- Efficient resolution of (±)-α-cyclopropylethanol by crystallization of its inclusion complex with chiral diols
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The two-step inclusion crystallization of the chiral diol TADDOL with α-cyclopropylethanol has been found to allow resolving the racemic alcohol to yield (R)- or (S)-enantiomer (> 98% ee).
- Vinogradov, Maxim G.,Kurilov, Dmitry V.,Chel'tsova, Galina V.,Ferapontov, Vladimir A.,Heise, Glenn L.
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Read Online
- Chiral Imidazo[1,5- a]pyridine-Oxazolines: A Versatile Family of NHC Ligands for the Highly Enantioselective Hydrosilylation of Ketones
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Herein we report the synthesis and application of a versatile class of N-heterocyclic carbene ligands based on an imidazo[1,5-a]pyridine-3-ylidine backbone that is fused to a chiral oxazoline auxiliary. The key step in the synthesis of these ligands involves the installation of the oxazoline functionality via a microwave-assisted condensation of a cyano-azolium salt with a wide variety of 2-amino alcohols. The resulting chiral bidentate NHC-oxazoline ligands form stable complexes with rhodium(I) that are efficient catalysts for the enantioselective hydrosilylation of structurally diverse ketones. The corresponding secondary alcohols are isolated in good yields (typically >90%) with good to excellent enantioselectivities (80-93% ee). The reported hydrosilylation occurs at ambient temperatures (40 °C), with excellent functional group tolerability. Even ketones bearing heterocyclic substituents (e.g., pyridine or thiophene) or complex organic architectures are hydrosilylated efficiently, which is discussed further in this report.
- Chinna Ayya Swamy,Varenikov, Andrii,Ruiter, Graham De
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supporting information
p. 247 - 257
(2020/02/04)
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- C1-Symmetric PNP Ligands for Manganese-Catalyzed Enantioselective Hydrogenation of Ketones: Reaction Scope and Enantioinduction Model
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A family of ferrocene-based chiral PNP ligands is reported. These tridentate ligands were successfully applied in Mn-catalyzed asymmetric hydrogenation of ketones, giving high enantioselectivities (92%~99% ee for aryl alkyl ketones) as well as high efficiencies (TON up to 2000). In addition, dialkyl ketones could also be hydrogenated smoothly. Manganese intermediates that might be involved in the catalytic cycle were analyzed. DFT calculation was carried out to help understand the chiral induction model. The Mn/PNP catalyst could discriminate two groups with different steric properties by deformation of the phosphine moiety in the flexible 5-membered ring.
- Zeng, Liyao,Yang, Huaxin,Zhao, Menglong,Wen, Jialin,Tucker, James H. R.,Zhang, Xumu
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p. 13794 - 13799
(2020/11/30)
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- Manganese Catalyzed Asymmetric Transfer Hydrogenation of Ketones Using Chiral Oxamide Ligands
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The asymmetric transfer hydrogenation of ketones using isopropyl alcohol (IPA) as hydrogen donor in the presence of novel manganese catalysts is explored. The selective and active systems are easily generated in situ from [MnBr(CO)5] and inexpensive C2-symmeric bisoxalamide ligands. Under the optimized reaction conditions, the Mn-derived catalyst gave higher enantioselectivity compared with the related ruthenium catalyst.
- Schneek?nig, Jacob,Junge, Kathrin,Beller, Matthias
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supporting information
p. 503 - 507
(2019/02/26)
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- Enantioselective Hydrogenation of Ketones using Different Metal Complexes with a Chiral PNP Pincer Ligand
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The synthesis of different metal pincer complexes coordinating to the chiral PNP ligand bis(2-((2R,5R)-2,5-dimethyl-phospholanoethyl))amine is described in detail. The characterized complexes with Mn, Fe, Re and Ru as metal centers showed good activities regarding the reduction of several prochiral ketones. Comparing these catalysts, the non-noble metal complexes produced best selectivities not only for aromatic substrates, but also for different kinds of aliphatic ones leading to enantioselectivities up to 99% ee. Theoretical investigations elucidated the mechanism and rationalized the selectivity. (Figure presented.).
- Garbe, Marcel,Wei, Zhihong,Tannert, Bianca,Spannenberg, Anke,Jiao, Haijun,Bachmann, Stephan,Scalone, Michelangelo,Junge, Kathrin,Beller, Matthias
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supporting information
p. 1913 - 1920
(2019/03/13)
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- Biocatalytic Racemization Employing TeSADH: Substrate Scope and Organic Solvent Compatibility for Dynamic Kinetic Resolution
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Racemization in combination with a kinetic resolution is the base for a dynamic kinetic resolution (DKR). Biocatalytic racemization was successfully performed for a broad scope of sec-alcohols by employing a single alcohol dehydrogenase (ADH) variant from Thermoanaerobacter pseudoethanolicus (formerly T. ethanolicus; TeSADH W110A I86A C295A). The catalyst employed as a lyophilized whole cell preparation or cell free extract, which tolerated various non-water miscible organic solvents under micro-aqueous or two-phase conditions, whereby cyclohexane and n-hexane suited best. Various concepts for combining the enzymatic racemization with an enzymatic kinetic resolution to achieve overall a bis-enzymatic DKR were evaluated. A proof of concept showed a successful DKR with racemization in aqueous phase combined with acylation in the organic phase.
- Pop?oński, Jaros?aw,Reiter, Tamara,Kroutil, Wolfgang
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p. 763 - 768
(2018/02/27)
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- Iridium and Rhodium Complexes Containing Enantiopure Primary Amine-Tethered N-Heterocyclic Carbenes: Synthesis, Characterization, Reactivity, and Catalytic Asymmetric Hydrogenation of Ketones
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The imidazolium salt [(S,S)-tBuNC3H3NCHPhCHPhNH2]PF6, (S,S)-11·HPF6 is a precursor to the enantiopure "Kaibene" ligand, tBu-Kaibene, (S,S)-11 featuring a tert-butyl group on the N-heterocyclic carbene (NHC) ring-nitrogen atoms. It has been prepared in high yield and purity by refluxing a chiral cyclic sulfamidate with 1-tert-butylimidazole. Similarly (S,S)-12·HPF6 with a mesityl group at the imidazolium ring-nitrogen atom has been prepared in the same fashion and serves as a source of Mes-Kaibene, (S,S)-12. These bidentate Kaibene ligands feature an NHC and a primary amine separated by a chiral linker. Salts (S,S)-11·HPF6 or (S,S)-12·HPF6 react with base and AgI or CuI to give a total of four M(Kaibene)2I compounds (M = Ag or Cu). At 22 °C, the amine-functionalized imidazolium cations undergo oxidative addition to iridium(I) in [IrCl(cod)]2 (cod = 1,5-cyclooctadiene) to generate iridium(III) hydride R-Kaibene compounds [IrHCl(cod)((S,S)-11)](PF6) (17) and [IrHCl(cod)((S,S)-12)](PF6) (18), respectively, each as a mixture of six configurational isomers. In contrast, the salt (S,S)-11·HPF6 reacts with [Ir(OtBu)(cod)]2 to produce a bimetallic iridium compound with (S,S)-11 as the bridging ligand. This compound contains interesting NH···Cl and NH···Ir noncovalent intramolecular interactions. Salt (S,S)-12·HPF6 reacts with silver oxide to yield [Ag2((S,S)-12)2](PF6)2 (20). Reagent 20 serves as an efficient transmetalation reagent to deliver to each rhodium in [RhCl(cod)]2 1 equiv of (S,S)-12 as a bidentate ligand to give [Rh(cod)((S,S)-12)](PF6). In the reaction between [IrCl(cod)]2 and 20, (S,S)-12 ends up coordinated in an iridium(III) hydride complex (22) as a tridentate ligand via the NHC, NH2, and a cyclometalated phenyl group. The two iridium hydride compounds, 18 and 22, are catalysts for the hydrogenation of a range of ketones (turnover number up to 499, turnover frequency up to 249 h-1, with er (enantiomeric ratio) up to 35:65 R:S).
- Wan, Kai Y.,Roelfes, Florian,Lough, Alan J.,Hahn, F. Ekkehardt,Morris, Robert H.
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supporting information
p. 491 - 504
(2018/02/17)
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- CHIRAL METAL COMPLEX COMPOUNDS
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The invention comprises novel chiral metal complex compounds of the formula (I) wherein M, PR2, R3 and R4 are outlined in the description, its stereoisomers, in the form as a neutral complex or a complex cation with a suitable counter ion. The chiral metal complex compounds can be used in asymmetric reactions, particularly in asymmetric reductions of ketones, imines or oximes.
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Page/Page column 18; 19; 21; 24; 25
(2018/11/10)
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- Iridium-Catalyzed Asymmetric Hydrogenation of Ketones with Accessible and Modular Ferrocene-Based Amino-phosphine Acid (f-Ampha) Ligands
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A series of tridentate ferrocene-based amino-phosphine acid (f-Ampha) ligands have been successfully developed. The f-Ampha ligands are extremely air stable and exhibited excellent performance in the Ir-catalyzed asymmetric hydrogenation of ketones (full conversions, up to >99% ee, and 500?000 TON). DFT calculations were performed to elucidate the reaction mechanism and the importance of the COOH group. Control experiments also revealed that the COOH group played a key role in this reaction.
- Yu, Jianfei,Long, Jiao,Yang, Yuhong,Wu, Weilong,Xue, Peng,Chung, Lung Wa,Dong, Xiu-Qin,Zhang, Xumu
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supporting information
p. 690 - 693
(2017/02/10)
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- Manganese(I)-Catalyzed Enantioselective Hydrogenation of Ketones Using a Defined Chiral PNP Pincer Ligand
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A new chiral manganese PNP pincer complex is described. The asymmetric hydrogenation of several prochiral ketones with molecular hydrogen in the presence of this complex proceeds under mild conditions (30–40 °C, 4 h, 30 bar H2). Besides high catalytic activity for aromatic substrates, aliphatic ketones are hydrogenated with remarkable selectivity (e.r. up to 92:8). DFT calculations support an outer sphere hydrogenation mechanism as well as the experimentally determined stereochemistry.
- Garbe, Marcel,Junge, Kathrin,Walker, Svenja,Wei, Zhihong,Jiao, Haijun,Spannenberg, Anke,Bachmann, Stephan,Scalone, Michelangelo,Beller, Matthias
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supporting information
p. 11237 - 11241
(2017/09/02)
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- Iridium Catalysts with f-Amphox Ligands: Asymmetric Hydrogenation of Simple Ketones
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A series of modular and rich electronic tridentate ferrocene aminophosphoxazoline ligands (f-amphox) have been successfully developed and used in iridium-catalytic asymmetric hydrogenation of simple ketones to afford corresponding enantiomerically enriched alcohols under mild conditions with superb activities and excellent enantioselectivities (up to 1"000"000 TON, almost all products up to >99% ee, full conversion). The resulting chiral alcohols and their derivatives are important intermediates in pharmaceuticals.
- Wu, Weilong,Liu, Shaodong,Duan, Meng,Tan, Xuefeng,Chen, Caiyou,Xie, Yun,Lan, Yu,Dong, Xiu-Qin,Zhang, Xumu
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supporting information
p. 2938 - 2941
(2016/07/06)
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- Asymmetric reduction of ketones catalyzed by α,α-diphenyl-(L)-prolinol modified with imidazolium ionic liquid and BH3·SMe2 as a recoverable catalyst
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The synthesis of α,α-diphenyl-4-trans-hydroxy-(L)-prolinol modified with imidazolium based ionic liquids was carried out with trans-α,α-diphenyl-4-hydroxy-(L)-prolinol, 5-bromovaleric acid or 1,5-dibromopentane and imidazole. α,α-Diphenyl-4-hydroxy-(L)-prolinol modified with imidazolium ionic liquid was treated with BH3·SMe2 which generate 1,3,2-oxazaborolidine, that acts as a catalyst for asymmetric reduction of prochiral ketones. α,α-Diphenyl-4-hydroxy-(L)-prolinol modified with imidazolium ionic liquids (PF6 anion) with BH3?SMe2 found to be an efficient catalyst (10 mol%) for the reduction of the acetophenone, gave 99% yield and 87-84% ee. The catalytic method has wide applicability for a variety of substrates. 1,3,2-oxazaborolidine containing ether linkage ionic liquid was recovered and reused up to 4 cycles with 99-91% yields and 87-81% ee's.
- Chauhan, ManMohan Singh,Singh, Surendra
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p. 184 - 189
(2015/02/19)
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- Enantioselective oxidation of racemic secondary alcohols catalyzed by chiral Mn(iii)-salen complexes with N-bromosuccinimide as a powerful oxidant
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We demonstrate an efficient enantioselective oxidation of secondary alcohols catalyzed by Mn(iii)-salen complex using N-bromosuccinimide (NBS) as the oxidant. The new protocol is very efficient for the oxidative kinetic resolution of a variety of secondary alcohols, including ortho-substituted benzylic alcohols. The Royal Society of Chemistry 2012.
- Xu, Daqian,Wang, Shoufeng,Shen, Zhiqiang,Xia, Chungu,Sun, Wei
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supporting information
p. 2730 - 2732
(2012/11/07)
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- 1-methyl 1′-cyclopropylmethyl (MCPM) as an anomeric protecting group
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A pragmatic approach for preparing glycoconjugates of complex oligosaccharides is to prepare the oligosaccharide as a building block with most of its protecting groups exchanged to protecting groups whose cleavage and other manipulations are highly compatible with the functional groups of complex aglycones. For such an approach the reducing end sugar of the building bloc must be protected with a cleavable protecting group during the oligosaccharide synthesis. We demonstrate that the acid labile 1-methyl 1′- cyclopropylmethyl (MCPM) can be effectively used for this purpose. A trisaccharide glycolipid and a disaccharide glycoamino acid are prepared. The absolute chirality of the MCPM in one key acceptor is determined by a combination of NMR NOE measurements, DFT molecular modeling and Noyori catalyst catalyzed asymmetric reduction.
- Yu, Siu Hong,Whitfield, Dennis M.
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supporting information; experimental part
p. 5750 - 5761
(2011/08/22)
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- The palladium-catalyzed aerobic kinetic resolution of secondary alcohols: Reaction development, scope, and applications
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The first palladium-catalyzed enantioselective oxidation of secondary alcohols has been developed, utilizing the readily available diamine (-)-sparteine as a chiral ligand and molecular oxygen as the stoichiometric oxidant. Mechanistic insights regarding the role of the base and hydrogen-bond donors have resulted in several improvements to the original system. Namely, addition of cesium carbonate and tert-butyl alcohol greatly enhances reaction rates, promoting rapid resolutions. The use of chloroform as solvent allows the use of ambient air as the terminal oxidant at 23°C, resulting in enhanced catalyst selectivity. These improved reaction conditions have permitted the successful kinetic resolution of benzylic, allylic, and cyclopropyl secondary alcohols to high enantiomeric excess with good-toexcellent selectivity factors. This catalyst system has also been applied to the desymmetrization of meso-diols, providing high yields of enantioenriched hydroxyketones.
- Ebner, David C.,Bagdanoff, Jeffrey T.,Ferreira, Eric M.,McFadden, Ryan M.,Caspi, Daniel D.,Trend, Raissa M.,Stoltz, Brian M.
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supporting information; experimental part
p. 12978 - 12992
(2010/06/19)
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- Mild and practical reductions of prochiral ketones to chiral alcohols using the chiral boronic ester TarB-H
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Chiral alcohols are prepared under mild conditions in high enantiomeric excesses using the tartaric acid derived chiral boronic ester TarB-H. The phenylboronic acid was quantitatively recovered and recycled using a simple extraction with sodium hydroxide and diethyl ether. Aromatic and aliphatic secondary alcohols were prepared in up to 99% ee. Georg Thieme Verlag Stuttgart.
- Eagon, Scott,Kim, Jinsoo,Singaram, Bakthan
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experimental part
p. 3874 - 3876
(2009/06/18)
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- Asymmetric reductions using the chiral boronic ester TarB-H: a practical and inexpensive procedure for synthesizing chiral alcohols
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Chiral alcohols are prepared in high enantiomeric excesses using an inexpensive and easily synthesized tartaric acid derived boronic ester (TarB-H) with sodium borohydride. The phenylboronic acid could be recovered quantitatively using a simple extraction with sodium hydroxide and diethyl ether. The optimized TarB-H system was used to reduce aromatic and aliphatic ketones in an open flask to chiral alcohols with enantiomeric excesses up to 99%.
- Eagon, Scott,Kim, Jinsoo,Yan, Katie,Haddenham, Dustin,Singaram, Bakthan
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p. 9025 - 9029
(2008/03/18)
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- Metallocenyl P-N ligands, preparation thereof, and use for asymmetric catalysis
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Bidentate phosphine-nitrogen ligands are disclosed which include a phosphine linked with a nitrogen heterocycle through a chiral ferrocene backbone. The ligands can include an imidazole or a dihydroimidazole linked to the ferrocene through the 2-position.
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Page/Page column 9-10
(2010/11/28)
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- Enantioselective reduction of aliphatic ketones using NaBH4 and TarB-NO2, a chiral boronic ester
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High enantioselectivities are obtained using a tartaric acid-derived boronic ester (TarB-NO2) in combination with NaBH4 for the asymmetric reduction of aliphatic ketones. The resulting alcohols are obtained in enantiomeric excesses ranging from 56% to 94%.
- Kim, Jinsoo,Singaram, Bakthan
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p. 3901 - 3903
(2007/10/03)
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- Tetradentate ligands and metal complexes thereof for asymmetric catalysis
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This invention relates to novel, substantially enantiomerically pure tetradentate ligands comprised of two phosphines and two secondary amines. These species have been used as ligands for metal catalysts for asymmetric reactions and have demonstrated good
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Page/Page column 10
(2008/06/13)
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- Designing the "Search pathway" in the development of a new class of highly efficient stereoselective hydrosilylation catalysts
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A highly efficient class of N-heterocyclic carbene-based catalysts for the asymmetric hydrosilylation of prochiral ketones was discussed. The potential pitfalls associated with the nonlinearity in the behavior of an enantioselective catalyst in response to the variations of key reaction parameters were also described. The modular design of a new catalyst is based essentially on a single assembly step of its structural and functional subunits. It was observed that the direct coupling of oxazolines and N-heterocyclic carbenes leads to chelating C,N ancillary ligands for asymmetric catalysis that combines both an 'anchor' unit and a stereodirecting element.
- Cesar, Vincent,Beliemin-Laponnaz, Stephane,Wadepohl, Hubert,Gade, Lutz H.
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p. 2862 - 2873
(2007/10/03)
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- Insight into the mechanism of oxidative kinetic resolution of racemic secondary alcohols by using manganese(III)(salen) complexes as catalysts
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The oxidative kinetic resolution of various racemic secondary alcohols with PhI(OAc)2 catalyzed by chiral [MnIII(salen)] complexes in the presence of KBr was studied in a water/organic solvent mixture. The dramatic, synergetic effect of additives, organic solvent, and the substituents of chiral salen ligands on the enantioselectivities of the reactions is reported. Results from UV/Vis spectroscopy and ESI-MS studies provide evidence that these reactions are induced by the formation of a high-valent manganese intermediate.
- Li, Zhen,Tang, Zhong H.,Hu, Xiao X.,Xia, Chun G.
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p. 1210 - 1216
(2007/10/03)
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- A modular assembly of chiral oxazolinylcarbene-rhodium complexes: Efficient phosphane-free catalysts for the asymmetric hydrosilylation of dialkyl ketones
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A novel class of chiral bidentate ligands with a carbene and an oxazoline moiety is obtained by the coupling of N-arylimidazoles and a 2-bromooxazoline derivative. The rhodium complex 1 catalyzes the hydrosilylation of aryl alkyl ketones and otherwise problematic dialkyl ketones in high yields and good enantioselectivities (up to 95% ee).
- Gade, Lutz H.,Cesar, Vincent,Bellemin-Laponnaz, Stephane
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p. 1014 - 1017
(2007/10/03)
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- Scope of enantioselective Palladium(II)-catalyzed aerobic alcohol oxidations with (-)-sparteine
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Evaluation of the substrate scope for Pd(II)/ (-)-sparteine catalyzed aerobic oxidative kinetic resolution of secondary alcohols is disclosed. An improved system is found with use of tert-butyl alcohol solvent in which benzylic and aliphatic alcohols as well as alcohols containing olefins are effectively oxidatively resolved. For substrates that successfully undergo oxidative kinetic resolution, krel values are generally between 10 and 20. Successful scale-up of various substrates to 10-mmol scale is described. Extension to oxidative desymmetrization of 1,3-meso-diols is successful with enantiomeric excesses ranging from 78 to 85%.
- Mandal, Sunil K.,Jensen, David R.,Pugsley, Jacob S.,Sigman, Matthew S.
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p. 4600 - 4603
(2007/10/03)
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- Palladium-catalyzed aerobic oxidative kinetic resolution of alcohols with an achiral exogenous base
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Substitution of exogenous (-)-sparteine for a more practical achiral base in the aerobic oxidative kinetic resolution of secondary alcohols is described. Carbonate bases are the most effective of those screened and allow for effective kinetic resolution of benzylic, allylic, and aliphatic substrates. The procedure was also successfully extended to the oxidative desymmetrization of meso diols.
- Mandal, Sunil K.,Sigman, Matthew S.
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p. 7535 - 7537
(2007/10/03)
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- Asymmetric Reductions of Prochiral Ketones with B-3-Pinanyl-9-borabicyclononane (Alpine-Borane) at Elevated Pressures
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The reduction of unhindered ketones, such as acetylenic ketones, with B-3-pinanyl-9-borabicyclononane (Alpine-Borane, prepared by hydroboration of α-pinene with 9-BBN) provides a simple means of forming chiral, nonracemic alcohols of known absolute configuration in high enantiomeric purity.A dehydroboration-reduction mechanism leading to racemic alcohol is believed to be responsible for erosion of the enantiomeric efficiency with more hindered ketones.The use of elevated pressures (2000-6000 atm) accelerates the asymmetric reduction mode while suppressing the undesired dehydroboration mode.The use of high pressure permits a studyof the scope and utility of Alpine-Borane in the absence of the competing side reaction.The reduction of ketones containing chiral centers was studied with use of the reagent from (+)-α-pinene. d-Carvone is reduced while l-carvone is not.Methyl-substituted cyclohexanones show no discrimination between enantiomers.For example, 2-methylcyclohexanone is reduced to a 1:1 mixture of cis- and trans-2-methylcyclohexanol, each of which is about 65 percent ee.In all cases, one may predict the absolute configuration of the product based on a simple model.The relative steric requirements of groups on the ketone may be catagorized as very small (CCH, CN, H, D); small (CH3, CO2CH3); medium (n-alkyl, trans-RHC=CH); medium large (CF3, i-Pr); large (Ar); and too large (tert-butyl).Effective asymmetric reductions are achieved when groups from nonadjacent catagories are attached to the carbonyl.
- Midland, M. Mark,McLoughlin, Jim I.,Gabriel, Josef
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p. 159 - 165
(2007/10/02)
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- Asymmetric Reduction of Prochiral Ketones with B-3-Pinanyl-9-borabicyclononane in Efficiencies Approaching 100percent. Simultaneous Rate Enhancement and Side Reaction Suppression via the Use of Elevated Pressures
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Elevated pressures (up to 6000 atm) significantly accelerate the asymmetric reduction of prochiral ketones with B-3-pinanyl-9-borabicyclononane while suppressing the competing dehydroboration-reduction process.In selected cases enantiomeric efficiencies approaching 100percent may now be achieved.
- Midland, M. Mark,McLoughlin, Jim I.
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p. 1316 - 1317
(2007/10/02)
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