Asymmetric Hydrogenation Of Methyl Research Articles

ChemInform Abstract: Development of the Asymmetric Hydrogenation Step for Multikilogram Production of Etamicastat

The asymmetric hydrogenation of methyl (6,8-difluoro-2H-chromen-3-yl)carbamate is a key step in the manufacturing route to etamicastat. A development of this step including the ruthenium or rhodium catalyst screening and the influence of the catalyst preparation (isolated, preformed in solution or in situ), solvent, temperature, pressure, additive, and concentration on the performance of the given ligand was discussed. Scale-up experiments for the best catalysts under optimized conditions were described.

Development of the Asymmetric Hydrogenation Step for Multikilogram Production of Etamicastat

The asymmetric hydrogenation of methyl (6,8-difluoro-2H-chromen-3-yl)carbamate is a key step in the manufacturing route to etamicastat. A development of this step including the ruthenium or rhodium catalyst screening and the influence of the catalyst preparation (isolated, preformed in solution or in situ), solvent, temperature, pressure, additive, and concentration on the performance of the given ligand was discussed. Scale-up experiments for the best catalysts under optimized conditions were described.

Direct experimental and computational evidence for the dihydride pathway in TangPHOS-Rh catalysed asymmetric hydrogenation

DFT computations of various possible reaction pathways in asymmetric hydrogenation of methyl (Z-α)acetylaminocinnamate catalysed by Rh-TangPHOS complex revealed the clear preference of the dihydride pathway. This conclusion was explicitly confirmed by the structure of the monohydride intermediate intercepted in the low temperature NMR hydrogenation experiments. DFT analysis of the origin of enantioselection showed that it takes place via obstructing the proper coordination of the double bond in the S-enantioselective pathway.

Neutral vs. cationic rhodium (I) complexes of bulky N-phosphino sulfinamide ligands: Coordination modes and its influence in the asymmetric hydrogenation of Z-MAC

Here we report the synthesis of a new N-di-tert-butylphosphino-tert-butylsulfinamide (PNSO) ligand and its corresponding p-tolylsulfinamide analog. The coordination of these compounds to rhodium to form a neutral and apolar complex is described, followed by the subsequent protonation of said complexes to quantitively form the more orthodox, cationic rhodium species containing a tetrafluoroboric counterion. The crystallographic structure of the tert-butylsulfinamide-derived cationic species was obtained and is elucidated. It outlines coordination from the sulfinamide group to the rhodium atom and shows no preference between O- and S-coordination as both complexes can be seen in one unit cell of the crystal. The efficacies of the neutral species and the salt species were tested in the asymmetric hydrogenation of methyl (Z)-α-acetamido cinnamate (Z-MAC). The p-tolylsulfinamide-derived complexes gave no hydrogenation while the tert-butylsulfinamide-derived ones produced hydrogenation with complete conversion but low enantioselectivities. The stereochemical outcome of the reaction was analyzed by means of the quadrant method.

Amino acid- and imidazolium-tagged chiral pyrrolidinodiphosphine ligands and their applications in catalytic asymmetric hydrogenations in ionic liquid systems

Herein we report the synthesis of amino acid- and imidazolium-tagged chiral pyrrolidinodiphosphine ligands and the catalytic efficiency and reusability of their corresponding Rh-catalysts in the asymmetric hydrogenation of methyl (Z)-2-acetamidocinnamate in different reaction media, including classical organic solvents, ionic liquid (IL) [bmim]BF4 (1-n-butyl-3-methyl-imidazolium tetrafluoroborate) and [bmim]BF4/cosolvent systems. The effects of the ionic tag structures, IL, cosolvents, Rh precursors, and halide impurities on catalytic activity and enantioselectivity were studied in detail. In the hydrogenation reaction, the amino acid- and imidazolium modified ligands gave higher ee values than the classical pyrrolidinodiphosphine, (2S,4S)-N-(tert-butoxycarbonyl)-4-(diphenylphosphino)-2-[(diphenylphosphino) methyl] pyrrolidine (BPPM), both in pure methanol and in the [bmim]BF4/MeOH system. The catalyst recycling experiments demonstrated that introducing the amino acid and imidazolium moieties into the pyrrolidinodiphosphine backbone resulted in much better immobilization and reusability of the Rh-catalysts in [bmim]BF4, and after several cycles there was no significant loss in activity, enantioselectivity, or Rh.

ChemInform Abstract: Asymmetric Hydrogenation of Methyl (Z)‐2‐Acetamido‐3‐(3,4‐dimethoxyphenyl)acrylate Catalyzed by Rh Complexes with Available Amidophosphite Ligands.

AbstractA convenient express procedure for the synthesis of the title acrylate (III) and its highly enantioselective asymmetric Rh‐catalyzed hydrogenation using synthetically available BINOL phosphite ligands are described.

Asymmetric hydrogenation of methyl (Z)-2-acetamido-3-(3,4-dimethoxyphenyl)acrylate catalyzed by Rh complexes with available amidophosphite ligands

A convenient express procedure for the preparation of methyl (Z)-2-acetamido-3-(3,4-dimethoxyphenyl)acrylate was developed. Asymmetric hydrogenation of this substrate in the presence of rhodium catalysts involving synthetically available amidophosphite ligands was carried out, which is characterized by high enantioselectivity (to 99.5% ee) and complete conversion. An approach to the selective formation of cationic complexes containing two ligands of different nature in one coordination sphere of rhodium was suggested.

ChemInform Abstract: Asymmetric Hydrogenation of Methyl 3,5-Dioxohexanoate-Catalyzed by Ru- binap Complex: A Short Step Asymmetric Synthesis of Dihydro-6-methyl- 2H-pyran-2-one.

ChemInform Abstract: Asymmetric Hydrogenation of Methyl 3,5-Dioxohexanoate-Catalyzed by Ru- binap Complex: A Short Step Asymmetric Synthesis of Dihydro-6-methyl- 2H-pyran-2-one.

Synthesis of atropisomeric 5,5′-linked biphenyl bisaminophosphine ligands and their applications in asymmetric catalysis

Atropisomeric 5,5′-linked biphenyl bisaminophosphine ligands 2 has been synthesized. The axial chirality of this type of ligands can be retained by macro-ring strain produced from 5,5′-linkage of biphenyl even without 6,6′-substituents on biphenyls. The Rh complex of bisaminophosphine 2a as a catalyst is effectively working in the asymmetric hydrogenation of methyl ( Z)-2-acetamido-3-arylacrylates, however, for hydrogenation of arylenamide, the low enantioselectivity was observed. When the ligands applied to Pd-catalyzed allylic alkylation, it is found that ligand 2b having a longer backbone linkage is a better ligand for enantioselection in the reaction.

Me-AnilaPhos: a new chiral phosphine–phosphoramidite ligand for a highly efficient Rh-catalyzed asymmetric olefin hydrogenation

A cationic rhodium(I) complex with a novel chiral phosphine–phosphoramidite ligand based on 2-diphenylphosphino- N-methylaniline and R-BINOL moieties has been synthesized. The complex provided remarkably high activity and enantioselectivity in the asymmetric hydrogenation of methyl ( Z)-α-acetamidocinnamate (100% conversion after 10 min, 98% ee) and dimethyl itaconate (100% conversion after 26 min, 96% ee) under ambient conditions (1 bar hydrogen pressure, room temperature) using 1 mol % of the catalyst in dichloromethane as solvent. On the other hand, when hydrogenation was performed in methanol, both conversion and enantioselectivity were significantly diminished, due to the partial decomposition of the rhodium/phosphine–phosphoramidite complex.

Coordination Chemistry and Asymmetric Catalysis with a Chiral Diphosphonite.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Chiral 1,2,5‐Triphenylphospholanium Tetrafluoroborate (I) as Ligand Precursor in Rh‐Catalyzed Asymmetric Hydrogenation of Methyl (Z)‐2‐Acetamidocinnamate.

Chiral 1,2,5‐Triphenylphospholanium Tetrafluoroborate (I) as Ligand Precursor in Rh‐Catalyzed Asymmetric Hydrogenation of Methyl (Z)‐2‐Acetamidocinnamate.

Coordination Chemistry and Asymmetric Catalysis with a Chiral Diphosphonite

AbstractThe improved synthesis of the chiral diphosphonite, XantBino (1), based on a xanthene backbone and bearing chiral binaphthyl groups on both P‐atoms is described together with its PdII and RhI complexes. The 31P NMR spectra of both complexes point out that the two phosphorus atoms are chemically inequivalent. The complex cis‐[PdCl2(1)] (2) is structurally characterized by NMR spectroscopy and X‐ray crystallography. The molecular structure reveals an unusually small bite angle for this member of the xantphos family of only 100°. The rhodium‐catalyzed asymmetric hydroformylation of styrene and vinyl acetate as well as the asymmetric hydrogenation of methyl (Z)‐2‐acetamidocinnamate, applying this chiral diphosphonite 1, are described. Low enantiomeric excesses are obtained in the asymmetric hydroformylation, while use of the catalyst precursor [Rh(cod)(1)]BF4 (3) results in a promising enantiomeric excess in the Rh‐catalyzed asymmetric hydrogenation. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

ChemInform Abstract: Tuning Diastereoselectivity with the Solvent: The Asymmetric Hydrogenation of Simple and Functionalized 1,3-Diketones with Ruthenium(amidophosphine-phosphinite) Catalysts.

Spectacular solvent effects in the asymmetric hydrogenation of methyl 3,5-dioxohexanoate (3) and 2,4-pentanedione (5) have been observed using Ru[(S)-Ph,Ph-oxoProNOP]X2 complexes (X=η3-C4H7, IIa; CF3CO2, IIb; (R)-MTPA, IIc) as catalyst precursors. β-Diketones 3 and 5 are respectively reduced to the corresponding β-diols 4 and 6. In both cases, an almost complete reversal in the diastereoselectivity of the reaction is observed when changing the solvent from CH2Cl2 (syn-4 in up to 92% de; meso-6 in up to 84% de) to a 1:1 CH2Cl2–CH3OH mixture (anti-4 and anti-6 in up to 84% de). The extent of this solvent effect is much less marked with Ru-atropisomeric diphosphine catalysts.

Influence of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymers on stereoselective catalysis in water

The first application of (EO)n-(PO)m-(EO)n triblock copolymers as surfactants in asymmetric hydrogenation is described. We observed a dependence of the activity and enantioselectivity on the asymmetric hydrogenation of methyl (Z)-α-acetamidocinnamate on the length of the (PO)m domain of the copolymer. The activity and enantioselectivity were observed to be independent of the hydrophilic-lipophilic-balance (HLB) or the critical micelle concentration (cmc) of the copolymer. The size of the (EO)n unit does not play an important role, however the addition of a small amount of SDS enhances the enantioselectivities significantly. The triblock copolymers were also successfully used as phase transfer reagent in two-phase Suzuki carbon-carbon coupling reactions. The use of polymeric reagents in micellar and phase-transfer systems has the advantage that these reagents can be easily separated from the reaction mixture by means of a membrane.

Tuning diastereoselectivity with the solvent: the asymmetric hydrogenation of simple and functionalized 1,3-diketones with ruthenium(amidophosphine–phosphinite) catalysts

Spectacular solvent effects in the asymmetric hydrogenation of methyl 3,5-dioxohexanoate (3) and 2,4-pentanedione (5) have been observed using Ru[(S)-Ph,Ph-oxoProNOP]X2 complexes (X=η3-C4H7, IIa; CF3CO2, IIb; (R)-MTPA, IIc) as catalyst precursors. β-Diketones 3 and 5 are respectively reduced to the corresponding β-diols 4 and 6. In both cases, an almost complete reversal in the diastereoselectivity of the reaction is observed when changing the solvent from CH2Cl2 (syn-4 in up to 92% de; meso-6 in up to 84% de) to a 1:1 CH2Cl2–CH3OH mixture (anti-4 and anti-6 in up to 84% de). The extent of this solvent effect is much less marked with Ru-atropisomeric diphosphine catalysts.

One-Pot and Sequential Asymmetric Hydrogenation of β,δ-Diketoesters into Functionalized 1,3-Diols: Fromanti- tosyn-Stereoselectivity

The asymmetric hydrogenation of methyl 3,5-dioxohexanoate (1) into mixtures of 3,5-dihydroxyesters (2) and 3-hydroxylactones (3) has been reinvestigated with a variety of ruthenium catalysts. Catalysts bearing diphosphanes which possess axial chirality such as (S)-MeO–Biphep give predominantly (3R,5S)-anti-2 in up to 78% de and 95% ee, affording an efficient synthesis of (S)-6-methyl-5,6-dihydro-2-pyrone [(S)-5] in up to 95% enantiomeric excess. On the contrary, some Ru-{amidophosphane-phosphinite} complexes catalyze sluggishly the formation of syn-2 in up to 92% de but with poor enantiomeric excesses. In all cases, methyl (R)-3-hydroxy-5-oxohexanoate [(R)-11] is the exclusive primary hydrogenation product, which can be isolated in high yields and enantiomeric excesses up to 78%. Further hydrogenation of enantiomerically enriched (R)-11 in a separate experiment affords (3R,5R)-syn-2 in high diastereomeric and enantiomeric excesses (up to 80% and 98%, respectively), provided a Ru-(R)-Binap-type catalyst is used.

Cationic BINAP-Ru(II) Halide Complexes: Highly Efficient Catalysts for Stereoselective Asymmetric Hydrogenation of .alpha.- and .beta.-Functionalized Ketones

Cationic ruthenium-BINAP complexes 5, 7, and 10 of the formula [RuX((S)-BINAP)(arene)]Y, where X=Cl, Br, I; Y=Cl, Br, I, BF 4 , B(C 6 H 5 ) 4 ; arene=benzene, p-cymene, ethyl benzoate, and their enantiomers have been prepared by the reaction of arene-ruthenium halide complexes 4, 6, and 9 with (S)-BINAP or (R)-BINAP. Structures of the complexes were established by spectroscopy, conductivity, and a single-crystal X-ray analysis (5d: orthorhombic, P2 1 2 1 2; a=20.141(2) A, b=18.504(1) A, c=12.241(1) A, V=4562.0(7) A 3 , Z=4, R=0.078 for unique 4177 reflections). BINAP derivatives with various substituents at the para and meta positions of four phenyl rings on phosphorous atoms and their cationic Ru(II) complexes have also been synthesized. These BINAP-Ru (II) complexes have been used as catalysts for the asymmetric hydrogenation of various unsaturated organic compounds such as α- and β-keto esters, allylic alcohols, and α,β-unsaturated carboxylic acids in excellent diastereo- and/or enantioselectivities. Catalytic activities and stereoselectivities depend highly on reaction conditions such as solvent, temperature, and additives. Variation of halogen ligands bound to ruthenium atom and substituents on four phenyl rings of BINAP also have exerted remarkable effects on the efficiency of the catalysis. Asymmetric hydrogenation of methyl (∓)-2-(benzamidomethyl)-3-oxobutanoate catalyzed by the species derived from 9c and 3,5-(tBu) 2 -BINAP afforded the corresponding syn-(2S,3R)-17 in 98% de and 99% ee

ChemInform Abstract: Enantioselective Synthesis of L‐ and D‐Isoserine via Asymmetric Hydrogenation of Methyl N‐Phthaloyl‐3‐amino‐2‐oxopropanoate.

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Enantioselective synthesis of L- and D-isoserine via asymmetric hydrogenation of methyl N-phthaloyl-3-amino-2-oxopropanoate

L- and D-isoserine were synthesized enantioselectively via asymmetric hydrogenation of 3-amino-2-oxoester 5 catalyzed by [RuCl(binap)(benzene)]CI. Recrystallization and deprotection of ( S)- 6 (81% ee) afforded enantiomerically pure L-isoserine. The enantioface selection by the catalyst was opposite to that observed in asymmetric hydrogenation of other 2-oxoesters, such as methyl phenylglyoxylate and methyl 2-oxocyclohexylacetate.