- Highly enantioselective aminoacylase-catalyzed transesterification of secondary alcohols
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The aminoacylase (N-acyl-L-amino acid amidohydrolase; E.C. 3.5.1.14) from Aspergillus melleus, a readily available inexpensive enzyme, catalyzes the transesterification of a wide range of chiral secondary arylalkanols with essentially absolute stereoselectivity (E> 500). Moreover, the productivities obtained with 1-phenylethanol, 1-phenylpropanol, 1-(1-naphthyl)ethanol and 1- (2-naphthyl)ethanol were substantially higher than those in the corresponding lipase-catalyzed transesterifications. (C) 2000 Elsevier Science Ltd.
- Bakker,Spruijt,Van Rantwijk,Sheldon
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- Hypervalent Iodine-Based Activation of Triphenylphosphine for the Functionalization of Alcohols
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The use of hypervalent iodine reagents as a general tool for the activation of PPh 3 and its application to the functionalization of alcohols is reported. Combination of PPh 3 with PhICl 2 or TolIF 2 gives dihalophosphoranes that are characterized by 31 P NMR, however, with PhIOAc 2, PhI(OTFA) 2, or the cyclic chloro(benzoyloxy)iodane, no phosphoranes were observed. Reaction of these iodanes with PPh 3 in the presence of primary, secondary, or tertiary alcohols results in either halogenation or acyl-transfer products in moderate to high yield.
- Eljo, Jasmin,Carle, Myriam S.,Murphy, Graham K.
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- CO2-expanded bio-based liquids as novel solvents for enantioselective biocatalysis
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For the first time, CO2-expanded bio-based liquids were reported as novel and sustainable solvents for biocatalysis. Herein, it was found that by expansion with CO2, 2-methyltetrahydrofuran (MeTHF), and other bio-based liquids, which were not favorable solvents for immobilized Candida antarctica lipase B (Novozym 435) catalyzed transesterification, were tuned into excellent reaction media. Especially, for the kinetic resolution of challenging bulky secondary substrates such as rac-1-adamantylethanol, the lipase displayed very high activity with excellent enantioselectivity (E value > 200) in CO2-expanded MeTHF (MeTHF concentration 10% v/v, 6 MPa), whereas there was almost no activity observed in conventional organic solvents.
- Hoang, Hai Nam,Nagashima, Yoshihiro,Mori, Shuichi,Kagechika, Hiroyuki,Matsuda, Tomoko
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- Disubstituted dialkoxysilane precursors in binary and ternary sol-gel systems for lipase immobilization
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The disubstituted dimethyldiethoxysilane (DMDEOS), methyl(phenyl) diethoxysilane (MPDEOS) and diphenyldiethoxysilane (DPDEOS) were used in binary silane precursor systems in combination with tetraethoxysilane (TEOS) for the immobilization of lipase from Pseudomonas fluorescens (Lipase AK). In addition, ternary silane precursor systems with TEOS and octyltriethoxysilane (OTEOS) or phenyltriethoxysilane (PTEOS) were also studied for encapsulation. The best performing ternary sol-gel preparations (418-736% activity yields of the immobilized enzyme with 1-phenylethanol rac-1a as compared to the native form) were tested as biocatalysts for kinetic resolutions of rac-1a, 1-phenylpropan-2-ol rac-1b and 4-phenylbutan-2-ol rac-1c. Because the catalytic properties and the operational stability of the DMDEOS-containing preparations proved to be superior to all the tested free and sol-gel entrapped Lipase AK biocatalysts in batch mode, the kinetic resolutions of rac-1a and rac-1b were performed with the TEOS/PTEOS/DMDEOS 4:1:1 Lipase AK in a continuous-flow reactor as well.
- Weiser, Diána,Boros, Zoltán,Hornyánszky, Gábor,Tóth, Alexandra,Poppe, László
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- CALB immobilized onto magnetic nanoparticles for efficient kinetic resolution of racemic secondary alcohols: Long-term stability and reusability
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In this study, an immobilization strategy for magnetic cross-linking enzyme aggregates of lipase B from Candida antarctica (CALB) was developed and investigated. Magnetic particles were prepared by conventional co-precipitation. The magnetic nanoparticles were modified with 3-aminopropyltriethoxysilane (APTES) to obtain surface amino-functionalized magnetic nanoparticles (APTES–Fe3O4) as immobilization materials. Glutaraldehyde was used as a crosslinker to covalently bind CALB to APTES–Fe3O4. The optimal conditions of immobilization of lipase and resolution of racemic 1-phenylethanol were investigated. Under optimal conditions, esters could be obtained with conversion of 50%, enantiomeric excess of product (eep) > 99%, enantiomeric excess of substrate (ees) > 99%, and enantiomeric ratio (E) > 1000. The magnetic CALB CLEAs were successfully used for enzymatic kinetic resolution of fifteen secondary alcohols. Compared with Novozym 435, the magnetic CALB CLEAs exhibited a better enantioselectivity for most substrates. The conversion was still greater than 49% after the magnetic CALB CLEAs had been reused 10 times in a 48 h reaction cycle; both ees and eep were close to 99%. Furthermore, there was little decrease in catalytic activity and enantioselectivity after being stored at ?20 ?C for 90 days.
- Xing, Xiu,Jia, Jun-Qi,Zhang, Jing-Fan,Zhou, Zi-Wen,Li, Jun,Wang, Na,Yu, Xiao-Qi
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- Discovery and Redesign of a Family VIII Carboxylesterase with High (S)-Selectivity toward Chiral sec-Alcohols
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Highly enantioselective lipase has been widely utilized in the preparation of versatile enantiopure chiral sec-alcohols through kinetic or dynamic kinetic resolution. Lipase is intrinsically (R)-selective, and it is difficult to obtain (S)-selective lipase. Recent crystal structures of a family VIII carboxylesterase have revealed that the spatial array of its catalytic triad is the mirror image of that of lipase but with a catalytic triad that is distinct from lipase. We, therefore, hypothesized that the family VIII carboxylesterase may exhibit (S)-enantioselectivity toward sec-alcohols similar to (S)-selective serine protease, whose catalytic triad is also spatially arrayed as its mirror image. In this study, a homologous enzyme (carboxylesterase from Proteobacteria bacterium SG_bin9, PBE) of a known family VIII carboxylesterase (pdb code: 4IVK) was prepared, which showed not only moderate (S)-selectivity toward sec-alcohols such as 3-butyn-2-ol and 1-phenylethyl alcohol but also (R)-selectivity toward particular sec-alcohols among the substrates explored. Furthermore, the (S)-selectivity of PBE has been significantly improved by rational redesign based on molecular modeling. Molecular modeling identified a binding pocket composed of Ser381, Ala383, and Arg408 for the methyl substituent of (R)-1-phenylethyl acetate and suggested that larger residues may increase the enantioselectivity by interfering with the binding of the slow-reacting enantiomer. As predicted, substituting Ser381with larger residues (Phe, Tyr, and Trp) significantly improved the (S)-selectivity of PBE toward all sec-alcohols explored, even the substrates toward which the wild-type PBE exhibits (R)-selectivity. For instance, the enantioselectivity toward 3-butyn-2-ol and 1-phenylethyl alcohol was improved from E = 5.5 and 36.1 to E = 2001 and 882, respectively, by single mutagenesis (S381F).
- Park, Areum,Park, Seongsoon
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p. 2397 - 2402
(2022/02/17)
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- Two-Step Protocol for Iodotrimethylsilane-Mediated Deoxy-Functionalization of Alcohols
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We have developed a two-step protocol for iodotrimethylsilane-mediated deoxy-functionalization of primary and secondary alcohols to afford products containing a C?N, C?S, or C?O bond. In the first step the alcohol undergoes iodination with iodotrimethylsilane, and in the second, the iodine atom is replaced by a N, S, or O nucleophile. Compared with traditional Mitsunobu reaction, non-acidic pre-nucleophiles can be used, and the reaction proceeds with retention of configuration. This operationally simple, highly efficient protocol can be used for some natural products and small-molecule drugs containing hydroxy-group.
- Chen, Yuming,He, Ru,Song, Hongjian,Yu, Guoqing,Li, Chenglin,Liu, Yuxiu,Wang, Qingmin
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p. 1179 - 1183
(2021/02/01)
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- Evaluation of gem-Diacetates as Alternative Reagents for Enzymatic Regio-and Stereoselective Acylation of Alcohols
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Geminal diacetates have been used as sustainable acyl donors for enzymatic acylation of chiral and nonchiral alcohols. Especially, it was revealed that geminal diacetates showed higher reactivity than vinyl acetate for hydrolases that are sensitive to acetaldehyde. Under optimized conditions for enzymatic acylation, several synthetically relevant saturated and unsaturated acetates of various primary alcohols were obtained in very high yields up to 98% without E/Z isomerization of the double bond. Subsequently, the acyl donor was recreated from the resulting aldehyde and reused constantly in acylation. Therefore, the developed process is characterized by high atomic efficiency. Moreover, it was shown that acylation using geminal diacetates resulted in remarkable regioselectivity by discriminating among the primary and secondary hydroxyl groups in 1-phenyl-1,3-propanediol providing exclusively 3-acetoxy-1-phenyl-propan-1-ol in good yield. Further, enzymatic kinetic resolution (EKR) and chemoenzymatic dynamic kinetic resolution (DKR) protocols were developed using geminal diacetate as an acylating agent, resulting in chiral acetates in high yields up to 94% with enantiomeric excesses exceeding 99%.
- Koszelewski, Dominik,Brodzka, Anna,Madej, Arleta,Trzepizur, Damian,Ostaszewski, Ryszard
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p. 6331 - 6342
(2021/05/06)
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- Pickering-Droplet-Derived MOF Microreactors for Continuous-Flow Biocatalysis with Size Selectivity
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Enzymatic microarchitectures with spatially controlled reactivity, engineered molecular sieving ability, favorable interior environment, and industrial productivity show great potential in synthetic protocellular systems and practical biotechnology, but their construction remains a significant challenge. Here, we proposed a Pickering emulsion interface-directed synthesis method to fabricate such a microreactor, in which a robust and defect-free MOF layer was grown around silica emulsifier stabilized droplet surfaces. The compartmentalized interior droplets can provide a biomimetic microenvironment to host free enzymes, while the outer MOF layer secludes active species from the surroundings and endows the microreactor with size-selective permeability. Impressively, the thus-designed enzymatic microreactor exhibited excellent size selectivity and long-term stability, as demonstrated by a 1000 h continuous-flow reaction, while affording completely equal enantioselectivities to the free enzyme counterpart. Moreover, the catalytic efficiency of such enzymatic microreactors was conveniently regulated through engineering of the type or thickness of the outer MOF layer or interior environments for the enzymes, highlighting their superior customized specialties. This study provides new opportunities in designing MOF-based artificial cellular microreactors for practical applications.
- Liang, Linfeng,Shi, Hu,Tian, Danping,Wang, Jun-Hao,Xue, Nan,Yang, Hengquan,Zhang, Xiaoming
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supporting information
p. 16641 - 16652
(2021/10/20)
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- Deoxyfluorination with CuF2: Enabled by Using a Lewis Base Activating Group
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Deoxyfluorination is a primary method for the formation of C?F bonds. Bespoke reagents are commonly used because of issues associated with the low reactivity of metal fluorides. Reported here is the development of a simple strategy for deoxyfluorination, using first-row transition-metal fluorides, and it overcomes these limitations. Using CuF2 as an exemplar, activation of an O-alkylisourea adduct, formed in situ, allows effective nucleophilic fluoride transfer to a range of primary and secondary alcohols. Spectroscopic investigations have been used to probe the origin of the enhanced reactivity of CuF2. The utility of the process in enabling 18F-radiolabeling is also presented.
- Bode, Bela E.,Chabbra, Sonia,Champion, Sue,Dawson, Daniel M.,Sood, D. Eilidh,Sutherland, Andrew,Watson, Allan J. B.
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supporting information
p. 8460 - 8463
(2020/04/10)
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- Base-Free Dynamic Kinetic Resolution of Secondary Alcohols with a Ruthenium-Lipase Couple
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We report the dynamic kinetic resolution (DKR) of various secondary alcohols by the combination of a ruthenium catalyst and an anionic surfactant-activated lipoprotein lipase. The DKR reactions performed under totally base-free conditions at room temperature provided the products of excellent enantiopurities (91-99% ee or greater) in high yields (92-99%). More importantly, the DKR of α-arylallyl alcohols was achieved for the first time with high yields (87-91%).
- Yun, Inyeol,Park, Jin Yong,Park, Jaiwook,Kim, Mahn-Joo
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p. 16293 - 16298
(2019/12/27)
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- Pickering Emulsion-Derived Liquid-Solid Hybrid Catalyst for Bridging Homogeneous and Heterogeneous Catalysis
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We describe a novel method to prepare a liquid-solid hybrid catalyst via interfacial growth of a porous silica crust around Pickering emulsion droplets, which allowed us to overcome the current limitations of both homogeneous and heterogeneous catalysts. The inner micron-scaled liquid (for example, ionic liquids) pool of the resultant catalyst can host free homogeneous molecular catalysts or enzymes to create a true homogeneous catalysis environment. The porous silica crust of the hybrid catalyst has excellent stability, which makes it amenable to packing directly in fixed-bed reactors for continuous flow catalysis. As a proof of concept, the enzymatic kinetic resolution of racemic alcohols, CrIII(salen) complex-catalyzed asymmetric ring opening of epoxides and Pd-catalyzed Tsuji-Trost allylic substitution reactions were used to verify the generality and versatility of our strategy for bridging homogeneous and heterogeneous catalysis. The hybrid catalyst-based continuous flow system exhibited a 1.6a16-fold enhancement in activity relative to homogeneous counterparts even over 1500 h, and the afforded enantioselectivities were completely equal to those obtained in the homogeneous counterpart systems. Interestingly, the catalytic efficiency can be tuned through rational engineering of the porous crust and the dimensions of the liquid pool, resulting in features of an innovatively designed catalyst. This contribution provides a new method to design efficient catalysts that can bridge the conceptual and technical gaps between homogeneous and heterogeneous catalysis.
- Zhang, Xiaoming,Hou, Yiting,Ettelaie, Rammile,Guan, Ruqun,Zhang, Ming,Zhang, Yabin,Yang, Hengquan
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supporting information
p. 5220 - 5230
(2019/03/11)
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- Expanding the Substrate Specificity of Thermoanaerobacter pseudoethanolicus Secondary Alcohol Dehydrogenase by a Dual Site Mutation
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Here, we report the asymmetric reduction of selected phenyl-ring-containing ketones by various single- and dual-site mutants of Thermoanaerobacter pseudoethanolicus secondary alcohol dehydrogenase (TeSADH). The further expansion of the size of the substrate binding pocket in the mutant W110A/I86A not only allowed the accommodation of substrates of the single mutants W110A and I86A within the expanded active site but also expanded the substrate range of the enzyme to ketones bearing two sterically demanding groups (bulky–bulky ketones), which are not substrates for the TeSADH single mutants. We also report the regio- and enantioselective reduction of diketones with W110A/I86A TeSADH and single TeSADH mutants. The double mutant exhibited dual stereopreference to generate the Prelog products most of the time and the anti-Prelog products in a few cases.
- Musa, Musa M.,Bsharat, Odey,Karume, Ibrahim,Vieille, Claire,Takahashi, Masateru,Hamdan, Samir M.
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p. 798 - 805
(2018/02/21)
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- Dehydroxylation of alcohols for nucleophilic substitution
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The Ph3P/ICH2CH2I system-promoted dehydroxylative substitution of alcohols was achieved to construct C-O, C-N, C-S and C-X (X = Cl, Br, and I) bonds. Compared with the previous approaches such as the Appel reaction and Mitsunobu reaction, this protocol offers some practical advantages such as safe operation and a convenient amination process.
- Chen, Jia,Lin, Jin-Hong,Xiao, Ji-Chang
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p. 7034 - 7037
(2018/07/05)
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- Nucleophilic Substitutions of Alcohols in High Levels of Catalytic Efficiency
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A practical method for the nucleophilic substitution (SN) of alcohols furnishing alkyl chlorides, bromides, and iodides under stereochemical inversion in high catalytic efficacy is introduced. The fusion of diethylcyclopropenone as a simple Lewis base organocatalyst and benzoyl chloride as a reagent allows notable turnover numbers up to 100. Moreover, the use of plain acetyl chloride as a stoichiometric promotor in an invertive SN-type transformation is demonstrated for the first time. The operationally straightforward protocol exhibits high levels of stereoselectivity and scalability and tolerates a variety of functional groups.
- Stach, Tanja,Dr?ger, Julia,Huy, Peter H.
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supporting information
p. 2980 - 2983
(2018/05/28)
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- Synthetically useful variants of industrial lipases from: Burkholderia cepacia and Pseudomonas fluorescens
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Industrial enzymes lipase PS (LPS) and lipase AK (LAK), which originate from Burkholderia cepacia and Pseudomonas fluorescens, respectively, are synthetically useful biocatalysts. To strengthen their catalytic performances, we introduced two mutations into hot spots of the active sites (residues 287 and 290). The LPS-L287F/I290A double mutant showed high catalytic activity and enantioselectivity for poor substrates for which the wild-type enzyme showed very low activity. The LAK-V287F/I290A double mutant was also an excellent biocatalyst with expanded substrate scope, which was comparable to the LPS-L287F/I290A double mutant. Thermodynamic parameters were determined to address the origin of the high enantioselectivity of the double mutant. The ΔΔH? term, but not the ΔΔS? term, was predominant, which suggests that the enantioselectivity is driven by a differential energy associated with intermolecular interactions around Phe287 and Ala290. A remarkable solvent effect was observed, giving a bell-shaped profile between the E values and the log&P or ? values of solvents with the highest E value in i-Pr2O. This suggests that an organic solvent with appropriate hydrophobicity and polarity provides the double mutant with some flexibility that is essential for excellent catalytic performance.
- Yoshida, Kazunori,Ono, Masakazu,Yamamoto, Takahiro,Utsumi, Takashi,Koikeda, Satoshi,Ema, Tadashi
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supporting information
p. 8713 - 8719
(2017/11/03)
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- Dual enzymatic dynamic kinetic resolution by Thermoanaerobacter ethanolicus secondary alcohol dehydrogenase and Candida antarctica lipase B
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The immobilization of Thermoanaerobacter ethanolicus secondary alcohol dehydrogenase (TeSADH) using sol-gel method enables its use to racemize enantiopure alcohols in organic media. Here, we report the racemization of enantiopure phenyl-ring-containing secondary alcohols using xerogel-immobilized W110A TeSADH in hexane rather than the aqueous medium required by the enzyme. We further showed that this racemization approach in organic solvent was compatible with Candida antarctica lipase B (CALB)-catalyzed kinetic resolution. This compatibility, therefore, allowed a dual enzymatic dynamic kinetic resolution of racemic alcohols using CALB-catalyzed kinetic resolution and W110A TeSADH-catalyzed racemization of phenyl-ring-containing alcohols.
- Karume, Ibrahim,Musa, Musa M.,Bsharat, Odey,Takahashi, Masateru,Hamdan, Samir M.,El Ali, Bassam
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p. 96616 - 96622
(2016/10/25)
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- Formamides as Lewis Base Catalysts in SNReactions—Efficient Transformation of Alcohols into Chlorides, Amines, and Ethers
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A simple formamide catalyst facilitates the efficient transformation of alcohols into alkyl chlorides with benzoyl chloride as the sole reagent. These nucleophilic substitutions proceed through iminium-activated alcohols as intermediates. The novel method, which can be even performed under solvent-free conditions, is distinguished by an excellent functional group tolerance, scalability (>100 g) and waste-balance (E-factor down to 2). Chiral substrates are converted with excellent levels of stereochemical inversion (99 %→≥95 % ee). In a practical one-pot procedure, the primary formed chlorides can be further transformed into amines, azides, ethers, sulfides, and nitriles. The value of the method was demonstrated in straightforward syntheses of the drugs rac-Clopidogrel and S-Fendiline.
- Huy, Peter H.,Motsch, Sebastian,Kappler, Sarah M.
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supporting information
p. 10145 - 10149
(2016/08/16)
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- Deracemization of Secondary Alcohols by using a Single Alcohol Dehydrogenase
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We developed a single-enzyme-mediated two-step approach for deracemization of secondary alcohols. A single mutant of Thermoanaerobacter ethanolicus secondary alcohol dehydrogenase enables the nonstereoselective oxidation of racemic alcohols to ketones, followed by a stereoselective reduction process. Varying the amounts of acetone and 2-propanol cosubstrates controls the stereoselectivities of the consecutive oxidation and reduction reactions, respectively. We used one enzyme to accomplish the deracemization of secondary alcohols with up to >99 % ee and >99.5 % recovery in one pot and without the need to isolate the prochiral ketone intermediate.
- Karume, Ibrahim,Takahashi, Masateru,Hamdan, Samir M.,Musa, Musa M.
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p. 1459 - 1463
(2016/05/02)
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- Selectivity Enhancement in Dynamic Kinetic Resolution of Secondary Alcohols through Adjusting the Micro-Environment of Metal Complex Confined in Nanochannels: A Promising Strategy for Tandem Reactions
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(Figure Presented). Dichloro(η6-p-cymene) (1-butyl-3-cyclohexyl-imidazolin-2-ylidene) ruthenium(II) (RuL) was synthesized and confirmed. Five heterogeneous catalysts with similar ruthenium cores were prepared by chemical immobilization method using various silica-based supports, including mesoporous silica SBA-15 of different pore sizes (Ru/Si-9, Ru/Si-8, and Ru/Si-7), nonporous silica particles (Ru/SiO2), and surface trimethylsilylated SBA-15 (Ru/SiMe). The dynamic kinetic resolution (DKR) of 1-phenylethanol, which includes metal-enzyme bicatalytic racemization in tandem with stereoselective acylation, gave product in 99% yield and 0% ee with homogeneous catalyst RuL, whereas the heterogeneous Ru/Si-8 exhibited high catalytic activity and enantioselectivity (up to 96% yield and 99% ee). The racemization and acylation abilities of different catalysts were analyzed. The influences of pore size and surface properties for heterogeneous catalysts were investigated, and the nanocage effect was found to be the key factor in stereoselectivity. The catalyst Ru/Si-8 performed well in reactions with various substrates and can be reused for at least seven times.
- Cao, Hui,Zhu, Xiao-Han,Wang, Dong,Sun, Zhenkun,Deng, Yonghui,Hou, Xiu-Feng,Zhao, Dongyuan
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- Thermoanaerobacter ethanolicus secondary alcohol dehydrogenase mutants with improved racemization activity
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Controlled racemization of enantiopure alcohols is a key step in dynamic kinetic resolution. We recently reported the racemization of enantiopure phenyl-ring-containing alcohols using W110A Thermoanaerobacter ethanolicus secondary alcohol dehydrogenase (W110A TeSADH), which relies on selectivity mistakes. Trp-110 lines the large pocket of the active site of TeSADH, which allows W110A TeSADH mutant to accommodate phenyl-ring-containing substrates in Prelog mode, albeit with selectivity mistakes. Here, we report the racemization of enantiopure phenyl-ring-containing alcohols using several Trp-110 mutants of TeSADH in the presence of the oxidized and reduced forms of nicotinamide-adenine dinucleotide. We observed a noticeable enhancement in racemization efficiency when W110G TeSADH was used compared with W110Q, W110M, W110L, W110I, and W110V. This observation was anticipated because the W110G mutation is expected to open the large pocket of the active site to a greater extent compared to other mutants of TeSADH at W110. Both enantiomers of 1-phenyl-2-propanol and 4-phenyl-2-butanol were fully racemized by W110G TeSADH. We also constructed a triple mutant of TeSADH, W110A/I86A/C295A, by site-directed mutagenesis with the aim of opening the two pockets of the active site of TeSADH. The W110A/I86A/C295A mutant was employed to racemize enantiopure phenyl-ring-containing alcohols. The current study demonstrates that W110G and W110A/I86A/C295A TeSADH are more efficient catalysts for the racemization of enantiopure secondary alcohols than the previously reported mutant W110A TeSADH [6].
- Musa, Musa M.,Patel, Jay M.,Nealon, Christopher M.,Kim, Chang Sup,Phillips, Robert S.,Karume, Ibrahim
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supporting information
p. 155 - 159
(2015/03/30)
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- Ligand effect in racemization and dynamic kinetic resolution of alcohols: Mechanism on cymene ruthenium complexes
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A family of ruthenium complexes with different ligands was utilized in racemization of (R)-1-phenylethanol to investigate the potential influence of the ligands coordinated to the ruthenium center. Kinetic experiments showed that 16-electron cymene ruthenium complex with two chloro-bridge bonds and 18-electron ones with easily dissociative ligands are highly active for catalytic racemization of alcohols. Possible racemization mechanism for cymene ruthenium complexes was then proposed. Computational analysis of dissociation energy barrier, NBO analysis and reaction potential energy surface suggest that ligand-dissociation process is the vital step of the racemization catalyzed by cymene ruthenium complexes. Thereafter, these complexes were applied in the DKR of secondary alcohols to verify their efficiency and applicability.
- Cao, Hui,Cai, Li-Hua,Wang, Chen-Xi,Zhu, Xiao-Han,Li, Zhi-Ming,Hou, Xiu-Feng
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- Mutation of Thermoanaerobacter ethanolicus secondary alcohol dehydrogenase at Trp-110 affects stereoselectivity of aromatic ketone reduction
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Alcohol dehydrogenases (ADHs) are enzymes that catalyze the reversible reduction of carbonyl compounds to their corresponding alcohols. We have been studying a thermostable, nicotinamide-adenine dinucleotide phosphate (NADP +)-dependent, secondary ADH from Thermoanaerobacter ethanolicus (TeSADH). In the current work, we expanded our library of TeSADH and adopted the site-saturation mutagenesis approach in creating a comprehensive mutant library at W110. We used phenylacetone as a model substrate to study the effectiveness of our library because this substrate showed low enantioselectivity in our previous work when reduced using W110A TeSADH. Five of the newly designed W110 mutants reduced phenylacetone at >99.9% ee, and two of these mutants exhibit an enantiomeric ratio (E-value) of over 100. These five mutants also reduced 1-phenyl-2-butanone and 4-phenyl-2-butanone to their corresponding (S)-configured alcohols in >99.9% ee. These new mutants of TeSADH will likely have synthetic utility for reduction of aromatic ketones in the future. This journal is the Partner Organisations 2014.
- Patel, Jay M.,Musa, Musa M.,Rodriguez, Luis,Sutton, Dewey A.,Popik, Vladimir V.,Phillips, Robert S.
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p. 5905 - 5910
(2014/08/05)
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- A Cationic Ruthenium Complex for the Dynamic Kinetic Resolution of Secondary Alcohols
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A synthetic protocol making use of a well-defined cationic ruthenium complex 2 enabling the racemization of enantiomerically pure secondary alcohols in the presence of a weak base (K2CO3) is described. The compatibility of 2 with Candida Antarctica lipase B (Novozym 435) allows the development of an efficient dynamic kinetic resolution of sec-alcohols in the absence of an additional strong base. This procedure involves the first example of a dynamic kinetic resolution of alcohols in the presence of a cationic ruthenium catalyst. In addition, we describe the conversion of ketones to the enantioenriched acetates in a one-pot reaction, probing the versatility of complex 2.
- Fernández-Salas, José A.,Manzini, Simone,Nolan, Steven P.
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supporting information
p. 13132 - 13135
(2016/02/19)
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- Core-Shell Composite as the Racemization Catalyst in the Dynamic Kinetic Resolution of Secondary Alcohols
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Beta-Silicalite-1 core-shell microcomposites with controllable shell thickness were synthesized and used as racemization catalysts in the one-pot dynamic kinetic resolution (DKR) of secondary alcohols by using lipase-catalyzed transesterification. The inert Silicalite-1 shell covered the external acidic sites of the Beta zeolite core, suppressing dehydration and non-enantioselective transesterification of the alcohol. The alcohols could penetrate the Silicalite-1 shell to access the acidic sites at the core Beta for racemization, however, the enzymatically formed (R)-esters were excluded owing to their larger size. As a result, the high ee of the (R)-ester products was conserved and dehydration side products were minimized. Owing to the shape selective nature of the composite racemization catalyst, small and readily available acyl donors could be used in the enzyme-catalyzed transesterification to obtain the esters with high enantiopurity. The DKR of 1-phenylethanol with isopropenyl acetate using an optimized core-shell catalyst, CS-60, gave 92% selectivity to ester formation and the desired (R)-1-phenylethyl acetate was formed with 94% ee.
- Wang, Jie,Do, Dong-Minh,Chuah, Gaik-Khuan,Jaenicke, Stephan
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p. 247 - 254
(2013/03/13)
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- A facile and green protocol for nucleophilic substitution reactions of sulfonate esters by recyclable ionic liquids [bmim][X]
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Ionic liquids [bmim][X] (X = Cl, Br, I, OAc, SCN) are highly efficient reagents for nucleophilic substitution reactions of sulfonate esters derived from primary and secondary alcohols. The counter anions (X-) of the ionic liquids, [bmim][X], effectively replace the sufonates affording the corresponding substitution products such as alkyl halides, acetates, and thiocyanides in excellent yields. The newly developed protocol is very environmentally attractive because the reactions use stoichiometric amounts of ionic liquids as sole reagents in most cases and do not require additional solvents, any other activating reagents, non-conventional equipment, or special precautions. Moreover, these ionic liquids can be readily recycled without loss of reactivity, making the whole process greener.
- Liu, Yajun,Xu, Yongnan,Jung, Sun Ho,Chae, Junghyun
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supporting information
p. 2692 - 2698,7
(2012/12/12)
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- A facile and green protocol for nucleophilic substitution reactions of sulfonate esters by recyclable ionic liquids [bmim][X]
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Ionic liquids [bmim][X] (X = Cl, Br, I, OAc, SCN) are highly efficient reagents for nucleophilic substitution reactions of sulfonate esters derived from primary and secondary alcohols. The counter anions (X-) of the ionic liquids, [bmim][X], effectively replace the sufonates affording the corresponding substitution products such as alkyl halides, acetates, and thiocyanides in excellent yields. The newly developed protocol is very environmentally attractive because the reactions use stoichiometric amounts of ionic liquids as sole reagents in most cases and do not require additional solvents, any other activating reagents, non-conventional equipment, or special precautions. Moreover, these ionic liquids can be readily recycled without loss of reactivity, making the whole process greener. Georg Thieme Verlag KG Stuttgart · New York.
- Liu, Yajun,Xu, Yongnan,Jung, Sun Ho,Chae, Junghyun
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supporting information
p. 2692 - 2698
(2013/01/15)
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- Synthesis of a wide range of thioethers by indium triiodide catalyzed direct coupling between alkyl acetates and thiosilanes
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An indium triiodide-catalyzed substitution of the acetoxy group in alkyl acetates with thiosilanes provides access to a variety of thioethers. The method is efficient for a wide scope of acetates such as primary alkyl, secondary alkyl, tertiary alkyl, allylic, benzylic, and propargylic acetates.
- Nishimoto, Yoshihiro,Okita, Aya,Yasuda, Makoto,Baba, Akio
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supporting information; experimental part
p. 1846 - 1849
(2012/06/18)
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- Dynamic kinetic resolution of a wide range of secondary alcohols: Cooperation of dicarbonylchlorido(pentabenzylcyclopentadienyl)ruthenium and CAL-B
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The substrate scope in the dynamic kinetic resolution ofsecondary alcohols was studied by using 31 structurallydifferent alcohols and isopropenyl acetate in the presence ofdicarbonylchlorido(pentabenzylcyclopentadienyl)rutheniumand Candida antarctica lipase B (Novozym 435, CAL-B) in toluene. The enzyme and the ruthenium complex were shown to function in a highly compatible manner allowing the conversion of the racemic alcohols into the (R)-acetates in practically theoretical yields and, in most cases, ee values exceeding 99%. The results are fully comparable to those published previously by using earlier reported, state-of-the-art ruthenium-based catalysts for the alcohol racemization. A clear benefit of the dicarbonylchlorido(pentabenzylcyclopentadienyl)ruthenium system, when compared to other (cyclopentadienyl)ruthenium racemization catalysts, is its simple and cost-efficient preparation. The substrate scope of 31 secondary alcohols was studied in the dynamic kinetic resolution by utilizing dicarbonylchlorido(pentabenzylcyclopentadienyl)rutheniumand Candida antarctica lipase B (CAL-B) in the acylation with isopropenyl acetate in toluene at room temperature. The secondary alcohols were transformed into highly enantiopure (R)-acetates (in most cases ee > 99%) in close to quantitative isolatedyields. Copyright
- Paeivioe, Mari,Mavrynsky, Denys,Leino, Reko,Kanerva, Liisa T.
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supporting information; experimental part
p. 1452 - 1457
(2011/04/22)
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- One-pot sequence for reductive-acetylation of carbonyl compounds with (N-methylimidazole)(tetrahydroborato)zinc complex
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Reductive-acetylation of variety of aliphatic and aromatic aldehydes and ketones, α,β-unsaturated carbonyl compounds are examined efficiently with (N-methylimidazole)(tetrahydroborato)zinc complex, [Zn(BH4) 2(nmi)], under mild condition in THF at room temperature or reflux conditions. The corresponding acetates were obtained in excellent yields (90-98 %).
- Setamdideh, Davood,Khezri, Behrooz
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experimental part
p. 5766 - 5772
(2012/07/28)
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- Indium-catalyzed retro-claisen condensation
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(Chemical Equation Presented) Retro-aldol reaction: Indium-catalyzed reaction of a 1,3-diketone with an alcohol proceeds under solvent-free conditions by nucleophilic attack of the alcohol on a carbonyl group of the 1,3-diketone and carbon-carbon bond cleavage by a retro-Claisen condensation to give an ester in high yield (see scheme). Using water and an amine as nucleophiles instead of an alcohol gave the corresponding carboxylic acid and amide.
- Kawata, Atsushi,Takata, Kazumi,Kuninobu, Yoichiro,Takai, Kazuhiko
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p. 7793 - 7795
(2008/09/18)
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- A facile and efficient one-step conversion of alcohol triphenylmethyl ethers to the corresponding acetates
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Alcohol triphenylmethyl (trityl) ethers were readily and efficiently transformed into the corresponding acetates by reaction with acetyl bromide. Triphenylmethyl ethers can also be transformed into the corresponding substituted acetates in high yields by the use of various substituted acetyl chlorides combined with sodium iodide.
- Kobayashi, Kumiko,Watahiki, Tsutomu,Oriyama, Takeshi
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p. 484 - 486
(2007/10/03)
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- Ionic liquid-coated enzyme for biocatalysis in organic solvent
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Ionic liquid-coated enzyme (ILCE) is described as a useful catalyst for biocatalysis in organic solvent. An ionic liquid, [PPMIM]-[PF6] (1, [PPMIM] = 1-(3′-phenylpropyl)-3-methylimidazolium), which is solid at room temperature and becomes liquid above 53°C, was synthesized in two steps from N-methylimidazole. The coating of enzyme was done by simply mixing commercially available enzyme with 1 in the liquid phase above 53°C and then allowing the mixture to cool. A representative ILCE, prepared with a lipase from Pseudomonas cepacia, showed markedly enhanced enantioselectivity without losing any significant activity.
- Lee, Jae Kwan,Kim, Mahn-Joo
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p. 6845 - 6847
(2007/10/03)
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- Biocatalysis in Ionic Liquids: Markedly Enhanced Enantioselectivity of Lipase
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matrix presented Lipase-catalyzed transesterifications in ionic liquids proceeded with markedly enhanced enantioselectivity. It was observed that lipases were up to 25 times more enantioselective in ionic liquids than in conventional organic solvents.
- Kim, Kwang-Wook,Song, Boyoung,Choi, Min-Young,Kim, Mahn-Joo
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p. 1507 - 1509
(2007/10/03)
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- Concerted catalytic reactions for conversion of ketones or enol acetates to chiral acetates
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(matrix presented) Enol acetates or ketones asymmetrically transformed to chiral acetates in high yields with high optical purities through multistep reactions catalyzed by a lipase and a ruthenium complex. 2,6-Dimethylheptan-4-ol was chosen as a suitable hydrogen donor, and 4-chlorophenyl acetate was used as an acyl donor for the conversion of ketones.
- Jung, Hyun M.,Koh, Jeong H.,Kim, Mahn-Joo,Park, Jaiwook
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p. 409 - 411
(2007/10/03)
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- Highly chemoselective catalytic hydrogenation of unsaturated ketones and aldehydes to unsaturated alcohols using phosphine-stabilized copper(I) hydride complexes
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A base metal hydrogenation catalyst composed of the phenyldimethylphosphine-stabilized copper(I) hydride complex provides for the highly chemoselective hydrogenation of unsaturated ketones and aldehydes to unsaturated alcohols, including the regioselective 1,2-reduction of α,β- unsaturated ketones and aldehydes to allylic alcohols. The active catalyst can be derived in situ by phosphine exchange using commercial [(Ph3P)CuH]6 or from the reaction of copper(l) chloride, sodium tert-butoxide, and dimethylphenylphosphine under hydrogen. The catalyst derived from 1,1,1- tris(diphenylphosphinomethyl)ethane is mechanistically interesting but less synthetically useful. (C) 2000 Elsevier Science Ltd.
- Chen, Jian-Xin,Daeuble, John F.,Brestensky, Donna M.,Stryker, Jeffrey M.
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p. 2153 - 2166
(2007/10/03)
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- Practical ruthenium/lipase-catalyzed asymmetric transformations of ketones and enol acetates to chiral acetates.
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Ketones were asymmetrically transformed to chiral acetates by one-pot processes using a lipase and an achiral ruthenium complex under 1 atm of hydrogen gas in ethyl acetate. Molecular hydrogen was also effective for the transformation of enol acetates to chiral acetates without additional acyl donors with the same catalyst system.
- Jung,Koh,Kim,Park
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p. 2487 - 2490
(2007/10/03)
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- Remarkably fast acylation of alcohols with benzoyl chloride promoted by TMEDA
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Reaction of alcohols with benzoyl chloride in the presence of TMEDA at - 78°C resulted in very fast acylation to afford the corresponding benzoates in excellent yields.
- Sano,Ohashi,Oriyama
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p. 1141 - 1144
(2007/10/03)
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- Process for the production of chiral unsaturated alcohols in high optical purity
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The catalytic asymmetric hydrogenation of enol esters with a vinyllic or acetylenic substituent proceeds with extremely high enantioselectivity using a Rhodium-chiral bisphosphine catalyst. This is at variance with the hydrogenation of enol esters bearing a saturated substituent, which are hydrogenated with only marginal enantioselectivity under the same conditions.
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- Asymmetric hydrogenation of acyclic enol esters
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High enantioselectivity has been observed for the catalytic asymmetric hydrogenation of enol esters bearing a vinylic (≤94% ee) or acetylenic (>97% ee) substituent using a rhodium-chiral bisphosphine catalyst. This is at variance with the hydrogenation of enol esters bearing a saturated substituent, which are hydrogenated with only moderate enantioselectivity under the same conditions.
- Boaz, Neil W.
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p. 5505 - 5508
(2007/10/03)
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- A New and Efficient Esterification Reaction via Mixed Anhydrides by the Promotion of a Catalytic Amount of Lewis Acid
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In the presence of a catalytic amount of Lewis acid, various carboxylic esters or S-phenyl carbothioates are prepared in excellent yields by the respective reactions of equimolar amounts of silyl carboxylates and alkyl silyl ethers or phenyl silyl sulfides with 4-trifluoromethylbenzoic anhydride.
- Miyashita, Mitsutomo,Shiina, Isamu,Miyoshi, So,Mukaiyama, Teruaki
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p. 1516 - 1527
(2007/10/02)
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- An Efficient Method for the Preparation of Carboxylic Esters via Mixed Anhydrides by the Promotion of a Catalytic Amount of Lewis Acid
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Various carboxylic esters are prepared in excellent yields by the reaction of nearly equimolar amounts of silyl derivatives of carboxylic acids and alcohols with p-trifluoromethylbenzoic anhydride in the presence of a catalytic amount of Lewis acid.
- Mukaiyama, Teruaki,Shiina, Isamu,Miyashita, Mitsutomo
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p. 625 - 628
(2007/10/02)
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- A one-pot reductive acetylation of aldehydes and ketones
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Sodium borohydride reduction of saturated aliphatic and aromatic aldehydes and ketones in ethyl acetate at reflux is a facile route for one-pot proparation of acetates from such carbonyl precursors.
- Rao,Nambudiry
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p. 1721 - 1727
(2007/10/02)
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- Baker's Yeast-mediated Preparation of Optically Active Aryl Alcohols and Diols for the Synthesis of Chiral Hydroxy Acids
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Baker's yeast reduction of 1-(4-methoxyphenyl)propan-2-one, 4-phenylbutan-2-one, and 2-hydroxy-1-(4-methoxyphenyl)ethanone (p-methoxyphenacyl alcohol), afforded in good yield and high optical purity the corresponding (S)-alcohols and the (R)-diol, but only after careful investigation of incubation conditions.Protection of the above hydroxy compounds, and ruthenium tetraoxide oxidation of their acetates, afforded the corresponding acetoxy acids in good yield and high optical purity. (S)-1-(p-Methoxyphenyl)ethane-1,2-diol could be prepared either by baker's yeast incubation of the acetate of p-methoxyphenacyl alcohol or 2-acetoxy-1-(4-methoxyphenyl)ethanone (24percent yield, 82percent ee) or from its (R)-enantiomer via a Mitsonobu reaction on its mono t-butyldimethylsilyl ether.
- Ferraboschi, Patrizia,Grisenti, Paride,Manzocchi, Ada,Santaniello, Enzo
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p. 2469 - 2474
(2007/10/02)
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- REDUCTION WITH METAL BOROHYDRIDE-TRANSITION METAL SALT SYSTEM. II. REDUCTION OF BENZYL ACETATES TO HYDROCARBONS WITH SODIUM BOROHYDRIDE-NICKEL(II) CHLORIDE
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Reductive cleavage of benzyl acetates selectively with nickel boride yielding corresponding hydrocarbons is described.
- He, Yun,Pan, Xinfu,Zhao, He,Wang, Shaofei
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p. 3051 - 3054
(2007/10/02)
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- Olivanic Acid Analogues. Part 2. Total Synthesis of Some C(6)-Substituted 7-Oxo-1-azabicyclohept-2-ene-2-carboxylates
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A number of 6-substituted 7-oxo-1-azabicyclohept-2-ene-2-carboxylates related to the olivanic acids were prepared from the phosphorane (32).Generation of the anion α to the azetidin-2-one carbonyl group, followed by reaction with electrophiles and intramolecular cyclisation using the Wittig procedure gave the bicyclic products; in all cases the thermodynamically favoured trans-stereochemisty about the azetidinone ring predominated.In contrast, some less readily available cis-substituted analogues were obtained from the cyclohexa-1,4-diene derived phosphorane (61).The synthetic utility of a masked acetonyl ester group for preparing the free acids of these azabicycloheptene ring systems is described.
- Bateson, John H.,Quinn, Alison M.,Smale, Terence C.,Southgate, Robert
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p. 2219 - 2234
(2007/10/02)
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- A USEFUL METHOD FOR SELECTIVE ACYLATION OF ALCOHOLS USING 2,2'-BIPYRIDYL-6-YL CARBOXYLATE AND CESIUM FLUORIDE
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Primary and secondary alcohols are acylated under mild conditions by the of use 2,2'-bipyridyl-6-yl carboxylates and cesium fluoride.Furthermore, the reaction is successfully applied to selective acylation of a primary carbinol group of diols containing primary and secondary carbinol groups or exclusive O-acylation of aromatic amino alcohols.
- Mukaiyama, Teruaki,Pai, Fong-Chang,Onaka, Makoto,Narasaka, Koichi
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p. 563 - 566
(2007/10/02)
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