- Enantioselective decarboxylative protonation and deuteration of β-ketocarboxylic acids
-
Enantioselective decarboxylative protonation of tetralone-derived β-ketocarboxylic acids was achieved with up to 89% enantiomeric excess (ee)-in the presence of a chiral primary amine catalyst. Furthermore, this method was applied to enantioselective deuteration to afford the corresponding α-deuterioketones with up to 88% ee.
- Mizutani, Haruna,Kawanishi, Ryouta,Shibatomi, Kazutaka
-
supporting information
p. 6676 - 6679
(2021/07/12)
-
- Highly Enantioselective Iridium-Catalyzed Hydrogenation of Conjugated Trisubstituted Enones
-
Asymmetric hydrogenation of conjugated enones is one of the most efficient and straightforward methods to prepare optically active ketones. In this study, chiral bidentate Ir-N,P complexes were utilized to access these scaffolds for ketones bearing the stereogenic center at both the α- and β-positions. Excellent enantiomeric excesses, of up to 99%, were obtained, accompanied with good to high isolated yields. Challenging dialkyl substituted substrates, which are difficult to hydrogenate with satisfactory chiral induction, were hydrogenated in a highly enantioselective fashion.
- Peters, Bram B. C.,Jongcharoenkamol, Jira,Krajangsri, Suppachai,Andersson, Pher G.
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p. 242 - 246
(2021/01/13)
-
- Indene Derived Phosphorus-Thioether Ligands for the Ir-Catalyzed Asymmetric Hydrogenation of Olefins with Diverse Substitution Patterns and Different Functional Groups
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A family of phosphite/phosphinite-thioether ligands have been tested in the Ir-catalyzed asymmetric hydrogenation of a range of olefins (50 substrates in total). The presented ligands are synthesized in three steps from cheap indene and they are air-stable solids. Their modular architecture has been crucial to maximize the catalytic performance for each type of substrate. Improving most Ir-catalysts reported so far, this ligand family presents a broader substrate scope, covering different substitution patterns with different functional groups, ranging from unfunctionalized olefins, through olefins with poorly coordinative groups, to olefins with coordinative functional groups. α,β-Unsaturated acyclic and cyclic esters, ketones and amides werehydrogenated in enantioselectivities ranging from 83 to 99% ee. Enantioselectivities ranging from 91 to 98% ee were also achieved for challenging substrates such as unfunctionalized 1,1′-disubstituted olefins, functionalized tri- and 1,1′-disubstituted vinyl phosphonates, and β-cyclic enamides. The catalytic performance of the Ir-ligand assemblies was maintained when the environmentally benign 1,2-propylene carbonate was used as solvent. (Figure presented.).
- Margalef, Jèssica,Biosca, Maria,de la Cruz-Sánchez, Pol,Caldentey, Xisco,Rodríguez-Escrich, Carles,Pàmies, Oscar,Pericàs, Miquel A.,Diéguez, Montserrat
-
supporting information
p. 4561 - 4574
(2021/04/05)
-
- Rhodium-catalyzed asymmetric hydrogenation of exocyclic α,β-unsaturated carbonyl compounds
-
A highly enantioselective hydrogenation of exocyclic α,β-unsaturated carbonyl compounds catalyzed by Rh/bisphosphine-thiourea (ZhaoPhos) has been developed, giving the corresponding α-chiral cyclic lactones, lactams and ketones with high yields and excellent enantioselectivities (up to 99% yield and 99% ee). Remarkably, the hydrogen bond between the substrate and the catalyst plays a critical role in this transformation. The synthetic utility of this protocol has been demonstrated by efficient synthesis of chiral 3-(4-fluorobenzyl)piperidine, a key chiral fragment of bioactive molecules.
- Yang, Jiaxin,Li, Xiuxiu,You, Cai,Li, Shuailong,Guan, Yu-Qing,Lv, Hui,Zhang, Xumu
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p. 856 - 859
(2020/02/15)
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- Enantioselective Protonation of Enol Esters with Bifunctional Phosphonium/Thiourea Catalysts
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Bifunctional phosphonium/thioureas derived from tert-leucine behaved as highly selective catalysts for enantioselective protonation of enol esters, providing α-chiral ketones in yields of up to 99% with high enantioselectivities (up to 98.5:1.5 er). Control experiments clarified that a bulky tert-butyl group and phosphonium and thiourea moieties were necessary to achieve such high stereoselectivity. In addition, mechanistic investigations indicated the catalyst was converted to the corresponding betaine species, which served as a monomolecular catalyst.
- Yamamoto, Eiji,Wakafuji, Kodai,Mori, Yusuke,Teshima, Gaku,Hidani, Yuki,Tokunaga, Makoto
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p. 4030 - 4034
(2019/06/07)
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- Giving a Second Chance to Ir/Sulfoximine-Based Catalysts for the Asymmetric Hydrogenation of Olefins Containing Poorly Coordinative Groups
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This work identifies a family of Ir/phosphite-sulfoximine catalysts that has been successfully used in the asymmetric hydrogenation of olefins with poorly coordinative or noncoordinative groups. In comparison with analogue Ir/phosphine-sulfoximine catalysts previously reported, the presence of a phosphite group extended the range of olefins than can be efficiently hydrogenated. High enantioselectivities, comparable to the best ones reported, have been achieved for a wide range of olefins containing relevant poorly coordinative groups such as α,β-unsaturated enones, esters, lactones, and lactams as well as alkenylboronic esters.
- Biosca, Maria,Pàmies, Oscar,Diéguez, Montserrat
-
p. 8259 - 8266
(2019/06/17)
-
- Phosphite-thioether/selenoether Ligands from Carbohydrates: An Easily Accessible Ligand Library for the Asymmetric Hydrogenation of Functionalized and Unfunctionalized Olefins
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A large family of phosphite-thioether/selenoether ligands has been easily prepared from accessible L-(+)-tartaric acid and D-(+)-mannitol and applied in the M-catalyzed (M=Ir, Rh) asymmetric hydrogenation of a broad number of substrates (46 in total). Its highly modular architecture has been crucial to maximize the catalytic performance. Improving most of the reported approaches, this ligand family presents a broad substrate scope. By selecting the ligand parameters high enantioselectivities (ee's up to 99 %) have therefore been achieved in a broad range of both, functionalized and unfunctionalized substrates. Interestingly, both enantiomers of the hydrogenation products can be usually achieved by changing the ligand parameters.
- Margalef, Jèssica,Borràs, Carlota,Alegre, Sabina,Alberico, Elisabetta,Pàmies, Oscar,Diéguez, Montserrat
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p. 2142 - 2168
(2019/04/13)
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- Formation, Alkylation, and Hydrolysis of Chiral Nonracemic N-Amino Cyclic Carbamate Hydrazones: An Approach to the Enantioselective α-Alkylation of Ketones
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The α-alkylation of ketones is a fundamental synthetic transformation. The development of asymmetric variants of this reaction is important given that numerous natural products, drugs, and related compounds exist as α-functionalized ketones or derivatives thereof. We previously reported our preliminary studies on the development of a new enantioselective ketone α-alkylation procedure using N-amino cyclic carbamate (ACC) auxiliaries. In comparison to other auxiliary-based methods, ACC alkylation offers a number of advantages and is both highly enantioselective and high yielding. Herein, we provide a full account of our studies on the enantioselective ACC ketone α-alkylation method.
- Huynh, Uyen,McDonald, Stacey L.,Lim, Daniel,Uddin, Md. Nasir,Wengryniuk, Sarah E.,Dey, Sumit,Coltart, Don M.
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p. 12951 - 12964
(2018/11/30)
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- Rhodium-Catalyzed Enantioselective Isomerization of Secondary Allylic Alcohols
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The first catalytic enantioselective isomerization of secondary allylic alcohols to access ketones with a α-tertiary stereocenter is presented. The racemic allylic alcohol substrates can be converted to the enantioenriched ketone products in a stereoconvergent fashion. The use of commercially available catalysts and mild reaction conditions makes this an attractive method in stereoselective synthesis.
- Liu, Tang-Lin,Ng, Teng Wei,Zhao, Yu
-
supporting information
p. 3643 - 3646
(2017/03/20)
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- First chemo-enzymatic synthesis of the (R)-Taniguchi lactone and substrate profiles of CAMO and OTEMO, two new Baeyer–Villiger monooxygenases
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Abstract: This study investigates the substrate profile of cycloalkanone monooxygenase and 2-oxo-Δ3-4,5,5-trimethylcyclopentenylacetyl-coenzyme A monooxygenase, two recently discovered enzymes of the Baeyer–Villiger monooxygenase family, used as whole-cell biocatalysts. Biooxidations of a diverse set of ketones were performed on analytical scale: desymmetrization of substituted prochiral cyclobutanones and cyclohexanones, regiodivergent oxidation of terpenones and bicyclic ketones, as well as kinetic resolution of racemic cycloketones. We demonstrated the applicability of the title enzymes in the enantioselective synthesis of (R)-(?)-Taniguchi lactone, a building block for the preparation of various natural product analogs such as ent-quinine. Graphical abstract: [Figure not available: see fulltext.]
- Rudroff, Florian,Fink, Michael J.,Pydi, Ramana,Bornscheuer, Uwe T.,Mihovilovic, Marko D.
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p. 157 - 165
(2017/01/17)
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- Alternatives to Phosphinooxazoline (t-BuPHOX) Ligands in the Metal-Catalyzed Hydrogenation of Minimally Functionalized Olefins and Cyclic β-Enamides
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This study presents a new series of readily accessible iridium- and rhodium-phosphite/oxazoline catalytic systems that can efficiently hydrogenate, for the first time, both minimally functionalized olefins and functionalized olefins (62 examples in total) in high enantioselectivities (ees up to >99%) and conversions. The phosphite-oxazoline ligands, which are readily available in only two synthetic steps, are derived from previous privileged 4-alkyl-2-[2-(diphenylphosphino)phenyl]-2-oxazoline (PHOX) ligands by replacing the phosphine moiety by a biaryl phosphite group and/or the introduction of a methylene spacer between the oxazoline and the phenyl ring. The modular design of the ligands has given us the opportunity not only to overcome the limitations of the iridium-PHOX catalytic systems in the hydrogenation of minimally functionalized Z-olefins and 1,1-disubstituted olefins, but also to expand their use to unfunctionalized olefins containing other challenging scaffolds (e.g., exocyclic benzofused and triaryl-substituted olefins) and also to olefins with poorly coordinative groups (e.g., α,β-unsaturated lactams, lactones, alkenylboronic esters, etc.) with enantioselectivities typically >95% ee. Moreover, both enantiomers of the hydrogenation product could be obtained by simply changing the configuration of the biaryl phosphite moiety. Remarkably, the new catalytic systems also provided excellent enantioselectivities (up to 99% ee) in the asymmetric hydrogenation of another challenging class of olefins – the functionalized cyclic β-enamides. Again, both enantiomers of the reduced amides could be obtained by changing the metal from Ir to Rh. We also demonstrated that environmentally friendly propylene carbonate can be used with no loss of enantioselectivity. Another advantage of the new ligands over the PHOX ligands is that the best ligands are derived from the affordable (S)-phenylglycinol rather than from the expensive (S)-tert-leucinol. (Figure presented.).
- Biosca, Maria,Magre, Marc,Coll, Mercè,Pàmies, Oscar,Diéguez, Montserrat
-
supporting information
p. 2801 - 2814
(2017/08/23)
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- Fluoride Anions in Self-Assembled Chiral Cage for the Enantioselective Protonation of Silyl Enol Ethers
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The potential of Song's chiral oligoethylene glycols (oligoEGs) as catalysts was explored in the enantioselective protonation of trimethylsilyl enol ethers in combination with alkali metal fluoride (KF and CsF) and in the presence of a proton source. Highly enantioselective protonations of various silyl enol ethers of α-substituted tetralones were achieved, producing chiral α-substituted tetralones in full conversion and with up to 99% ee. The established protocol was successfully extended to the synthesis of biologically relevant chiral α-substituted chromanone and thiochromanone derivatives.
- Paladhi, Sushovan,Liu, Yidong,Kumar, B. Senthil,Jung, Min-Jung,Park, Sang Yeon,Yan, Hailong,Song, Choong Eui
-
supporting information
p. 3279 - 3282
(2017/06/23)
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- Diphenylphosphinobiphenyl-oxazoline ligand and its ionic metal complex and its enantiomer or racemate preparation method and application
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The invention discloses a preparation method and an application for phosphine-oxazoline ligand, and ionic metal complex, enantiomer or racemate thereof. The ligand and the ionic metal complex thereof have the following structural formulas. The phosphine ligand related by the invention employs biphenyl as a skeleton, and realizes completely transmission from planar chirality to axial chirality through an asymmetric desymmerization. The synthetic method is simple and economic, omits a common and complex chiral separation process in the preparation of the chiral ligand. The obtained chiral ligand has the advantages of high reactive activity, good enantiomorphous selectivity and the like in a model reaction.
- -
-
Paragraph 0103-0105
(2017/01/31)
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- Iridium-Catalyzed Asymmetric Hydrogenation with Simple Cyclohexane-Based P/S Ligands: In Situ HP-NMR and DFT Calculations for the Characterization of Reaction Intermediates
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We report a reduced but structurally valuable phosphite/phosphinite-thioether ligand library for the Ir-hydrogenation of 40 minimally functionalized alkenes, including relevant examples with poorly coordinative groups. We found that enantiomeric excesses are mainly dependent on the substrate structure and on some ligand parameters (i.e., the type of thioether/phosphorus moieties and the configuration of the phosphite group), whereas the substituents of the biaryl phosphite moiety had little impact. By tuning the ligand parameters we were able to find highly selective catalysts for a range of substrates (ees up to 99%). These phosphite/phosphinite-thioether ligands have a simple backbone and thus yield simple NMR spectra that reduce signal overlap and facilitate the identification of relevant intermediates. Therefore, by combining HP-NMR spectroscopy and theoretical studies, we were also able to identify the catalytically competent Ir-dihydride alkene species, which made it possible to explain the enantioselectivity obtained.
- Borràs, Carlota,Biosca, Maria,Pàmies, Oscar,Diéguez, Montserrat
-
supporting information
p. 5321 - 5334
(2015/11/18)
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- Extending the substrate scope of bicyclic p-oxazoline/thiazole ligands for ir-catalyzed hydrogenation of unfunctionalized olefins by introducing a biaryl phosphoroamidite group
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This study identifies a series of Ir-bicyclic phosphoroamidite-oxazoline/thiazole catalytic systems that can hydrogenate a wide range of minimally functionalized olefins (including E- and Z-tri- and disubstituted substrates, vinylsilanes, enol phosphinates, tri- and disubstituted alkenylboronic esters, and ?±,?2-unsaturated enones) in high enantioselectivities (ee values up to 99%) and conversions. The design of the new phosphoroamidite-oxazoline/thiazole ligands derives from a previous successful generation of bicyclic N-phosphane-oxazoline/thiazole ligands, by replacing the N-phosphane group with a p-acceptor biaryl phosphoroamidite moiety. A small but structurally important family of Ir-phosphoroamidite-oxazoline/thiazole precatalysts has thus been synthesized by changing the nature of the Ndonor group (either oxazoline or thiazole) and the configuration at the biaryl phosphoroamidite moiety. The substitution of the N-phosphane by a phosphoroamidite group in the bicyclic N-phosphane-oxazoline/thiazole ligands extended the range of olefins that can be successfully hydrogenated.
- Biosca, Maria,Paptchikhine, Alexander,P??mies, Oscar,Andersson, Pher G.,Di??guez, Montserrat
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supporting information
p. 3455 - 3464
(2015/03/04)
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- SpinPhox/iridium(I)-catalyzed asymmetric hydrogenation of cyclic α-alkylidene carbonyl compounds
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Optically active medium-sized cyclic carbonyl compounds bearing an α-chiral carbon center are of interest in pharmaceutical sciences and asymmetric synthesis. Herein, SpinPhox/IrI catalysts have been demonstrated to be highly enantioselective in the asymmetric hydrogenation of the Ci£C bonds in the exocyclic α,β-unsaturated cyclic carbonyls, including a broad range of α-alkylidene lactams, unsaturated cyclic ketones, and lactones. It is noteworthy that the procedure can be successfully used in the asymmetric hydrogenation of the challenging α-alkylidenelactam substrates with six- or seven-membered rings, thus affording the corresponding optically active carbonyl compounds with an α-chiral carbon center in generally excellent enantiomeric excesses (up to 98 % ee). Synthetic utility of the protocol has also been demonstrated in the asymmetric synthesis of the anti-inflammatory drug loxoprofen and its analogue, as well as biologically important ε-aminocaproic acid derivatives. Take it for a spin: SpinPhox/IrI complexes are highly efficient and versatile in the enantioselective hydrogenation of a broad spectrum of exocyclic α,β-unsaturated carbonyl compounds, especially the challenging α-alkylidene lactam substrates with six- or seven-membered rings. The synthetic utility of the present protocol is demonstrated in the asymmetric synthesis of biologically important loxoprofen and ε-aminocaproic acid derivatives. Copyright
- Liu, Xu,Han, Zhaobin,Wang, Zheng,Ding, Kuiling
-
supporting information
p. 1978 - 1982
(2014/03/21)
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- Modified Marko's aerobic oxidation of alcohols under atmospheric pressure with air or molecular oxygen at room temperature
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A modified version of Marko's aerobic oxidation procedure, using highly pure (99.995+%) CuCl with 4,7-diphenyl-1,10-phenanthroline (dpPhen), DBAD, and Cs2CO3 (98% purity) successfully oxidized primary and secondary alcohols to the corresponding aldehydes and ketones in excellent yield at room temperature with either air or molecular oxygen under atmospheric pressure.
- Nishii, Takeshi,Ouchi, Tomomi,Matsuda, Aya,Matsubara, Yuka,Haraguchi, Yuuko,Kawano, Tomomi,Kaku, Hiroto,Horikawa, Mitsuyo,Tsunoda, Tetsuto
-
p. 5880 - 5882,3
(2020/07/31)
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- Development of catalysts for the stereoselective hydrogenation of α,β-unsaturated ketones
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Iridium phosphinitoxazoline complexes were found to be new efficient catalysts for the asymmetric hydrogenation of arylated α,β- unsaturated ketones. Linear as well as cyclic substrates are hydrogenated with similar success, giving selectivities of up to 99.7% ee.
- Maurer, Frauke,Huch, Volker,Ullrich, Angelika,Kazmaier, Uli
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experimental part
p. 5139 - 5143
(2012/07/03)
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- Asymmetric bioreduction of activated carbon-carbon double bonds using Shewanella yellow enzyme (SYE-4) as novel enoate reductase
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Shewanella yellow enzyme (SYE-4), a novel recombinant enoate reductase, was screened against a variety of different substrates bearing an activated double bond, such as unsaturated cyclic ketones, diesters, and substituted imides. Dimethyl- and ethyl esters of 2-methylmaleic acid were selectively reduced to (R)-configured succinic acid derivatives and various N-substituted maleimides furnished the desired (R)-products in up to >99% enantiomeric excess. Naturally occurring (+)-carvone was selectively reduced to (-)-cis- dihydrocarvone and (-)-carvone was converted to the diastereomeric product, respectively. Overall SYE-4 proved to be a useful biocatalyst for the selective reduction of activated CC double bonds and complements the pool of synthetic valuable enoate reductases.
- Iqbal, Naseem,Rudroff, Florian,Brigé, Ann,Van Beeumen, Jozef,Mihovilovic, Marko D.
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experimental part
p. 7619 - 7623
(2012/09/07)
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- A facile and practical method of preparing optically active α-monosubstituted cycloalkanones by thermodynamically controlled deracemization
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Racemic 2-monosubstituted cycloalkanones were converted to R-isomers when TADDOLs (e.g., 1a, b) were used as host molecules in alkaline aqueous MeOH. The efficiency of this thermodynamically controlled deracemization was strongly influenced by the mixture ratio of the solvent, H2O/MeOH. Based on this finding, an improved method of preparing (R)-2-monosubstituted cycloalkanones with higher optical purity was developed. For example, (R)-2-(4-methylbenzyl)cyclohexanone (5) was obtained in 85% yield with 98% ee, when a 1:1 mixture of H2O/MeOH was used as the solvent in the presence of 1a.
- Kaku, Hiroto,Nakamaru, Aya,Inai, Makoto,Nishii, Takeshi,Horikawa, Mitsuyo,Tsunoda, Tetsuto
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experimental part
p. 9450 - 9455
(2011/01/12)
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- Iridium-catalyzed highly enantioselective hydrogenation of exocyclic α,β-unsaturated carbonyl compounds
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By using the iridium complex of a phosphine-oxazoline ligand with an axis-unfixed biphenyl backbone, a highly enantioselective hydrogenation of the C=C bond of exocyclic α,β-unsaturated carbonyl compounds to afford α-chiral cyclic ketones, lactones and lactams was developed.
- Tian, Fengtao,Yao, Dongmei,Liu, Yuanyuan,Xie, Fang,Zhang, Wanbin
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experimental part
p. 1841 - 1845
(2010/10/21)
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- Induced allostery in the directed evolution of an enantioselective Baeyer-Villiger monooxygenase
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The molecular basis of allosteric effects, known to be caused by an effector docking to an enzyme at a site distal from the binding pocket, has been studied recently by applying directed evolution. Here, we utilize laboratory evolution in a different way, namely to induce allostery by introducing appropriate distal mutations that cause domain movements with concomitant reshaping of the binding pocket in the absence of an effector. To test this concept, the thermostable Baeyer-Villiger monooxygenase, phenylacetone monooxygenase (PAMO), was chosen as the enzyme to be employed in asymmetric Baeyer-Villiger reactions of substrates that are not accepted by the wild type. By using the known X-ray structure of PAMO, a decision was made regarding an appropriate site at which saturation mutagenesis is most likely to generate mutants capable of inducing allostery without any effector compound being present. After screening only 400 transformants, a double mutant was discovered that catalyzes the asymmetric oxidative kinetic resolution of a set of structurally different 2-substituted cyclohexanone derivatives as well as the desymmetrization of three different 4-substituted cyclohexanones, all with high enantioselectivity. Molecular dynamics (MD) simulations and covariance maps unveiled the origin of increased substrate scope as being due to allostery. Large domain movements occur that expose and reshape the binding pocket. This type of focused library production, aimed at inducing significant allosteric effects, is a viable alternative to traditional approaches to designed directed evolution that address the binding site directly.
- Wu, Sheng,Acevedo, Juan Pablo,Reetz, Manfred T.
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experimental part
p. 2775 - 2780
(2010/10/03)
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- Facile separation catalyst system: Direct diastereoselective synthesis of (E)-α,β-unsaturated ketones catalyzed by an air-stable Lewis acidic/basic bifunctional organobismuth complex in ionic liquids
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The catalyst system that comprises an air-stable bifunctional Lewis acidic/basic organobismuth complex and [Bmim]BF4 is highly efficient in the cross-condensation of aldehydes with ketones. Through switching the reaction from homogeneous to heterogeneous, the system shows facile separation ability and facile reusability.
- Qiu, Renhua,Qiu, Yimiao,Yin, Shuangfeng,Song, Xingxing,Meng, Zhengong,Xu, Xinhua,Zhang, Xiaowen,Luo, Shenglian,Au, Chak-Tong,Wong, Wai-Yeung
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scheme or table
p. 1767 - 1771
(2011/02/23)
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- Laboratory evolution of robust and enantioselective Baeyer-Villiger monooxygenases for asymmetric catalysis
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The Baeyer-Villiger Monooxygenase, Phenylacetone Monooxygenase (PAMO), recently discovered by Fraaije, Janssen, and co-workers, is unusually thermostable, which makes it a promising candidate for catalyzing enantioselective Baeyer-Villiger reactions in organic chemistry. Unfortunately, however, its substrate scope is very limited, reasonable reaction rates being observed essentially only with phenylacetone and similar linear phenyl-substituted analogs. Previous protein engineering attempts to broaden the range of substrate acceptance and to control enantioselectivity have been met with limited success, including rational design and directed evolution based on saturation mutagenesis with formation of focused mutant libraries, which may have to do with complex domain movements. In the present study, a new approach to laboratory evolution is described which has led to mutants showing unusually high activity and enantioselectivity in the oxidative kinetic resolution of a variety of 2-aryl and 2-alkylcyclohexanones which are not accepted by the wild-type (WT) PAMO and of a structurally very different bicyclic ketone. The new strategy exploits bioinformatics data derived from sequence alignment of eight different Baeyer-Villiger Monooxygenases, which in conjunction with the known X-ray structure of PAMO and induced fit docking suggests potential randomization sites, different from all previous approaches to focused library generation. Sites harboring highly conserved proline in a loop of the WT are targeted. The most active and enantioselective mutants retain the high thermostability of the parent WT PAMO. The success of the "proline" hypothesis in the present system calls for further testing in future laboratory evolution studies.
- Reetz, Manfred T.,Wu, Sheng
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supporting information; experimental part
p. 15424 - 15432
(2010/02/16)
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- Homogeneous pd-catalyzed enantioselective decarboxylative protonation
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General homogeneous conditions for the palladium-catalyzed synthesis of carbonyl compounds with tertiary carbon stereocenters at the a-position are reported. The highly reactive catalyst tolerates a variety of substrate substitution and functionality, and generates enantioenriched cyclic ketones from racemic allyl ss-ketoester starting materials.
- Marinescu, Smaranda C.,Nishimata, Toyoki,Mohr, Justin T.,Stoltz, Brian M.
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supporting information; experimental part
p. 1039 - 1042
(2009/04/06)
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- A bronsted acid catalyst for the enantioselective protonation reaction
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A highly reactive and robust chiral Bronsted acid catalyst, chiral N-triflyl thiophosphoramide, was developed. The first metal-free Bronsted acid catalyzed enantioselective protonation reaction of silyl enol ethers was demonstrated using this chiral Bronsted acid catalyst. The catalyst loading could be reduced to 0.05 mol % without any deleterious effect on the enantioselectivity. Copyright
- Cheol, Hong Cheon,Yamamoto, Hisashi
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supporting information; scheme or table
p. 9246 - 9247
(2009/02/02)
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- Highly enantioselective synthesis of optically active ketones by iridium-catalyzed asymmetric hydrogenation
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(Chemical Equation Presented) Close to perfect enantioselectivity (up to 99% ee, see scheme) is found for the formation of α-substituted ketones by the asymmetric hydrogenation of enones with an iridium-phosphinooxazoline catalyst. In an operationally simple process, both linear and cyclic substrates react well and afford the desired products in high yields. A wide variety of substituents are tolerated, thus making the method synthetically appealing.
- Lu, Sheng-Mei,Bolm, Carsten
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supporting information; experimental part
p. 8920 - 8923
(2009/05/30)
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- A light-driven stereoselective biocatalytic oxidation
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Let the sunshine in: Light can be used to drive enantioselective Baeyer-Villiger oxidations of cyclic ketones catalyzed by a flavin-dependent enzyme. Photochemical reduction of the flavin using ethylenediaminetetraacetate (EDTA) as the sacrificial electron donor closes the catalytic cycle, thus providing a means to directly regenerate reduced flavin cofactors without the need for costly nicotinamide cofactors as electron donors. (Chemical Equation Presented).
- Hollmann, Frank,Taglieber, Andreas,Schulz, Frank,Reetz, Manfred T.
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p. 2903 - 2906
(2008/03/13)
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- Catalytic asymmetric protonation of lithium enolates using amino acid derivatives as chiral proton sources
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Asymmetric protonation of lithium enolates was examined using commercially available amino acid derivatives as chiral proton sources. Among the amino acid derivatives tested, Nβ-L-aspartyl-L-phenylalanine methyl ester was found to cause significant asymmetric induction in the protonation of lithium enolates. The enantiomeric excess (up to 88% ee) of the products obtained in the presence of a catalytic amount of the chiral proton source was higher than those obtained in the stoichiometric reaction.
- Mitsuhashi, Kaori,Ito, Rie,Arai, Takayoshi,Yanagisawa, Akira
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p. 1721 - 1724
(2007/10/03)
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- Catalytic enantioselective decarboxylative protonation
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We report a highly enantioselective, general catalytic system for the facile synthesis of tertiary stereocenters by protonation adjacent to cyclic ketones. The method relies on catalytic decarboxylative protonation of readily accessible racemic quaternary β-ketoesters. A range of substituted cycloalkanone compounds can be accessed through this process with high levels of enantioselectivity. Copyright
- Mohr, Justin T.,Nishimata, Toyoki,Behenna, Douglas C.,Stoltz, Brian M.
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p. 11348 - 11349
(2007/10/03)
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- A modified thermodynamically controlled deracemization of 2-allylcyclohexanone and its application to asymmetric synthesis of (R)-(-)-epilachnene
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The efficiency of thermodynamically controlled deracemization was influenced considerably by the solvent used. Based on this finding, an improved method was developed, by which 2-allylcyclohexanone was converted to the R-isomer of 93% ee in 72% yield. As an application of the method, (R)-(-)-epilachnene, an antipode of the defensive droplets from the Mexican bean beetle, Epilachna varivestis, was synthesized in short steps.
- Kaku, Hiroto,Okamoto, Natsuko,Nakamaru, Aya,Tsunoda, Tetsuto
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p. 516 - 517
(2007/10/03)
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- Thermodynamically controlled deracemization of 2-alkylcycloalkanones utilizing host-guest inclusion complexation
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Based on host-guest inclusion complexation in the solid state, α-substituted cycloalkanones were deracemized using optically active host compound, TADDOL (2a) in alkaline conditions.
- Kaku, Hiroto,Ozako, Shinobu,Kawamura, Shiho,Takatsu, Shinobu,Ishii, Masayuki,Tsunoda, Tetsuto
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p. 847 - 850
(2007/10/03)
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- Stereoselective reactions. Part 31: Catalytic asymmetric alkylation of achiral lithium enolates using a chiral tetradentate amine in the presence of an achiral bidentate amine
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Catalytic asymmetric alkylation of achiral lithium enolates of 1- tetralone and cyclohexanone with reactive alkyl halides was realized by using a combination of a chiral tetradentate amine (~0.05 equiv.) and an achiral bidentate amine (2 equiv.).
- Imai, Mitsuko,Hagihara, Atsushi,Kawasaki, Hisashi,Manabe, Kei,Koga, Kenji
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p. 179 - 185
(2007/10/03)
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- Asymmetric hydrolysis of enol esters with two esterases from Marchantia polymorpha
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Two esterases participating in the asymmetric hydrolysis of α-alkylated enol acetates to α-chiral ketones were isolated from the cultured cells of Marchantia polymorpha. These two esterases had opposite enantioselectivities and both of them reversed the stereoselectivity of protonation into the enol intermediate in the hydrolysis when the chain length and the bulkiness of α-substituents were increased. Copyright (C) 2000 Elsevier Science Ltd.
- Hirata, Toshifumi,Shimoda, Kei,Kawano, Tsuyoshi
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p. 1063 - 1066
(2007/10/03)
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- Enantioselective protonation of samarium enolates derived from α- heterosubstituted ketones and lactone by SmI2-mediated reduction
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SmI2-mediated reductive cleavage of α-heterosubstituents of α-alkyl or α-aryl ketones and lactone gave the corresponding 'thermodynamic samarium enolates'. Enantioselective protonation of the samarium enolates with C2- symmetric chiral diols afforded the corresponding ketones and lactone in moderate to high enantioselectivities.
- Nakamura, Yutaka,Takeuchi, Seiji,Ohgo, Yoshiaki,Yamaoka, Makoto,Yoshida, Akihiro,Mikami, Koichi
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p. 4595 - 4620
(2007/10/03)
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- Efficient asymmetric protonation of enolates with readily accessible chiral α-sulfinyl alcohols
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The efficient asymmetric protonation of lithium enolates of 2- alkylcycloalkanones (87-96% ee) with readily accessible chiral α-sulfinyl alcohols is described. Optimal stereoselection is achieved for each lithium enolate at a different reaction temperature in the range -40 to -100°C.
- Asensio, Gregorio,Aleman, Pedro,Cuenca, Ana,Gil, Jesus,Medio-Simon, Mercedes
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p. 4073 - 4078
(2007/10/03)
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- Conformational control in proton sources for enantioselective protonation of samarium enolate derived from α-methoxy-substituted ketones
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High enantioselectivity is achieved in the asymmetric protonation of samarium enolate, regioselectively generated by SmI2-mediated reduction of 2-methoxy-substituted cydohexanones using achiral diamine- or pro-atropisomeric 2,2′-biphenol-derived chiral diols as proton sources by virtue of the conformational control.
- Mikami, Koichi,Yamaoka, Makoto,Yoshida, Akihiro,Nakamura, Yutaka,Takeuchi, Seiji,Ohgo, Yoshiaki
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p. 607 - 608
(2007/10/03)
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- Stereoselective reactions. 30. Enantioselective alkylation of the lithium enolates of six-membered cyclic ketones using tetradentate chiral amines in the presence of lithium bromide
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An efficient enantioselective alkylation of the lithium enolates of cyclohexanone and 1-tetralone with reactive alkyl halides was realized using a stoichiometric amount of a tetradentate chiral amine as a ligand for the lithium in the presence of lithium bromide in toluene.
- Murakata, Masatoshi,Yasukata, Tatsuro,Aoki, Takumi,Nakajima, Makoto,Koga, Kenji
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p. 2449 - 2458
(2007/10/03)
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- Deracemization of 2-alkylcyclohexanones utilizing host-guest molecular association with optically active host compounds in basic suspension media
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Based on host-guest inclusion complexation in the solid state, α- substituted cyclohexanones 2α-c were deracemized using optically active host compounds in alkaline conditions to optically active 2 in excellent chemical yield with high enantiomeric excess.
- Tsunoda, Tetsuto,Kaku, Hiroto,Nagaku, Miwa,Okuyama, Etsuko
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p. 7759 - 7760
(2007/10/03)
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- Enantioface-differentiating protonation with chiral γ-hydroxyselenoxides
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Enantioface-differentiating protonation of a chiral metal enolates of α-alkylcarbonyl compounds 7 has been developed using chiral γ-hydroxyselenoxides 1 as a proton source. Reaction of zinc bromide enolates of 2-benzyl- and 2-n-propylcyclohexanones with (S(Se))-1e gave (S)-2-benzylcyclohexanone 7a and (R)-2-n-propylcyclohexanone 7c in high enantiomeric excess, respectively. Intramolecular hydrogen bonding of the selenoxide 1, chelation effects between 1 and metal enolate, and 2-exo-hydroxy-10-bornyl-framework could contribute to this asymmetric induction.
- Takahashi, Tamiko,Nakao, Naoki,Koizumi, Toru
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p. 3293 - 3308
(2007/10/03)
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- Highly enantiofacial protonation of prochiral lithium enolates with chiral β-hydroxy sulfoxides
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Highly enantioselective protonation of prochiral lithium enolates is disclosed. The present method employed (S,R(s)) CF3-hydroxy sulfoxide (3b) as the chiral protonating agent, and the protonation or lithium enolates of cyclohexanone derivatives with 3b proceeded with high enantioselectivities.
- Kosugi, Hiroshi,Hoshino, Kunihide,Uda, Hisashi
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p. 6861 - 6864
(2007/10/03)
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- The first example of enantioselective protonation of prochiral enolates with chiral γ-hydroxyselenoxides
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Enantioselective protonation of a simple enolate has been developed using an optically pure γ-hydroxyselenoxide 1 as a chiral proton source. Reaction of zinc bromide enolate 7b with (Sse)-selenoxide (Sse)-1c gave (S)-2-benzylcyclohexanone (S)-8 with high enantioselectivity. Intramolecular hydrogen bonding between hydroxy group and seleninyl-oxygen of 1 would contribute to this asymmetric induction.
- Takahashi, Tamiko,Nakao, Naoki,Koizumi, Toru
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p. 207 - 208
(2007/10/03)
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- Application of Microbial Enantiofacially Selective Hydrolysis in Natural Product Synthesis
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Pichia farinosa IAM 4682 mediated enantiofacially selective hydrolysis worked efficiently (65-70percent yield) on the interface-bioreactor in a reproducible manner, which established the product, (R)-2-benzylcyclohexanone (84-87percent e.e.), to be the starting material for the synthesis of optically active natural products.Methyl (R)-3-hydroxy-12-methyltridecanoate, a constituent of lipopolysaccharide, and (R)-1,3-nonanediol, a secretion of cucumber fly, were synthesized via this common intermediate, of which the optically active secondary alcohol moiety was derived from the above chiral ketone by Baeyer-Villiger oxidation.Final products were enantiomerically enriched to 94-95percent e.e., by the lipase-mediated enantioselective transesterification, which could remove the minor enantiomer as the corresponding acetate.
- Katoh, Osamu,Sugai, Takeshi,Ohta, Hiromichi
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p. 1935 - 1944
(2007/10/02)
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- β-HYDROXY SULFOXIDE DERIVATIVES AS A POWERFUL CHIRAL PROTONATING REAGENT
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Highly enantioselective protonation of prochiral lithium enolates using enantiomerically pure β-hydroxy sulfoxides are described.
- Kosugi, Hiroshi,Hoshino, Kunihide,Uda, Hisashi
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p. 401 - 402
(2007/10/02)
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- Hydrochloride of chiral piperazine as a chiral proton source
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Asymmetric protonation utilizing hydrochlorides of chiral piperazine derivatives has been investigated. Protonation of the lithium enolate derived from 1-acetoxy-2-benzylcyclohexene with (2R,5R)-2,5-diphenylpiperazine monohydrochloride (2) resulted in a formation of (S)-2-benzylcyclohexanone in 70% ee. The enantioface-differentiating protonation with the salts of related chiral piperazine derivatives are also discussed.
- Fuji,Tanaka,Miyamoto
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p. 247 - 259
(2007/10/02)
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- Stereoselective reactions. XXI. Asymmetric alkylation of α-alkyl β-keto esters to α,α-dialkyl β-keto esters having either (R)- Or (S)-chiral quaternary center depending on the solvent system
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Asymmetric alkylation reaction of chiral enamines prepared from α-alkyl β-keto esters and (S)-valine tert-butyl ester leading to either enantiomer is described. Lithiated chiral enamines can be alkylated with alkyl halides in a toluene solvent in the presence of HMPA to give, after hydrolysis, α,α-dialkyl β-keto esters in 70-99%ee. The reactions in the presence of THF, dioxolane, or trimethylamine, instead of HMPA, afford the corresponding antipodes with enantiomeric purities of 44-92%ee. The present method provides a procedure for the synthesis of both enantiomers of α,α-dialkyl β-keto esters in high enantiomeric purities starting from the same chiral enamines.
- Ando, Kaori,Takemasa, Yataka,Tomioka, Kiyoshi,Koga, Kenji
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p. 1579 - 1588
(2007/10/02)
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- Preparation of optically active ketones via enantioface-differentiating protonation of prochiral enolates
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Enantioselective protonation of the prochiral lithium enolate (2) of 2-benzylcyclohexanone (3) was developed. Reaction of 2 with methyl (S)-α-hydroxyisocaproate (15) as a chiral proton source afforded (R)-3 in a high optical yield. This reaction is widely applicable to the preparation of various α-substituted optically active ketones.
- Matsumoto,Ohta
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p. 4729 - 4732
(2007/10/02)
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- Enzyme-mediated enantioface-differentiating hydrolysis of α-substituted cycloalkanone enol esters
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A new type of enzymatic hydrolysis, enantioface-differentiating hydrolysis of enol esters, is disclosed. As a result of screening, Pichia miso IAM 4682, a type of yeast, was selected as the best strain to perform the enantioselective hydrolysis of enol esters to give α-chiral ketones. For example, incubation of 1-acetoxy-2-methylcyclohexene (4a) with P. miso afforded (S)-2-methylcyclohexanone (5) in high optical yield. This enzymatic hydrolysis is applicable to various α-substituted cycloalkanone enol esters, and thereby chiral six-, eight-, ten-, and twelve-membered-ring ketones of 70-96% enantiomeric excess (ee) are easily prepared.
- Matsumoto, Kazutsugu,Tsutsumi, Seiji,Ihori, Tamiko,Ohta, Hiromichi
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p. 9614 - 9619
(2007/10/02)
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- Enantioselective Alkylation at the α-Position of Cyclic Ketones using a Chiral Lithium Amide as a Base in the Presence of Lithium Bromide
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An efficient enantioselective alkylation reaction at the α-position of cyclic ketones (1, 2) can be realized in up to 92percent enantiomeric excess (e.e) by first forming their lithium enolates using a chiral lithium amide 4 in the presence of lithium bromide, followed by treatment with alkyl halides.
- Murakata, Masatoshi,Nakajima, Makoto,Koga, Kenji
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p. 1657 - 1658
(2007/10/02)
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