Rhodium-catalyzed Asymmetric Transfer Hydrogenation Research Articles

Rhodium-Catalyzed Asymmetric Hydrogenation and Transfer Hydrogenation of α-Nitro Ketones.

A catalytic protocol for the enantioselective hydrogenation and transfer hydrogenation of α-nitro ketones was developed, providing a wide range of β-nitro-α-phenylethanols with high yields and excellent enantioselectivities (up to 98% yield and up to >99.9% ee). Compatibility with a wide range of solvents and bases demonstrates the robustness of this reaction. The synthetic potential of the protocol was demonstrated by the high TON experiment as well as the application in the synthesis of key intermediates of mirabegron (S/C = 10,000, 95% yield, 99% ee).

Rhodium-Catalyzed Asymmetric Transfer Hydrogenation of Aryl Ketones Involving Free Phenolic Hydroxyl Group(s).

A straightforward asymmetric transfer hydrogenation for accessing enantiomerically enriched secondary benzyl alcohols involving free phenolic hydroxyl group(s) under mild conditions was developed. Various of optical pure aryl alcohols with a remarkable functional group compatibility were achieved with 78 %-97 % yields, 84 %->99 % ee's and up to 10 000 TON. This rhodium-catalyzed reaction could be performed in a gram-scale without loss of the efficiency. Furthermore, the synthetic utility has also been demonstrated in the asymmetric synthesis of (S)-adrenaline and (S)-phenylephrine.

Dynamic Kinetic Resolution of β-Cyano α-Ketoesters via Asymmetric Transfer Hydrogenation.

An efficient rhodium-catalyzed asymmetric transfer hydrogenation of β-cyano α-ketoesters via dynamic kinetic resolution has been developed. Despite the challenge posed by multiple functional groups, the reaction proceeded smoothly under mild conditions, generating versatile synthons with two adjacent stereocenters in high yields with excellent enantio- and diastereoselectivities. Furthermore, the power of this strategy is highlighted by the scale-up reaction and the follow-up synthesis of cytoxazone and paclitaxel intermediates.

Substrate Channeling in Compartmentalized Nanoreactors.

Thermo- and photoresponsive nanoreactors based on shell cross-linked micelles (SCMs) for the rhodium-catalyzed asymmetric transfer hydrogenation (ATH) of ketones have been developed from poly(2-oxazoline) triblock terpolymers. The nanoreactors incorporate thermoresponsive poly(2-isopropyl-2-oxazoline) as the hydrophilic corona and are covalently cross-linked with a photoswitchable spiropyran molecule. UV irradiation or changes in temperature trigger morphology switching of the polymer-based nanoreactors that alters the hydrophobicity in separate layers of the SCMs, resulting in dynamic substrate selectivity of the ATH in water. Control experiments and kinetic studies show that the thermoresponsive outer layer induces the gated behavior for more hydrophobic substrates, whereas the photoresponsive cross-linking layer induces the gated behavior for less hydrophobic substrates. The nanoreactors mimic the multichannels in Nature, transporting substrates and reagents into the catalytic core which can be controlled through external triggers such as temperature and light wavelengths. Additionally, the nanoreactors can be easily recovered and reused with continued high activity and selectivities.

Rhodium-Catalyzed Asymmetric Hydrogenation and Transfer Hydrogenation of 1,3-Dipolar Nitrones.

Owing to their distinctive 1,3-dipolar structure, the catalytic asymmetric hydrogenation of nitrones to hydroxylamines has been a formidable and longstanding challenge, characterized by intricate enantiocontrol and susceptibility to N-O bond cleavage. In this study, the asymmetric hydrogenation and transfer hydrogenation of nitrones were accomplished with a tethered TsDPEN-derived cyclopentadienyl rhodium(III) catalyst (TsDPEN: p-toluenesulfonyl-1,2-diphenylethylene-1,2-diamine), the reaction proceeds via a novel 7-membered cyclic transition state, producing chiral hydroxylamines with up to 99 % yield and >99 % ee. The practical viability of this methodology was underscored by gram-scale catalytic reactions and subsequent transformations. Furthermore, mechanistic investigations and DFT calculations were also conducted to elucidate the origin of enantioselectivity.

Enantioselective synthesis of the bioactive flavanones lonchocarpol A and 6-(1,1-dimethylallyl)naringenin by catalytic asymmetric transfer hydrogenation

Practical enantioselective syntheses of the natural products lonchocarpol A and 6-(1,1-dimethylallyl)naringenin as well as their optical antipodes are reported. A rhodium-catalyzed asymmetric transfer hydrogenation of readily available racemic substrates with virtually complete kinetic resolution served as the key step. Solvent-controlled, clay-catalyzed [1,3] or [3,3] shifts of prenyl aryl ethers were used to install the C-6 prenyl or 1,1-dimethylallyl substituent of the target flavanones.

Access to Chiral Succinimides by Rhodium-Catalyzed Asymmetric Transfer Hydrogenation

Access to Chiral Succinimides by Rhodium-Catalyzed Asymmetric Transfer Hydrogenation

Synthesis of Enantioenriched β-Hydroxy-γ-Acetal Enamides by Rhodium-Catalyzed Asymmetric Transfer Hydrogenation.

The asymmetric reduction of β-keto-γ-acetal enamides has been investigated. A wide range of enantioenriched β-hydroxy-γ-acetal enamides were obtained through asymmetric transfer hydrogenation catalyzed by a tethered Rh(III)-DPEN complex with yields up to quantitative and enantioselectivities up to 99%. The reaction proved to be highly chemoselective toward the reduction of the carbonyl group over the C═C bond.

Rhodium-catalyzed asymmetric transfer hydrogenation of 4-quinolone derivatives

4-Quinolone derivatives were conveniently reduced to 1,2,3,4-tetrahydroquinoline-4-ols with excellent enantioselectivities through asymmetric transfer hydrogenation using a tethered rhodium complex and formic acid/triethylamine as the hydride source.

Rh-Mediated Asymmetric-Transfer Hydrogenation of 3-Substituted Chromones: A Route to Enantioenriched cis-3-(Hydroxymethyl)chroman-4-ol Derivatives through Dynamic Kinetic Resolution.

Enantioenriched cis-3-(hydroxymethyl)chroman-4-ol derivatives were conveniently prepared by rhodium-catalyzed asymmetric transfer hydrogenation of 3-formylchromones through a dynamic kinetic resolution process. The reaction proceeded under mild conditions using a low catalyst loading and HCO2H/Et3N (5:2) as the hydrogen source, delivering the reduced compounds in good yields, high diastereomeric ratio (up to 98:2 dr), and excellent enantioselectivities (up to >99% ee).

The first application of C2-symmetric ferrocenyl phosphinite ligands for rhodium-catalyzed asymmetric transfer hydrogenation of various ketones

Homogeneous catalysis has been responsible for many major recent developments in synthetic organic chemistry. The combined use of organometallic and coordination chemistry has produced a number of new and powerful synthetic methods for important classes of compounds in general and for optically active substances in particular. For this aim, a new class of chiral modular C2-symmetric ferrocenyl phosphinite ligands has been prepared in good yields by using the inexpensive 1,1′-ferrocenedicarboxyaldehyde and various ferrocene based-amino alcohols as starting materials, and applied in the rhodium(I)-catalyzed asymmetric transfer hydrogenation (ATH) of aromatic ketones to give corresponding secondary alcohols with excellent enantioselectivities and reactivities using isoPrOH as the hydrogen source (up to 99% conversion and 99%ee). The substituents on the backbone of the ligands are found to exhibit a remarkable effect on both the activity and % ee. The structures of these ligands and their complexes have been elucidated by a combination of multinuclear NMR spectroscopy, IR spectroscopy and elemental analysis.

Designer substrate library for quantitative, predictive modeling of reaction performance.

Assessment of reaction substrate scope is often a qualitative endeavor that provides general indications of substrate sensitivity to a measured reaction outcome. Unfortunately, this field standard typically falls short of enabling the quantitative prediction of new substrates' performance. The disconnection between a reaction's development and the quantitative prediction of new substrates' behavior limits the applicative usefulness of many methodologies. Herein, we present a method by which substrate libraries can be systematically developed to enable quantitative modeling of reaction systems and the prediction of new reaction outcomes. Presented in the context of rhodium-catalyzed asymmetric transfer hydrogenation, these models quantify the molecular features that influence enantioselection and, in so doing, lend mechanistic insight to the modes of asymmetric induction.

ChemInform Abstract: Second‐Generation Amino Acid Furanoside Based Ligands from D‐Glucose for the Asymmetric Transfer Hydrogenation of Ketones.

A novel series of modular amino acid thioamide ligands functionalized with carbohydrates were introduced and employed in the rhodium-catalyzed asymmetric transfer hydrogenation (ATH) of aryl alkyl ...

Rhodium-Catalyzed Asymmetric Transfer Hydrogenation

Rhodium-Catalyzed Asymmetric Transfer Hydrogenation

Flower-like mesoporous silica: a bifunctionalized catalyst for rhodium-catalyzed asymmetric transfer hydrogenation of aromatic ketones in aqueous medium

Functionalized flower-like mesoporous silica with a chiral organorhodium functionality incorporated within its silica framework is prepared through an assembly of chiral 4-((trimethoxysilyl)ethyl)phenylsulfonyl-1,2-diphenylethylenediamine and tetraethoxysilane under a cooperative dual-template approach followed by complexation with organorhodium complexes. Structural characterization discloses its mesostructure and well-defined single-site chiral organorhodium functionality, while electron microscopy analyses reveal the uniformly distributed three-dimensional spherical flowers constructed by the stacking of leaf-shaped nanoflakes. In particular, as a bifunctionalized heterogeneous catalyst, it shows excellent catalytic activity and high enantioselectivity in the asymmetric transfer hydrogenation of aromatic ketones in aqueous medium (more than 99% conversion and up to 97% ee). The superior catalytic performance is attributed to the synergistic effect of the salient cetyltrimethylammonium bromide phase-transfer function and confined chiral organorhodium catalytic nature. Furthermore, this heterogeneous catalyst could be recovered easily and reused repeatedly (ten times) without affecting its ee value, showing a practical application in asymmetric synthesis.

Asymmetric Transfer Hydrogenation of Ketones Catalyzed by Rhodium Block Copolymer Complexes in Aqueous Micelles

High activity and enantioselectivity were achieved in the rhodium-catalyzed asymmetric transfer-hydrogenation reactions of ketones in pure water using a novel amphiphilic block polypeptide ligand. The covalent linkage of the catalyst to the block copolymer plays a significant role and provides higher conversions and better recyclability than regular micellar or nonmicellar systems.

Dynamic kinetic resolution in the stereoselective synthesis of 4,5-diaryl cyclic sulfamidates by using chiral rhodium-catalyzed asymmetric transfer hydrogenation

The dynamic kinetic resolution of 4,5-diaryl cyclic sulfamidate imines was achieved via asymmetric transfer hydrogenation using a HCO(2)H/Et(3)N mixture as the hydrogen source and chiral Rh catalysts (R,R)- or (S,S)-RhCl(TsDPEN)Cp* affording the corresponding cyclic sulfamidates in good yields with up to >20 : 1 dr and up to >99% ee.

Enantioselective Synthesis of Cyclic Sulfamidates by Using Chiral Rhodium-Catalyzed Asymmetric Transfer Hydrogenation

Asymmetric transfer hydrogenation (ATH) of cyclic sulfamidate imines 4 and 9, using a HCO(2)H/Et(3)N mixture as the hydrogen source and well-defined chiral Rh catalysts (S,S)- or (R,R)-2, Cp*RhCl(TsDPEN), effectively produces the corresponding cyclic sulfamidates with excellent yields and enantioselectivities at room temperature within 0.5 h. ATH of 4,5-disubstituted imines 9, having preexisting stereogenic centers, is shown to take place with dynamic kinetic resolution.

Fine-tuning catalytic activity and selectivity—[Rh(amino acid thioamide)] complexes for efficient ketone reduction

Amino acid-derived thioamides are prepared and evaluated as ligands in the rhodium-catalyzed asymmetric transfer hydrogenation of ketones in 2-propanol. It is found that increasing the steric bulk at the C-terminus of the ligand had a positive impact on both activity and selectivity in the reduction reaction. In order to find the optimum catalyst, a study is performed on a series of thioamide ligands having substituents of varying size.

Rhodium-catalyzed asymmetric transfer hydrogenation of alkyl and aryl ketones in aqueous media

A novel lipophilic rhodium catalyst was evaluated in the enantioselective transfer hydrogenation of ketones in water using sodium formate as the hydride donor, and in the presence of sodium docecylsulfonate. Alkyl alkyl ketones were reduced in good yields and in moderate to good enantioselectivities, and the reduction of aryl alkyl ketones proceeded with excellent enantioselectivity (up to 97% ee).