- Asymmetric Supported Reactions: Synthesis Of Chiral Amines
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Deracemization of amines, linked via Schiff bases to a chiral polyacrylic polymer has been studied.An enantiomeric excess of 72percent has been obtained with α-methyl benzylamine.
- Calmes, Monique,Daunis, Jacques,Hanouneh, Ahmad,Jacquier, Robert
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- Effective Guest Inclusion by a 6-O-Modified β-Cyclodextrin Dimer in Organic Solvents
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A 6-O-tert-butyldimethylsilylated β-cyclodextrin (TBDMS-β-CD) dimer, in which two TBDMS-β-CD rings are connected in a head-to-head fashion by a m-xylylene linker, effectively forms inclusion complexes with pyrene and naphthalene in nonpolar organic solvents such as cyclohexane and benzene. This TBDMS-β-CD dimer shows a higher inclusion ability toward these guests than a TBDMS-β-CD dimer bearing a p-xylylene linker due to the greater cooperation of the two TBDMS-β-CD rings for the guest inclusion. Unlike the corresponding monomer, the TBDMS-β-CD dimer bearing a m-xylylene linker is also a good host even in polar organic solvents such as tetrahydrofuran. High chiral recognition of aromatic amines and alcohol is realized by utilizing inclusion within the cavity of the TBDMS-β-CD dimer in cyclohexane. In particular, an extremely high binding selectivity for (S)-1-(1-naphthyl)ethylamine and (S)-1-(1-naphthyl)ethanol over the corresponding (R)-isomers is achieved. Moreover, by utilizing the high chiral recognition with the TBDMS-β-CD dimer in cyclohexane, a non-enzymatic kinetic resolution of racemic 1-(1-naphthyl)ethylamine via enantioselective N-benzoylation is attained with an enantiomer excess of up to 87 % and an s-factor of 15.
- Asahara, Chizuru,Iwamoto, Takuya,Akashi, Mitsuru,Shigemitsu, Hajime,Kida, Toshiyuki
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- Biocatalytic transamination with near-stoichiometric inexpensive amine donors mediated by bifunctional mono- and di-amine transaminases
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The discovery and characterisation of enzymes with both monoamine and diamine transaminase activity is reported, allowing conversion of a wide range of target ketone substrates with just a small excess of amine donor. The diamine co-substrates (putrescine, cadaverine or spermidine) are bio-derived and the enzyme system results in very little waste, making it a greener strategy for the production of valuable amine fine chemicals and pharmaceuticals.
- Galman, James L.,Slabu, Iustina,Weise, Nicholas J.,Iglesias, Cesar,Parmeggiani, Fabio,Lloyd, Richard C.,Turner, Nicholas J.
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- Isopropylidene glycerol hydrogen phthalate: A new resolving agent application to the resolution of 1-arylethylamines
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Hydrogen phthalates of (R)- and (S)-isopropylidene glycerol, obtainable from racemic isopropylidene glycerol by reaction with phthalic anhydride and successive resolution with (S)- and (R)-1-phenylethylamine or, alternatively, from (R)- and (S)-isopropylidene glycerol, were regarded as potential new resolving agents A range of important 1-arylethylamines was selected to test their resolving capability. In particular, trial resolutions were carried out using equivalent amounts of racemic amine and hydrogen phthalate of (R)-isopropylidene glycerol The salts of the S isomers selectively crystallized from methanol or 2-propanol allowing to recover the (S)-1-arylethylamines in high chemical and optical yields. Copyright
- Pallavicini, Marco,Valoti, Ermanno,Villa, Luigi,Piccolo, Oreste
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- Nonenzymatic kinetic resolution of amines in ionic liquids
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Ionic liquids are remarkably suitable and clean media for performing nonenzymatic kinetic resolution (KR) of amines through enantioselective N-acetylation: high levels of selectivity were obtained with a large variety of amines at room temperature (up to s = 30). Georg Thieme Verlag Stuttgart.
- Sabot, Cyrille,Subhash, Pithani V.,Valleix, Alain,Arseniyadis, Stellios,Mioskowski, Charles
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- (2-naphthyl)glycolic acid: A tailored resolving agent for p-substituted 1-arylethylamines
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A tailored resolving agent for p-substituted l-arylethylamines, which was designed on the basis of a criterion derived from our crystal-structure study, namely that the racemate and the resolving agent should have similar molecular lengths, is described. The designed enantiopure (2- naphthyl)glycolie acid (2-NGA) showed excellent resolving ability for a wide variety of p-substituted l-arylethylamines.
- Kinbara, Kazushi,Harada, Yoshiko,Saigo, Kazuhiko
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- n-Butylamine as an alternative amine donor for the stereoselective biocatalytic transamination of ketones
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Formal reductive amination has been a main focus of biocatalysis research in recent times. Among the enzymes able to perform this transformation, pyridoxal-5′-phosphate-dependent transaminases have shown the greatest promise in terms of extensive substrate scope and industrial application. Despite concerted research efforts in this area, there exist relatively few options regarding efficient amino donor co-substrates capable of allowing high conversion and atom efficiency with stable enzyme systems. Herein we describe the implementation of the recently described spuC gene, coding for a putrescine transaminase, exploiting its unusual amine donor tolerance to allow use of inexpensive and readily-available n-butylamine as an alternative to traditional methods. Via the integration of SpuC homologues with tandem co-product removal and cofactor regeneration enzymes, high conversion could be achieved with just 1.5 equivalents of the amine with products displaying excellent enantiopurity.
- Slabu, Iustina,Galman, James L.,Iglesias, Cesar,Weise, Nicholas J.,Lloyd, Richard C.,Turner, Nicholas J.
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- Chemoenzymatic Approaches to the Synthesis of the Calcimimetic Agent Cinacalcet Employing Transaminases and Ketoreductases
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Several chemoenzymatic routes have been explored for the preparation of cinacalcet, a calcimimetic agent. Transaminases (TAs) and ketoreductases (KREDs) turned out to be useful biocatalysts for the preparation of key optically active precursors. Thus, the asymmetric amination of 1-acetonaphthone yielded an enantiopure (R)-amine, which can be alkylated in one step to yield cinacalcet. Alternatively, the bioreduction of the same ketone resulted in an enantiopure (S)-alcohol, which was easily converted into the previous (R)-amine. In addition, the reduction was efficiently performed with the KRED and its cofactor co-immobilized on the same porous surface. This self-sufficient heterogeneous biocatalyst presented an accumulated total turnover number (TTN) for the cofactor of 675 after 5 consecutive operational cycles. Finally, in a preparative scale synthesis the TA-based approach was performed in aqueous medium and led to enantiopure cinacalcet in two steps and 50% overall yield. (Figure presented.).
- Marx, Lisa,Ríos-Lombardía, Nicolás,Farnberger, Judith F.,Kroutil, Wolfgang,Benítez-Mateos, Ana I.,López-Gallego, Fernando,Morís, Francisco,González-Sabín, Javier,Berglund, Per
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- Efficient kinetic resolution of racemic amines using a transaminase in combination with an amino acid oxidase
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A range of enantiomerically pure (R)- and (S)-configured chiral amines has been prepared in excellent e.e. (99%) by combining a transaminase enzyme with an amino acid oxidase and catalytic quantities of pyruvate.
- Truppo, Matthew D.,Turner, Nicholas J.,Rozzell, J. David
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- Optical resolution and absolute configuration of the chiral pentamethylcyclopentadienylrhenium carbonyl complex 5-C5Me5)Re(NO)(PPh3)(CO)>+BF4-
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Reaction of racemic ester (η5-C5Me5)Re(NO)(PPh3)(CO2CH3) and (-)-(S)-α-(1-naphthyl)ethylamine gives amide (η5-C5Me5)Re(NO)(PPh3)(CONHCH(CH3)C10H7) (3) as a (SS)-/(RS)- diastereomer mixture.Crystallization gives the less soluble diastereomer (-)-(RS)-3 (77percent, 98percent diastereomeric excess).Subsequent reaction with CF3CO2H and then NaBF4 gives carbonyl complex (-)-(R)-5-C5Me5)Re(NO)(PPh3)(CO)>+BF4- (91percent, 99percent enantiomeric excess), which is in turn reduced (Li(C2H5)3BH/BH3 * THF) to methyl complex (-)-(R)-(η5-C5Me5)Re(NO)(PPh3)(CH3) (97percent).These serve as convenient precursors to a variety of other optically active complexes.Preparations of enantiomeric complexes, diastereomer (-)-(RR)-3, and recycling of the chiral α-(1-naphthyl)ethylamine auxilliary are also described.The structure and absolute configuration of (-)-(RS)-3 is verified crystallographically (orthorhombic, P212121 (no. 19), a 12.348(4), b 13.198(5), c 22. 168(9) Angstroem, Z = 4).
- Huang, Yo-Hsin,Niedercorn, Francine,Arif, Atta M.,Gladysz, J.A.
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- 6-TIPS-β-Cyclodextrin-Modified Fe3O4 for Facile Enantioseparation of 1-(1-Naphthyl)ethylamine
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A new type of chiral magnetic nanoparticle was prepared from covalently linked magnetic nanoparticles (Fe3O4) and heptakis-(6-O-triisopropylsilyl)-β-cyclodextrin (6-TIPS-β-CD). The resulting selectors (TIPS-β-CD-MNPs) combined the good magnetic properties Fe3O4 and efficient chiral recognition ability of 6-TIPS-β-CD. The enantioselectivity of TIPS-β-CD-MNPs towards 1-(1-naphthyl)ethylamine was six times higher than that of the parent β-CD modified Fe3O4 particles.
- Wang, Lu,Liang, Xiang-Yong,Ding, Li-Sheng,Zhang, Sheng,Li, Bang-Jing
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- Highly efficient resolutions with isopropylidene glycerol 3-carboxy-2-naphthoate
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A number of chiral 1-arylethylamines and 1-alkylethylamines were resolved with the 3-carboxy-2-naphthoate of isopropylidene glycerol 2, previously reported to be an even more efficient resolving agent for 1-phenylethylamine than the corresponding hemiphthalate 1. The results obtained for the 1-arylethylamines confirm such a trend, revealing impressive resolution ability, in particular, for 1-(4-bromophenyl)-, 1-(4-nitrophenyl)- and 1-(2-naphthyl)ethylamine, whose enantiomers were almost quantitatively separated with (S)-2 by a single precipitation of the less soluble (S,S) diastereomeric salt. Additionally, the success of the resolutions of 1-alkylethylamines (1-phenyl-2-propylamine, 1-cyclohexylethylamine and 2-butylamine), which could not be resolved with 1, indicates that the novel carboxy ester 2 has a wider range of application than 1.
- Pallavicini, Marco,Bolchi, Cristiano,Fumagalli, Laura,Valoti, Ermanno,Villa, Luigi
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- A METHOD FOR PREPARATION OF DIASTEREOMERIC LACTATE SALTS OF 1-(1-NAPHTHYL)ETHYL AMINE AND PURE ENANTIOMERS OF 1-(1-NAPHTHYL)ETHYL AMINE
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The invention relates to method for preparation of pure enantiomers of 1-(1-naphthyl)ethyl amine by preparing lactate salt with chiral lactic acid as resolving agent. The method comprises reaction of L-lactic acid or D-lactic acid with racemic 1-(1-naphthyl)ethyl amine to form diastereomeric salts of (R/S)-1-(1-naphthyl)ethyl amine-(D/L)-lactate from which pure enantiomer is isolated. The invention also comprises method for preparation of compound with enriched enantiomers of 1-(1-naphthyl)ethyl amine from the mother liquor separated from the diastereomeric lactate salt. The enriched enantiomer is reacted with pure enantiomers of mandelic acid or lactic acid, preferably D-mandelic acid or L-mandelic acid and converted to diastereomeric mandelate salt. Pure (R)- or (S)-1-(1-naphthyl)ethyl amine is obtained from the diastereomeric mandelate salt. The chiral purity of pure enantiomer obtained is between 99% and 100%.
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Paragraph 0051
(2021/09/11)
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- Enantioselective synthesis of (R)-Cinacalcet via cobalt-catalysed asymmetric Negishi cross-coupling
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A novel enantioselective synthesis of (R)-cinacalcet with 99% enantiomeric excesses (ee) has been achieved. The main strategies of the approach include a gram-scale cobalt-catalysed asymmetric cross-coupling of racemic ester with arylzinc reagent, Hoffman-type rearrangement of acidamide, the amidation of chiral amine, and improving the ee of chiral amide from 87% to 99% via recrystallization.
- Sun, Xiao,Wang, Xueyang,Liu, Feipeng,Gao, Zidong,Bian, Qinghua,Wang, Min,Zhong, Jiangchun
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p. 682 - 687
(2019/08/07)
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- Method for asymmetrically synthesizing (R)-cinacalcet
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The invention discloses a new method for asymmetrically synthesizing (R)-cinacalcet. The method includes: taking racemic 2-bromo-propionic acid (4-methoxybenzyl) ester as a starting raw material, andbeing in asymmetric Negishi cross coupling reaction with 2-nathphyl zinc bromide under catalysis of CoI2 and chiral ligand to generate (R)-2-(1-nathphyl) propionic acid (4-methoxybenzyl) ester; beingin reaction with oxalyl chloride through LiOH reduction to generate (R)-2-(1-nathphyl) propionyl chloride; being reaction with ammonia water to generate (R)-2-(1-nathphyl) propionamide, and allowing Hofmann degradation to obtain (R)-1-nathphalene ethylamine; being in reaction with 3-(trifluoromethyl) phenylpropionic acid to generate (R)-N-(1-nathphalene ethyl)-3-(3-trifluoromethylphenyl) propionamide, and allowing LiAlH4 reduction to obtain (R)-cinacalcet. Cobalt catalyzed asymmetric Negishi cross coupling reaction is utilized for the first time to build the chiral center of (R)-cinacalcet, the method is mild in reaction condition and environment-friendly, and optical purity of (R)-cinacalcet is high (99%ee).
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- Efficient resolution of (R,S)-1-(1-naphthyl)ethylamine by Candida antarctica lipase B in ionic liquids
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The resolution of (R,S)-1-(1-naphthyl)ethylamine ((R,S)-NEA) by Candida antarctica lipase B (CALB) in ionic liquids (ILs) containing 1-alkyl-3-methylimidazolium cations ([Cnmim]+) and [Tf2N]?, [BF4]?, and [PF6]? anions was investigated. When the alkyl chain on the cation contained less than six carbons, the lipase activity corresponded with the hydrophobicity of the ILs, but further increase in the chain length suppressed the enzyme activity. The enzyme activity decreased depending on the anion, where [Tf2N]? > [PF6]? > [BF4]?. The effects of acyl donors, pH, temperature, water activity, and substrate concentration on the resolution were determined. Under the optimal conditions, the conversion of (R,S)-NEA and enantiomer excess of (R)-n-octyl acyl-NEA was 49.3% and 99.2%, respectively. The resolution kinetics of (R,S)-NEA by CALB in [C6mim][Tf2N] were studied and a ping-pong mechanism with a two substrate inhibition model was selected. The kinetic parameters of the fitting results were as follows: Michaelis constant of (R,S)-NEA Kma, 461.8 mmol/L; Michaelis constant of vinyl n-octanoateKmb, 262.1 mmol/L; inhibition constant of (R,S)-NEA Kia, 8737.2 mmol/L; inhibition constant of vinyl n-octanoateKib, 62336.8 mmol/L; maximum reaction rate rmax, 0.352 mmol/(mg min). Moreover, circular dichroism revealed that incubation of CALB in [C6mim][Tf2N] resulted in increased β-sheet content; its secondary structure was stable.
- Wang, Bin,Zhang, Chao,He, Qinting,Qin, Hengfei,Liang, Guobin,Liu, Weiqiao
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p. 116 - 121
(2018/03/01)
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- A methof for preparing (R)- (+) - 1 - naphthalene of ethylamine
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The invention discloses a splitting method for preparing (R)-(+)-1-naphthyl ethylamine, and belongs to the field of splitting of mixed levorotatory/dextrorotary compounds. In the provided method, (+)-4-phenyl-2-hydroxy-5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinane is taken as the main splitting agent and (+)-4-(2-chlorophenyl)-2-hydroxy-5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinane is taken as the auxiliary splitting agent so as to split mixed levorotatory/dextrorotary 1-naphthyl ethylamine, and finally (R)-(+)-1-naphthyl ethylamine and (S)-(+)-1-naphthyl ethylamine with a high optical purity can be obtained. The obtained (R)-(+)-1-naphthyl ethylamine has an optical purity as high as 99% e.e. or more. The provided method has the characteristics of high yield, recoverable splitting agent, simple operation, and suitability for industrial production.
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Paragraph 0040-0044; 0045-0049; 0050-0054; 0075-0078
(2017/08/25)
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- PROCESS FOR THE PREPARATION OF CHIRAL AMINES FROM PROCHIRAL KETONES
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There is provided a method for the preparation of an enantiomerically enriched amine from a prochiral ketone.
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Page/Page column 5; 6
(2015/12/11)
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- Mechanism-Guided Engineering of ω-Transaminase to Accelerate Reductive Amination of Ketones
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Asymmetric reductive amination of ketones using ω-transaminases (ω-TAs) offers a promising alternative to the chemocatalytic synthesis of chiral amines. One fundamental challenge to the biocatalytic strategy is the very low enzyme activities for most ketones compared with native substrates (i.e., cat/KM for acetophenone). The W58L mutant afforded an efficient synthesis of enantiopure amines (i.e., >99% ee) using isopropylamine as an amino donor.
- Han, Sang-Woo,Park, Eul-Soo,Dong, Joo-Young,Shin, Jong-Shik
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p. 1732 - 1740
(2015/06/02)
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- Kinetic resolution of primary amines via enantioselective N-acylation with acyl chlorides in the presence of supramolecular cyclodextrin nanocapsules
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The non-enzymatic kinetic resolution of primary amines via enantioselective N-acylation with acyl chlorides was accomplished for the first time by using the selective sequestration of one enantiomer within a supramolecular cyclodextrin (CD) nanocapsule in nonpolar solvents. In addition, the first example of a crystalline structure for an inclusion complex between an acyl chloride and a CD derivative is reported.
- Asahara, Haruyasu,Kida, Toshiyuki,Iwamoto, Takuya,Hinoue, Tomoaki,Akashi, Mitsuru
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p. 197 - 203
(2014/01/06)
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- PROCESS FOR THE RACEMIZATION OF OPTICALLY ACTIVE ARYLALKYLAMINES
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Many optically active amines are valuable pharmaceuticals and intermediates for the preparation of active compounds. It is frequently the case that only one of the two enantiomers is active or not harmful, so that isolation of this enantiomer from the racemic mixture is necessary. Processes for racemate resolution make it possible to separate racemic mixtures into their enantiomers. Here, it is useful to once again racemize the enantiomer which is not required and recirculate it to racemate resolution and thus improve the yield of the desired enantiomer. The present invention relates to processes for the racemization of optically active amines, in particular arylalkylamines, in the presence of hydrogen and a hydrogenation/dehydrogenation catalyst comprising nickel, cobalt and copper as active components at elevated temperature.
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- Chiral recognition and kinetic resolution of aromatic amines via supramolecular chiral nanocapsules in nonpolar solvents
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Herein we report the first example of chiral recognition and kinetic resolution of aromatic amine guests using supramolecular nanocapsules assembled from cyclodextrin derivatives in nonpolar media. With these nanocapsules, an extremely high chiral recognition of 1-(1-naphthyl)ethylamine (1) in cyclohexane was achieved, with a binding selectivity of up to 41 for (S)-1(R)-1. In addition, kinetic resolution of 1 through enantioselective N-acylation was accomplished with an enantiomeric excess of up to 91%.
- Kida, Toshiyuki,Iwamoto, Takuya,Asahara, Haruyasu,Hinoue, Tomoaki,Akashi, Mitsuru
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supporting information
p. 3371 - 3374
(2013/04/24)
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- Asymmetric synthesis of nonracemic primary amines via spiroborate-catalyzed reduction of pure (E)- and (Z)-O-benzyloximes: Applications toward the synthesis of calcimimetic agents
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Highly enantiopure (1-aryl)- and (1-naphthyl)-1-ethylamines were synthesized by the borane-mediated reduction of single-isomeric (E)- and (Z)-O-benzyloxime ethers using the stable spiroborate ester derived from (S)-diphenyl valinol and ethylene glycol as the chiral catalyst. Primary (R)-arylethylamines were prepared by the reduction of pure (Z)-ethanone oxime ethers in up to 99% ee using 15% of catalyst. Two convenient and facile approaches to the synthesis of new and known calcimimetic analogues employing enantiopure (1-naphthalen-1-yl)ethylamine as chiral precursor are described.
- Ou, Wenhua,Espinosa, Sandraliz,Meléndez, Héctor J.,Farré, Silvia M.,Alvarez, Jaime L.,Torres, Valerie,Martínez, Ileanne,Santiago, Kiara M.,Ortiz-Marciales, Margarita
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p. 5314 - 5327
(2013/07/25)
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- N-BIPHENYLMETHYLINDOLE MODULATORS OF PPARG
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The invention provides molecular entities that bind with high affinity to PPARG (PPAR3), inhibit kinase-mediated, e.g., cdk5-mediated, phosphorylation of PPARG, but do not exert an agonistic effect on PPARG. Compounds of the invention can be used for treatment of conditions in patients wherein PPARG plays a role, such as diabetes, insulin resistance, impaired glucose tolerance, pre-diabetes, hyperglycemia, hyperinsulinemia, obesity, or inflammation. In methods of treatment of these conditions using a compound of the invention, the compound can avoid producing side effects of significant weight gain, edema, impairment of bone growth or formation, or cardiac hypertrophy, or any combination thereof, in the patient receiving the compound. Methods of preparation of the compounds, bioassay methods for evaluating compounds of the invention as non-agonistic PPARG binding compounds, and pharmaceutical compositions are also provided.
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Page/Page column 184
(2012/12/14)
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- Solvent-free kinetic resolution of primary amines catalyzed by Candida antarctica lipase B: Effect of immobilization and recycling stability
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Highly enantioselective (E >200) N-acylation of nine racemic primary amines with isopropyl methoxyacetate in the presence of Candida antarctica lipase B (Novozym 435) has been reported to yield the unreacted (S)-amines (ee ≥98%) and produced the (R)-amides (ee ≥95%) at 50% conversion under solvent-free conditions. One of the amines and the acyl donor have been used in an equimolar ratio at room temperature (23 °C). Under the reaction conditions, the reuse stability of Novozym 435 with 1-phenylethylamine (as a model compound) has been shown to be poor while somewhat improved stability has been observed with an in-house prepared sol-gel CAL-B catalyst.
- Paeivioe, Mari,Perkioe, Paeivi,Kanerva, Liisa T.
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experimental part
p. 230 - 236
(2012/06/15)
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- Efficient synthesis and practical resolution of 1-(naphthalen-1-yl) ethanamine, a key intermediate for cinacalcet
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An efficient synthesis of 1-(naphthalen-1-yl)ethanamine (RS-2) and its practical resolution to optically pure (1R)-(naphthalen-1-yl)ethanamine (R-(+)-2), a key intermediate in the synthesis of cinacalcet hydrochloride (1), is described. The resolution of RS-2 using R-(-)-mandelic acid as a resolving agent in ethanol was established on an industrial scale to give pure R-(+)-2 with >99.8% ee after liberation of the amine from its mandelate salt. An efficient process for the racemization of undesired isomer S-(-)-2 is also provided to maximize the yield of desired enantiomer.
- Mathad, Vijayavitthal T.,Shinde, Gorakshanath B.,Ippar, Sharad S.,Niphade, Navnath C.,Panchangam, Raghavendra K.,Vankawala, Pravinchandra J.
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p. 341 - 346
(2011/04/15)
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- Enantiopure cyclic O-substituted phenylphosphonothioic acid: Synthesis and chirality-recognition ability
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As a new acidic selector (resolving agent), we synthesized an enantiopure O-alkyl phenylphosphonothioic acid with a seven-membered ring ((R)-5), which was designed on the basis of the results for the enantioseparation of 1-arylethylamine derivatives with acyclic O-ethyl phenylphosphonothioic acid (I). The phosphonothioic acid (R)-5 showed unique chirality-recognition ability in the enantioseparation of 1-naphthylethylamine derivatives, aliphatic secondary amines, and amino alcohols; the ability was complementary to that of I. The X-ray crystallographic analyses of the less- and more-soluble diastereomeric salts showed that hydrogen-bonding networks in the salt crystals are 21-column-type with a single exception which is cluster-type. In the cases of the 21-column-type crystals, stability of the crystals is firstly governed by hydrogen bonds to form a 21-column and secondly determined by intra-columnar T-shaped CH/π interaction(s), intra-columnar hydrogen bond(s), inter-columnar van der Waals interaction and/or inter-columnar T-shaped CH/π interaction(s). In contrast, the cluster-type salt crystal is stabilized by the assistance of inter-cluster T-shaped CH/π and van der Waals interactions. To realize still more numbers of intra- and inter-columnar and -cluster T-shaped CH/π interactions, the seven-membered ring of (R)-5 plays a considerable role. Copyright
- Ribeiro, Nigel,Kobayashi, Yuka,Maeda, Jin,Saigo, Kazuhiko
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experimental part
p. 438 - 448
(2012/01/02)
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- COMPOSITIONS AND METHODS FOR CYCLOFRUCTANS AS SEPARATION AGENTS
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The present invention relates to derivatized cyclofructan compounds, compositions comprising derivatized cyclofructan compounds, and methods of using compositions comprising derivatized cyclofructan compounds for chromatographic separations of chemical species, including enantiomers. Said compositions may comprise a solid support and/or polymers comprising derivatized cyclofructan compounds.
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Page/Page column 45-49; 61
(2010/12/31)
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- Separation of the phenoxy acid herbicides and their enantiomers by capillary zone electrophoresis in presence of highly sulphated cyclodextrins
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The study of the chiral compounds and their fate in the environment is receiving an increasing attention - enantiomeric ratios are being measured and enantioselective degradation processes are being reported. It is particularly important with the toxic compounds like the pesticides, which are being freely used in the environment to control the harmful pests. Capillary zone electrophoresis was used for the chiral and mutual separation of four phenoxy acid herbicides using highly sulphated cyclodextrins (HSCD) in the buffer. The CE runs were performed with reverse polarity (anode in the outlet vial) using the acidic ammonium formate buffer (20 mmol, pH 3). Under these conditions of suppressed the electroendoosmotic flow (EOF), the analytes are mobilized to the anode by entering into host guest relation with the migrating negatively charged sulphated cyclodextrin. The phenoxy acid herbicides selected for the purpose were fenoprop, dicloprop, mecoprop and 2,4-DB. The α-HSCD and β-HSCD have been tested as resolving agents in the CE for the separation of the enantiomers of the herbicides. Though the chiral separation of the dicloprop and mecoprop were achieved with α-HSCD but it was not able to resolve fenoprop. With β-HSCD the required base line separation was achieved. Potential difference selected was 10 kV. The limit of detection (S/N=3) achieved in present case is 0.15 ppm for fenoprop, 0.14 ppm for dicloprop and mecoprop and 0.11 ppm for 2,4-DB.
- Malik, Ashok Kumar,Aulakh, Jatinder Singh,Fekete, Agnes,Philippe, Schmitt-Kopplin
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experimental part
p. 1163 - 1167
(2010/08/20)
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- Optically active amines by enzyme-catalyzed kinetic resolution
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Chiral amines are resolved by an enzyme-catalyzed kinetic resolution. Key steps are the selective acylation of one enantiomer with isopropyl methoxyacetate, separation of the resulting amide from the unreacted antipode, and finally amide hydrolysis. The p
- Ditrich, Klaus
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experimental part
p. 2283 - 2287
(2009/04/06)
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- Highly selective enzymatic kinetic resolution of primary amines at 80°C: A comparative study of carboxylic acids and their ethyl esters as acyl donors
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(Chemical Equation Presented) Optimization of the kinetic resolution of 2-amino-4-phenyl-butane was achieved at 80°C using CAL-B-catalyzed aminolysis of carboxylic acids and their ethyl esters. The reactions carried out with long chain esters and the corresponding acids as acyl donors proceeded with remarkably high enantioselectivity. The use of carboxylic acids as acylating agents led to a marked acceleration of the reaction rate compared to their ester counterparts. Laurie acid led to enantiomeric excesses superior to 99.5% for both the remaining amine and the corresponding lauramide at 50% conversion (reached in 3 h). These optimized conditions were applied to the resolution of a series of aliphatic and benzylic amines.
- Nechab, Malek,Azzi, Nadia,Vanthuyne, Nicolas,Bertrand, Michele,Gastaldi, Stephane,Gil, Gerard
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p. 6918 - 6923
(2008/02/11)
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- Amidation of amines with esters catalyzed by Candida antarctica lipase (CAL)
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Candida antarctica lipase (CAL) is used to convert amines and esters into amides, especially as a chiral resoluting catalyst for the enantioselective amidation of racemic esters or racemic amines in an effort to demonstrate the ability of lipase to differentiate between enantiomeric substrates. It is a very useful synthetic method for amides. The effects of substrate modification on the yield and enantiomeric excess (ee) are studied. The R-enantiomer will react faster for racemic mixture of amine in which the amino group attaches directly to the chiral carbon, and the same for racemic mixture of ester in which the carbonyl group attaches directly to the chiral carbon. The enantioselectivity of CAL is complicated for the amidation of racemic mixture of amine with racemic mixture of ester.
- Yang, Bo,Zhang, Yanjun,Zhang, Shusheng,Izumi
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p. 1312 - 1316
(2007/10/03)
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- PROCESS FOR THE PREPARATION OF AROMATIC AMINES
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There is provided a process for the preparation of aromatic amines of Formula (1): where Rx is optionally substituted aryl and Ry is optionally substituted hydrocarbyl, which comprises: (a) reducing a compound of Formula (2): to give a compound of Formula (3): then, (b) reacting a compound of Formula (3) with a leaving group donor, to give a compound of Formula (4); and, (c) reacting a compound of Formula (4) with ammonia to give the compound of Formula (1).
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Page/Page column 24
(2008/06/13)
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- Kinetic resolution of amines: A highly enantioselective and chemoselective acetylating agent with a unique solvent-induced reversal of stereoselectivity
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Solvents lend a hand: Changing the polarity of the reaction solvent from 1,3-dimethyltetrahydropyrimidin-2-one (DMPU) to toluene reverses the stereo-selectivity observed in the acetylation of amines with (1S,2S)-1 (see scheme). Optimizing the reaction conditions led to an unprecedented 90% ee (S) in DMPU at -20°C with a 33% conversion.
- Arseniyadis, Stellios,Valleix, Alain,Wagner, Alain,Mioskowski, Charles
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p. 3314 - 3317
(2007/10/03)
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- Highly Enantioselective Hydrogen-Transfer Reductive Amination: Catalytic Asymmetric Synthesis of Primary Amines
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Ammonium formate is the hydrogen source in the catalytic asymmetric reductive amination of ketones presented here (Leuckart-Wallach-type reaction). The reaction proceeds smoothly in methanol in the presence of Ir, Rh, and Ru catalysts. Primary amines were obtained as products in good yields with high enantioselectivities after hydrolytic workup when [((R)-tol-binap) RuCl 2] was used as the catalyst (see scheme). R1, R 2=alkyl, aryl.
- Kadyrov, Renat,Riermeier, Thomas H.
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p. 5472 - 5474
(2007/10/03)
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- Enzymatic resolution of bicyclic 1-heteroarylamines using Candida antarctica lipase B
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Candida antarctica lipase B has been used to kinetically resolve a structurally diverse series of bicyclic 1-heteroaryl primary amines by enantioselective acetylation. High yields of either enantiomer could be obtained with excellent enantioselectivity (90-99% ee), while the undesired enantiomer could, in some cases, be recycled by thermal racemization. The absolute stereochemistry of the products was confirmed by an X-ray crystal structure.
- Skupinska, Krystyna A.,McEachern, Ernest J.,Baird, Ian R.,Skerlj, Renato T.,Bridger, Gary J.
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p. 3546 - 3551
(2007/10/03)
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- Synthesis of enantiomerically pure amino-substituted fused bicyclic rings
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This invention describes various processes for synthesis and resolution of racemic amino-substituted fused bicyclic ring systems. One process utilizes selective hydrogenation of an amino-substituted fused bicyclic aromatic ring system. An alternative process prepares the racemic amino-substituted fused bicyclic ring system via nitrosation. In addition, the present invention describes the enzymatic resolution of a racemic mixture to produce the (R)- and (S)-forms of amino-substituted fused bicyclic rings as well as a racemization process to recycle the unpreferred enantioner. Further provided by this invention is an asymmetric synthesis of the (R)- or (S)-enantiomer of primary amino-substituted fused bicyclic ring systems.
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- Process for preparing optically active amines and optically active carboxylic acids, and intermediates for preparation
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Disclosed is a process for preparing an optically active 1-aryl- or 2-aryl-alkylamines of formulas Ia, Ib and Ic with high optical purity and high yield. The process uses an optically active 1- or 2-naphthylglycolic acid of the general formula II as a resolving agent. Also disclosed is a process for praparing an optically active 1- or 2-naphthylglycolic acid of formula II using an optically active 1-aryl- or 2-aryl-alkylamines of formulas Ia, Ib and Ic as the resolving agents
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- Deprotection of 2-pyridyl sulfonyl group from pyridine-2-sulfonamides by magnesium in methanol
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Convenient deprotection of various pyridine-2-sulfonamides prepared by sulfonylation of primary and secondary amines with pyridine-2-sulfonylchloride was achieved by magnesium in methanol at 0°C to the corresponding amines in good yield.
- Chwang Siek Pak,Dong Sung Lim
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p. 2209 - 2214
(2007/10/03)
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- Highly enantioselective hydrogenation of acyclic imines catalyzed by Ir-f-binaphane complexes
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The key control factor in the hydrogenation of imines is the chiral ferrocene phosphane ligand f-binaphane. High yields and enantioselectivities were obtained in the Ir-catalyzed conversion of imines into amines [Eq. (1)].
- Xiao, Denming,Zhang, Xumu
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p. 3425 - 3428
(2007/10/03)
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- Catalytic asymmetric hydroboration/amination and alkylamination with rhodium complexes of 1,1′-(2-diarylphosphino-1-naphthyl)isoquinoline
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Catecholboronate esters formed by asymmetric hydroboration of arylalkenes are not directly converted to amines by reaction with hydroxylamine-O-sulfonic acid. Prior conversion to a trialkylborane by reaction with ZnEt2 or MeMgCl permits a subsequent amination reaction to occur with essentially complete retention of configuration, leading to a range of primary α-arylalkylamines in up to 97% enantiomeric excess (ee). Secondary, but not tertiary amines may be formed by a related pathway when in situ generated alkylchloramines are employed as the aminating agent. The catalytic asymmetric hydroboration, β-alkylation and amination steps may be combined in a single stage. Overall, this provides a practical procedure for the synthesis of enantiomerically enriched arylamines, exemplified inter alia by the synthesis of (S)-1,2,3,4-tetrahydro-1-naphthylamine in 95-97% ee and of (R)-N-(cyclohexyl)-1′-(4-methoxyphenyl)ethylamine in 93 % ee.
- Fernandez, Elena,Maeda, Kenji,Hooper, Mark W.,Brown, John M.
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p. 1840 - 1846
(2007/10/03)
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- A high-performance, tailor-made resolving agent: Remarkable enhancement of resolution ability by introducing a naphthyl group into the fundamental skeleton1
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A novel resolving agent, 2-naphthylglycolic acid (2-NGA), was designed for p-substituted 1-arylethylamines on the basis of the consideration that a rigid and large naphthyl group would be favorable for the close packing of supramolecular hydrogen-bond sheets formed between the carboxy groups of 2-NGA and the amino groups of p-substituted 1-arylethylamines. Racemic 2-NGA was readily available from commercially available raw materials, and both enantiopure forms could be obtained by simple diastereomeric resolution with enantiopure 1-phenyl-ethylamine. Thus-prepared enantiopure 2-NGA was found to have an excellent resolution ability not only for p-substituted 1-arylethylamines, but also for a wide variety of chiral primary amines. X-Ray crystallographic analyses of the less- and more-soluble diastereomeric salts revealed that this excellent resolution ability of 2-NGA arose from the formation of a supramolecular hydrogen-bond sheet with the primary amine, as we had expected, and also from the possible achievement of an infinite chain of CH... π interaction between its naphthyl group and the aromatic group of the amine, which was formed in the hydrophobic region of the supramolecular hydrogen-bond sheet.
- Kinbara, Kazushi,Harada, Yoshiko,Saigo, Kazuhiko
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p. 1339 - 1347
(2007/10/03)
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- Saponification agents. 2. Synthesis of arylisocyanates with ethyl lactate and their use in racemic bases saponification
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Reaction of the arylisocyanates 2a-c with ethyl (S)-(-)-lactate, followed by careful saponification, afforded the corresponding chiral acids (S)-(-)- 4a-c. The latter were successfully used for the resolution of various racemic bases belonging to both the ephedrine and α-aryl ethylamine series.
- Brown,Moudachirou
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p. 10309 - 10320
(2007/10/02)
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- Asymmetric Synthesis Using Chirally Modified Borohydrides. Part 3. Enantioselective Reduction of Ketones and Oxime Ethers with Reagents Prepared from Borane and Chiral Amino Alcohols
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The asymmetric reduction of aromatic and aliphatic ketones, halogeno ketones, keto esters, and ketone oxime ethers with reagents prepared from borane and chiral amino alcohols has been investigated.When α,α-diphenyl-β-amino alcohols, such as (2S,3R)-(-)-2-amino-3-methyl-1,1-diphenylpentanol (2d), were used as a chiral auxiliary, very high enantioselectivities (ca. 90percent e.e.) were obtained in the reduction of various ketones and oxime ethers.
- Itsuno, Shinichi,Nakano, Michio,Miyazaki, Koji,Masuda, Hirofumi,Ito, Koichi,et al.
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p. 2039 - 2044
(2007/10/02)
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- SynThesis, Optical Resolution, and Absoiyte - Pseudotetrahedrai organorheniym complexes (i7-C5H5)Re(NO)(PPh,)(X)
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Reaction of [(C6H5)Re(NO)(PPh3)(CO)]+BF,r (1) with CH,ONa/CH3OH affords the ester (??C5H6)Re(NO)(PPh3)(COOCH3) (2). Reaction of 2 with (-)-(S)-a-(l-naphthyi)ethyIamine or (+)-(R)-a(l-naphthyl)ethykmine gives amide (^C6H5)Re(NO)(PPh3XCO:NHCH(CH3)C10H7) (8). The diastereomers of 8 are separated by benzene/hexane reerystallization; (-)-(BS)-8 and (+)-(SA)-8 are least soluble. These are treated with CF3C02H and NaBF4 to give (-)-(A)-l and (+)-(S)-l, respectively. Resolved 1 is then used to prepare optically active 2, (i?-C5HB)Re(NO)(PPh3)(CH8) (3), [()7-C5H5)Re(NO}(PPh3)(==H2)]+PF6-(4), (i7-C5H6)Re(NO)(PPhg)(CH2C6H 5) (9), (7j-C5HB)Re(NO){PPh3){CH2CH3) (10), and (7?-C5H5)Re(NO)(PPh3)(CHO) (11) via known procedures. An X-ray crystal structure of (-)-(A)-9 (space group P212121, a = 12.874 (5) A, b = 11.889 (3) A, c = 16.077 (7) K,Z~4,R = 0.034) establishes the absolute configurations of resolved 1-4 and 8-11. Also described are the following: ORD and CD spectra; several unsuccessful resolution attempts; the synthesis of [(jl-C5H5)Re(NO)(PPh3)(CH 2P+Ph2(0-i-menthyl))]+PF6+ (?) (used as an optical purity assay); comparisons with isostructural chiral organometallic complexes.
- Merrifield, James H.,Strouse, Charles T,Giadysz
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p. 1204 - 1211
(2008/10/08)
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- OPTICALLY ACTIVE F-2-ISOPROPOXYPROPIONIC ACID: A NOVEL DERIVATIZING AGENT FOR GAS CHROMATOGRAPHIC ANALYSIS
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F-2-Isopropoxypropionic acid (PIPA) was resolved into enantiomers via its diastereomeric (+)-1-phenylethylamide. (+)-F-2-Isopropoxypropionyl derivatives of several chiral 1-arylalkylamines and α-amino acids were effectively resolved by gas chromatography at low temperature.
- Kawa, Hajimu,Yamaguchi, Fumihiko,Ishikawa, Nobuo
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p. 745 - 748
(2007/10/02)
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