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 (<SCP>l</SCP>)-phenylalanine p-anisidineamide and (<SCP>l</SCP>)-valine o-anisidineamide with [Ru(p-cymene)Cl<INF>2</INF>]<INF>2</INF> have been isolated and characterized as the half-sandwich complexes [(η⁶-p-cymene)Ru(κ²-N,N‘-aminoamidato)Cl] (<BO>10</BO> and <BO>11</BO>, respectively). An ESI-MS study conducted on the acetophenone reduction catalyzed by <BO>11</BO> has led to the detection of the organometallic intermediates involved in the catalytic cycle:  the precatalyst <BO>11</BO>, the 16e^- complex [(η⁶-p-cymene)Ru(κ²-N,N‘-diamide)] <BO>12</BO>, and the hydride [(η⁶-p-cymene)Ru(κ²-N,N‘-aminoamidato)H] <BO>13</BO>.