Rhodium-Catalyzed Enantioselective Hydrogenation Research Articles

A new easily accessible chiral phosphite–phosphoramidite ligand based on 2-anilinoethanol and R-BINOL moieties for Rh-catalyzed asymmetric olefin hydrogenation

A novel chiral phosphite–phosphoramidite ligand based on 2-anilinoethanol and R-BINOL moieties has been synthesized in one-pot. The ligand was evaluated in the rhodium-catalyzed enantioselective hydrogenation of α- and β-dehydroamino acid derivatives and dimethyl itaconate in three different solvents at 25 °C, at 1 or 50 bar of hydrogen pressure. The solvent and the pressure effect are discussed.

Design and Preparation of a Chiral Ligand Based on a Pseudorotaxane Skeleton: Application to Rhodium-Catalyzed Enantioselective Hydrogenation of Enamides

We have prepared a novel pseudorotaxane molecule which works as a chiral bidentate ligand having a phosphine moiety in an axle and a phosphite moiety in a wheel as two coordination sites and applied it successfully to the rhodium-catalyzed enantioselective hydrogenation of enamides (up to 96% ee). To the best of our knowledge, this is the first successful example of the use of the pseudorotaxane molecule as a chiral ligand for homogeneous transition-metal-catalyzed asymmetric reactions.

Josiphos Ligands with an Imidazolium Tag and their Application for the Enantioselective Hydrogenation in Ionic Liquids

AbstractJosiphos ligands bearing an imidazolium moiety show high efficiency and reusability for the rhodium‐catalyzed enantioselective hydrogenation of methyl acetamidoacrylate (MAA) and dimethyl itaconate (DMI) in biphasic co‐solvent/ionic liquid combinations.

Enantioselective rhodium-catalyzed hydrogenation of enol carbamates in the presence of monodentate phosphines

The rhodium-catalyzed asymmetric hydrogenation of different acyclic and cyclic enol carbamates to give optically active carbamates has been examined in the presence of chiral monodentate ligands based on a 4,5-dihydro-3 H-dinaphthophosphepine motif 4. The enantioselectivity is largely dependent upon the reaction conditions, the nature of substituents on the phosphorus ligand and structure of the enol carbamate. By applying the optimized reaction conditions, enantioselectivities of up to 96% ee have been achieved.

Hydrogen Bonding Makes a Difference in the Rhodium-Catalyzed Enantioselective Hydrogenation Using Monodentate Phosphoramidites

A new generation of monodentate phosphoramidite ligands bearing a primary amine moiety was found to display comparable or better efficiency than bisphosphines in the Rh-catalyzed asymmetric hydrogenation of challenging substrates, such as (Z)-methyl alpha-acetoxyacrylate or (E)-beta-aryl itaconate derivatives, affording the corresponding hydrogenation products with excellent enantioselectivities (up to >99% ee). The presence of intermolecular hydrogen bonding (HB) between two monodentate ligands in the catalyst was found to be critical for excellent catalyst performance. This finding provides a basis for design and development of further catalyst systems using this type of monodentate phosphoramidite ligands.

Readily Available Phosphine−Phosphoramidite Ligands for Highly Efficient Rh-Catalyzed Enantioselective Hydrogenations

A new family of air- and moisture-stable phosphine-phosphoramidite ligands (PEAPhos) has been prepared from commercially available and inexpensive (S)-alpha-phenylethylamine through a two- or three-step transformation and successfully applied in the rhodium-catalyzed enantioselective hydrogenations of a variety of substrates, in which up to 99.9% ee was obtained for all of these kinds of substrates.

Rhodium-Catalyzed Enantioselective Hydrogenation of β-Phthalimide Acrylates to Synthesis of β2-Amino Acids

[Structure: see text] The enantioselective hydrogenation of beta-phthalimide acrylates provides the corresponding chiral beta2-amino acids in excellent enantiomeric excess catalyzed by Rh-monophosphorus.

Rhodium-catalyzed enantioselective hydrogenation of ketopantolactone

Hydrogenation of ketopantolactone was investigated on a 5 wt.% Rh/Al 2O 3 catalyst modified by cinchonidine (CD) and its O-methyl (MeOCD) and O-phenyl (PhOCD) derivatives. Weakly polar solvents, moderate pressure, and relatively high modifier/substrate ratios were advantageous for enantioselection. Chiral modification resulted in significant rate acceleration. The major enantiomer was ( R)-pantolactone in the presence of CD and MeOCD, while an inversion was observed when using the bulky PhOCD. The similar ees measured with CD and MeOCD indicated that the OH function of CD is not involved in the enantioselection. The nonlinear behaviour of CD–PhOCD mixtures is probably due to the weaker adsorption of the latter modifier on rhodium. The highest ee achieved in this study with CD was 40%, less than half of that reported for CD-modified platinum. The lower efficiency of the rhodium–cinchona system is attributed partly to the weaker adsorption of the modifier and the faster hydrogenation of the quinoline ring of the alkaloid resulting in a gradual loss of enantioselectivity at high pressures.

Modular Monodentate Phosphoramidite Ligands for Rhodium-Catalyzed Enantioselective Hydrogenation

A new class of monodentate phosphoramidite ligands (DpenPhos) has been developed on the basis of the modular concept for Rh(I)-catalyzed asymmetric hydrogenations of a variety of olefin derivatives, affording the corresponding optically active compounds in excellent yields and enantioselectivities. The ligands have the advantages of facile preparation, tunable structure, and broad scope of substrates in their Rh(I) complex-catalyzed asymmetric hydrogenations.

Rhodium-Catalyzed Enantioselective Hydrogenation of β,β-Disubstituted α-Acetamido Acrylates Using Cheap Monodentate P-Ligands

The asymmetric Rh-catalyzed hydrogenation of β,β-disubstituted α-acetamido acrylates, which are notoriously difficult substrates, is possible using readily available BINOL-derived monodentate phosphites or phosphonites. Essentially quantitative conversion and enantioselectivities of 95-97% ee are readily achieved, making the process industrially viable.

New efficient synthesis of Taniaphos ligands: application in ruthenium- and rhodium-catalyzed enantioselective hydrogenations

A third generation of Taniaphos 1,5-diphosphine ferrocene ligands with the new and interesting ( S Fc,3 S)- and ( R Fc,3 R)-configurations has been prepared. With these ligands, the ruthenium-catalyzed hydrogenation of CO bonds proceeded with high diastereo- and enantioselectivity (up to >99% de and 97% ee). Good results were also obtained for the rhodium-catalyzed hydrogenation of CC (up to 96% ee) and CN bonds (up to 65% ee).

Chiral Monophosphites and Monophosphonites as Ligands in Asymmetric Transition Metal Catalysis.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Enantioselective hydrogenation of itaconate using rhodium bihelicenol phosphite complex. Matched/mismatched phenomena between helical and axial chirality

Phosphites prepared from bihelicenol, menthol (or 1-phenylethanol), and PCl 3 are effective ligands for the rhodium-catalyzed enantioselective hydrogenation of dimethyl itaconate. Stereochemistry of the helicene moiety plays an important role in the asymmetric induction, and matched/mismatched phenomena are observed between helical and axial chirality.

Chiral monophosphites and monophosphonites as ligands in asymmetric transition metal catalysis

Chiral monophosphites, monophosphonites derived from BINOL are more effective ligandsin enantioselective rhodium-catalyzed hydrogenation of olefins, as compared to bidentate bis-phosphites.An appreciable increase in enantioselectivity is attained with the use of mixtures of two different monodentate phosphites and phosphonites in rhodium-catalyzed hydrogentation.

Highly enantioselective rhodium-catalyzed hydrogenation of beta-dehydroamino acid derivatives using monodentate phosphoramidites.

New and very easily accessible monodentate phosphoramidite ligands have been developed that lead to excellent ee's and full conversions in the hydrogenation of (E)- and (Z)-beta-dehydroamino acid derivatives with both aliphatic and aromatic side chains. Particularly, two different catalytic systems were established for (E)-beta-(acylamino)acrylates (98-99% ee) and (Z)-beta-(acylamino)acrylates (92-95% ee) based on phosphoramidites 2 and 3, respectively.

Electronic Differences between Coordinating Functionalities of Chiral Phosphine−Phosphites and Effects in Catalytic Enantioselective Hydrogenation

A convenient synthesis of new chiral phosphine−phosphites (P−OP) has been described. The versatility of the synthetic protocol developed has allowed the preparation of ligands with different phosphine fragments and the choice of the stereogenic element location. Analyses of the values of 1JPSe of the corresponding diselenides are in accord with the expected lower σ-donor ability of the phosphite fragment, with respect to the phosphine group, and with an increase of phosphine basicity after substitution of phenyl substituents by methyl groups. Inspection of υ(CO) values on a series of complexes RhCl(CO)(P−OP) demonstrated a variable π-aceptor ability of the phosphite group, compensating for the change of basicity of the phosphine functionality, as well as having a rather reduced electron density at the metal center compared with diphosphine analogues. The distinct nature of the phosphorus functionalities has also been evidenced in rhodium-catalyzed enantioselective hydrogenation of methyl Z-α-acetamido-cinnamate (MAC). Thus, the coordination mode of the substrate is governed by the chiral ligand, directing the olefinic bond to a cis position with respect to the phosphite group, as demonstrated by NMR studies performed with [Rh(P−OP)(MAC)]+ complexes. In consequence, the phosphite group has a greater impact on the enantioselectivity of the product. However, the optical purity of the process also depends on the nature of the phosphine group, and hence, an appropriate election of both phosphorus functionalities is required for the attainment of excellent enantioselectivities (99% ee).

Monodentate Chiral Spiro Phosphoramidites: Efficient Ligands for Rhodium-Catalyzed Enantioselective Hydrogenation of Enamides

Monodentate Chiral Spiro Phosphoramidites: Efficient Ligands for Rhodium-Catalyzed Enantioselective Hydrogenation of Enamides

Monodentate chiral spiro phosphoramidites: efficient ligands for rhodium-catalyzed enantioselective hydrogenation of enamides.

Monodentate phosphorus ligands, too, can be effective: Chiral amine derivatives can be obtained in high enantioselectivities (up to 99.7 % ee) by the asymmetric hydrogenation of enamides in the presence of rhodium complexes of the chiral spiro phosphorus ligands (S)-1, the first monodentate P ligands that are effective in this class of reactions.

An enantioselective synthesis of ( R)-4-piperidinylglycine

An efficient process for the synthesis of ( R)- N- t-Boc-4-piperidinylglycine 8a, an unnatural amino acid, via enantioselective rhodium-catalyzed hydrogenation of the Cbz-enamide 5a is described. Subsequent deprotection of 8a affords unprotected ( R)-4-piperidinylglycine 9 in good yield.

ChemInform Abstract: Rhodium-Catalyzed Enantioselective Hydrogenation Using Chiral Monophosphonite Ligands.

Abstract Surprisingly high enantioselectivities in the Rh-catalyzed hydrogenation of itaconic acid dimethyl ester and methyl-2-acetamido acrylate are observed upon using chiral monophosphonite ligands derived from binaphthol (ee up to 94%). Although appropriate chelating diphosphonites are more effective, the easy modular synthesis of the chiral monophosphonites may allow for the optimization of a given asymmetric hydrogenation reaction.