- Cobalt-Catalyzed Asymmetric Hydrogenation of α,β-Unsaturated Carboxylic Acids by Homolytic H2 Cleavage
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The asymmetric hydrogenation of α,β-unsaturated carboxylic acids using readily prepared bis(phosphine) cobalt(0) 1,5-cyclooctadiene precatalysts is described. Di-, tri-, and tetra-substituted acrylic acid derivatives with various substitution patterns as well as dehydro-α-amino acid derivatives were hydrogenated with high yields and enantioselectivities, affording chiral carboxylic acids including Naproxen, (S)-Flurbiprofen, and a d-DOPA precursor. Turnover numbers of up to 200 were routinely obtained. Compatibility with common organic functional groups was observed with the reduced cobalt(0) precatalysts, and protic solvents such as methanol and isopropanol were identified as optimal. A series of bis(phosphine) cobalt(II) bis(pivalate) complexes, which bear structural similarity to state-of-the-art ruthenium(II) catalysts, were synthesized, characterized, and proved catalytically competent. X-band EPR experiments revealed bis(phosphine)cobalt(II) bis(carboxylate)s were generated in catalytic reactions and were identified as catalyst resting states. Isolation and characterization of a cobalt(II)-substrate complex from a stoichiometric reaction suggests that alkene insertion into the cobalt hydride occurred in the presence of free carboxylic acid, producing the same alkane enantiomer as that from the catalytic reaction. Deuterium labeling studies established homolytic H2 (or D2) activation by Co(0) and cis addition of H2 (or D2) across alkene double bonds, reminiscent of rhodium(I) catalysts but distinct from ruthenium(II) and nickel(II) carboxylates that operate by heterolytic H2 cleavage pathways.
- Chirik, Paul J.,Shevlin, Michael,Zhong, Hongyu
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supporting information
(2020/03/13)
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- Chemoenzymatic Cascade Synthesis of Optically Pure Alkanoic Acids by Using Engineered Arylmalonate Decarboxylase Variants
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Arylmalonate decarboxylase (AMDase) catalyzes the cofactor-free asymmetric decarboxylation of prochiral arylmalonic acids and produces the corresponding monoacids with rigorous R selectivity. Alteration of catalytic cysteine residues and of the hydrophobic environment in the active site by protein engineering has previously resulted in the generation of variants with opposite enantioselectivity and improved catalytic performance. The substrate spectrum of AMDase allows it to catalyze the asymmetric decarboxylation of small methylvinylmalonic acid derivatives, implying the possibility to produce short-chain 2-methylalkanoic acids with high optical purity after reduction of the nonactivated C=C double bond. Use of diimide as the reductant proved to be a simple strategy to avoid racemization of the stereocenter during reduction. The developed chemoenzymatic sequential cascade with use of R- and S-selective AMDase variants produced optically pure short-chain 2-methylalkanoic acids in moderate to full conversion and gave both enantiomers in excellent enantiopurity (up to 83 % isolated yield and 98 % ee).
- Enoki, Junichi,Mügge, Carolin,Tischler, Dirk,Miyamoto, Kenji,Kourist, Robert
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p. 5071 - 5076
(2019/03/17)
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- 2-Isopropylbenzimidazole and 2-methylbenzimidazole as bulky proton sources: Stereoselective protonation and application to the synthesis of γ- and δ-lactones
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2-Isopropylbenzimidazole and 2-methylbenzimidazole have been found to be effective bulky proton sources for stereoselective protonation of chiral enolate anions. 2-Isopropylbenzimidazole worked in the stereoselective protonation of the Birch reduction of chiral α,β-unsaturated imides. On the other hand, 2-methylbenzimidazole was found to be the best protonation reagent in the isomerization reaction of α,β-unsaturated imide into β,γ-unsaturated imide. The Birch reduction using 2-isopropylbenzimidazole realized a concise and stereoselective synthesis of δ-lactone 14, a sex pheromone of Macrocentrus grandii, while the isomerization reaction using 2-methylbenzimidazole was employed in the highly stereoselective synthesis of the γ-lactone intermediate in the synthesis of depsipeptide antibiotics. These bulky proton sources would be powerful tools to achieve a concise synthesis of natural products.
- Sengupta, Aakash,Hosokawa, Seijiro
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supporting information
p. 411 - 414
(2019/01/05)
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- Systematic methodology for the development of biocatalytic hydrogen-borrowing cascades: Application to the synthesis of chiral α-substituted carboxylic acids from α-substituted α,β-unsaturated aldehydes
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Ene-reductases (ERs) are flavin dependent enzymes that catalyze the asymmetric reduction of activated carbon-carbon double bonds. In particular, α,β-unsaturated carbonyl compounds (e.g. enals and enones) as well as nitroalkenes are rapidly reduced. Conversely, α,β-unsaturated esters are poorly accepted substrates whereas free carboxylic acids are not converted at all. The only exceptions are α,β-unsaturated diacids, diesters as well as esters bearing an electron-withdrawing group in α- or β-position. Here, we present an alternative approach that has a general applicability for directly obtaining diverse chiral α-substituted carboxylic acids. This approach combines two enzyme classes, namely ERs and aldehyde dehydrogenases (Ald-DHs), in a concurrent reductive-oxidative biocatalytic cascade. This strategy has several advantages as the starting material is an α-substituted α,β-unsaturated aldehyde, a class of compounds extremely reactive for the reduction of the alkene moiety. Furthermore no external hydride source from a sacrificial substrate (e.g. glucose, formate) is required since the hydride for the first reductive step is liberated in the second oxidative step. Such a process is defined as a hydrogen-borrowing cascade. This methodology has wide applicability as it was successfully applied to the synthesis of chiral substituted hydrocinnamic acids, aliphatic acids, heterocycles and even acetylated amino acids with elevated yield, chemo- and stereo-selectivity. A systematic methodology for optimizing the hydrogen-borrowing two-enzyme synthesis of α-chiral substituted carboxylic acids was developed. This systematic methodology has general applicability for the development of diverse hydrogen-borrowing processes that possess the highest atom efficiency and the lowest environmental impact. This journal is
- Knaus, Tanja,Mutti, Francesco G.,Humphreys, Luke D.,Turner, Nicholas J.,Scrutton, Nigel S.
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supporting information
p. 223 - 233
(2015/02/19)
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- Enantioselective hydrogenation of α,β-unsaturated carboxylic acid over cinchonidine-modified Pd nanoparticles confined in carbon nanotubes
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We report the enantioselective hydrogenation of α,β-unsaturated acid catalyzed by Pd nanoparticles in carbon nanotubes (CNTs) taking the advantage of the channels as nanoreactors. The Pd nanocatalyst inside the channels of CNTs shows higher activity and e
- Guan, Zaihong,Lu, Shengmei,Li, Can
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- Enantioselective rearrangement coupled with water addition: Direct synthesis of enantiomerically pure saturated carboxylic acids from α,β-unsaturated aldehydes
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A novel type of organic synthesis enabling a direct one-pot transformation of α,β-unsaturated aldehydes into saturated carboxylic acids is described. As sole reagent water is required, which is integrated completely in the product. This tandem process proceeds under perfect atom economy, and consists of two coupled redox biotransformations without the need of external co-substrates for cofactor regeneration. The initial reduction of the C=C double bond of an α,β-unsaturated aldehyde is catalyzed by an NADPH-dependent ene reductase, leading to the formation of the saturated aldehyde and NADP+. The aldehyde intermediate is then oxidized to the corresponding carboxylic acid, thus regenerating NADPH for the next catalytic cycle. When using prochiral α,β-unsaturated aldehydes as substrates the corresponding carboxylic acids are formed enantioselectively with up to >99 % ee as demonstrated, e.g., for the transformation of citral to (S)-citronellic acid. Making a splash with citral: The direct one-pot transformation of α,β-unsaturated aldehydes to saturated carboxylic acids using only water proceeds with perfect atom economy. This tandem process involves two redox biotransformations without need of additional external co-substrates for cofactor regeneration. With, for example, citral as prochiral α,β-unsaturated aldehyde, transformation to (S)-citronellic acid proceeds with >99 % conversion and >99 % ee.
- Winkler, Till,Groeger, Harald,Hummel, Werner
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p. 961 - 964
(2014/05/06)
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- Enantioselective hydrogenation of α,β-unsaturated carboxylic acids on Pd nanocubes
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Pd nanocubes of 6-19 nm in size were synthesized using a seeded growth method and examined for enantioselective hydrogenation of α,β- unsaturated carboxylic acids. It was found that the Pd nanocubes had two types of active sites on the planes and at the edges, respectively. Small nanocubes having a higher edge/plane ratio were more active in enantioselective hydrogenation of α,β-unsaturated carboxylic acids, but afforded a lower enantioselectivity because their sharp edges could not offer stable adsorption of the chiral modifier and the reaction intermediates. In contrast, large nanocubes with a higher fraction of flat planes provided a higher enantioselectivity but a much lower activity.
- Chen, Chunhui,Zhan, Ensheng,Ta, Na,Li, Yong,Shen, Wenjie
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p. 2620 - 2626
(2013/09/24)
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- Efficient cluster-based catalysts for asymmetric hydrogenation of α-unsaturated carboxylic acids
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The new clusters [H4Ru4(CO)10(μ-1,2-P- P)], [H4Ru4(CO)10(1,1-P-P)] and [H 4Ru4(CO)11(P-P)] (P-P=chiral diphosphine of the ferrocene-based Josiphos or Walphos ligand families) have been synthesised and characterised. The crystal and molecular structures of eleven clusters reveal that the coordination modes of the diphosphine in the [H4Ru 4(CO)10(μ-1,2-P-P)] clusters are different for the Josiphos and the Walphos ligands. The Josiphos ligands bridge a metal-metal bond of the ruthenium tetrahedron in the "conventional" manner, that is, with both phosphine moieties coordinated in equatorial positions relative to a triangular face of the tetrahedron, whereas the phosphine moieties of the Walphos ligands coordinate in one axial and one equatorial position. The differences in the ligand size and the coordination mode between the two types of ligands appear to be reflected in a relative propensity for isomerisation; in solution, the [H4Ru4(CO)10(1,1-Walphos)] clusters isomerise to the corresponding [H4Ru4(CO) 10(μ-1,2-Walphos)] clusters, whereas the Josiphos-containing clusters show no tendency to isomerisation in solution. The clusters have been tested as catalysts for asymmetric hydrogenation of four prochiral α-unsaturated carboxylic acids and the prochiral methyl ester (E)-methyl 2-methylbut-2-enoate. High conversion rates (>94 %) and selectivities of product formation were observed for almost all catalysts/catalyst precursors. The observed enantioselectivities were low or nonexistent for the Josiphos-containing clusters and catalyst (cluster) recovery was low, suggesting that cluster fragmentation takes place. On the other hand, excellent conversion rates (99-100 %), product selectivities (99-100 % in most cases) and good enantioselectivities, reaching 90 % enantiomeric excess (ee) in certain cases, were observed for the Walphos-containing clusters, and the clusters could be recovered in good yield after completed catalysis. Results from high-pressure NMR and IR studies, catalyst poisoning tests and comparison of catalytic properties of two [H4Ru4(CO)10(μ-1,2-P-P)] clusters (P-P=Walphos ligands) with the analogous mononuclear catalysts [Ru(P-P)(carboxylato)2] suggest that these clusters may be the active catalytic species, or direct precursors of an active catalytic cluster species. Copyright
- Moberg, Viktor,Duquesne, Robin,Roehrs, Oliver,Nachtigall, Jonny,Nordlander, Ebbe,Contaldi, Simone,Monari, Magda,Damoense, Llewellyn,Green, Michael,Hutton, Alan T.,Santelia, Daniela,Haukka, Matti
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p. 12458 - 12478,21
(2020/08/24)
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- Synthesis and absolute configuration of (S)-(+)-chichimol ketone: the defensive secretion of walking stick Agathemera elegans
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The first enantioselective synthesis of chichimol ketone (4-methyl-1-hepten-3-one) is described and the absolute configuration of the main semiochemical compound is determined as having an (S)-configuration. The synthesis features the use of a ruthenium c
- Espinoza-Moraga, Marlene,Cornejo-Morales, Roxana,Santos, Leonardo Silva
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scheme or table
p. 1062 - 1064
(2009/09/30)
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- Iridium-catalyzed enantioselective hydrogenation of α,β- unsaturated carboxylic acids
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A highly efficient iridium-catalyzed hydrogenation of α,β-unsaturated carboxylic acids has been developed by using chiral spiro-phosphino-oxazoline ligands, affording α-substituted chiral carboxylic acids in exceptionally high enantioselectivities and reactivities. Copyright
- Li, Shen,Zhu, Shou-Fei,Zhang, Can-Ming,Song, Song,Zhou, Qi-Lin
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supporting information; experimental part
p. 8584 - 8585
(2009/02/03)
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- Highly efficient asymmetric hydrogenation of α,β-unsaturated carboxylic acids catalyzed by ruthenium(II)-dipyridylphosphine complexes
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Two types of catalysts [RuL(benzene)Cl]Cl and Ru(OCOCH3) 2L with the dipyridylphosphine ligands P-Phos and Xyl-P-Phos were applied in the asymmetric hydrogenation of α,β-unsaturated carboxylic acids. The cationic complexes [RuL(benzene)Cl]Cl were found to be superior to the corresponding neutral complex Ru(OCOCH3)2L in this type of reactions. The catalysts exhibited excellent activities and enantioselectivities (up to 97% ee) in the asymmetric hydrogenation.
- Qiu, Liqin,Li, Yue-Ming,Kwong, Fuk Yee,Yu, Wing-Yiu,Fan, Qing-Hua,Chan, Albert S. C.
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p. 517 - 520
(2008/02/08)
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- Asymmetric hydrogenation of α,β-unsaturated carboxylic acids catalyzed by ruthenium(II) complexes of spirobifluorene diphosphine (SFDP) ligands
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The ruthenium diacetate complexes ligated by chiral spirobifluorene diphosphines (SFDP) were very effective catalysts for the asymmetric hydrogenation of tiglic acid derivatives and α-methylcinnamic acid derivatives with high activities and excellent enantioselectivities (up to 98% ee). The α-aryloxybutenoic acids can also be hydrogenated by these catalysts to provide the corresponding saturated α-aryloxybutanoic acids in high yields (89-93%) and enantioselectivities (up to 95% ee). In this reaction, the SFDP ligand with para-methyl groups on the P-phenyl rings gave the best results.
- Cheng, Xu,Xie, Jian-Hua,Li, Sheng,Zhou, Qi-Lin
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p. 1271 - 1276
(2007/10/03)
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- Highly rigid diphosphane ligands with a large dihedral angle based on a chiral spirobifluorene backbone
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High and wide: The high rigidity and large dihedral angle of chiral, spirobifluorene-based diphosphane ligands lead to excellent reactivity and enantioselectivity in the ruthenium-catalyzed asymmetric hydrogenation of α,β-unsaturated carboxylic acids (see scheme).
- Cheng, Xu,Zhang, Qi,Xie, Jian-Hua,Wang, Li-Xin,Zhou, Qi-Lin
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p. 1118 - 1121
(2007/10/03)
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- Enantiomeric partitioning using fluorous biphase methodology for lipase-mediated (trans)esterifications
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Lipase-catalysed (trans)esterification reactions in homogenous perfluorocarbon-hydrocarbon solvents enabled direct enantiomeric partitioning (up to 95% ee) of the products by liquid-liquid separation.
- Beier, Petr,O'Hagan, David
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p. 1680 - 1681
(2007/10/03)
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- Substrate-modifier but not catalyst-modifier: Heterogeneous hydrogenation of C=O and C=C using cinchonidine
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Literature results and our own, concerning hydrogenation of ethyl pyruvate and 2-methyl pentenoic acid over Al2O3-supported platinum and palladium using cinchonidine (CD), indicate that CD activates pyruvate (through enol formation) and modifies the unsaturated acid (salt formation), but not the catalyst, and that CD may even poison the catalyst (palladium more than platinum). Therefore, the modifier's properties must fit the substrate's properties and not be a catalyst poison, the best sequence for addition of the reactants being: first a mixture of substrate/CD and then the supported Pt and/or Pd catalyst.
- Solladié-Cavallo,Marsol,Hoernel,Garin
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p. 4741 - 4744
(2007/10/03)
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- Enantioselective esterification of 2-methylpentanoic acid catalised via immobilized lipases in chrysotile and microemulsion-based gels
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Immobilized lipases in chrysotile and microemulsion-based gel (MBG) or organogel were used in the resolution of racemic 2-methylpentanoic acid that is a valuable synthetic intermediate for the preparation of, among other compounds, a number of steriochemically pure insect pheromones.
- De Jesus, Paulo Cesar,Da Silva, Pedro Luiz Ferreira,Joao, Jair Juarez,Da Graca Nascimento, Maria
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p. 2893 - 2901
(2007/10/03)
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- Highly efficient enantioselective synthesis of optically active carboxylic acids by Ru(OCOCH3)2[(S)-H8-BINAP]
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In the presence of a catalytic amount of Ru(OCOCH3)2[(S)-H8-BINAP] [H8-BINAP = 2,2′-bis-(diphenylphosphino)-5,5′,6,6′,7,7′,8,8′- octahydro-1,1′-binaphthyl], the asymmetric hydrogenation of α,β- and β,γ-unsaturated carboxylic acids afforded the corresponding saturated carboxylic acids in higher enantiomeric excesses and at faster reaction rates than those using the Ru(OCOCH3)2[(R)-BINAP] catalyst [BINAP = 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl]. The hydrogenation of (E)-2-alkyl-2-alkenoic acids by the H8-BINAP catalyst system produced saturated acids in 95-97% ee. 2-Methylcinnamic acid was treated with H8-BINAP-Ru(II) complex as a catalyst to yield a hydrogenated product in much higher ee than that produced by BINAP-Ru(II) (89 and 30% ee, respectively). This homogeneous catalysis using H8-BINAP-Ru(II) established a promising synthetic route to (S)-ibuprofen in up to 97% ee. Asymmetric hydrogenation of β-disubstituted acrylic acids also proceeded smoothly with good enantioselectivities (70-93% ee). In addition, the hydrogenation of trisubstituted acrylic acids (up to 88% ee) was investigated. Hydrogen pressure effect on the sense and level of enantioselection was shown to be substrate dependent. The difference between the H8-BINAP- and BINAP-Ru(II) complexes was also discussed.
- Uemura, Toshitsugi,Zhang, Xiaoyoung,Matsumura, Kazuhiko,Sayo, Noboru,Kumobayashi, Hidenori,Ohta, Tetsuo,Nozaki, Kyoko,Takaya, Hidemasa
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p. 5510 - 5516
(2007/10/03)
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- Process for producing optically active carboxylic acid
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A process for the production of an optically active carboxylic acid (I), which comprises subjecting an olefinic carboxylic acid (II) to asymmetric hydrogenation using a complex as a catalyst consisting of an optically active phosphine (III) and a ruthenium compound. Complex of STR1 with a ruthenium compound STR2 According to the process of the present invention, optically active carboxylic acids can be produced with high yield.
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- Biotransformations of γ-methyl-β-ketosulfones: Stereoselectivity of 3-methyl-1-(phenylsulfonyl)hexan-2-one reductions by various yeasts
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The stereoselectivity of the reduction of rac-3-methyl-1-(phenylsulfonyl)hexan-2-one (1) to 3-methyl-1-(phenylsulfonyl)hexan-2-ol (2) diastereomers by more than 20 yeasts was studied. Reduction of carbonyl group in 1 proceeds with a high Re-face enantioselectivity: Candida guillermondii (98.9% e.e), C. zeylanoides (>99.9%), and Kloeckera apiculata (99.6%), respectively and the (R)-1 enantiomer usually reacted faster. The enantioselectivity was determined by GC on chiral cyclodextrine phases and absolute configurations of products were assigned by NMR spectroscopy and a chemical correlation.
- Svatos, Ales,Hunkova, Zdenka,Kren, Vladimir,Hoskovec, Michal,Saman, David,Valterova, Irena,Vrkoc, Jan,Koutek, Bohumir
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p. 1285 - 1294
(2007/10/03)
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- Lipase catalyzed resolution of chiral acids using their mixed carboxylic carbonic anhydrides
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Mixed carboxylic-carbonix anhydrides are efficient irreversible acyl transfer reagents for lipase-catalyzed esterification in organic media, and can be used for the resolution of chiral carboxylic acids.
- Guibe-Jampel, Eryka,Bassir, Mohamed
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p. 421 - 422
(2007/10/02)
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- Lipase-Catalyzed Enantioselective Esterification of 2-Methylalkanoic Acids
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A preference for (S)-enantiomers has been observed in the course of the esterification of racemic 2-methylalkanoic acids catalyzed by lipase from Candida cylindracea in heptane.
- Engel, Karl-Heinz
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p. 165 - 168
(2007/10/02)
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- Chiral 2-alkylbranched acids, esters and alcohols. Preparation and stereospecific flavour evaluation
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Racemic 2-alkylbranched acids are transformed to diastereomeric derivatives with (S)-2-hydroxy-3-phenylpropionic acid-N-methylamide of (S)-(-)-1-phenylethylamine and separated by liquid chromatography to pure diastereoisomers, which are subsequently hydrolyzed to yield optically pure acids. Enantiomeric alcohols are generated by LiAlH4-reduction of the corresponding acids, esters are synthesized by different methods. The odour impression of the enantiomeric compounds is investigated.
- Rettinger,Burschka,Scheeben,Fuchs,Mosandl
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p. 965 - 968
(2007/10/02)
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- ASYMMETRIC INDUCTION AT C(β) AND C(α) OF N-ENOYL SULTAMS BY 1,4-HYDRIDE ADDITION/ENOLATE TRAPPING
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Conjugate addition of L-Selectride to α,β-enoyl sultams 1 and 4 followed by electrophilic trapping of the resulting enolates gave in one operation saturated imides with high β- and/or α- stereodifferentiation.
- Oppolzer, Wolfgang,Poli, Giovanni
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p. 4717 - 4720
(2007/10/02)
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- A Conceptually Different Approach to the Asymmetric Synthesis of α-Substituted Carbonyl Compounds
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A new approach has been demonstrated for the asymmetric synthesis of α-substituted carbonyl compounds.Thus, the key assymetric carbon-carbon bond formation is accomplished by the highly diastereoselective addition of organoaluminum reagents to the chiral α,β-unsaturated acetal derived from the α,β-unsaturated aldehyde and (R,R)-tartaric acid diamide to furnish the 1,4-adduct preferentially along with the 1,2-adduct as a minor product.Subsequent oxidation of the combined adducts with ozone or the system potassium permanganate/sodium periodate gives rise to the optically active α-substituted aldehyde, ketone, or carboxylic acid, respectively, with high enantioselectivities.The present method has been applied to the facile synthesis of an anti-inflammatory agent and the principal alarm pheromone of the leaf-cutting ant Atta texana in optically active forms.
- Maruoka, Keiji,Nakai, Shuichi,Sakurai, Minoru,Yamamoto, Hisashi
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p. 130 - 132
(2007/10/02)
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- Synthesis of S-(+)-4-methyl-3-heptanone, the principal alarm pheromone of Atta texana, and its enantiomer
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The principal alarm pheromone of Atta texana S-(+)-4-methyl-3-heptanone, and its enantiomer have been prepared synthetically in high optical purity.
- Riley,Silverstein
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p. 1171 - 1174
(2007/10/12)
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