Enantioselective Rh-Catalyzed Hydrogenation Research Articles

Kinetic and Thermodynamic Considerations in the Rh-Catalyzed Enantioselective Hydrogenation of 2-Pyridyl-Substituted Alkenes.

The mechanism of asymmetric hydrogenation of 2-pyridyl alkenes catalyzed by chiral Rh-phosphine complexes at ambient temperature is examined using kinetic, spectroscopic, and computational tools. The reaction proceeds with reversible substrate binding followed by rate-determining addition of hydrogen. Substrate binding occurs only through the pyridine nitrogen in contrast to other substrate classes exhibiting stronger substrate direction. The lack of influence of hydrogen pressure on the product enantiomeric excess suggests that a pre-equilibrium in substrate binding is maintained across the pressure range investigated. An off-cycle Rh-hydride species is implicated in the mild catalyst deactivation observed. In contrast to Ru-phosphine-catalyzed reactions of the same substrate class, the stereochemical outcome in this system correlates generally with the relative stability of the E and Z rotamers of the substrate.

Facile access to chiral 1-pyrrolines through Rh-catalyzed enantioselective partial hydrogenation of unprotected simple pyrroles

Highly enantioselective Rh-catalyzed partial hydrogenation of unprotected simple 2-alkyl-5-aryl-disubstituted pyrroles has been successfully developed, generating a series of chiral 1-pyrroline derivatives generally with excellent results (95%–99% yields, 91%–96% ee). Moreover, 2,5-aryl-1H-pyrroles were hydrogenated well in high yields and good enantioselectivities. This efficient protocol features easily accessible substrates, wide substrate scope, well functional group compatibility, commercially available rhodium precursor and chiral ligand. It provides a versatile route to access chiral 1-pyrroline derivatives that are of great importance in organic synthesis and pharmaceutical chemistry.

Catalytic Asymmetric Hydrogenation of Tetrasubstituted Unsaturated Lactams: An Efficient Approach to Enantioenriched 3,4-Disubstituted Piperidines.

Asymmetric hydrogenation of tetrasubstituted alkenes remains a formidable challenge in asymmetric catalysis. We report herein an unprecedented Rh-catalyzed enantioselective and diastereoselective hydrogenation of easily accessed α,β-disubstituted unsaturated lactams to afford synthetically valuable chiral lactams with 1,2-consecutive stereocenters. The reaction could be performed on the gram scale, and the products could be concisely transformed to enantiomerically pure trans-3,4-disubstituted piperidines, which are prevalent structural units in medicinal agents.

Rh-catalyzed asymmetric hydrogenation of α-aryl-β-alkylvinyl esters with chiral ferrocenylphosphine-phosphoramidite ligand

An enantioselective Rh-catalyzed hydrogenation of E/Z mixtures of trisubstituted vinyl esters has been disclosed. With a combination of [Rh(COD)2]BF4 and a structurally fine-tuning chiral ferrocenylphosphine-phosphoramidite ligand as the catalyst, a variety of E/Z mixtures of α-aryl-β-alkylvinyl esters have been successfully hydrogenated in high yields and with good to high enantioselectivities (up to 96% ee). The presence of a small amount of tBuOH proved to be beneficial to improve the hydrogenation outcome.

Highly Chemo- and Enantioselective Rh-Catalyzed Hydrogenation of β-Sulfonyl-α,β-unsaturated Ketones: Access to Chiral γ-Ketosulfones.

Rh-catalyzed highly chemo- and enantioselective hydrogenation of β-sulfonyl-α,β-unsaturated ketones was first successfully developed. Remarkably, a variety of enantioenriched γ-ketosulfones were generated in good to high yields with excellent chemo/enantioselectivities (82-99% yields, >99:1 chemoselectivity, 88 to >99% ee). Moreover, the gram-scale asymmetric hydrogenation was carried out smoothly in 97% yield and 97% ee. Preliminary DFT computations furnished a reasonable explanation for the high chemoselectivity and enantioselectivity.

Asymmetric Synthesis of Chiral Spiroketal Bisphosphine Ligands and Their Application in Enantioselective Olefin Hydrogenation.

A series of chiral spiroketal bisphosphine ligands containing 1,1'-spirobi(3 H,3' H)isobenzofuran backbones was accessed through asymmetric synthesis and subsequently tested in enantioselective Rh-catalyzed hydrogenation of α-dehydroamino acid esters. The ligand providing the highest enantioselectivity (up to 99.5%) was obtained in seven steps in an overall 38% yield. The synthesis could be performed on a gram scale, and no kinetic resolution of enantiomers is required. Overall, the developed ligand provides an easily accessible alternative to SDP ligands as well as other chiral bisphosphine ligands.

ChemInform Abstract: Rhodium‐Catalyzed Enantioselective Hydrogenation of Oxime Acetates.

Rh-catalyzed enantioselective hydrogenation of oxime acetates was first reported, which afforded a new approach for chiral amine synthesis.

Synthesis of enantiopure β2-homoalanine derivatives via rhodium catalyzed asymmetric hydrogenation

The stereoselective synthesis of chiral β2-homoalanine derivatives with 99% ee by the Rh-catalyzed enantioselective hydrogenation of prochiral 2-aminomethyl acrylates is described. The subsequent transformation to chiral 3-amino-2-methylpropanols is also demonstrated.

Rhodium-Catalyzed Enantioselective Hydrogenation of Oxime Acetates

Rh-catalyzed enantioselective hydrogenation of oxime acetates was first reported, which afforded a new approach for chiral amine synthesis.

Enantioselective Rh-Catalyzed Hydrogenation of 3-Aryl-4-phosphonobutenoates with a P-Stereogenic BoPhoz-Type Ligand

A series of chiral 3-aryl-4-phosphonobutyric acid esters were synthesized in high enantioselectivities (93-98% ee) via the Rh-catalyzed asymmetric hydrogenation of the corresponding 3-aryl-4-phosphonobutenoates using a P-stereogenic BoPhoz-type phosphine-aminophosphine ligand. The methodology has been successfully applied to the asymmetric synthesis of a potential GABA(B) antagonist, (R)-phaclofen, in high enantioselectivity.

Chiral Phosphine−Phosphite Ligands with a Substituted Ethane Backbone. Influence of Conformational Effects in Rhodium-Catalyzed Asymmetric Olefin Hydrogenation and Hydroformylation Reactions

A family of chiral (3,3′-di-tert-butyl-5,5′,6,6′-tetramethyl-2,2′-biphenol-derived) phosphine−phosphite ligands (P−OP) with a substituted ethane backbone has been synthesized and the performance of these ligands in the Rh-catalyzed enantioselective hydrogenation and hydroformylation of several representative olefins analyzed. Corresponding cationic rhodium complexes provide highly enantioselective catalysts for the hydrogenation of methyl (Z)-α-acetamidocinnamate (MAC) and dimethyl itaconate. The catalyst comparison indicates that, for the two substrates, product configuration is determined by the configuration of the phosphite. Regarding matching and mismatching effects in these hydrogenations, small effects were observed in the reduction of MAC, while for the itaconate the bigger difference between the matched and mismatched cases was of 21% ee. On the other hand, Rh catalysts based on P−OP ligands showed good levels of activity and regioselectivity in the hydroformylation of styrene and allyl cyanide, ...

Enantioselektive Katalyse, 63 [1] Optisch Aktive Phosphine Aus Dicarbonsäuren Und Ihr Einsatz in Der Enantioselektiven Hydrierung

Two optically active bident phosphine ligands were synthesized from derivatives of succinic acid as starting materials. The optical resolution of the acids was carried out with cinchonidine and (S)-α-phenylethylamine. In the Rh-catalyzed enantioselective hydrogenation of α-acetamidocinnamic acid, the bisphosphine with a phenyl substituent in the 2-position of the four-carbon chain gave an enantiomeric excess of 17%. The enantiomeric excess was twice as high with the corresponding thienyl substituted bisphosphine.

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.

Chiral 1-phenylethylamine-derived phosphine-phosphoramidite ligands for highly enantioselective Rh-catalyzed hydrogenation of β-(acylamino)acrylates: significant effect of substituents on 3,3′-positions of binaphthyl moiety

A series of new chiral phosphine-phosphoramidite ligands with a 3,3'-substituted binaphthyl moiety were prepared from 1-phenylethylamine, and successfully applied in the Rh-catalyzed asymmetric hydrogenation of beta-(acylamino)-acrylates. The research disclosed that the substituents on the 3,3'-positions of binaphthyl moiety significantly influenced the enantioselectivity.

Enantioselective Rh-catalyzed transfer hydrogenation of α-sulfonyloxy heteroaryl ketones; asymmetric synthesis of ( S)-bufuralol

Asymmetric transfer hydrogenation of α-sulfonyloxy heteroaryl ketones mediated by Cp∗RhCl[( S,S)-TsDPEN] using an azeotropic mixture of formic acid/triethylamine afforded the corresponding diol-2-monosulfonates in excellent yield with high enantioselectivity. This led to the asymmetric synthesis of ( S)-bufuralol.

Highly Enantioselective Rh-Catalyzed Hydrogenation of β,γ-Unsaturated Phosphonates with Chiral Ferrocene-Based Monophosphoramidite Ligands

An enantioselective synthesis of chiral alkylphosphonates bearing a beta-stereogenic center, based on the Rh-catalyzed asymmetric hydrogenation of corresponding beta-substituted beta,gamma-unsaturated phosphonates with a ferrocene-based monophosphoramidite ligand under the mild hydrogenation conditions, was developed, in which an ee value of up to 98% was obtained.

Enantioselective Rh-Catalyzed Hydrogena-tion of 3-Aryl-2-phosphonomethylpropenoates

Enantioselective Rh-Catalyzed Hydrogena-tion of 3-Aryl-2-phosphonomethylpropenoates

Enantioselective Rh-catalyzed hydrogenation of N-acyl dehydroamino esters and enamides with monodentate phosphoramidite ligands

Chiral monodentate phosphoramidite ligands were conveniently prepared from 1,1′-bi-2-naphthol (BINOL) and (S)-pyrrolidine in good yields, which were effective chiral ligands in the enantioselective rhodium-catalyzed hydrogenation of dehydroamino esters and enamides at low hydrogenation pressure. High conversion rate (up to 99% for dehydroamino esters and enamides) and good enantioselectivity (up to 96.3% ee for dehydroamino esters and 91.7% ee for enamides) were obtained.

Enantioselective Rh-Catalyzed Hydrogenation of 3-Aryl-2-phosphonomethylpropenoates by a New Class of Chiral Ferrocenyl Diphosphine Ligands

A new class of chiral ferrocenyl diphosphine ligands with an imidazole ring, (R(c),S(Fc))-ImiFerroPhos, has been prepared from acylferrocenes through a five-step transformation and successfully applied in the Rh-catalyzed asymmetric hydrogenation of various 3-aryl-substituted 2-phosphonomethylpropenoates, in which a series of chiral 3-phosphono-2-arylmethylpropanoic acid derivatives were achieved in ee values of up to 98%.

Highly Enantioselective Rh-catalyzed Transfer Hydrogenation of α-Functionalized Arylketones

Asymmetric transfer hydrogenation of α-functionalized arylketones has been studied. The chiral Rh-catalyst effectively performed in transfer hydrogenation of α-mesyloxyketones with an azeotropic mixture of formic acid/triethylamine to produce optically active 1-arylethandiols with excellent enantioselectivity.