Asymmetric Hydrogenation Of Β-keto Esters Research Articles

Cinchona-Alkaloid-Derived NNP Ligand for Iridium-Catalyzed Asymmetric Hydrogenation of β-Keto Ester.

The Ir-catalyzed asymmetric hydrogenation of β-keto esters with Cinchona-alkaloid-derived NNP ligands has been developed. β-Hydroxy esters of opposite configuration were afforded smoothly with 91.5-99.1 and 81.6-99.3% ee, respectively, using NNP L2 and L7 derived from quinidine and quinine separately even on the gram scale. The protocol for the preparation of β-hydroxy esters of opposite configuration by the simple conversion of ligand configurations offered further opportunities for the synthesis of biologically active molecules and drugs.

Highly efficient and recyclable chiral phosphine-functionalized polyether ionic liquids for asymmetric hydrogenation of β-keto esters.

Herein, based on the concept of integration of phosphine ligands and ionic liquids (ILs), a class of chiral phosphine-functionalized polyether ionic liquids (CPF-PILs) were synthesized by ion-exchange reaction between polyether imidazolium ILs and a phenyl-sulfonated (S)-(-)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP) chiral diphosphine ligand, and employed in the Ru-catalyzed homogeneous asymmetric hydrogenation of β-keto esters. The resulting CPF-PILs combined the dual functions of the chiral phosphine ligand and ILs, allowing efficient recovery and recycling of the chiral catalysts using only a catalytic amount of CPF-PILs. The effects of various factors, including the chiral catalyst structure, solvent properties, reaction temperature, hydrogen pressure, and hydrobromic acid dosage, on catalytic performance were thoroughly investigated, as well as the cycling stability and universality of the chiral catalysts were examined. The findings of the present study demonstrated that, under optimal reaction conditions, the model substrate methyl acetoacetate underwent quantitative conversion to methyl β-hydroxybutyrate with a 97% enantiomeric excess (ee). The chiral catalyst used in this process can be recycled up to 12 times and showed good applicability to structurally various β-keto esters. The present study presents a novel approach for using ILs in asymmetric hydrogenation reactions in an environmentally friendly manner.

Synthesis and characterization of a high-purity chiral 5,5'-disulfonato-BINAP ligand and its application in asymmetric hydrogenation of β-keto esters

Abstract 2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (BINAP) is a widely used chiral phosphine ligand, and the sulfonated BINAP is one of the important water-soluble BINAP derivatives. In this article, we report an improved oleum sulfonation method for the synthesis of the high-purity 5,5′-disulfonato-(S)-BINAP ligand with an industrially acceptable high yield. By optimizing the sulfonation conditions and improving the workup process, the yield of 5,5′-disulfonated products was enhanced to 73 %. Furthermore, an acetonitrile extraction protocol was developed for the purification of sulfonated products by efficiently removing phosphine oxides, by which the content of phosphine oxide can be controlled below 3 %. The structure of 5,5′-disulfonato-(S)-BINAP was characterized with the elemental analysis, FT-IR, 1H NMR, 13C NMR, 31P NMR, 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC, and HR-MS, which unambiguously confirmed that the sulfo groups are introduced at the 5,5′-position of the binaphthyl ring skeleton in (S)-BINAP. The prepared high-purity 5,5′-disulfonato-(S)-BINAP was evaluated in the Ru-catalyzed asymmetric hydrogenation of β-keto esters, which exhibited high catalytic activity, enantioselectivity and excellent catalytic stability.

Iridium-catalyzed asymmetric hydrogenation of β-keto esters with new phenethylamine-derived tridentate P,N,N-ligands

A new class of phenethylamine-derived tridentate P,N,N-ligands has been successfully developed. These ligands exhibited good performance in the Ir-catalyzed asymmetric hydrogenation of β-keto esters, affording the corresponding β-hydroxy esters in moderate to good enantioselectivities.

Iridium-catalyzed asymmetric hydrogenation of β-keto esters with f-amphox ligands

ABSTRACTThe iridium-catalyzed asymmetric hydrogenation of β-keto esters with chiral tridentate P,N,N-ligands (f-amphox) has been developed. Under the optimized conditions, a wide range of β-keto esters can be hydrogenated smoothly, affording the corresponding β-hydroxy esters in good to excellent enantioselectivities (up to 95% ee).

Chiral BINAP-based hierarchical porous polymers as platforms for efficient heterogeneous asymmetric catalysis

Two vinyl-functionalized chiral 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP) ligands, (S)-4,4′-divinyl-BINAP and (S)-5,5′-divinyl-BINAP, were successfully synthesized. Chiral BINAP-based porous organic polymers (POPs), denoted as 4-BINAP@POPs and 5-BINAP@POPs, were efficiently prepared via the copolymerization of vinyl-functionalized BINAP with divinyl benzene under solvothermal conditions. Thorough characterization using nuclear magnetic resonance spectroscopy, thermogravimetric analysis, extended X-ray absorption fine structure analysis, and high-angle annular dark-field scanning transmission electron microscopy, we confirmed that chiral BINAP groups were successfully incorporated into the structure of the materials considered to contain hierarchical pores. Ru was introduced as a catalytic species into the POPs using different synthetic routes. Systematic investigation of the resultant chiral Ru/POP catalysts for heterogeneous asymmetric hydrogenation of β-keto esters revealed their excellent chiral inducibility as well as high activity and stability. Our work thereby paves a path towards the use of advanced hierarchical porous polymers as solid chiral platforms for heterogeneous asymmetric catalysis.

Microfluidic chip reactor and the stereoselective hydrogenation of methylacetoacetate over (R)-Ru-BINAP in the [N8222][Tf2N]/methanol/water mixed phase

Homogeneous asymmetric catalysts represented by organometallics of transition elements reveal very high activity and stereoselectivity in asymmetric hydrogenation of β-ketoesters. Recently, it appeared efficient to use ionic liquids of the [NR222][Tf2N] type for accommodation of the chiral catalytic complex. Even on the industrial scale it is becoming attractive to carry out hydrogenations with such immobilised complexes in a continuous regime in microreactors. Attention was paid to the stereoselective hydrogenation of methylacetoacetate (MAA) to isomeric (R)−(+) or (S)−(−)-methyl-3-hydroxybutanoates over a chiral ([RuCl((R)-BINAP)(p-cymene)]Cl) complex immobilised in the mixed [N8222][Tf2N]/methanol/water solvent phase, and performed inside of a microfluidic chip reactor. It was shown that the reaction could be successfully carried out in such an arrangement with a very high enantioselectivity (above 99%) and at very high conversion of MAA (above 97%). It was proven that the participation of a specific solvent (methanol or the mixture [N8222][Tf2N]/methanol/water) essentially influences the mechanism of the reaction. The solvents actively participate in the re-coordination of the catalytic complex in a series of reactions which is reflected in the values of reaction enthalpies. The specific process output was also evaluated.

Ir-catalyzed asymmetric hydrogenation of β-keto esters with chiral ferrocenyl P,N,N-ligands

The Ir-catalyzed asymmetric hydrogenation of β-keto esters with chiral ferrocenyl P,N,N-ligands has been developed, providing the corresponding β-hydroxy esters in good to excellent enantioselectivities.

Illustrating Catalysis with Interlocking Building Blocks: A BINAP–Ruthenium Complex Catalyzed Asymmetric Hydrogenation

A unique method has been developed using an interlocking building-block model equipped with magnets to illustrate the catalytic asymmetric hydrogenation of β-keto esters by a BINAP–ruthenium complex to enhance students’ understanding of this process. A BINAP–ruthenium block model, mimicking the coordination environment around the metal center in the real complex, can be used to convert the β-keto ester model into a β-hydroxy ester model. This model was used to provide a greater understanding of the essence of the catalytic reaction and to assist students in their understanding of its mechanism.

A new class of tunable dendritic diphosphine ligands: synthesis and applications in the Ru-catalyzed asymmetric hydrogenation of functionalized ketones.

A series of tunable G0-G3 dendritic 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP) ligands was prepared by attaching polyaryl ether dendrons onto the four phenyl rings on the P atoms. Their ruthenium complexes were employed in the asymmetric hydrogenation of β-ketoesters, α-ketoesters, and α-ketoamides to reveal the effects of dendron size on the catalytic properties. The second- and third-generation catalysts exhibited excellent enantioselectivities, which are remarkably higher than those obtained from the small molecular catalysts and the first-generation catalyst. Molecular modeling indicates that the incorporation of bulky dendritic wedges can influence the steric environments around the metal center. In addition, the ruthenium catalyst bearing a second-generation dendritic ligand could be recycled and reused seven times without any obvious decrease in enantioselectivity.

Synthesis of BINAP ligands with imidazole tags for highly enantioselective Ru-catalyzed asymmetric hydrogenation of β-keto esters in ionic liquid systems

The imidazole-tagged BINAP ligands were synthesized and used for Ru-catalyzed asymmetric hydrogenation of β-keto esters in ionic liquid (IL) systems. The Ru-BINAP catalysts with the imidazolium tags show high catalytic activity and enantioselectivity, which closely parallel the performance of unmodified BINAP. The catalyst recycling experiments using [bmim]Tf2N/MeOH system demonstrated that introducing imidazolium moieties to the BINAP backbone can effectively enhance the affinity of the Ru-catalysts to the IL, reduce Ru leaching and improve catalysts stability, and after several cycles no significant loss of activity and enantioselectivity was observed.

Axial Chirality Control by 2,4‐Pentanediol for the Alternative Synthesis of C3*‐TunePhos Chiral Diphosphine Ligands and Their Applications in Highly Enantioselective Ruthenium‐Catalyzed Hydrogenation of β‐Keto Esters

AbstractA highly efficient strategy for the synthesis of a series of C3*‐TunePhos chiral diphosphine ligands was well established with several remarkable features. The synthetic utility of these ligands was explored for the ruthenium‐catalyzed asymmetric hydrogenation of β‐keto esters. Up to 99% ee values were achieved for the enantioselective synthesis of β‐hydroxy acid derivatives, which are very important chiral building blocks for the synthesis of a variety of natural products and biologically active molecules.

Quaternary ammonium salts ionic liquids for immobilization of chiral Ru-BINAP complexes in asymmetric hydrogenation of β-ketoesters

Chiral catalytic complex ( R)—[RuCl(binap)(p-cymene)]Cl was used in asymmetric hydrogenation of methyl acetoacetate to methyl-3-hydroxybutyrate in the mixed methanol-ionic liquid phase. Quaternary ammonium salts ionic liquids, namely n-alkyl-triethylammonium bis(trifluoromethane sulfonyl) imides (N R222 Tf 2N, R = 6, 7, 8, 10, 12, 14), were prepared and employed in this transformation. Enough evidence was provided that only a small amount of this type of IL in a conventional solvent was necessary to accommodate the catalytic complex and that the reaction could be carried out with very high enantioselectivity. Similarly it was proved that under optimized conditions the catalytic complex immobilized in this manner could be used repeatedly. A part of the work was focused on the role of the alkyl chain length in the N R222 Tf 2N ionic liquid which was found as very essential. Role of the reaction impurities with origin in the synthesis of the employed ILs was also investigated.

Chirally functionalized mesoporous organosilicas with built-in BINAP ligand for asymmetric catalysis

The chirally functionalized periodic mesoporous organosilica (PMO) with C2-symmetric chiral building blocks, BINAP (2,2′-bis(diphenylphosphino)-1,1′-binaphthyl), in the pore wall was successfully synthesized for the first time using a successive co-condensation and post-synthesis modification method. Chiral BINAPO (2,2′-bis(diphenylphosphinooxide)-1,1′-binaphthyl) bridging mesoporous organosilica with highly ordered 2-D hexagonal structure was first synthesized by co-condensation of (R)-5,5′-bis(3-triethoxysilylpropyl-1-ureyl)-2,2′-bis(diphenylphosphinooxide)-1,1′-binaphthy with tetramethoxylsilane in the presence of block copolymer P123 as template under weakly acidic conditions. The BINAPO in the pore wall of PMO was reduced with trichlorosilane to generate BINAP using a post-synthesis modification method. The chiral PMO with built-in BINAP (coordination with [RuCl2-(benzene)]2) is an efficient solid catalyst for the asymmetric hydrogenation of β-keto esters with ee as high as 99%, which is among the highest ever reported for the chirally functionalized PMOs in asymmetric catalysis.

General Enantioselective Synthesis of Butyrolactone Natural Products via Ruthenium‐SYNPHOS®‐Catalyzed Hydrogenation Reactions

AbstractEnantioselective syntheses of several paraconic acids have been achieved using catalyzed asymmetric hydrogenation of β‐keto esters with SYNPHOS® as a ligand. This strategy allowed the short synthesis of biologically active (−)‐methylenolactocin 1, (−)‐protolichesterinic acid 2, (−)‐phaseolinic acid 3 and (+)‐roccellaric acid 4.

Total synthesis of dolastatin 10 through ruthenium-catalyzed asymmetric hydrogenations

A total synthesis of dolastatin 10, a potent inhibitor of microtubule assembly, which displayed remarkable antineoplastic activity, is reported. Our synthetic approach was based upon ruthenium-promoted asymmetric hydrogenation of β-keto esters derived from ( S)-Boc-proline and ( S)-Boc-isoleucine for the construction of the two key units: (2 R,3 R)-Boc-dolaproine (Dap) and (3 R)-Boc-dolaisoleucine (Dil).

Highly Enantioselective Catalytic Asymmetric Hydrogenation of β‐Keto Esters in Room Temperature Ionic Liquids.

AbstractFor Abstract see ChemInform Abstract in Full Text.

The role of the solvent in the asymmetric hydrogenation of β-keto esters with Ru-BINAP

The influence of the solvent on the asymmetric hydrogenation of methyl acetoacetate, as a representative β-keto esters, with Ru-BINAP was studied. The highest activities were measured when the reaction proceeded in methanol, ethanol or isopropanol. These solvents, which also act as proton donors, accelerate product release from the reaction intermediate. The presence of water in the reaction mixture has been found to be detrimental for both activity and enantioselectivity. All results could be explained by the existence of two different solvent dependent reaction pathways for product release.

Highly enantioselective catalytic asymmetric hydrogenation of beta-keto esters in room temperature ionic liquids.

Polar phosphonic acid-derived Ru-BINAP systems were used to catalyze asymmetric hydrogenation of beta-keto esters in room temperature ionic liquids (RTILs) with complete conversions and ee values higher than those obtained from homogeneous reactions in MeOH (up to 99.3%), and were recycled by simple extraction and used for four times without the loss of activity and enantioselectivity.

A RAIRS, STM and TPD study of the Ni [formula omitted]/ R, R-tartaric acid system: Modelling the chiral modification of Ni nanoparticles

Asymmetric hydrogenation of β-keto esters over chirally modified Ni catalysts is a rare example of a heterogeneously catalysed enantioselective process. To date, little is known on a fundamental level about the surface of Ni nanoparticles following adsorption of the chiral modifier, e.g. R, R-tartaric acid. We report an investigation of the adsorption of R, R-tartaric acid onto a model catalyst surface, Ni{1 1 1}. We show that the two-dimensional packing, molecular conformation and thermal stability of the modified surfaces are all inextricably linked and critically dependent on sample temperature, arrival rate of the modifiers at the surface and the presence or absence of coadsorbed CO. We report the formation of ordered adlayers of tartrate species whose thermal stability increases with increasing coverage and is also dependent on adsorption temperature.