Direct Observations of the Metal−Ligand Bifunctional Addition Step in an Enantioselective Ketone Hydrogenation

The transition state for the metal-ligand bifunctional addition step in Noyori's enantioselective ketone hydrogenation was investigated using intramolecular trapping experiments. The bifunctional addition between the Ru dihydride trans-[Ru((R)-BINAP)(H)(2)((R,R)-dpen)] and the hydroxy ketone 4-HOCH(2)C(6)H(4)(CO)CH(3) at -80 °C exclusively formed the corresponding secondary ruthenium alkoxide trans-[Ru((R)-BINAP)(H)(4-HOCH(2)C(6)H(4)CH(CH(3))O)((R,R)-dpen)]. Combined with the results of control experiments, this observation provides strong evidence for the formation of a partial Ru-O bond in the transition state.

The commercially available chiral diamine quincorine-amine, originally derived from quinine, was found to be a highly active catalyst for ruthenium-catalyzed hydrogenation of ketones. The complex formed between the quincorine-amine, containing both a primary and a quinuclidine amino function, and RuCp*Cl catalyzes the hydrogenation of aromatic and aliphatic ketones in up to 90% ee approximately 24 times faster than previously reported Ru-diamine complexes. The pseudo-enantiomer of the quincorine-amine, i.e., quincoridine-amine, also showed high activity; however, the enantioselectivities obtained with this catalyst were lower. The reason for the lower, but opposite stereoselectivity seen with the quincoridine-amine, as compared to the quincorine-amine, was rationalized by a kinetic and computational study of the mechanism of the reaction. The theoretical calculations also revealed a significantly lower activation barrier for the alcohol-mediated split of dihydrogen, as compared to the nonalcohol-mediated process, a finding of utmost implication also for the diphosphine/diamine-mediated enantioselective hydrogenation of ketones.

The employment of a facile ligand to achieve the efficient enantioselective hydrogenation of ketones is of great interest and importance. Herein, we disclose Ir-catalyzed asymmetric hydrogenation of simple ketones using readily available P,N,N-ligands derived from 1,2-diphenylethylenediamine with a tertiary amine terminus, giving rise to the corresponding alcohols with high reactivity (up to 9800 TON) and enantioselectivity (up to >99% ee). The utility of this protocol has been demonstrated by the gram-scale synthesis of (S)-3-(dimethylamino)-1-(thiophen-2-yl)propan-1-ol using (R,R)-L4, which is the key intermediate for the synthesis of (S)-duloxetine.

Novel chiral cobalt complexes containing a PNNP‐type ligand were synthesized using a straightforward method. The structures of the cobalt complexes have been fully characterized by X‐ray crystallography, high resolution mass spectrometry (HRMS), and electron paramagnetic resonance (EPR). Using H2 as the hydrogen source, the cobalt‐catalyzed asymmetric hydrogenation of various ketones was investigated, and the corresponding chiral alcohols were afforded with up to 99 % yield and 95 % ee. To the best of our knowledge, this is the first example of a cobalt‐catalyzed enantioselective hydrogenation of ketones with molecular hydrogen.

A new class of well-defined ruthenium catalysts for enantioselective transfer hydrogenation of various ketones

Zwitterion formation: a feasible mechanism for the Pt-catalyzed enantioselective hydrogenation of ketones?

An in situ attenuated total reflection study of the chiral solid-liquid interface created by cinchonidine adsorption on a Pt/Al(2)O(3) model catalyst is presented. Experiments were performed in the presence of dissolved hydrogen, that is under conditions used for the heterogeneous enantioselective hydrogenation of alpha-functionalized ketones. Cinchonidine adsorbs via the quinoline moiety. The adsorption mode is coverage dependent and several species coexist on the surface. At low concentration (10(-6)M) a predominantly flat adsorption mode prevails. At increasing coverage two different tilted species, alpha-H abstracted and N lone pair bonded cinchonidine, are observed. The latter is only weakly bound and in a fast dynamic equilibrium with dissolved cinchonidine. At high concentration (10(-4)-10(-3) M) all three species coexist on the Pt surface. A slow transition from an adsorbate layer with a high fraction of alpha-H abstracted cinchonidine to one with a high fraction of N lone pair bonded cinchonidine is observed with the cinchonidine concentration being the driving force for the process. The reverse transition in the absence of dissolved cinchonidine is fast. Cinchonidine competes with solvent decomposition products for adsorption sites on the Pt, which may contribute to the observed solvent dependence of the heterogeneous enantioselective hydrogenation of ketones by cinchonidine-modified Pt.

One chiral element is enough: A new ruthenium catalyst containing a rigid chiral diamine (BIDN) and a commercially available inexpensive achiral phosphane (DPPF) is highly efficient for the enantioselective hydrogenation of ketones (see scheme). High reactivity (S/C up to 100 000) and excellent enantioselectivities (up to 99 % ee) were obtained.

Ruthenium catalysts bearing di­phosphine and diamine ligands are particularly effective at mediating asymmetric ketone hydrogenation (see Review below). The authors present a new catalyst that shows superior reactivity compared to previous generations.

The addition reactions of the simplest silylenoid H2SiLiF with ethylene were studied theoretically. The geometries of the stationary points along the potential energy surfaces were optimized using DFT B3LYP method with the 6-311+G(d,p) basis set, and the single point energies were calculated at QCISD/6-311++G(d,p) level of theory. The theoretical calculations demonstrated that the addition reaction of H2SiLiF and C2H4 can occur through two different pathways. One is path A via a three-membered ring transition state, the other is path B, while through a four-membered ring transition state. The calculated energy barriers of path A and path B are 58.90 and 248.08 kJ∙mol(-1), respectively. Therefore, pathway A is more favorable than pathway B. The solvent effect on the addition reactions were investigated using the PCM model, and the calculated results indicated that in the THF solvent, the addition reaction is much easier than that in vacuum. The present work provided a new pathway to synthesize silicon heterocyclic compounds.

Review: 64 refs.

Aminophosphine phosphinite (AMPP) and enantioselective hydrogenation of ketones: further developments

Stereo- and enantio-selective hydrogenation of ketones using iridium catalysts containing a carboxylate ligand: Journal of molecular catalysis, 33 (1985) 71-75

Not so precious! The combination of copper acetate and chiral monodentate ligands allows the enantioselective hydrogenation of carbonyl compounds to take place in good to high yields with moderate to good enantioselectivities (see scheme).

Steric and electronic effects in enantioselective hydrogenation of ketones on platinum modified by cinchonidine: Directing effect of the trifluoromethyl group