Philippe Dupau

Iron‐Catalyzed Hydrogenation of Esters to Alcohols

The reduction of esters to alcohols is an important chemical transformation frequently used in industry and in academic research laboratories as well. The two classical protocols for reduction are based on the use of a stoichiometric amount of a hydride reagent and, alternatively, catalytic heterogeneous hydrogenation. The former method suffers from severe drawbacks such as the toxicity of the reagents and the generated waste. From an ecological point of view, the latter method is more promising as the reducing agent is molecular hydrogen. One excellent example is the large-scale reduction of fatty esters to give the corresponding alcohols, precursors for plasticizers and surfactants, in the presence of a copper chromite catalyst. However, heterogeneous hydrogenation using metal oxide based catalysts is poorly chemoselective; high pressures and temperatures are often required. These harsh conditions are not compatible with other unsaturated functional groups (alkenes, alkynes, nitro functions). Homogeneous catalysis is an alternative as the reduction can be performed under milder conditions and the functional group tolerance is higher. Since the pioneering work by Grey and Pez, tremendous improvements, concerning reaction conditions, selectivities, and catalytic efficiencies, have been described for the homogeneous hydrogenation of esters. Most of the catalytic systems reported up to now are based on ruthenium. However, owing to environmental concerns, these noble metals should be replaced by Earth-abundant ones, such as iron. In this context, the groups lead by Milstein, Guan and Fairweather, and Beller reported in 2014 the first examples of homogenous iron-based complexes as catalysts for the hydrogenation of esters under relatively mild conditions. The three groups reported the use of structurally related iron complexes with [Fe(H)2(CO)] or [Fe(H)(HBH3)(CO)] fragments coordinated to a phosphorous/nitrogen-based tridentate pincer-type ligand (Figure 1), and it appeared that the nature of the PNP ligand has an important influence on the substrate scope. Milstein and co-workers reported the hydrogenation of highly activated trifluoroacetate derivatives using PNP–iron complex 1 (PNP = 2,6-(di-tert-butylphosphinomethyl)pyridine) in the presence of a strong base (KH or potassium or sodium alkoxide). Reactions were performed under moderate hydrogen pressure (usually 5 to 25 bars) at mild temperatures (40 8C) in the presence of 1 mol% of 1 and 5 mol% NaOMe in 1,4-dioxane. In related studies with ruthenium complexes a cooperative effect between the PNP ligand and the metal was evoked. Again, ligand involvement was also proposed to activate molecular hydrogen. The proposed ligand dearomatization/aromatization process intrinsically requires only one equivalent of base relative to metal, but in this reduction a higher amount of base (up to 10 mol%) increased the catalytic activity and was thought to facilitate both the formation of the dearomatized intermediate and the removal of the acetal intermediate. Complex 1 displays some nice selectivity towards fluorinated aryl groups and ethers but also more interestingly towards nonpolarized and poorly substituted C=C bonds introduced on the ester moiety. Interestingly, the authors reported that further heating led to unexpected lower conversions, probably due to catalyst deactivation/degradation. Moreover, complex 1 appeared to be quite sensitive to steric hindrance of the ester moiety. Conversions dramatically decreased with an increase of the steric demand on the ester (isopropyl or methylcyclohexyl derivatives). Nevertheless, the interest in such a system is understandably quite limited due to the lack of conversion of slightly less activated difluoroacetate and less electron-demanding esters, such as acetate and benzoate derivatives. Independently, Guan and Fairweather, and Beller reported the use of an iron pincer complex bearing a bis(diisopropylphosphinoethyl)amine) ligand, which was previously described by Gusev for the homogeneous osmium-catalyzed hydrogenation of esters. With this ligand, Guan and Fairweather reported that the corresponding [(PNP)Fe(H)(Br)(CO)] precursor was slightly active in the presence of KOtBu. But more importantly, both research groups noticed that the Figure 1. Iron complexes for the hydrogenation of esters.

Ruthenium-Catalyzed Highly Chemoselective Hydrogenation of Aldehydes

The use of a [(ethylenediamine)(dppe)Ru(OCOtBu)2] [dppe=1,2‐bis(diphenylphosphino)ethane] complex under base‐free conditions allowed highly efficient and selective hydrogenation of aldehydes in the presence of ketones in addition to olefins. Even in the case of highly sensitive 1,6‐ketoaldehydes, the desired ketoalcohols were obtained in high yields with 94–99 % overall selectivity at complete aldehyde conversion with a TON up to 30 000. The lack of requirement for strong basic co‐catalysts and polar protic solvents also allowed efficient and highly chemoselective reduction of aldehydes bearing other functional groups, such as epoxides, carboxylic acids, esters, amides, and nitriles emphasizing the potential synthetic utility of the catalyst.

Unexpected Role of Anionic Ligands in the Ruthenium‐Catalyzed Base‐Free Selective Hydrogenation of Aldehydes

Bigger and better: The replacement of anionic chloride ligands in Noyori-type [(diamine)(diphosphine)RuCl2 ] catalysts with bulky carboxylate ligands enabled the efficient selective hydrogenation of a variety of aldehydes under base-free conditions. Turnover numbers of up to 100 000 were reached in the presence of a bulky carboxylic acid co-catalyst. This type of catalytic system probably operates through an inner-sphere mechanism.