Asymmetric hydrogenation on chirally modified Pt: origin of hydrogen in the N-H-O interaction between cinchonidine and ketone

An understanding of the chiral site-substrate interaction is a necessary prerequisite for the rational design and development of efficient heterogeneous asymmetric catalysts. For the enantioselective hydrogenation of α-ketoesters on cinchona-modified platinum, it has earlier been proposed that the crucial interaction is an N-H-O type hydrogen bonding between the quinuclidine N atom of cinchonidine and the α-carbonyl O atom of the substrate. The involved hydrogen atom has been proposed to originate either from protonation (in protic solvent) or from dissociatively adsorbed hydrogen (in aprotic solvent), but experimental evidence for the latter was lacking so far. In this study, in situ attenuated total reflection infrared spectroscopy combined with modulation excitation spectroscopy and phase sensitive detection provides clear evidence that in aprotic media, hydrogen dissociated on Pt is involved in the N-H-O interaction between the chiral modifier, cinchonidine, and the ketone. In the absence of Pt (pure alumina support), no such interaction occurs, indicating the crucial role of dissociated hydrogen in the formation of the diastereomeric transition complex.     

Monitoring Surface Processes During Heterogeneous Asymmetric Hydrogenation of Ketones on a Chirally Modified Platinum Catalyst by Operando Spectroscopy

Surface processes occurring at the catalytic chiral surface of a cinchona‐modified Pt catalyst during the asymmetric hydrogenation of activated ketones have been monitored for the first time using operando ATR‐IR spectroscopy. Fundamental information about this catalytic system could be gained, including the chiral modification process of the catalyst, the surface interaction of reactant ketone with preadsorbed chiral modifier, the role of hydrogen as well as the influence of the product enantiomers in the catalytic cycle. The formation of a diastereomeric transient surface complex between ketone and chiral modifier was found to be related to the ketone consumption. Among the studied activated ketones, a correlation between stereoselection and the strength of the intermolecular hydrogen bond was identified. Dissociated hydrogen from the catalytic surface is found to play a crucial role in the formation of the diastereomeric surface complex.     

Competition at chiral metal surfaces: fundamental aspects of the inversion of enantioselectivity in hydrogenations on platinum

O-Phenylcinchonidine (PhOCD) is known to efficiently induce inversion of enantioselectivity with respect to cinchonidine (CD) in the enantioselective hydrogenation of various activated ketones on Pt/Al(2)O(3). To understand the origin of the switch of enantioselective properties of the catalyst, the adsorption of PhOCD has been studied by in situ ATR-IR spectroscopy, in the presence of organic solvent and dissolved hydrogen, i.e., under conditions used for catalytic hydrogenation. The adsorption structures and energies of the anchoring group of CD and PhOCD were calculated on a Pt 38 cluster, using relativistically corrected density functional theory (DFT). Both approaches indicate that both modifiers are adsorbed via the quinoline ring and that the spatial arrangement of the quinuclidine skeleton is critical for the chiral recognition. New molecular level information on the conformation of CD relative to PhOCD adsorbed on a surface is extracted from the ATR spectra and supported by DFT calculations. The result is a clearer picture of the role played by the phenyl group in defining the chiral space created by the modifiers on Pt. Moreover, when CD was added to a pre-equilibrated adsorbed layer of PhOCD, a chiral adsorbed layer was formed with CD as the dominant modifier, indicating that CD adsorbs more strongly than PhOCD. Conversely, when PhOCD was added to preadsorbed CD, no significant substitution occurred. The process leading to nonlinear effects in heterogeneous asymmetric catalysis has been characterized by in situ spectroscopy, and new insight into a heterogeneous catalytic R-S switch system is provided.     

Rhodium-catalyzed asymmetric hydrogenation through dynamic kinetic resolution: asymmetric synthesis of anti-β-hydroxy-α-amino acid esters

Rhodium-catalyzed asymmetric hydrogenation of α-amino-β-keto ester hydrochlorides through dynamic kinetic resolution is described. The hydrogenation proceeds with the catalyst derived from a Rh complex and a chiral ferrocenylphosphine under hydrogen in the presence of sodium acetate in acetic acid to afford anti-β-hydroxy-α-amino acid esters with 58–83% ee in a diastereomeric ratio of 92:8–97:3.     

A Cinchona Alkaloid‐Functionalized Mesostructured Silica for Construction of Enriched Chiral β‐Trifluoromethyl‐β‐Hydroxy Ketones over An Epoxidation‐Relay Reduction Process

A cinchona alkaloid‐functionalized heterogeneous catalyst is prepared through a thiol‐ene click reaction of chiral N‐(3,5‐ditrifluoromethylbenzyl)quininium bromide and a mesostructured silica, which is obtained by co‐condensation of 1,2‐bis(triethoxysilyl)ethane and 3‐(triethoxysilyl)propane‐1‐thiol. Structural analyses and characterizations disclose its well‐defined chiral single‐site active center, and electron microscopy images reveal its monodisperse property. As a heterogenous catalyst, it enables an efficient asymmetric epoxidation of achiral β‐trifluoromethyl‐β,β‐disubstituted enones, the obtained chiral products can then be converted easily into enriched chiral β‐trifluoromethyl‐β‐hydroxy ketones through a sequential epoxidation‐relay reduction process. Furthermore, such a heterogeneous catalyst can be recovered conveniently and reused in asymmetric epoxidation of 4,4,4‐trifluoro‐1,3‐diphenylbut‐2‐enone, showing an attractive feature in a practical construction of enriched chiral β‐CF₃‐substituted molecules.     

Catalytic Enantioselective Amination of Alcohols by the Use of Borrowing Hydrogen Methodology: Cooperative Catalysis by Iridium and a Chiral Phosphoric Acid

The catalytic asymmetric reduction of ketimines has been explored extensively for the synthesis of chiral amines, with reductants ranging from Hantzsch esters, silanes, and formic acid to H₂ gas. Alternatively, the amination of alcohols by the use of borrowing hydrogen methodology has proven a highly atom economical and green method for the production of amines without an external reductant, as the alcohol substrate serves as the H₂ donor. A catalytic enantioselective variant of this process for the synthesis of chiral amines, however, was not known. We have examined various transition‐metal complexes supported by chiral ligands known for asymmetric hydrogenation reactions, in combination with chiral Brønsted acids, which proved essential for the formation of the imine intermediate and the transfer‐hydrogenation step. Our studies led to an asymmetric amination of alcohols to provide access to a wide range of chiral amines with good to excellent enantioselectivity.     

Asymmetric Hydrogenation of α-Hydroxy Ketones: A Reaction Sensitive toward Electronic Effect of Substrates

以[RuCl2(benzene)]2 和 SunPhos为原料现场制备的催化剂,催化不对称氢化α-羟基酮类化合物可获得手性1, 2-二醇类化合物,ee值最高达99%。     

Palladium/Zinc Co-Catalyzed Asymmetric Hydrogenation of γ-Keto Carboxylic Acids

A palladium-catalyzed asymmetric hydrogenation of levulinic acid has been successful developed by using Zn(OTf)₂ as co-catalyst. The present method not only has provided a strategy in the palladium-catalyzed asymmetric hydrogenation of ketone, but also allowed the preparation of a wide range of chiral γ-valerolactones in good yields with excellent enantioselectivities.     

Asymmetric Hydrogenations (Nobel Lecture)

The start of the development of catalysts for asymmetric hydrogenation was the concept of replacing the triphenylphosphane ligand of the Wilkinson catalyst with a chiral ligand. With the new catalysts, it should be possible to hydrogenate prochiral olefins. Knowles and his co‐workers were convinced that the phosphorus atom played a central role in this selectivity, as only chiral phosphorus ligands such as (R,R)‐DIPAMP, whose stereogenic center lies directly on the phosphorus atom, lead to high enantiomeric excesses when used as catalysts in asymmetric hydrogenation reactions. This hypothesis was disproven by the development of ligands with chiral carbon backbones. Although the exact mechanism of action of the phosphane ligands is not incontrovertibly determined to this day, they provide a simple entry to a large number of chiral compounds.     

Highly Acidic Conjugate‐Base‐Stabilized Carboxylic Acids Catalyze Enantioselective oxa‐Pictet–Spengler Reactions with Ketals

Acyclic ketone‐derived oxocarbenium ions are involved as intermediates in numerous reactions that provide valuable products, however, they have thus far eluded efforts aimed at asymmetric catalysis. We report that a readily accessible chiral carboxylic acid catalyst exerts control over asymmetric cyclizations of acyclic ketone‐derived trisubstituted oxocarbenium ions, thereby providing access to highly enantioenriched dihydropyran products containing a tetrasubstituted stereogenic center. The high acidity of the carboxylic acid catalyst, which exceeds that of the well‐known chiral phosphoric acid catalyst TRIP, is largely derived from stabilization of the carboxylate conjugate base through intramolecular anion‐binding to a thiourea site.     

Biomimetic Hydrogenation Catalyzed by a Manganese Model of [Fe]‐Hydrogenase

[Fe]‐hydrogenase is an efficient biological hydrogenation catalyst. Despite intense research, Fe complexes mimicking the active site of [Fe]‐hydrogenase have not achieved turnovers in hydrogenation reactions. Herein, we describe the design and development of a manganese(I) mimic of [Fe]‐hydrogenase. This complex exhibits the highest activity and broadest scope in catalytic hydrogenation among known mimics. Thanks to its biomimetic nature, the complex exhibits unique activity in the hydrogenation of compounds analogous to methenyl‐H₄MPT⁺, the natural substrate of [Fe]‐hydrogenase. This activity enables asymmetric relay hydrogenation of benzoxazinones and benzoxazines, involving the hydrogenation of a chiral hydride transfer agent using our catalyst coupled to Lewis acid‐catalyzed hydride transfer from this agent to the substrates.     

Cobalt‐Catalyzed Asymmetric Hydrogenation of C=N Bonds Enabled by Assisted Coordination and Nonbonding Interactions

An efficient cobalt‐catalyzed asymmetric hydrogenation of C=N bonds has been realized. Chiral hydrazines were obtained in high yields and with excellent enantioselectivities (95–98 % ee). The hydrogenation went smoothly at up to 2000 substrate/catalyst and on a gram scale. The success of this reaction relies on the presence of an NHBz group in the substrates, with the reactivity and enantioselectivity improved by an assisted coordination to the cobalt atom and a nonbonding interaction with the ligand. Furthermore, this reaction has practical applications for the synthesis of several useful chiral nitrogen‐containing compounds.     

Synthesis of polymer microspheres functionalized with chiral ligand by precipitation polymerization and their application to asymmetric transfer hydrogenation

Monodisperse, crosslinked poly(divinylbenzene) and poly(methacrylic acid‐co‐ethylene glycol dimethacrylate) microspheres with (1R,2R)‐N¹‐toluenesulfonyl‐1,2‐diphenylethylene‐1,2‐diamine ((R,R)‐TsDPEN) moiety were successfully prepared by precipitation polymerization. Introduction site of the (R,R)‐TsDPEN moiety into the polymer microspheres could be controlled by changing the order of addition of the corresponding monomers. The functionalized polymer microspheres were applied to asymmetric transfer hydrogenation of ketone and imine. Polymer microsphere‐supported chiral catalysts showed good reactivity and enantioselectivity in the catalytic asymmetric transfer hydrogenations. Chiral secondary alcohol was quantitatively obtained with 94% ee in the asymmetric transfer hydrogenation of acetophenone in water. We also found that introduction site of the chiral catalyst and hydrophobicity of the microspheres, as well as degree of the crosslinking, affected the yield and enantioselectivity of chiral product in this reaction. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3340–3349, 2010     

Synthesis of chiral hydantoin derivatives by homogeneous Pd-catalyzed asymmetric hydrogenation

5-Aryl substituted chiral hydantoin derivatives were synthesized via asymmetric hydrogenation of prochiral exocyclic alkenes using a Pd/BINAP catalyst. Moderate to good enantioselectivity were obtained (21–90% ee). A chiral Brönsted acid additive was found to be a key factor to obtain high enantioselectivity.     

Aminosulf(ox)ides as ligands for Iridium(I)-catalyzed asymmetric transfer hydrogenation

A new class of efficient catalysts was developed for the asymmetric transfer hydrogenation of unsymmetrical ketones. A series of chiral N,S-chelates (6-22) was synthesized to serve as ligands in the iridium(I)-catalyzed reduction of ketones. Both formic acid and 2-propanol proved to be suitable as hydrogen donors. Sulfoxidation of an (R)-cysteine-based aminosulfide provided a diastereomeric ligand family containing a chiral sulfur atom. The two chiral centers of these ligands showed a clear effect of chiral cooperativity. In addition, aminosulfides containing two asymmetric carbon atoms in the backbone were synthesized. Both the sulfoxide-containing beta-amino alcohols and the aminosulfides derived from 1,2-disubstituted amino alcohols gave rise to high reaction rates and moderate to excellent enantioselectivities in the reduction of various ketones. The enantioselective outcome of the reaction was favorably affected by selecting the most appropriate hydrogen donor. Enantioselectivities of up to 97% were reached in the reduction of aryl-alkyl ketones.     

Diastereo‐ and Enantioselective anti‐Selective Hydrogenation of α‐Amino‐β‐keto Ester Hydrochlorides and Related Compounds Using Transition‐Metal–Chiral‐Bisphosphine Catalysts

This review describes our recent works on the diastereo‐ and enantioselective synthesis of anti‐β‐hydroxy‐α‐amino acid esters using transition‐metal–chiral‐bisphosphine catalysts. A variety of transition metals, namely ruthenium (Ru), rhodium (Rh),iridium (Ir), and nickel (Ni), in combination with chiral bisphosphines, worked well as catalysts for the direct anti‐selective asymmetric hydrogenation of α‐amino‐β‐keto ester hydrochlorides, yielding anti‐β‐hydroxy‐α‐amino acid esters via dynamic kinetic resolution (DKR) in excellent yields and diastereo‐ and enantioselectivities. The Ru‐catalyzed asymmetric hydrogenation of α‐amino‐β‐ketoesters via DKR is the first example of generating anti‐β‐hydroxy‐α‐amino acids. Complexes of iridium and axially chiral bisphosphines catalyze an efficient asymmetric hydrogenation of α‐amino‐β‐keto ester hydrochlorides via dynamic kinetic resolution. A homogeneous Ni–chiral‐bisphosphine complex also catalyzes an efficient asymmetric hydrogenation of α‐amino‐β‐keto ester hydrochlorides in an anti‐selective manner. As a related process, the asymmetric hydrogenation of the configurationally stable substituted α‐aminoketones using a Ni catalyst via DKR is also described.     

新型手性胺膦-铱体系催化芳香酮的不对称转移氢化

合成了含-CH_3取代基的PNNP型手性双胺双膦配体, 并采用核磁共振、质谱、红外光谱及圆二色光谱等方法对其进行了表征. 在异丙醇溶液中, 考察了该配体与[IrHCI_2(COD)]_2组成的手性胺膦-铱体系对多种芳香酮的不对称转移氢化性能. 结果表明, 该手性胺膦-铱体系是催化多种芳香酮不对称氢转移氢化的优秀催化剂. 在室温下, 用该体系催化1,1-二苯基丙酮时, 可得到99%的转化率和99% ee的对映选择性.     

1,3‐Difunctionalization of Aminocyclopropanes via Dielectrophilic Intermediates

We report an oxidative ring‐opening strategy to transform acyl, sulfonyl or carbamate protected aminocyclopropanes into 1,3‐dielectrophilic carbon intermediates bearing a halide atom (Br, I) and a N,O‐acetal. Replacing the alkoxy group of the N,O‐acetal can be achieved under acidic conditions through an elimination–addition pathway, while substitution of the halides by nucleophiles can be done under basic conditions through a S_N2 pathway, generating a wide range of 1,3‐difunctionalized propylamines. A proof of concept for asymmetric induction was realized using a chiral phosphoric acid (CPA) as catalyst, highlighting the potential of the method in enantioselective synthesis of important building blocks.     

A novel design of roof-shaped anthracene-fused chiral prolines as organocatalysts for asymmetric Mannich reactions

A new class of artificial anthracene-fused chiral proline catalysts has been synthesized from the Diels–Alder adduct of anthracene and maleic anhydride via lithiation/carboxylation of 6 as a key step. Chiral resolution of racemic amino acids was carried out through the formation of diastereomeric esters with (−)-menthol. The absolute configuration of the chiral amino acid was determined by X-ray crystallographic analysis. The utility of the catalyst was confirmed by effecting asymmetric three-component Mannich reactions between aldehyde, ketone, and amine (yield up to 76%, ee up to 90%).     

Catalytic Asymmetric Hydrogenation of Pyrimidines

The asymmetric hydrogenation of pyrimidines proceeded with high enantioselectivity (up to 99 % ee) using an iridium catalyst composed of [IrCl(cod)]₂, a ferrocene‐containing chiral diphosphine ligand (Josiphos), iodine, and Yb(OTf)₃ (cod=1,5‐cyclooctadiene). The chiral catalyst converted various 4‐substituted pyrimidines into chiral 1,4,5,6‐tetrahydropyrimidines in high yield. The lanthanide triflate is crucial for achieving the high enantioselectivity as well as for activating the heteroarene substrate.