Computational Mechanistic Study of Fe-Catalyzed Hydrogenation of Esters to Alcohols: Improving Catalysis by Accelerating Precatalyst Activation with a Lewis Base

DFT calculations have been performed to gain mechanistic insight into ester hydrogenation to alcohols (exemplified by PhCO2CH3 +2H2 → PhCH2OH + CH3OH), catalyzed by a well-defined Fe-PNP pincer hydridoborohydride complex (1). The entire catalytic process includes precatalyst activation to an active species trans-dihydride complex 2, 2-catalyzed transformation of PhCO2CH3 + H2 → PhCHO + CH3OH, hydrogenation of PhCHO to PhCH2OH, and catalyst regeneration via H2 addition to the dehydrogenated 2 (i.e., complex 5). The transformation, PhCO2CH3 + H2 → PhCHO + CH3OH, proceeds via hydrogenation of PhCO2CH3 to a hemiacetal PhCH(OH)(OCH3), followed by decomposition of the hemiacetal to methanol and benzaldehyde. The Fe-complex 5 was found to be capable of facilitating the decomposition of the hemiacetal. The ineffectiveness of the catalytic system in hydrogenating methyl salicylate is attributed to the intrinsically lower reactivity of the ester toward C═O reduction and a very facile side-reaction, which is adding the phenol OH group of the hemiacetal intermediate stemmed from methyl salicylate to the Fe–N active site of 5. Computations of various catalyst initiation pathways show that the initiation without the aid of an additive is very unfavorable, thus we suggest the use of a Lewis base such as NR3 (R = Me and Et) and PR3 (R = nBu and tBu) to accelerate precatalyst (1) activation, because a Lewis base could form a stable adduct (BH3–NR3/PR3) with the BH3 moiety of 1. In agreement with greatly enhanced kinetics and thermodynamics of the initiation process suggested by the DFT calculations, experimental study shows that the addition of a catalytic amount of NEt3 doubled the yield of benzyl alcohol from the hydrogenation of methyl benzoate, when compared to the case without using any additive. The trans effect of the hydride on the reactivity of 2 and steric effect of the pincer substituents on the stability of 2 are also discussed.