Development of 4,4‘-Substituted-XylBINAP Ligands for Highly Enantioselective Hydrogenation of Ketones

A family of 4,4‘-substituted-xylBINAPs was synthesized in multistep sequences and characterized
by NMR spectroscopy and mass spectrometry. Ru(diphosphine)(diamine)Cl2 complexes based on
these 4,4‘-substituted-xylBINAPs and chiral diamines (DPEN and DAIPEN) were synthesized by
treatment of [(benzene)RuCl2]2 with 4,4‘-substituted-xylBINAP followed by chiral diamine, and
characterized by 1H and 31P NMR spectroscopy and mass spectrometry. These Ru complexes were
used for asymmetric hydrogenation of aromatic ketones in a highly enantioselective manner with
complete conversion. With 0.1% catalyst loading, complete conversion and enantioselectivity greater
than 99% were obtained for most of the aromatic ketones examined. These Ru catalysts thus gave
the highest ee for asymmetric hydrogenation of aromatic ketones among all of the catalysts reported
in the literature. A single-crystal X-ray diffraction study of Ru[(R)-L4][(R,R)-DPEN]Cl2 indicated
that the 4-methyl group of the naphthyl ring and the methyl groups of the two xylyl moieties form
a fence on the opposite side of the DPEN ligand of the Ru center. These three methyl groups will
have significant repulsive interactions with the bulky aryl ring of the hydrogen-bonded aromatic
ketone in the disfavored transition state. These results support our hypothesis of combining dual
modes of enantiocontrol (i.e., the substituents on 4,4‘-positions of the binaphthyl framework and
the methyl groups on the bis(xylyl)phosphino moieties) to achieve higher stereoselectivity in the
hydrogenation of aromatic ketones.