A Mechanism Displaying Autocatalysis:  The Hydrogenation of Acetophenone Catalyzed by RuH(<i>S</i>-binap)(app) Where app Is the Amido Ligand Derived from 2-Amino-2-(2-pyridyl)propane

Abstract

The 2-(aminomethyl)pyridine (ampy) ligand is known to activate ruthenium complexes for the catalytic hydrogenation of ketones. Here we prepare well-defined catalysts using the new ligand 2-amino-2-(2-pyridyl)propane (appH) in order to elucidate the role of the pyridyl group. The ligand has two methyl groups on the α-carbon to block β-hydride elimination reactions. It reacts with RuHCl( S -binap)(PPh 3 ) to produce the orange-yellow complex RuHCl( S -binap)(appH) ( 2 ). In the presence of a strong base (KO t Bu), complex 2 is converted into an active catalyst for the H 2 -hydrogenation of acetophenone in benzene under mild conditions (20 °C, 5 atm H 2 ). Solutions of 2 rapidly react with KO t Bu under an argon atmosphere to produce a deep red amidohydrido complex RuH( S -binap)(app) ( 3 ), which is an active catalyst. A crystal structure determination of 3 represents the first structure of a Ru-binap hydrido-amido complex. It reveals a five-coordinate Ru(II) center with a short Ru−N(amido) distance (1.962(3) Å) and a trigonal planar geometry at the amido nitrogen. The kinetic experiments using 3 as a catalyst and acetophenone as a substrate in benzene show that the rate of 1-phenylethanol production is dependent on both catalyst and H 2 concentrations. These results parallel the behavior of the conventional Noyori-type Ru(II) catalysts with diamine ligands. However, unique features of catalysis with 3 are as follows: (1) the formation of a dihydride is thermodynamically unfavorable at 1 atm H 2, 20 °C; (2) the rate shows a dependence on the product concentration since it increases as the product builds up during the reaction in an autocatalytic fashion. A significant increase in the initial rate is observed when a critical concentration of rac -1-phenylethanol is present at the beginning of the reaction. The addition of 2-propanol in benzene raises the rate as well, and the fastest H 2 -hydrogenation is achieved if 2-propanol is used as a solvent. This “alcohol effect” is favored by the pyridyl ligand app since it was not observed for the similar catalyst RuH(NHCMe 2 CMe 2 NH 2 )(binap). While 3 is an exceptional catalyst for H 2 -hydrogenation in 2-propanol (TOF > 6700 h -1 at 20 °C, 5 atm H 2 ), it has a lower activity in transfer hydrogenation from the same solvent under comparable conditions (TOF 110 h -1 at 20 °C, 1 atm Ar). DFT calculations on the model amido complex Ru(H)(PH 3 ) 2 (HNCH 2 C 5 H 4 N) ( 4 ) confirm that the splitting of H 2 to give the trans dihydride is the turnover-limiting step and lies 9 kcal/mol in free energy above the transition state for the ketone hydrogenation step. The formation of the dihydride is entropically unfavorable. The theoretical activation barrier for H 2 splitting is lowered by 5 kcal/mol by an alcohol-assisted mechanism but still remains higher in energy than the ketone hydrogenation step. This latter step can also be alcohol-assisted and can result in a different ee in the product alcohol than without alcohol assistance, as observed experimentally for reactions using 2-propanol versus benzene as the solvent. With alcohol present, an alkoxohydridoruthenium(II) complex is calculated to be the catalyst resting state.