were much less active for the pressure hydrogenation of ketones, where 1 and 2 produced racemic product alcohols, while 3 yielded chiral alcohols with an enantiomeric excess of up to 70% (R) at turnover frequencies up to 80 h-1 and turnover numbers of 100 for a range of ketones at 50 °C and 20 atm H2. This is a rare example of asymmetric pressure hydrogenation using an iron complex. Unlike the case of ATH, there is no effect on the rate upon the addition of KOtBu beyond the 2 equiv needed to convert the precursor complex to the active amido(ene-amido) and amine(ene-amido)hydrido forms. Both AH and ATH reactions share the same iron hydride intermediate formed by reaction of the amido(ene-amido) iron complex with either dihydrogen or 2-propanol. Kinetic studies on the H2 hydrogenation of acetophenone catalyzed by 1, activated by base in benzene, using the method of initial rates indicated that the heterolytic splitting of the dihydrogen at the amido(ene-amido) iron complex is the turnover-limiting step of the catalytic cycle for hydrogenation. For 1 in benzene at 323 K over the ranges of concentrations [1] = (2.4-4.8) × 10-4 M and [ketone] = (3.6-7.2) × 10-2 M, and of H2 pressures = 10-20 atm, the rate law is rate = k[1][H2], with k = 0.16 ± 0.01 M-1 s-1, ΔH‡ = 10.0 ± 0.2 kcal mol-1, and ΔS‡ = -31.0 ± 0.5 cal mol-1 K-1. Detailed DFT calculations also support the finding that the barrier for H2 splitting is the turnover-limiting step. The higher barrier for H2 activation compared to isopropanol activation in order to generate the active amine(ene-amido)hydrido form explains why this system is biased toward ATH over AH.