Chiral monodentate phosphorus ligands for rhodium-catalyzed asymmetric hydrogenation

This review reports the recent developments in the field of asymmetric hydrogenation in the presence of metal catalysts containing monodentate phosphorus ligands. Besides monophosphines, that have been used at the origin of asymmetric hydrogenation, it mainly includes the use of monophosphites and monophosphoramidites, which when associated to rhodium precursors have recently led to very efficient enantioselective catalytic systems.     

Chiral ferrocenyl diphosphines for asymmetric transfer hydrogenation of acetophenone

The synthesis of new optically pure ferrocenyl diphosphines have been realized from (R)-(+)-N,N-dimethylaminoethylferrocene. Particularly, dissymmetric ferrocenyl diphosphines have been synthesized. The diphosphines have been used as ligands in asymmetric transfer hydrogenation of acetophenone in the presence of Ru catalysts.     

Chiral counteranion-aided asymmetric hydrogenation of acyclic imines

When combined with a chiral phosphate counteranion, a chiral diamine-ligated Ir(III) catalyst displayed excellent enantioselectivities in the asymmetric hydrogenation of a wide range of acyclic imines, affording chiral amines in up to 99% ee.     

Chiral rhodium carboxylates as asymmetric hydrogenation catalysts

The comparative catalytic activities of a few chiral rhodium carboxylato complexes in combination with chiral and achiral phosphines are described. In the hydrogenation of α-acetamidocinnamic acid and its methyl ester, differences are observed in turnover numbers and enantioselectivities. Diastereomeric interactions between chiral carboxylato and chiral phosphine moieties resulting in different rates are clearly seen. Arrhenius plots of (+) and (-) DIOP [DIOP = 2,3 isopropylidene 2,3 dihydroxy-1,4bis (diphenylphosphino) butane] with rhodium (-) mandalato complex give markedly different activation energies.     

Chiral phosphoric acid-catalyzed asymmetric transfer hydrogenation of quinazolinones

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Chiral porous hybrid solids for practical heterogeneous asymmetric hydrogenation of aromatic ketones

Chiral porous zirconium phosphonates containing Ru-BINAP-DPEN moieties were synthesized via a molecular building-block approach, and characterized by a variety of techniques including TGA, adsorption isotherms, XRD, SEM, IR, and microanalysis. These hybrid solids were used for enantioselective heterogeneous asymmetric hydrogenation of aromatic ketones with remarkably high ee values of up to 99.2%. These solid catalysts can also be easily recycled and reused for eight times without the loss of activity and enantioselectivity. Ready tunability of such a molecular building-block approach will allow the optimization of these hybrid materials and promise to lead to other practically useful heterogeneous asymmetric catalysts.     

Chiral phosphine-phosphoramidite ligands for highly efficient Ir-catalyzed asymmetric hydrogenation of sterically hindered N-arylimines

A mild and general iridium-catalyzed, highly enantioselective hydrogenation of sterically hindered N-arylimines with a new H(8)-BINOL-derived phosphine-phosphoramidite ligand has been developed. The present catalytic system features high turnover numbers (up to 100000) and good to perfect enantioselectivities (up to 99% ee) for the hydrogenation of a variety of sterically hindered N-arylimines.     

Chiral carborane-derived thiophosphites: A new generation of ligands for Rh-catalyzed asymmetric hydrogenation

A new class of chiral monodentate ligands - carborane-containing thiophosphites have been synthesized and tested in the Rh-catalyzed asymmetric hydrogenation of prochiral olefins with the result of up to 99% ee. The dependence of the enantioselectivity on the electronic properties of the carboranyl substituent has been studied.     

Chiral phosphine-phosphite ligands in the highly enantioselective rhodium-catalyzed asymmetric hydrogenation.

We have investigated a series of enantiopure phosphine-phosphite ligands (P(1)-P(2) = ligands 1-4) in the rhodium-catalyzed asymmetric hydrogenation reaction. Intermediate [Rh(P(1)-P(2))(cod)]BF(4) and [Rh(P(1)-P(2))(5)]BF(4) complexes (cod = 1,5-cyclooctadiene; 5 = methyl acetamidoacrylate ester) were observed by (31)P[(1)H] NMR. The [Rh(P(1)-P(2))(cod)]BF(4) complexes were precursors to active catalysts of the asymmetric hydrogenation reaction of several prochiral dehydroamino acid derivatives under mild reaction conditions (1 bar of hydrogen and 20 degrees C). The enantiomeric excess reached up to 99%.     

Chiral hetero- and carbocyclic compounds from the asymmetric hydrogenation of cyclic alkenes

Several types of chiral hetero- and carbocyclic compounds have been synthesized by using the asymmetric hydrogenation of cyclic alkenes. N,P-Ligated iridium catalysts reduced six-membered cyclic alkenes with various substituents and heterofunctionality in good to excellent enantioselectivity, whereas the reduction of five-membered cyclic alkenes was generally less selective, giving modest enantiomeric excesses. The stereoselectivity of the hydrogenation depended more strongly on the substrate structure for the five- rather than the six-membered cyclic alkenes. The major enantiomer formed in the reduction of six-membered alkenes could be predicted from a selectivity model and isomeric alkenes had complementary enantioselectivity, giving opposite optical isomers upon hydrogenation. The utility of the reaction was demonstrated by using it as a key step in the preparation of chiral 1,3-cis-cyclohexane carboxylates.     

Chiral pyranoside phosphite-oxazolines: a new class of ligand for asymmetric catalytic hydrogenation of alkenes

We have described the first successful application of a phosphite-oxazoline ligand library in the asymmetric Ir-catalyzed hydrogenation of several unfunctionalized olefins. The introduction of a bulky biaryl phosphite moiety in the ligand design is highly adventitious in the product outcome. By carefully selecting the ligand components, we obtained high activities (TOFs up to >1500 mol x (mol x h)(-1) at 1 bar of H2) and enantioselectivities (ee values up to >99%) and, at the same time, show a broad scope for different substrate types. So, this is an exceptional ligand class that competes favorably with a few other ligand series that also provide high ee values for tri- and disubstituted substrate types.     

Chiral sulfur-containing ligands for iridium(I)-catalyzed asymmetric transfer hydrogenation of aromatic ketones

New efficient catalyst systems, coupled with IrCl(COD)PPh₃ and chiral [SNNS]-type ligands, were employed in the asymmetric transfer hydrogenation of aromatic ketones under mild reaction conditions. The corresponding optically active alcohols were obtained in high yield and good to excellent enantioselectivities (up to 96% ee). The chiral Ir(I) complexes with the ligands of [SNNS]-type were also prepared and characterized, which showed good enantioselectivity and high activity. The reactions can be performed in air and the catalytic experiments are greatly simplified.     

Chiral monophosphites derived from carbohydrate: conformational effect in catalytic asymmetric hydrogenation

[reaction: see text]. The carbohydrate-derived chiral monophosphites with additional groups have been synthesized and used for asymmetric hydrogenation of dimethyl itaconate and enamides. Up to 99.6% ee and 98.5% ee have been obtained, respectively.     

Chiral diphosphites derived from D-glucose: new highly modular ligands for the asymmetric catalytic hydrogenation

A series of novel diphosphite ligands derived from readily available D-(+)-glucose have been synthesized. These ligands were screened in the Rh-catalyzed hydrogenation of a series of alpha,beta-unsaturated carboxylic acid derivatives. Both excellent enantioselectivities (ee up to >99%) and activities were achieved. The advantage of these ligands is that their modular nature allows an easy systematic variation in the configuration of the stereocenters (C-3, C-5) at the ligand backbone and in the biaryl substituents, so the optimum configuration for maximum enantioselectivity in asymmetric hydrogenation can be determined. Results show that enantiomeric excesses depend strongly on the absolute configuration of C-3 and slightly on the stereocenter carbon C-5, while the sense of the enantiodiscrimination is predominantly controlled by the configuration of the biaryls at the phosphite moieties. Moreover, the presence of bulky substituents at the ortho-positions of the biaryl diphosphite moieties has a positive effect on enantioselectivity.     

Unusual deactivation in the asymmetric hydrogenation of itaconic acid

The formation of unusual Rh(III) substrate complexes from [Rh(DIPAMP)(MeOH)₂]BF₄ and itaconic acid has been detected which leads to the deactivation of the catalyst. The influence of different parameters on the formation of such complexes, namely substrate concentration, reaction time, temperature, acidic and basic additives, was investigated with different NMR methods. Two different Rh(III) substrate complexes are formed whose ratio is strongly dependent on substrate concentration and reaction time. The pH value of the solution shows a strong influence on the chemical shifts of the ³¹P NMR signals of such complexes. A catalyst-mediated esterification of itaconic acid in methanol was detected. Extended investigations provide detailed ¹H, ¹³C and ³¹P NMR data for the Rh(III) complexes and information about their stability in solution.     

Biomimetic asymmetric hydrogenation: in situ regenerable Hantzsch esters for asymmetric hydrogenation of benzoxazinones

A catalytic amount of Hantzsch ester that could be regenerated in situ by Ru complexes under hydrogen gas has been employed in the biomimetic asymmetric hydrogenation of benzoxazinones with up to 99% ee in the presence of chiral phosphoric acid. The use of hydrogen gas as a reductant for the regeneration of Hantzsch esters makes this hydrogenation an ideal atom economic process.