- KB3H8: An environment-friendly reagent for the selective reduction of aldehydes and ketones to alcohols
-
Selective reduction of aldehydes and ketones to their corresponding alcohols with KB3H8, an air- and moisture-stable, nontoxic, and easy-to-handle reagent, in water and THF has been explored under an air atmosphere for the first time. Control experiments illustrated the good selectivity of KB3H8 over NaBH4 for the reduction of 4-acetylbenzaldehyde and aromatic keto esters. This journal is
- Li, Xinying,Mi, Tongge,Guo, Wenjing,Ruan, Zhongrui,Guo, Yu,Ma, Yan-Na,Chen, Xuenian
-
p. 12776 - 12779
(2021/12/10)
-
- Evaluation of gem-Diacetates as Alternative Reagents for Enzymatic Regio-and Stereoselective Acylation of Alcohols
-
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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- 4CzIPN catalyzed photochemical oxidation of benzylic alcohols
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A green photoredox oxidation of benzylic primary and secondary alcohols to aldehydes and ketones with air as an oxidant was reported. The oxidation shows broad substrate scope and excellent selectivity over benzylic alcohols to the aliphatic alcohols. Further mechanistic studies revealed a quinuclidine mediated HAT process, and blue LEDs promoted 4CzlPN (1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene) photoredox cycle were involved in our oxidation.
- Zhang, Heng,Guo, Tianyun,Wu, Mingzhong,Huo, Xing,Tang, Shouchu,Wang, Xiaolei,Liu, Jian
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supporting information
(2021/02/20)
-
- Photochemical oxidation of benzylic primary and secondary alcohols utilizing air as the oxidant
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A mild and green photochemical protocol for the oxidation of alcohols to aldehydes and ketones was developed. Utilizing thioxanthenone as the photocatalyst, molecular oxygen from air as the oxidant and cheap household lamps or sunlight as the light source, a variety of primary and secondary alcohols were converted into the corresponding aldehydes or ketones in low to excellent yields. The reaction mechanism was extensively studied.
- Nikitas, Nikolaos F.,Tzaras, Dimitrios Ioannis,Triandafillidi, Ierasia,Kokotos, Christoforos G.
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p. 471 - 477
(2020/02/13)
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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)
-
- Novel highly potent and selective sigma1 receptor antagonists effectively block the binge eating episode in female rats
-
In this paper, the benzo-cracking approach was applied to the potent sigma1 (σ1) receptor antagonist 1 to afford the less conformationally constrained 1,3-dioxane derivatives 2 and 3. To evaluate the effect of the increase in the distance between the two hydrophobic structural elements that flank the basic function, the cis and trans diastereomers of 4 and 5 were also prepared and studied. Compounds 2 and 3 showed affinity values at the σ1 receptor significantly higher than that of the lead compound 1. In particular, 3 displayed unprecedented selectivity over the σ2 receptor, the phencyclidine site of the NMDA receptor, and opioid receptor subtypes, as well as over the dopamine transporter. Docking results supported the structure-activity relationship studies. Due to its interesting biological profile, derivative 3, selected for an in vivo study in a validated preclinical model of binge eating, was able to counteract the overeating of palatable food only in binging rats, without affecting palatable food intake in the control group and anxiety-like and depression-related behaviors in female rats. This result strengthened the involvement of the σ1 receptor in the compulsive-like eating behavior and supported the σ1 receptor as a promising target for the management of eating disorders.
- Del Bello, Fabio,Quaglia, Wilma,Cifani, Carlo,Di Bonaventura, Emanuela Micioni,Botticelli, Luca,Giorgioni, Gianfabio,Pavletic, Pegi,Piergentili, Alessandro,Bonifazi, Alessandro,Schepmann, Dirk,Vistoli, Giulio,Micioni Di Bonaventura, Maria Vittoria
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p. 3107 - 3116
(2020/11/10)
-
- Oxygenation of styrenes catalyzed by N-doped carbon incarcerated cobalt nanoparticles
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NCI-Co catalyzed olefin oxygenation reactions were investigated. Among the metals examined, including noble metals, the reaction proceeded specifically on Co catalysts, and nitrogen dopant was crucial for the catalytic activity. The presence of NaBH4 as a hydride source, the corresponding alcohols were obtained in high yields. The substrates bearing a reductant-sensitive functional group were made tolerant by changing the reductant and using an additive, and furthermore, the corresponding ketones were accessed by changing reaction conditions. A preliminary examination of other SOMOphiles suggested that the heterogeneous catalyst systems have the potential to be applied to more general hydrofunctionalization of olefins to form various kinds of bonds. Several mechanistic studies suggested that the reaction proceeded in a heterogeneous manner and formed a radical intermediate on cobalt nanoparticle species.
- Yasukawa, Tomohiro,Kobayashi, Shū
-
supporting information
p. 1980 - 1985
(2019/12/24)
-
- Copper-Catalyzed Stereospecific Hydroboration of Internal Allylic Alcohols
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An effective Cu-catalyzed stereospecific hydroboration of aliphatic and aromatic 1,1,2-trisubstituted internal allylic alcohols has been reported. This reaction proceeds via a silyl ether transient protection of allylic alcohols and subsequent stereospecific hydroboration. Followed by an oxidative workup, an array of acyclic, cyclic, and heterocyclic 1,3-diols was synthesized in good to excellent yields with good functional group tolerance and excellent diastereomeric ratios (> 20:1).
- Ji, Enhui,Meng, Haiwen,Zheng, Yue,Ramadoss, Velayudham,Wang, Yahui
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p. 7367 - 7371
(2019/11/22)
-
- Diastereoselectivity in the boron aldol reaction of α-alkoxy and α,β-bis-alkoxy methyl ketones
-
In this work, using DFT calculations, we investigated the 1,4 and 1,5 asymmetric induction in boron enolate aldol reactions of α-alkoxy and α,β-bisalkoxy methyl ketones. We evaluated the steric influence of alkyl substituents at the α position and the stereoelectronic influence of the oxygen protecting groups at the α and β positions. Theoretical calculations revealed the origins of the 1,4 asymmetric induction in terms of the nature of the β-substituent. The synergistic effect between the α,β-syn and α,β-anti-bisalkoxy stereocenters was elucidated. In the presence of the β-alkoxy center, the reaction proceeds through the Goodman-Paton 1,5-stereoinduction model, experiencing a minor influence of the α-alkoxy center.
- Fernandes, Alessandra A. G.,Leonarczyk, Ives A.,Ferreira, Marco A. B.,Dias, Luiz Carlos
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p. 3167 - 3180
(2019/03/26)
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- Aryl Boronic Acid Catalysed Dehydrative Substitution of Benzylic Alcohols for C?O Bond Formation
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A combination of pentafluorophenylboronic acid and oxalic acid catalyses the dehydrative substitution of benzylic alcohols with a second alcohol to form new C?O bonds. This method has been applied to the intermolecular substitution of benzylic alcohols to form symmetrical ethers, intramolecular cyclisations of diols to form aryl-substituted tetrahydrofuran and tetrahydropyran derivatives, and intermolecular crossed-etherification reactions between two different alcohols. Mechanistic control experiments have identified a potential catalytic intermediate formed between the aryl boronic acid and oxalic acid.
- Estopi?á-Durán, Susana,Donnelly, Liam J.,Mclean, Euan B.,Hockin, Bryony M.,Slawin, Alexandra M. Z.,Taylor, James E.
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supporting information
p. 3950 - 3956
(2019/02/16)
-
- Catalysis of Radical Cyclizations from Alkyl Iodides under H2: Evidence for Electron Transfer from [CpV(CO)3H]-
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Radical cyclizations are most often achieved with Bu3SnH in the presence of a radical initiator, but environmental considerations demand that alternative reagents be developed - ones that can serve as a synthetic equivalent to the hydrogen atom. We have revisited [CpV(CO)3H]-, a known replacement for Bu3SnH, and found that it can be used catalytically under H2 in the presence of a base. We have carried out tin-free catalytic radical cyclizations of alkyl iodide substrates. The reactions are atom-efficient, and the conditions are mild, with broad tolerance for functional groups. We have, for example, achieved the first 5-exo radical cyclization involving attack onto a vinyl chloride. We suggest that the radicals are generated by an initial electron transfer.
- Kuo, Jonathan L.,Lorenc, Chris,Abuyuan, Janine M.,Norton, Jack R.
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supporting information
p. 4512 - 4516
(2018/04/10)
-
- Lewis Base-Promoted Ring-Opening 1,3-Dioxygenation of Unactivated Cyclopropanes Using a Hypervalent Iodine Reagent
-
A facile and effective system has been developed for the regio- and chemoselective ring-opening/electrophilic functionalization of cyclopropanes through C?C bond activation by [bis(trifluoroacetoxy)iodo]benzene with the aid of the Lewis basic promoter p-toluenesulfonamide. The p-toluenesulfonamide-promoted system works well for a wide range of cyclopropanes, resulting in the formation of 1,3-diol products in good yields and regioselectivity.
- Gieuw, Matthew H.,Ke, Zhihai,Yeung, Ying-Yeung
-
supporting information
p. 3782 - 3786
(2018/03/13)
-
- Synthetic Method of Intermediate for Fesoterodine
-
The present invention relates to a method for producing 3-(3-diisopropylamino-1-phenylpropyl)-4-hydroxy benzenemethanol, which is an intermediate product useful for producing fesoterodine, by using ethyl benzoylacetate as a starting material. The producin
- -
-
Paragraph 0060; 0061
(2017/12/01)
-
- Silver-Catalyzed C(sp3)-H Chlorination
-
A silver-catalyzed chlorination of benzylic, tertiary, and secondary C(sp3)-H bonds was developed. The reaction proceeded with as low as 0.2 mol % catalyst loading at room temperature under air atmosphere with synthetically useful functional group compatibility. The regioselectivity and reactivity tendencies suggest that the chlorination proceeded through a radical pathway, but an intermediate alkylsilver species cannot be ruled out.
- Ozawa, Jun,Kanai, Motomu
-
supporting information
p. 1430 - 1433
(2017/03/23)
-
- SELECTIVE CARBON-CARBON BOND CLEAVAGE BY EARTH ABUNDANT VANADIUM COMPOUNDS UNDER VISIBLE LIGHT PHOTOCATALYSIS
-
Provided herein a vanadium(V) complex of formula I, where R1 to R8 are as defined herein. Also provided herein are reactions making use of the vanadium(V) complex of formula I, such as selective sp3-sp3 carbon-carbon bond cleavage under visible light photocatalysis and photodegradation of lignin.
- -
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Page/Page column 34
(2016/09/22)
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- Chemoselective oxidant-free dehydrogenation of alcohols in lignin using Cp?Ir catalysts
-
A remarkably effective method of chemoselective dehydrogenation of alcohols in lignin has been developed with an iridium catalyst. An additional operation of Zn/NH4Cl via a two-step one pot process could further promote the cleavage of the C-O bond in β-O-4 units in lignin. And this reaction system was also applicable to native lignin as the molecular weight of native lignin decreased obviously as detected by gel permeation chromatography (GPC). Additionally, this is the first to date generation of the by-product H2 from native lignin and the by-product was straightforwardly captured by 1-decene. A probable mechanistic pathway was also proposed with the help of density functional theory (DFT) calculations.
- Zhu, Rui,Wang, Bing,Cui, Minshu,Deng, Jin,Li, Xinglong,Ma, Yingbo,Fu, Yao
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supporting information
p. 2029 - 2036
(2016/04/19)
-
- NOVEL RUTHENIUM COMPLEX AND METHOD FOR PREPARING METHANOL AND DIOL
-
Provided is a method for preparing methanol and diol from cyclic carbonate, comprising: under a hydrogen atmosphere, in an organic solvent, and with the presence of a ruthenium complex (Ru(L)XYY') and an alkali, conducting a hydrogenation reduction reaction on the cyclic carbonate or polycarbonate to obtaib methanol and diol. Also provided is a ruthenium complex prepared from ruthenium and a tridentate amido diphosphine ligand. Also provided is a deuterated methanol and deuterated diol preparation method by substituting the hydrogen and ruthenium complex with deuterium.
- -
-
Paragraph 0090
(2015/09/23)
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- Formal synthesis of fesoterodine by acid-facilitated aromatic alkylation
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The competitive muscarinic receptor antagonist fesoterodine is a congener of tolterodine and has better efficiency compared to tolterodine. In this study, we present an efficient synthesis of the fesoterodine intermediate 3-(3-diisopropylamino-1-phenylpropyl)-4-hydroxybenzaldehyde from ethyl benzoylacetate by Friedel-Crafts alkylation in the presence of an acid as a key reaction step. The synthesis is carried out by the reduction of the ketoester to a 1,3-diol, diisopropylamine substitution, and Friedel-Crafts alkylation, followed by reduction and chiral resolution.
- Lee, Youngeun,Shabbir, Saira,Jeong, Yuri,Ban, Jaeyoung,Rhee, Hakjune
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p. 2885 - 2889
(2016/02/05)
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- CATALYTIC REDUCTIVE CLEAVAGE OF A β-Ο-4 BOND OF ETHERS OR POLYETHERS SUCH AS LIGNIN
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The present invention relates to a method of reducing a β-O-4 bond to the corresponding C-H bond in a substrate, by use of a hydrogen donor and a metal catalyst in a solvent. Thereby it is possible to depolymerize a polymer having a repeating β-O-4 bond.
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Page/Page column 5
(2014/03/26)
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- Synthesis of novel chiral TBBt derivatives with hydroxyl moiety. Studies on inhibition of human protein kinase CK2α and cytotoxicity properties
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The efficient method for the synthesis of novel 4,5,6,7-tetrabromo-1H- benzotriazole (TBBt) derivatives bearing a single stereogenic center has been developed. New compounds with a variety of substituents at the meta- and para-position of the phenyl ring are reported. All of the presented compounds were obtained using classical synthetic methods, such as bromination of benzotriazole, and its subsequent alkylation by monotosylated arylpropane-1,3-diols, which in turn have been synthesized through reduction of the corresponding prochiral β-keto esters, and the selective monotosylation of the primary hydroxyl group. The influence of the new and previously reported N-hydroxyalkyl TBBt derivatives on the activity of human protein kinase CK2α catalytic subunit was examined. The most active were derivatives with N-hydroxyalkyl substituents (IC50 in 0.80-7.35 μM range). A binding mode of (R)-1-(4,5,6,7-tetrabromo-2H-benzotriazol-2-yl)butan-3-ol 7b to hCK2α has been proposed based on in silico docking studies. Additionally, MTT-based cytotoxicity tests demonstrated high activities of novel 1-aryl-3-TBBt-propan-1-ol and 3-TBBt-propan-1,2-diol derivatives against human peripheral blood T lymphoblast (CCRF-CEM), and moderate anti-tumor activities against human breast adenocarcinoma (MCF7) cell lines.
- Borowiecki, Pawe?,Wawro, Adam M.,Wińska, Patrycja,Wielechowska, Monika,Bretner, Maria
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supporting information
p. 364 - 374
(2014/08/05)
-
- Synthesis of oxacyclic scaffolds via dual ruthenium hydride/Bronsted acid-catalyzed isomerization/cyclization of allylic ethers
-
A ruthenium hydride/Bronsted acid-catalyzed tandem sequence is reported for the synthesis of 1,3,4,9-tetrahydropyrano[3,4-b]indoles (THPIs) and related oxacyclic scaffolds. The process was designed on the premise that readily available allylic ethers would undergo sequential isomerization, first to enol ethers (Ru catalysis), then to oxocarbenium ions (Bronsted acid catalysis) amenable to endo cyclization with tethered nucleophiles. This methodology provides not only an attractive alternative to the traditional oxa-Pictet-Spengler reaction for the synthesis of THPIs, but also convenient access to THPI congeners and other important oxacycles such as acetals.
- Ascic, Erhad,Ohm, Ragnhild G.,Petersen, Rico,Hansen, Mette R.,Hansen, Casper L.,Madsen, Daniel,Tanner, David,Nielsen, Thomas E.
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supporting information
p. 3297 - 3300
(2014/04/03)
-
- Studies on the chemoenzymatic synthesis of (R)- and (S)-methyl 3-aryl-3-hydroxypropionates: The influence of toluene-pretreatment of lipase preparations on enantioselective transesterifications
-
Two series (para- and meta-substituted) of racemic methyl esters of 3-aryl-3-hydroxypropionic acid were prepared after which the enantiomers were separated by an enzyme-catalyzed transesterification. Several lipases were investigated as the catalyst. The influence of the enzyme pretreatment, as well as substrate concentration, reaction temperature, stirring manner, and substrate conversion on the stereochemical outcome of the biotransformation process were investigated in detail. The best results were achieved by using solvent-pretreated lipase from Pseudomonas fluorescens or Burkholderia cepacia suspended in toluene, and vinyl acetate as the acetyl group donor.
- Borowiecki, Pawel,Bretner, Maria
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p. 925 - 936
(2013/09/23)
-
- Design, synthesis, and evaluation of novel cyclic phosphates of 5-aminosalicylic acid as cytochrome P450-activated prodrugs
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Four novel cyclic phosphates of the anti-inflammatory agent 5-aminosalicylic acid (5-ASA) were designed and synthesized as cytochrome P450 (CYP)-activated prodrugs. These prodrugs can be used for targeting into gut wall, since these types of cyclic phosph
- Huttunen, Kristiina M.,Tani, Niina,Juvonen, Risto O.,Raunio, Hannu,Rautio, Jarkko
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p. 532 - 537
(2013/08/24)
-
- Selective reduction of aldehydes and ketones to alcohols with ammonia borane in neat water
-
Chemoselective reduction of various carbonyl compounds to alcohols with ammonia borane (AB), a nontoxic, environmentally benign, and easily handled reagent, in neat water was achieved in quantitative conversions and high isolated yields. Interestingly, α- and β-keto esters were selectively reduced to corresponding hydroxyl esters by AB, while diols were obtained when sodium borohydride was used as a reducing agent. The procedure is also compatible with the presence of a variety of base-labile protecting groups, such as tosyl, acetyl, benzoyl, ester groups, and acid-labile protecting groups such as trityl and TBDMS groups, and others, such as the unsaturated double bond, nitro and cyano groups. Finally, a kilo scale reaction of methyl benzoylformate with AB was conducted in water and gave methyl mandelate in 94% yield.
- Shi, Lei,Liu, Yingying,Liu, Qingfeng,Wei, Bin,Zhang, Guisheng
-
scheme or table
p. 1372 - 1375
(2012/06/04)
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- Nickel-catalyzed reductive cyclization of organohalides
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A mild and convenient nickel-catalyzed method for free-radical cyclization of organohalides is described. The use of a NiCl2DME/Pybox complex as the catalyst and zinc powder in methanol efficiently promotes the reductive cyclization of various
- Kim, Hyejin,Lee, Chulbom
-
supporting information; experimental part
p. 2050 - 2053
(2011/06/25)
-
- Reduction of aromatic and aliphatic keto esters using sodium borohydride/MeOH at room temperature: a thorough investigation
-
Reduction of keto esters is a valuable alternative to produce diols. Sodium borohydride/MeOH system at room temperature and short reaction time efficiently reduced α, β, γ, and δ-keto esters having α-keto esters as the most reactive. The ester functionality was reduced effectively due to the presence of oxo group that somehow facilitates the formation of ring intermediate. As expected, the chemoselective experiments showed that ester functionality was not reduced using this system. This study presents a simple, easy, and benign reduction process of various keto esters to its corresponding diols.
- Kim, Juryoung,De Castro, Kathlia A.,Lim, Minkyung,Rhee, Hakjune
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supporting information; experimental part
p. 3995 - 4001
(2010/07/05)
-
- Mild deprotection of methylene acetals in combination with trimethylsilyl triflate-2,2′-bipyridyl
-
The facile deprotection of methylene acetal protection of diols under mild conditions is established. The combination of trimethylsilyl triflate (TMSOTf) and 2,2′-bipyridyl followed by a weakly acidic hydrolysis was effective and the substrates having acid sensitive functional groups can be tolerated under the stated conditions. The selective deprotection between methylene acetal and benzophenone ketal was achieved.
- Fujioka, Hiromichi,Senami, Kento,Kubo, Ozora,Yahata, Kenzo,Minamitsuji, Yutaka,Maegawa, Tomohiro
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experimental part
p. 426 - 428
(2011/02/26)
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- Organic metal compound and process for preparing optically-active alcohols using the same
-
The present invention provides an asymmetric reduction catalyst effective in preparing optically-active alcohol compounds having various functional groups, and a process for preparing optically-active alcohol compounds using said asymmetric reduction catalyst. The organic metal compound of the present invention is represented by the following general formula (1): wherein R1 and R2 may be mutually identical or different, and are an alkyl group, a phenyl group, a naphthyl group, a cycloalkyl group, or an alicyclic ring formed by binding R1 and R2, which may have a substituent; R3 is a hydrogen atom or an alkyl group; Cp is a cyclopentadienyl group, which may have a substituent, bound to M1 via a π bond; X1 is a halogen atom or a hydrido group; M1 is rhodium or iridium; and * denotes asymmetric carbon.
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Page/Page column 8; 12
(2009/04/24)
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- Regio- and stereoselective ring opening of enantiomerically enriched 2-aryl oxetanes and 2-aryl azetidines with aryl borates
-
(Chemical Equation Presented) The regioselective ring opening of 2-aryl-substituted four-membered heterocyclic rings with phenols, including catechol, was achieved by the use of aryl borates in mild and neutral reaction conditions without the aid of any transition metal catalysts. While β-alkyl azetidines were found not to be reactive, optically active N-tosyl azetidines gave the corresponding β-aryloxy amines in a racemic form, thus indicating the considerable carbocationic character of the transition state. The introduction of a hydroxyl group in the azetidine ring (i.e., an azetidinol), able to anchor the aryl borate and to direct the subsequent nucleophilic delivery, was shown to determine the ring-opening process with predominant inversion of configuration. When enantiomerically enriched 2-aryl oxetanes were used, the reduced extent of racemization observed (up to 93:7 er) was rationalized by an intramolecular delivery through a six-membered transition state, giving β-aryloxy alcohols with a predominant retention of configuration (i.e., a syn-stereoselective ring opening). The aryloxy alcohols obtained, endowed with suitable functionalities, can be cyclized to give access to enantiomerically enriched 2-aryl-1,5-benzodioxepins.
- Bertolini, Ferruccio,Crotti, Stefano,Di Bussolo, Valeria,Macchia, Franco,Pineschi, Mauro
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experimental part
p. 8998 - 9007
(2009/04/11)
-
- 1,3-Diol synthesis via controlled, radical-mediated C-H functionalization
-
The invention of a method for the synthesis of 1,3-diols from the corresponding alcohols is described, via controlled, radical-mediated C-H functionalization. The sequence described herein entails near quantitative conversion to the corresponding trifluoroethyl carbamate, followed by a variant of the Hofmann-Loffler-Freytag reaction, cyclization, and hydrolysis to provide the 1,3-diols. In addition to the 10 examples presented herein, the syntheses of four natural products are facilitated by this directed oxyfunctionalization. This methodology is demonstrated to be orthogonal to other known C-H oxidations. Finally, this sequence is efficient, practical, inexpensive, and scalable. Copyright
- Chen, Ke,Richter, Jeremy M.,Baran, Phil S.
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p. 7247 - 7249
(2008/12/21)
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- Selective nosylation of 1-phenylpropane-1,3-diol and perchloric acid mediated Friedel-Crafts alkylation: Key steps for the new and straightforward synthesis of tolterodine
-
We have developed a new and straightforward synthesis of racemic tolterodine [N,N-diisopropyl-3-(2-hydroxy-5-methyl-phenyl)-3-phenylpropanamine]. The synthesis involves selective nosylation on the primary alcohol of 1-phenylpropane-1,3-diol using 4-nitrob
- De Castro, Kathlia A.,Rhee, Hakjune
-
experimental part
p. 1841 - 1844
(2009/04/04)
-
- Reduction of ethyl benzoylacetate and selective protection of 2-(3-hydroxy-1-pheny|propyl)4-methylphenol: A new and facile synthesis of tolterodine
-
A new and facile synthesis of tolterodine using ethyl benzoylacetate as the starting material was developed. Reduction using sodium borohydride in methanol followed by Friedel-Crafts alkylation utilizing FeCl3 ·6H2O as catalyst lead to the known 2-(3-hydroxyl- phenylpropyl)-4-methylphenol intermediate. Consecutive protection of phenolic OH withp-toluenesulfonyl chloride via two-phase reaction and conversion of aliphatic OH using p-nitrobenzenesulfonyl chloride facilitates direct substitution of duesopropylamine. After simultaneous deprotection of the tosyl group, optically pure (R)-tolterodine·L-tartrate was obtained by resolution using L-tartaric acid with 99.99% purity.
- De Castro, Kathlia A.,Jungnam, Ko,Daejong, Park,Sungdae, Park,Hakjune, Rhee
-
p. 918 - 921
(2012/12/30)
-
- Novel cyclic phosphate prodrug approach for cytochrome P450-activated drugs containing an alcohol functionality
-
Purpose. A cyclic phosphate prodrug of a descriptive molecule containing an alcohol functionality was designed, synthesized and characterized in vitro as a cytochrome P450 (CYP) -selective prodrug. Materials and Methods. To achieve efficient CYP-oxidation
- Huttunen, Kristiina M.,Maehoenen, Niina,Leppaenen, Jukka,Vepsaelaeinen, Jouko,Juvonen, Risto O.,Raunio, Hannu,Kumpulainen, Hanna,Jaervinen, Tomi,Rautio, Jarkko
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p. 679 - 687
(2008/01/27)
-
- Phosphoramidate and phosphate prodrugs of (-)-β-D-(2R,4R)-dioxolane- thymine: Synthesis, anti-HIV activity and stability studies
-
A series of phosphoramidate and phosphate prodrugs of DOT were synthesized via dichlorophosphate or H-phosphonate chemistry and evaluated for their anti-HIV activity against LAI M184V mutants in PBM cells as well as for their cytotoxicity. The antiviral and cytotoxic profiles of the prodrugs were compared with that of the parent compound (DOT), and it was found that four aryl phosphoramidates 5, 18, 20, and 26 showed a significant enhancement (8- to 12-fold) in anti-HIV activity without cytotoxicity. Chemical stability of these prodrugs was evaluated in phosphate buffer at pH values of biological relevance (i.e., pH 2.0 and 7.4). Enzymatic hydrolysis was also studied in esterase or lipase in buffer solution. Chemical stability studies indicate that the phosphoramidates have good chemical stability at pH 2.0 and at pH 7.4 phosphate buffer. Phosphoramidate prodrugs were hydrolyzed in vitro by esterase or lipase and found to be better substrates for lipases than for esterases. 1,3-Diol cyclic phosphates showed potent anti-HIV activity without increasing the cytotoxicity compared with that of DOT and have good chemical and enzymatic stability. Long-chain lipid phosphates, although showed potent anti-HIV activity, exhibited increased cytotoxicity.
- Liang, Yuzeng,Narayanasamy, Janarthanan,Schinazi, Raymond F.,Chu, Chung K.
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p. 2178 - 2189
(2007/10/03)
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- Investigations into the use of a polyfluorooctanol as an auxiliary component for an aldol reaction
-
Results are reported on the efficiency of polyfluorooctanol as a perfluorous auxiliary component in the aldol reaction between the enolate derived from polyfluorooctyl acetate and 2-fluorobenzaldehyde. Reduction of the corresponding polyfluoro β-hydroxy ester with Super Hydride gave the required 1,3-diol in good yield.
- Eames, Jason,Khanom, Hasina
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p. 266 - 277
(2007/10/03)
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- Facile reduction of aromatic aldehydes, ketones, diketones and oxo aldehydes to alcohols by an aqueous TiCl3/NH3 system: Selectivity and scope
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A simple and rapid procedure for the almost quantitative reduction of aromatic aldehydes, ketones, diketones and oxo aldehydes to alcohols by use of TiCl3/NH3 in aqueous methanol solution is reported. The reducing system distinguishes between different classes of aldehydes and/or ketones, and many functionalities that usually do not survive under reducing conditions are tolerated well. The concept of reversal of chemoselectivity has also been developed. A mechanism based on two sequential one-electron transfers from TiIII to the carbonyl carbon atom is proposed, the second SET becoming operative only in the presence of ammonium ion (either added or formed in situ). Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.
- Clerici, Angelo,Pastori, Nadia,Porta, Ombretta
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p. 3326 - 3335
(2007/10/03)
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- Pd-catalyzed kinetic resolution of benzylic alcohols: A practical synthesis of (R)-tomoxetine and (S)-fluoxetine hydrochlorides
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A convenient synthetic route to (R)-tomoxetine hydrochloride (90% ee) and (S)-fluoxetine hydrochloride (84% ee) is described. (S)-3-Phenyl-3-hydroxypropyl p-toluenesulphonate, the key intermediate, is obtained by the oxidative kinetic resolution of the corresponding racemic 3-phenyl-3-hydroxypropyl p-toluenesulphonate using (-)-sparteine/Pd(II)/O2 (1 atm) catalytic system.
- Ali, Iliyas Sayyed,Sudalai, Arumugam
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p. 5435 - 5436
(2007/10/03)
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- Thermolysis of a spiro-fused oxadiazoline: The carbonyl ylide-cyclic carbene-diradical sequence
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Thermolysis of spiro-fused oxadiazoline 1 in benzene led to loss of N2 to form a carbonyl ylide intermediate. Most of the ylide fragmented to acetone and 4-phenyl-1,3-dioxane-2-ylidene, which could be trapped with tert-butyl alcohol. In the absence of the trapping agent, the major pathway followed by the carbene was fragmentation to a diradical, 5-phenyl-2-oxa-1-oxo-1,5-pentanediyl. The latter diradical coupled to α-phenyl-δ-butyrolactone and decarboxylated to afford cyclopropylbenzene. Other products from the reaction were those of apparent insertion of the carbene into a C-H bond of the benzene solvent and into a C-H bond of acetone. Such reactions appear to be without precedent - alternative, non-carbene mechanisms are proposed.
- Merkley, Nadine,Warkentin, John
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p. 1187 - 1195
(2007/10/03)
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- Direct reduction of alcohols: Highly chemoselective reducing system for secondary or tertiary alcohols using chlorodiphenylsilane with a catalytic amount of indium trichloride
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The direct reduction of alcohols using chlorodiphenylsilane as A hydride source in the presence of a catalytic amount of indium trichloride is described. Benzylic alcohols, secondary alcohols, and tertiary alcohols were effectively reduced to give the corresponding alkanes in high yields. A compound bearing both primary and secondary hydroxyl groups was reduced only at the secondary site to afford the primary alcohol after workup with Bu4NF. This system showed high chemoselectivity only for the hydroxyl group while not reducing other functional groups that are readily reduced by standard reducing systems. Thus alcohols bearing ester, chloro, bromo, or nitro groups, which are sensitive to LiAlH4 or Zn/H+, were selectively reduced only at the hydroxyl sites by the chlorodiphenylsilane/InCl3 system. NMR studies revealed the reaction course. The hydrodiphenyl-silyl ether is initially formed and then, with InCl3 acting as a Lewis acid, forms an oxonium complex, which accelerates the desiloxylation with donation of the hydrogen to the carbon.
- Yasuda,Onishi,Ueba,Miyai,Baba
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p. 7741 - 7744
(2007/10/03)
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- Hydroformylation of epoxides catalyzed by cobalt and hemilabile P-O ligands
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Complexes of cobalt efficiently catalyze the hydroformylation of epoxides in the presence of hemilabile P-O chelating ligands to give β-hydroxyaldehydes in high selectivities and yields.
- Weber,Englert,Ganter,Keim,Moethrath
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p. 1419 - 1420
(2007/10/03)
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- The phenylthiocyclopropylsilyl group: A useful latent hydroxy group
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The α-dimethyl(1-phenylthio)cyclopropylsilyl group was used as a new masked hydroxy group. Three procedures have been devised to allow the oxidation of this silicon group in the presence of various functionalities. The desired alcohols are obtained in high yields with retention of configuration at the carbon centre. (C) 2000 Elsevier Science Ltd.
- Angelaud, Rémy,Landais, Yannick
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p. 2025 - 2036
(2007/10/03)
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- Reduction of carboxylic acids by tetraalkyl ammonium borohydride
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Tetraalkylammonium borohydride reduces carboxylic acids to the corresponding alcohols in good yields utilizing only stoichiometric quantities of hydride and also in the absence of any Lewis acids.
- Narasimhan,Swarnalakshmi,Balakumar
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p. 941 - 946
(2007/10/03)
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- New reactivity of methoxyhydridosilane in the catalytic activation system
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Hydroxy esters are reduced by trimethoxysilane in the presence of a catalytic amount of lithium methoxide to yield diols, while for simple esters the alcohol exchange reaction takes place preferentially. Through the exchange reaction, lactones, without a hydroxy group are reduced. Tosylimines are also reduced in the system.
- Hojo, Makoto,Murakami, Chikara,Fujii, Atsuko,Hosomi, Akira
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p. 911 - 914
(2007/10/03)
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- Zeolite (H-ZSM 5) catalysed regio and stereoselective reduction of 2,3- epoxy alcohols to 1,2-diols and vinylic epoxides to homoallylic alcohols with sodium cyanoborohydride
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A variety of 2,3-epoxy alcohols and vinylic epoxides (having the epoxide moieties at the terminal positions) undergo reduction with zeolite H-ZSM 5/NaCNBH3 combination of reagent system in refluxing dichloroethane to give 1,2-diols and homoally
- Gupta,Vankar
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p. 1369 - 1372
(2007/10/03)
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- Almond oxynitrilase-catalyzed transformation of aldehydes is strongly influenced by naphthyl and alkoxy substituents
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Different α- and β-substituted aldehydes have been submitted to the catalytic action of almond oxynitrilase (PaHNL), in order to explore the influence of a stereocenter already present in the substrate on the selectivity of this enzyme. The results indicate that naphthyl and alkoxy substituents in the α- and also in the β-position to the aldehyde group significantly influence the stereochemical outcome of the PaHNL-catalyzed transformation.
- Roda, Gabriella,Riva, Sergio,Danieli, Bruno
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p. 3939 - 3949
(2007/10/03)
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- Synthesis of benzanilide derivatives as dual acting agents with α1- adrenoceptor antagonistic action and steroid 5-α reductase inhibitory activity
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Synthesis of benzanilide derivatives which have dual α1-adrenoceptor antagonistic action and steroid 5α-reductase inhibitory activity and their structure-activity relationships is described.
- Yoshida, Kiyoshi,Horikoshi, Yoichiro,Eta, Masaaki,Chikazawa, Jun,Ogishima, Masayuki,Fukuda, Yohichi,Sato, Hiroki
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p. 2967 - 2972
(2007/10/03)
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- Aldol reactions on solid phase. Sc(OTf)3-catalyzed aldol reactions of polymer-supported silyl enol ethers with aldehydes providing convenient methods for the preparation of 1,3-diol, β-hydroxy carboxylic acid, and β-hydroxy aldehyde libraries
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Aldol reactions on solid phase have been achieved. In the presence of a catalytic amount of scandium triflate (Sc(OTf)3), polymer-supported silyl enol ethers reacted with aldehydes to afford the corresponding β-hydroxy thioester derivatives, which were reduced to 1,3-diol and β-hydroxy aldehyde derivatives, or hydrolyzed to β-hydroxy carboxylic acid derivatives.
- Kobayashi, Shu,Hachiya, Iwao,Yasuda, Masaru
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p. 5569 - 5572
(2007/10/03)
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- Selective synthesis of substituted benzylic alcohols from aromatic substrates included in β-cyclodextrin
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The regio- and enantioselective reduction of substituted styrenic epoxides and aromatic ketones by borohydride in the presence of β-cyclodextrin is described. The regioselectivity is related to the hydrophobicity of the substrate, which governs its penetration inside the cavity of the cyclodextrin and is favorable to the β-opening of the epoxide. The stereoselectivity observed during the reduction is mainly dependent on the non-covalent interactions between the upper rim of the cyclodextrin and the substrate included in it. The chimioselectivity observed during the reduction of ketoester is assumed to be dependent on an alkoxyborohydride intermediate formed in the first step of the reaction. Elsevier.
- Doussot, Joel,Guy, Alain,Garreau, Robert,Falguieres, Annie,Cossy, Janine,Amsterdamsky, Claude
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p. 161 - 166
(2007/10/03)
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