Transfer Hydrogenation of Acetophenone Catalyzed by Half-Sandwich Ruthenium(II) Complexes Containing Amino Amide Ligands. Detection of the Catalytic Intermediates by Electrospray Ionization Mass Spectrometry

A series of natural amino acid (alanine, valine, phenylalanine, and isoleucine) amides have been synthesized and fully characterized. They have been used as supporting ligands in the Ru(II)-catalyzed asymmetric transfer hydrogenation (ath) of acetophenone in the presence of i-PrOH/KOH. Secondary amides impart high reactivity to the corresponding Ru(II) complexes, with TOFs up to 1680 h-1 and ee's up to 47%. The amino acid and the substituents of the amide nitrogen govern the activity and the enantioselectivity of the catalytic processes. The precatalysts obtained by reacting (l)-phenylalanine p-anisidineamide and (l)-valine o-anisidineamide with [Ru(p-cymene)Cl2]2 have been isolated and characterized as the half-sandwich complexes [(η 6-p-cymene)Ru(κ 2-N,N‘-aminoamidato)Cl] (10 and 11, respectively). An ESI-MS study conducted on the acetophenone reduction catalyzed by 11 has led to the detection of the organometallic intermediates involved in the catalytic cycle: the precatalyst 11, the 16e- complex [(η 6-p-cymene)Ru(κ 2-N,N‘-diamide)] 12, and the hydride [(η 6-p-cymene)Ru(κ 2-N,N‘-aminoamidato)H] 13.