Antonio Zanotti-Gerosa

Quinaphos and Dihydro‐Quinaphos Phosphine–Phosphoramidite Ligands for Asymmetric Hydrogenation

New derivatives of the Quinaphos ligands and the related Dihydro-Quinaphos ligands based on the more flexible 1,2,3,4-tetrahydroquinoline backbone have been prepared and fully characterised. A general and straightforward separation protocol was devised, which allowed for the gram-scale isolation of the R(a),S(c) and S(a),R(c) diastereomers. These new phosphine-phosphoramidite ligands have been applied in the Rh-catalysed asymmetric hydrogenation of functionalised olefins with the achievement of excellent enantioselectivities (> or = 99%) in most cases and turnover frequency (TOF) values of up to > or = 20,000 h(-1). These results substantiate the practical utility of readily accessible Quinaphos-type ligands, which belong to the most active and selective category of ligands for Rh-catalysed hydrogenation known to date.

Computational study of the factors controlling enantioselectivity in ruthenium(II) hydrogenation catalysts

The reduction of prochiral ketones catalyzed by Ru(diphosphine)(diamine) complexes has been studied at the DFT-PBE level of theory. Calculations have been conducted on real size systems [trans-Ru(H)2(S, S-dpen)(S-xylbinap) + acetophenone], [trans-Ru(H)2(S, S-dpen)(S-tolbinap) + acetophenone] and [trans-Ru(H)2(S, S-dpen)(S-xylbinap) + cyclohexyl methyl ketone] with the aim of identifying the factors controlling the enantioselectivity in Ru(diphosphine)(diamine) catalysts. The high enantiomeric excess (99%) in the hydrogenation of acetophenone catalyzed by trans-Ru(H)2(S, S-dpen)(S-xylbinap) has been explained in terms of the existence of a stable intermediate along the reaction pathway associated with the (R)-alcohol. The formation of this intermediate is hindered with the competitive pathways, which consequently increases the activation energy for the hydrogen transfer acetophenone/(S)-phenylethanol reaction. For the [trans-Ru(H)2(S, S-dpen)(S-tolbinap) + acetophenone] system, the lower enantioselectivity (i.e. 80%) is rationalized by the smaller differences in the activation energy between the competitive pathways which differentiate between the two diastereomeric approaches of the prochiral ketone. The DFT-PBE results suggest that this reaction is driven to the (R)-product only by the process of binding the acetophenone to the active site of the trans-Ru(H) 2(S, S-dpen)(S-tolbinap) catalyst. For the hydrogenation of cyclohexyl methyl ketone catalyzed by trans-Ru(H)2(S, S-dpen)(S-xylbinap), the low performance in the enantioselective hydrogenation of the dialkyl ketone (i.e. 37%) is again explained by the small differences in the activation and binding energies which are the factors which could effectively differentiate between the two alkyl groups.

Iridium‐Catalyzed Chemoselective and Enantioselective Hydrogenation of (1‐Chloro‐1‐Alkenyl) Boronic Esters

Organoboron compounds play important roles in chemistry, especially in the field of organometallic catalysis where boronic acids, boronic esters, and trifluoroborates are invaluable for the construction of C O, C N, or C C bonds through various coupling reactions. a-Amino boronic acids, primarily obtained from (a-chloroalkyl) boronic esters, are a recent addition to this class of compounds, expanding them into completely new areas of use. They are a crucial structural element in a new class of anti-cancer peptide drugs. One member of this class of drugs, which contains a “borleucine” moiety, is marketed under the name bortezomib (Scheme 1).

On the economic application of DuPHOS rhodium(I) catalysts: a comparison of COD versus NBD precatalysts

Abstract The effectiveness of cyclooctadiene and norbornadiene precatalysts of the type [Rh(DuPHOS)(diolefin)]BF 4 in catalytic asymmetric hydrogenation of various prochiral olefins has been examined. In some of the systems studied, the NBD complex gave rise to the catalytically active species more rapidly than the corresponding COD complex, as expected. However, as catalyst loadings were reduced to levels more conducive to economic manufacture, the difference between the use of COD and NBD precatalysts became increasingly insignificant. This was conveniently highlighted by the formation of low enantiomeric excess products upon using an equimolar mixture of ( S , S ) and ( R , R ) precatalysts, bearing COD and NBD respectively. With other substrates, the system displayed no induction time for either precatalyst and identical reaction profiles were observed.

The Development of Phosphine-Free "Tethered" Ruthenium(II) Catalysts for the Asymmetric Reduction of Ketones and Imines.

In this account, we describe the design, synthesis and applications of tethered versions of the Ru(II)/N-tosyl-1,2-diphenylethylene-1,2-diamine (TsDPEN) class of catalyst that are commonly used for asymmetric transfer hydrogenation and asymmetric hydrogenation of ketones and imines. The review covers key aspects of the reaction mechanisms and examples of applications, including industrial applications to pharmaceutically important target molecules. In addition, closely related catalysts based on Rh(III) and Ir(III) are also described.

Transfer Hydrogenation and Hydrogenation of Commercial‐Grade Aldehydes to Primary Alcohols Catalyzed by 2‐(Aminomethyl)pyridine and Pincer Benzo[h]quinoline Ruthenium Complexes

The chemoselective reduction of commercial‐grade aldehydes (97–99 %) to primary alcohols is achieved with cis‐[RuCl2(ampy)(PP)] [ampy=2‐(aminomethyl)pyridine; PP=1,4‐bis(diphenylphosphino)butane, 1,1′‐ferrocenediyl‐bis(diphenylphosphine)] and pincer [RuCl(CNNR)(PP)] [PP=1,3‐bis(diphenylphosphino)propane, 1,4‐bis(diphenylphosphino)butane, 1,1′‐ferrocenediyl‐bis(diphenylphosphine); HCNNR=4‐substituted‐2‐aminomethyl‐benzo[h]quinoline; R=Me, Ph] complexes by transfer hydrogenation and hydrogenation reactions. Aromatic, conjugated, and aliphatic aldehydes are converted quantitatively to the corresponding alcohols using 2‐propanol with potassium carbonate at substrate/catalyst ratios up to 100 000 by transfer hydrogenation, whereas aldehyde hydrogenation (5–20 atm of H2) is achieved efficiently in MeOH in the presence of KOtBu at substrate/catalyst ratios up to 40 000.

Reaction of the conjugate base of propenylpyrrolidinocarbene chromium pentacarbonyl complex with electrophiles

Abstract The conjugate base of pentacarbonyl(propenylpyrrolidinocarbene)chromium(O) is easily generated at −78 °C with LDA and reacts with electrophilic reagents to provide the corresponding addition products in satisfactory to good yields. The α/γ regioselectivity depends on the nature of the electrophile and is also discussed in comparison with the behavior of the anions of crotonamides

Chemoselective Transfer Hydrogenation of Aldehydes with HCOONH4 Catalyzed by RuCl(CNNPh)(PP) Pincer Complexes

Aldehydes were chemoselectively reduced to primary alcohols by using HCOONH4 as the hydrogen donor through transfer hydrogenation catalyzed by benzo[h]quinoline pincer complexes RuCl(CNNPh)(PP) at substrate to catalyst molar ratios of 2000 to 20 000. This practical reaction performed with aldehydes of commercial‐grade purity in a water/toluene biphasic system afforded alcohols without the formation of condensation or amination side products.

Development of a Stepwise Reductive Deoxygenation Process by Ru‐Catalysed Homogeneous Ketone Reduction and Pd‐Catalysed Hydrogenolysis in the Presence of Cu Salts

A stepwise catalytic reduction of ketone 1 to alcohol 2 and subsequently to aryl(imidazo[1,2‐b]pyridazinyl)methane 3 is described, which provides synthetically useful chemoselectivity at acceptably low catalyst loadings. Undesired reactive sites include an aryl chloride, heteroarylchloride and benzylic amine group. The presence of these functional groups presents a significant challenge to chemoselectivity for both reduction steps. For selective CO reduction of highly functionalised 1, high chemoselectivity was observed at low catalyst loading by using Wills’ tethered Ru transfer‐hydrogenation catalyst 13. The selective hydrogenolysis of 2 was then accomplished under acidic hydrogenation conditions by using a Pd/C catalyst in the presence of Cu salts. This procedure has been demonstrated on a multi‐gram scale, which makes this approach a viable method to use a combination of homogeneous and heterogeneous catalysis.

New insights into the enantioselectivity in the hydrogenation of prochiral ketones

The high enantioselectivity in the hydrogenation of acetophenone catalysed by trans-Ru(H)2(S,S-dpen)(S-xylbinap) is explained in terms of the existence of a stable intermediate formed when the reactant enters the catalyst pocket fixing the molecular orientation.