New chiral Fe-cyclopentadienone complexes as pre-catalysts for asymmetric hydrogenation

In recent years, Fe-cyclopentadienone complexes (1 in Figure 1)1 have become a hot research topic for a series of reasons: A) Firstly, they are a demonstration of how a ‘non-innocent ligand’ can influence and modify the reactivity of a metal: analogously to what reported for the Shvo’s Ru complexes,2 their ligand, swinging between the cyclopentadienone (2) and the hydroxycyclopentadienyl form (3), enables a Fe(0)/Fe(II) catalytic cycle which does not belong to the typical reactivity of Fe-complexes. In this way, after activation by creation of a vacant coordination site, Fe-cyclopentadienone complexes are able to split H2, and thus catalyze both the hydrogenation of carbonyl compounds and the de-hydrogenation of alcohols according to a concerted outer-sphere mechanism where, again, the ligand is actively involved with its OH group (Figure 1).3 B) Secondly, they rely on a cheap, relatively non-toxic and environmentally benign metal such as Fe, which is nowadays increasingly considered for developing sustainable catalysts.4 C) Last but not least, they are perfectly stable to air, moisture and even chromatography, which simplifies their isolation and purification. Activation (by creation of a vacant coordination site) may be performed in situ, i.e. where catalysis is to take place. As efficient chiral Fe-cyclopentadienones for enantioselective reductions are currently missing, we recently developed a new class of (R)-BINOL-derived complexes (Figure 2).5 Considering the previously reported BINOL-derived catalysts and the above-mentioned mechanism,3 we envisioned that 3,3’-substituents on the binaphthyl moiety would be needed to ensure an efficient transfer of stereochemical information from the catalyst’s stereoaxis to the substrate. We thus prepared the complexes CK1, CK2 and CK3 (Figure 2), which were screened in the asymmetric hydrogenation (AH) of ketones after in situ activation (vide supra) by reaction with Me3NO. As expected, complex CK2, bearing the biggest 3,3’-substituents on the binaphthyl system, allowed to obtain the best enantiomeric excess with acetophenone (50% e.e.) and was thus screened on a series of other ketones reaching up to 77% e.e.. Starting from 3,3’-dihydroxysubstituted complex CK3, the synthesis of new complexes bearing bulkier 3,3’-substituents (esters, ethers, aryl rings) has been undertaken. The obtained second-generation pre-catalysts will be tested in the AH of ketones and imines, as well as in hydrogen borrowing processes.