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%.     

Monophosphite ligands derived from carbohydrates and H8-BINOL: highly enantioselective Rh-catalyzed asymmetric hydrogenations

A series of monophosphite ligands derived from carbohydrates and H₈-BINOL have been synthesized. Excellent enantioselectivities (over 99% ee) were obtained when these ligands were applied in the Rh-catalyzed asymmetric hydrogenation of dimethyl itaconate and enamides.     

Novel phosphine-phosphite and phosphine-phosphinite ligands for highly enantioselective asymmetric hydrogenation

Two novel phosphine-phosphite (S,R)-o-BINAPHOS and phosphine-phosphinite (S)-o-BIPNITE ligands based on ortho phenyl substituted (S)-BINOL have been synthesized. Extremely high enantioselectivity (over 99% ee in most cases) has been achieved for the Rh-catalyzed asymmetric hydrogenation of α-dehydroamino acid derivatives.     

Highly enantioselective Rh-catalyzed transfer hydrogenation of N-sulfonyl ketimines

Several imine species comprising N-sulfinyl and N-sulfonyl ketimine, oxime, and enamine derivatives were subjected to asymmetric transfer hydrogenation in an azeotropic mixture of formic acid/triethylamine. Among them, the Rh-catalyzed transfer hydrogenation of N-sulfonyl ketimine afforded the corresponding 1-arylalkylamines in excellent yield and with high enantioselectivity.     

New unsymmetrical hybrid ferrocenylphosphine-phosphoramidite ligands derived from H8-BINOL for highly efficient Rh-catalyzed enantioselective hydrogenation

A series of new H₈-BINOL-derived unsymmetrical hybrid ferrocenylphosphine-phosphoramidite ligands have been synthesized and successfully used in Rh-catalyzed asymmetric hydrogenations. The same or higher enantioselectivities (99.9% ee) were achieved in the hydrogenation of dimethyl itaconate and α-dehydroamino acid esters as those obtained with BINOL-derived analogues. However, slightly lower enantioselectivities (99.0% ee) were obtained in the hydrogenation of enamides.     

Cymantrene-derived monodentate phosphites: New ligands for Rh-catalyzed enantioselective hydrogenation

Novel chiral monodentate phosphite ligands bearing cymantrene fragment have been prepared. Phosphite 4 with PPh₃, instead of CO-ligand, in cymantrene moiety provided higher enantioselectivity than its unsubstituted analogue 3 in hydrogenation of (Z)-methyl-2-acetamido-3-phenylacrylate.     

Application of phosphine-phosphite ligands in the iridium catalyzed enantioselective hydrogenation of 2-methylquinoline

The hydrogenation of 2-methylquinoline with Ir catalysts based on chiral phosphine-phosphites has been investigated. It has been observed that the reaction is very sensitive to the nature of the ligand. Optimization of the catalyst, allowed by the highly modular structure of these phosphine-phosphites, has improved the enantioselectivity of the reaction up to 73% ee. The influence of additives in this reaction has also been investigated. Contrary to the beneficial influence observed in related catalytic systems, iodine has a deleterious effect in the present case. Otherwise, aryl phosphoric acids produce a positive impact on catalyst activity without a decrease on enantioselectivity.     

P/S ligands derived from carbohydrates in Rh-catalyzed hydrosilylation of ketones

Reported is the synthesis of a number of diastereomerically pure cationic Rh(I)-complexes I starting from phosphinite thioglycosides. These complexes were used in the asymmetric hydrosilylation of prochiral ketones. The reactivity and enantioselectivity of the reaction was shown to be dependent on the pyranose ring, the substituent at the sulfur atom, the hydroxylic protective groups and most significantly on the alkene co-ligand.     

Highly enantioselective hydrogenation of enol ester phosphonates catalyzed by rhodium phosphine-phosphite complexes

Chiral phosphine-phosphites provide versatile catalysts for the highly enantioselective hydrogenation of alpha-acyloxy alpha, beta-unsaturated phosphonates.     

Readily available, recoverable and soluble polymer-monophosphite ligands for highly enantioselective Rh-catalyzed hydrogenation

A new family of readily available, recoverable and soluble polymer-monophosphite ligands were prepared and successfully used in the Rh-catalyzed asymmetric hydrogenation of enamides and beta-dehydroamino acid esters, in which up to 99 and 99.9% ee were obtained, respectively.     

Readily available chiral phosphine–aminophosphine ligands derived from 1-phenylethylamine for Rh-catalyzed enantioselective hydrogenations

A series of new chiral phosphine–aminophosphine ligands have been prepared via a two- or three-step transformation from commercially available and inexpensive (S)-1-phenylethylamine, and successfully used in the rhodium-catalyzed asymmetric hydrogenation of various enamides, β-dehydroamino acid esters, and dimethyl itaconate. The results show that the ligand structure plays an important influence on both the reactivity and enantioselectivity. Ligand 2d bearing a N–H proton and two F-atoms on the 3,5-positions of the phenyl ring of the aminophosphino moiety was most effective for the hydrogenation of enamides and (Z)-β-aryl-β-(acylamino)acrylates, whereas ligand 1b showed the highest enantioselectivities in the hydrogenation of (Z)-β-alkyl-β-(acylamino)acrylates and dimethyl itaconate.     

New chiral 1,3-diphosphine ligands for Rh-catalyzed enantioselective hydrogenation: a search for electronic effects

New electron-rich chiral 1,3-diphosphines of the BDPP type were prepared from 1,3-diphenylpropane-1,3-diol by an economically feasible synthetic approach. The σ-donor properties of the phosphines were determined by measurement of J(³¹P–⁷⁷Se) coupling constants in the corresponding phosphine selenides. For comparison related, but electronically different, 1,3-diphosphines were considered. The new diphosphines showed good enantioselectivities as ligands in the Rh-catalyzed enantioselective hydrogenation of benchmark substrates and β-amino acid precursors (up to 98% ee). The electronic effects on the outcome of the enantioselective catalysis have been analyzed.     

New chiral phosphine-phosphite ligands in the enantioselective palladium-catalyzed allylic alkylation

A series of chiral phosphine-phosphite ligands 1-6 have been synthesized and used in the enantioselective palladium-catalyzed reaction of rac-1,3-diphenyl-2-propenyl acetate with dimethyl malonate as nucleophile. Ligands 1a, 2, 3, 5a, 6a, and 6b have been synthesized starting from racemic tert-butylphenylphosphinoborane. The use of dynamically resolved Li phosphide (-)-sparteine provided the optically pure ligands. Crystals of the allylpalladium (6a) complex were obtained, suitable for X-ray crystal structure determination. The X-ray crystal structure of the allylpalladium (6a) complex revealed a longer palladium-carbon bond distance trans to the phosphine moiety indicating that the attack of the nucleophile takes place at the carbon trans to the phosphine moiety. This was confirmed by the fact that the phosphine moiety did not affect the enantioselectivity directly. Under mild reaction conditions, enantioselectivities up to 83% were obtained (25 degrees C) with ligand 1e. Systematic variation of the ligand bridge and the phosphite moiety showed that the configuration of the product is controlled by the atropisomerism of the biphenyl substituent at the phosphite moiety. The conformation of the biphenyl group, in turn, is controlled by the substituent at the chiral carbon in the bridge. Ligands with large bite angles yielded higher enantioselectivities.     

New modular P-chiral ligands for Rh-catalyzed asymmetric hydrogenation

New modular P-chiral ligands have been prepared from commercially available (S)-α,α-diphenylprolinol. With these new types of ligands, up to 95% ee was achieved in the Rh-catalyzed asymmetric hydrogenation of functionalized olefins.     

Carboranylphosphites as new ligands for Rh-catalyzed asymmetric hydrogenation

First representatives of chiral carborane-based phosphite ligands were synthesized. The enantiomeric excess in the Rh-catalyzed hydrogenation of dimethyl itaconate with the use of these ligands reaches 67% in CH₂Cl₂ and 62% in supercritical CO₂, the ee and conversion being strongly dependent on the hydrogen pressure. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 337–340, February, 2008.     

A novel class of P-O monophosphite ligands derived from D-mannitol: broad applications in highly enantioselective Rh-catalyzed hydrogenations

We report on a new class of P-O monophosphite ligands (designated 3a-k) with a double six-membered-ring backbone onto which are attached additional groups and on applications of their Rh complexes in the hydrogenation of enamides, alpha-dehydroamino acid esters, dimethyl itaconate, and beta-(acylamino)acrylates. Our results demonstrate that the Rh complexes with ligands 3a-k exhibit high enantioselectivity and reactivity in asymmetric hydrogenation reactions. An ee value of up to 98.0% was obtained for the hydrogenation of alpha-dehydroamino acid esters, and the ee values were all over 99% for the other three types of substrate, with a turnover number of up to 5000.     

Asymmetric synthesis of chiral Roche ester and its derivatives via Rh-catalyzed enantioselective hydrogenation with chiral phosphine-phosphoramidite ligands

Methyl 3-hydroxy-2-methylpropionate, known as the Roche ester, was prepared with high enantioselectivity (up to 96.7% ee) via the Rh-catalyzed asymmetric hydrogenation of methyl 2-hydroxymethylacrylate with a chiral 1,2,3,4-tetrahydro-1-naphthylamine-derived phosphine-phosphoramidite ligand (THNAPhos 5a) even at a low catalyst loading (0.1 mol %). An investigation on the substrate scope revealed that the ester group present in the substrate has a significant effect on the enantioselectivity, and the substrate with the bulkier ester group tended to give lower enantioselectivity.     

C2-symmetric diphosphinite ligands derived from carbohydrates. The strong influence of remote stereocenters on asymmetric rhodium-catalyzed hydrogenation

Modular ligands of C(2) symmetry (13a-e, 14a,b,d, and ent-9), systematically modified at positions 2 and 5, were easily prepared from d-glucosamine, D-glucitol, and tartaric acid, respectively. The application of these ligands in the rhodium-catalyzed hydrogenation of methyl acetamidoacrylate, methyl acetamidocinnamate, and dimethyl itaconate shows that both the configuration and the substituents at positions 2 and 5 of the tetrahydrofuran backbone have a strong influence on the enantioselectivty of the processes.     

Synthesis of novel chiral monophosphine ligands derived from isomannide and isosorbide. Application to enantioselective hydrogenation of olefins

A new class of monophosphine ligands has been prepared from natural chirality renewable source, 1,4:3,6-dianhydrohexitol compounds, via a nucleophilic substitution process, or a hydrophosphination reaction involving microwave activation. These ligands have been evaluated for the rhodium-catalyzed enantioselective hydrogenation of olefins giving good conversion and enantioselectivity up to 95% and 96% ee, respectively.