- Nickel-Catalyzed Multicomponent Coupling: Synthesis of α-Chiral Ketones by Reductive Hydrocarbonylation of Alkenes
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A nickel-catalyzed, multicomponent regio- and enantioselective coupling via sequential hydroformylation and carbonylation from readily available starting materials has been developed. This modular multicomponent hydrofunctionalization strategy enables the straightforward reductive hydrocarbonylation of a broad range of unactivated alkenes to produce a wide variety of unsymmetrical dialkyl ketones bearing a functionalized α-stereocenter, including enantioenriched chiral α-aryl ketones and α-amino ketones. It uses chiral bisoxazoline as a ligand, silane as a reductant, chloroformate as a safe CO source, and a racemic secondary benzyl chloride or an N-hydroxyphthalimide (NHP) ester of a protected α-amino acid as the alkylation reagent. The benign nature of this process renders this method suitable for late-stage functionalization of complex molecules.
- Chen, Jian,Zhu, Shaolin
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supporting information
p. 14089 - 14096
(2021/09/13)
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- Organocatalytic asymmetric [4+2] cyclization of 2-benzothiazolimines with azlactones: Access to chiral benzothiazolopyrimidine derivatives
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An organocatalytic asymmetric domino Mannich/cyclization reaction between 2-benzothiazolimines with azlactones has been successfully developed. With the bifunctional squaramide catalyst, this formal [4+2] cyclization occurs with good to high yields and excellent stereoselectivities (up to 99% ee, >20?:?1 dr), providing an efficient and mild access to chiral benzothiazolopyrimidines bearing adjacent tertiary and quaternary stereogenic centers.
- Ni, Qijian,Wang, Xuyang,Xu, Fangfang,Chen, Xiaoyun,Song, Xiaoxiao
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supporting information
p. 3155 - 3158
(2020/03/23)
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- Asymmetric trifluoromethylthiolation of azlactones under chiral phase transfer catalysis
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The first enantioselective method for the installation of the SCF3 group at the C-4 position of azlactones is described in the present communication under quinidinium phase transfer catalysis. The higher performance of substrates containing electron-rich 2-aryl groups at the azlactone was rationalized using DFT calculations.
- Alemán, José,Bernardi, Luca,Borello, Fabio,Cano, Rafael,Capaccio, Vito,Díaz-Tendero, Sergio,De Riccardis, Francesco,Della Sala, Giorgio,Rodríguez, Ricardo I.,Sicignano, Marina
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supporting information
p. 2914 - 2920
(2020/04/28)
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- A Facile Approach to the Synthesis of Benzothiazoles from N-Protected Amino Acids
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Abstract: –A simple trituration method for the synthesis of 2-substituted benzothiazoles derived from N-protected amino acids and 2-aminothiophenol using molecular iodine as a mild Lewis acid catalyst has been proposed. The reaction occurs in one step for 20–25 min in solve-free conditions and provides the target products in excellent yields.
- Arfan, M.,Fatima, T.,Mannan, A.,Tahira, A.
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p. 292 - 297
(2020/04/21)
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- Asymmetric Aza-Diels-Alder Reactions of in Situ Generated β,β-Disubstituted α,β-Unsaturated N-H Ketimines Catalyzed by Chiral Phosphoric Acids
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A novel asymmetric synthesis of dihydropyridinones with vicinal quaternary stereocenters has been realized by asymmetric aza-Diels-Alder reactions of 3-amido allylic alcohols with oxazolones enabled by chiral phosphoric acid catalysis. A series of aryl/alkyl- and alkyl/alkyl-disubstituted 3-amido allylic tertiary alcohols and 4-substituted oxazolones could be well tolerated in these reactions, producing dihydropyridinones with excellent diastereoselectivities and high enantioselectivities. Mechanistic study and control experiments were performed to shed light on the reaction mechanism, in which a configurationally defined β,β-disubstituted α,β-unsaturated N-H ketimine was proposed as the key intermediate.
- He, Shunlong,Gu, Huanchao,He, Yu-Peng,Yang, Xiaoyu
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supporting information
p. 5633 - 5639
(2020/07/14)
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- Reactivity of Z- and E-isomers of 2-benzamido-3-phenylacrylohydrazide towards some carbon electrophiles. A comparative study
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Z- and E-isomers of 2-benzamido-3-phenylacrylohydrazide 2a, 2b have different relative reactivities towards some carbon electrophiles had been discussed.The Z-isomer underwent cyclization to give imidazole derivative 3 and triazine derivative 4, whereas the latter E-isomer does not undergo such cyclization. The reaction of 2a and/or 2b with 1,2-dibenzylidene hydrazine at different reaction conditions afforded the Schiff bases 6, 8 and the triazolidine derivative 9. Reactions of 2a, 2b with formic acid and phthalic anhydride gave the different cyclization products 10–14, respectively. The structures of all the new synthesized compounds were established from their IR, 1H-NMR and mass spectra as well as elemental analyses.
- Abou-Elregal, Mohsen K.,Youssef, Ahmed S. A.,Hemdan, Magdy M.,Samir, Sandy S.
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p. 2369 - 2378
(2019/07/03)
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- Enantioselective synthesis of pyrano[2,3-: C] pyrrole via an organocatalytic [4 + 2] cyclization reaction of dioxopyrrolidines and azlactones
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An enantioselective [4 + 2] cyclization reaction of dioxopyrrolidines and azlactones has been successfully developed through a squaramide catalysis strategy. This protocol provides an efficient and mild access to obtain pyrano[2,3-c]pyrrole scaffolds containing contiguous quaternary and tertiary stereogenic centers in excellent yields (up to 99%) with high levels of diastereo- and enantioselectivities (up to 99% ee). Two possible pathways were proposed to explain the observed stereoselectivity.
- Wang, Yichen,Chen, Yuzhen,Li, Xiaoping,Mao, Yukang,Chen, Weiwen,Zhan, Ruoting,Huang, Huicai
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supporting information
p. 3945 - 3950
(2019/04/30)
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- Asymmetric construction of dihydrobenzofuran-2,5-dione derivatives via desymmetrization of p-quinols with azlactones
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The desymmetrization of p-quinols through a chiral bisguanidinium hemisalt catalyzed enantioselective Michael addition/lactonization cascade reaction with azlactones was reported. 3-Amino-benzofuran-2,5-diones containing a chiral amino acid residue were achieved with up to 99% ee and >19?:?1 dr. An exploration of the structure of the catalyst bisguanidinium was undertaken, revealing a bifunctional catalytic model.
- Xie, Lihua,Dong, Shunxi,Zhang, Qian,Feng, Xiaoming,Liu, Xiaohua
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supporting information
p. 87 - 90
(2019/01/03)
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- Novel Triazole Compounds and Use thereof
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The novel triazole compound of the present invention is suitable for use as a pharmaceutical composition and an antioxidant composition for the treatment or prevention of diseases selected from the group consisting of gastrointestinal diseases, duodenal diseases, liver diseases, and renal diseases. (by machine translation)
- -
-
Paragraph 0075; 0076
(2019/12/13)
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- Tertiary-butoxycarbonyl (Boc) – A strategic group for N-protection/deprotection in the synthesis of various natural/unnatural N-unprotected aminoacid cyanomethyl esters
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A number of cyanomethyl esters of natural/unnatural aminoacids with un-protected amino functionality were synthesized because of their synthetic and medicinal importance. Critical N-Boc deprotection methods in the presence of labile (hydrolytic sensitivity) cyanomethyl functionality were screened thoroughly and it was found that readily available 4M HCl in 1,4-dioxane solution (2–4 equiv); acetonitrile, 0 °C, 2–4 h was a suitable condition. This condition was generalized and successfully applied to a variety of alkyl, alkynyl, aryl, heteroaryl, benzyl, azido, spiro amino acid cyanomethylesters irrespective of the nature of the amine (primary or secondary) and the distance between the amine and ester group to achieve final deprotected amino esters with high yield, and purity compared to other commonly known N-protecting groups (Cbz, Fmoc, Ac, Bn, Bz etc.). It was also demonstrated that N-Boc protected aminoacid cyanomethylesters are stable enough to carry out further functionalization compared to N-unprotected counterparts.
- Karmakar, Ananta,Basha, Mushkin,Venkatesh Babu,Botlagunta, Murali,Malik, Noormohamed Abdul,Rampulla, Richard,Mathur, Arvind,Gupta, Arun Kumar
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p. 4267 - 4271
(2018/11/03)
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- Formation of Non-Natural α,α-Disubstituted Amino Esters via Catalytic Michael Addition
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The enolate monoanion of amino esters is explored, and the first catalytic Michael addition of α-amino esters is demonstrated. These studies indicate that the acidity of the αC-H is the primary factor determining reactivity. Thus, polyfluorophenylglycine amino esters yield novel α-amino esters in the presence of a catalytic amount of a guanidine-derived base and Michael acceptors. Reactivity requires an acidic N-H, which is accomplished using common protecting groups such as N-Bz, N-Boc, and N-Cbz. Calculations and labeling experiments provide insight into the governing principles in which a key C-to-N proton transfer occurs, resulting in an expansion of the scope to include a number of natural amino esters. The study culminates with a late-stage functionalization of peptidic γ-secretase inhibitor, DAPT.
- Teegardin, Kip A.,Gotcher, Lacey,Weaver, Jimmie D.
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supporting information
p. 7239 - 7244
(2018/11/25)
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- Polyfluoroarylation of oxazolones: Access to non-natural fluorinated amino acids
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Herein, conditions are provided for the formation and use of the oxazolone enolate for the nucleophilic substitution of highly fluorinated (hetero)arenes, which after unmasking yield highly fluorinated non-natural amino acids and derivatives. In addition, the properties and chemical behavior of this new class of amino acids are explored. The utility is demonstrated in the one pot synthesis of medicinally relevant 2-aminohydantoins.
- Teegardin, Kip A.,Weaver, Jimmie D.
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supporting information
p. 4771 - 4774
(2017/07/06)
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- Bifunctional squaramide-catalyzed synthesis of chiral dihydrocoumarins via ortho-quinone methides generated from 2-(1-tosylalkyl)phenols
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A bifunctional squaramide-catalyzed reaction of azlactones with o-quinone methides in situ generated from 2-(1-tosylalkyl)-phenols has been successfully developed under basic conditions, providing an efficient and mild access to chiral dihydrocoumarins bearing adjacent tertiary and quaternary stereogenic centers in high yields with excellent diastereo- and enantioselectivities.
- Zhou, Ji,Wang, Mao-Lin,Gao, Xiang,Jiang, Guo-Fang,Zhou, Yong-Gui
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supporting information
p. 3531 - 3534
(2017/03/30)
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- Enantiodivergent asymmetric catalysis with the tropos BIPHEP ligand and a proline derivative as chiral selector
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A catalytic system based on the tropos ligand BIPHEP and (S)-proline methyl ester as chiral selector was studied for Rh-catalysed asymmetric catalysis. By careful control of the catalyst preformation conditions, the enantioselectivity could be completely reversed in asymmetric hydrogenation of prochiral olefins maintaining the same absolute level in favorable cases. The enantiodivergent asymmetric catalysis could be rationalised by the interplay of the dynamic chirality (tropos) of the phosphine ligand and the coordination of the proline selector. Treating a suitable Rh-BIPHEP precursor with the (Sc)-proline-based ionic liquid led to an equimolar mixture of (RaSc)- and (SaSc)-diastereomers that is kinetically stable at 0 °C. At higher temperature, an irreversible diastereomerisation process was observed resulting in the diastereomerically pure (RaSc)-complex [Rh{(Ra)-BIPHEP}{(Sc)-ProlOMe}]. Whereas the use of the pure (RaSc)-complex led to 51% ee (R) in the hydrogenation of methyl 2-acetamidoacrylate, the S-product was formed with almost identical enantioselectivity when the (RaSc)/(SaSc)-mixture was applied under identical conditions. This inversion was associated with the relative stability of the diastereomers in the equilibria forming the catalytically active substrate complex. The possibility to use this different reactivity to control the direction of enantioselectivity was demonstrated for the hydrogenation of different substrates whereby ee's of up to 80% could be achieved. Moreover, the (RaSc)-complex led to high enantioselectivities of up 86% ee in the asymmetric hydroboration of styrene, approaching the performance of the atropos BINAP ligand for this reaction.
- Oczipka,Müller,Leitner,Franciò
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p. 678 - 683
(2015/12/30)
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- The Role of the Amino Protecting Group during Parahydrogenation of Protected Dehydroamino Acids
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A series of dehydroamino acids endowed with different protective groups at the amino and carboxylate moieties and with different substituents at the double bond have been reacted with parahydrogen. The observed ParaHydrogen Induced Polarization (PHIP) effects in the 1H NMR spectra are strongly dependent on the amino protecting group. DFT calculations allowed us to establish a relationship between the structures of the reaction intermediates (whose energies depend on the amido substitution) and the observed PHIP patterns.
- Cerutti, Erika,Viale, Alessandra,Nervi, Carlo,Gobetto, Roberto,Aime, Silvio
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p. 11271 - 11279
(2015/12/01)
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- Enantioselective construction of tetrasubstituted stereogenic carbons through bronsted base catalyzed michael reactions: α′-hydroxy enones as key enoate equivalent
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Catalytic and asymmetric Michael reactions constitute very powerful tools for the construction of new C-C bonds in synthesis, but most of the reports claiming high selectivity are limited to some specific combinations of nucleophile/electrophile compound types, and only few successful methods deal with the generation of all-carbon quaternary stereocenters. A contribution to solve this gap is presented here based on chiral bifunctional Bronsted base (BB) catalysis and the use of α′-oxy enones as enabling Michael acceptors with ambivalent H-bond acceptor/donor character, a yet unreported design element for bidentate enoate equivalents. It is found that the Michael addition of a range of enolizable carbonyl compounds that have previously demonstrated challenging (i.e., α-substituted 2-oxindoles, cyanoesters, oxazolones, thiazolones, and azlactones) to α′-oxy enones can afford the corresponding tetrasubstituted carbon stereocenters in high diastereo- and enantioselectivity in the presence of standard BB catalysts. Experiments show that the α′-oxy ketone moiety plays a key role in the above realizations, as parallel reactions under identical conditions but using the parent α,β-unsaturated ketones or esters instead proceed sluggish and/or with poor stereoselectivity. A series of trivial chemical manipulations of the ketol moiety in adducts can produce the corresponding carboxy, aldehyde, and ketone compounds under very mild conditions, giving access to a variety of enantioenriched densely functionalized building blocks containing a fully substituted carbon stereocenter. A computational investigation to rationalize the mode of substrate activation and the reaction stereochemistry is also provided, and the proposed models are compared with related systems in the literature.
- Badiola, Eider,Fiser, Bla,Gmez-Bengoa, Enrique,Mielgo, Antonia,Olaizola, Iurre,Urruzuno, Iaki,Garca, Jess M.,Odriozola, Jos M.,Razkin, Jess,Oiarbide, Mikel,Palomo, Claudio
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supporting information
p. 17869 - 17881
(2015/02/19)
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- Peptide-catalyzed conversion of racemic oxazol-5(4 H)-ones into enantiomerically enriched α-amino acid derivatives
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We report the development and optimization of a tetrapeptide that catalyzes the methanolytic dynamic kinetic resolution of oxazol-5(4H)-ones (azlactones) with high levels of enantioinduction. Oxazolones possessing benzylic-type substituents were found to perform better than others, providing methyl ester products in 88:12 to 98:2 er. The mechanism of this peptide-catalyzed process was investigated through truncation studies and competition experiments. High-field NOESY analysis was performed to elucidate the solution-phase structure of the peptide, and we present a plausible model for catalysis.
- Metrano, Anthony J.,Miller, Scott J.
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p. 1542 - 1554
(2014/03/21)
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- Bronsted acid accelerated Pd-catalyzed direct asymmetric allylic alkylation of azlactones with simple allylic alcohols: A practical access to quaternary allylic amino acid derivatives
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A Bronsted acid accelerated Pd-catalyzed asymmetric allylic alkylation of azlactones with simple allylic alcohols under mild reaction conditions has been realized, which provides a direct and readily scalable approach for the synthesis of all-carbon quaternary allylic amino acid derivatives in excellent yields and good enantioselectivities. (Chemical Equation Presented).
- Zhou, Hui,Yang, Huameng,Liu, Muwen,Xia, Chungu,Jiang, Gaoxi
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supporting information
p. 5350 - 5353
(2015/01/09)
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- Organocatalyzed asymmetric 1,4-addition of azlactones to α,β-unsaturated trichloromethyl ketones: Synthesis of α,α-disubstituted α-amino acid derivatives
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The first asymmetric 1,4-addition of azlactones to α,β-unsaturated trichloromethyl ketones catalyzed by cinchona alkaloid derived bifunctional thiourea catalysts was developed. A series of α,α-disubstituted α-amino acid derivatives bearing a quaternary stereocenter at the α-position were obtained in high yields with excellent diastereo- and enantioselectivities (up to -20:1 dr and 99% ee). In addition, the trichloromethyl moiety in these adducts was identified as a good leaving group.
- Zhang, Jinlong,Liu, Xihong,Wu, Chongyang,Zhang, Panpan,Chen, Jianbo,Wang, Rui
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supporting information
p. 7104 - 7108
(2015/01/16)
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- Bispalladacycle-catalyzed Michael addition of in situ formed azlactones to enones
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The development and further evolution of the first catalytic asymmetric conjugate additions of azlactones as activated amino acid derivatives to enones is described. Whereas the first-generation approach started from isolated azlactones, in the second-generation approach the azlactones could be generated in situ starting from racemic N-benzoylated amino acids. The third evolution stage could make use of racemic unprotected α-amino acids to directly form highly enantioenriched and diastereomerically pure masked quaternary amino acid products bearing an additional tertiary stereocenter. The step-economic transformations were accomplished by cooperative activation by using a robust planar chiral bis-Pd catalyst, a Br?nsted acid (HOAc or BzOH; Ac=acetyl, Bz=benzoyl), and a Br?nsted base (NaOAc). In particular the second- and third-generation approaches provide a rapid and divergent access to biologically interesting unnatural quaternary amino acid derivatives from inexpensive bulk chemicals. In that way highly enantioenriched acyclic α-amino acids, α-alkyl proline, and α-alkyl pyroglutamic acid derivatives could be prepared in diastereomerically pure form. In addition, a unique way is presented to prepare diastereomerically pure bicyclic dipeptides in just two steps from unprotected tertiary α-amino acids. Flourishing step economy: The evolution of the catalytic asymmetric addition of azlactones to enones is described. The first-generation approach started from isolated azlactones. In the second-generation approach azlactones could be generated in situ from racemic N-benzoylated amino acids. The third evolution stage could directly use racemic unprotected α-amino acids to form a large number of highly enantioenriched quaternary amino acids derivatives (see figure). Copyright
- Weber, Manuel,Jautze, Sascha,Frey, Wolfgang,Peters, René
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supporting information
p. 14792 - 14804
(2013/01/15)
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- Polyclonal antibodies: A cheap and efficient tool for screening of enantioselective catalysts
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Enantioselective polyclonal antibodies have been produced and characterized to develop a high-throughput screening method for lipase activity fingerprinting, with a view to the enantioselective hydrolysis of azlactones.
- MacOvei, Cristian,Vicennati, Paola,Quinton, Julia,Nevers, Marie-Claire,Volland, Herve,Creminon, Christophe,Taran, Frederic
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supporting information; experimental part
p. 4411 - 4413
(2012/05/20)
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- Bispalladacycle-catalyzed bronsted acid/base-promoted asymmetric tandem azlactone formation-michael addition
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Cooperative activation by a soft bimetallic catalyst, a hard Bronsted acid, and a hard Bronsted base has allowed the formation of highly enantioenriched, diastereomerically pure masked α-amino acids with adjacent quaternary and tertiary stereocenters in a single reaction starting from racemic N-benzoylated amino acids. The products can, for example, be used to prepare bicyclic dipeptides.
- Weber, Manuel,Jautze, Sascha,Frey, Wolfgang,Peters, Rene
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supporting information; experimental part
p. 12222 - 12225
(2010/11/03)
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- Regioselective synthesis of tetrasubstituted pyrroles by 1,3-dipolar cycloaddition and spontaneous decarboxylation
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We developed a novel regioselective synthesis of tetrasubstituted pyrroles via the classic 1,3-dipolar cycloaddition of α,β-unsaturated benzofuran-3(2H)-one and azlactones (1) followed by spontaneous decarboxylation. The complete regiochemical control of tetrasubstituted pyrroles was confirmed by the orthogonal synthesis of complementary regioisomers (7a and 7b) simply by using different azlactones (1a and 1b, respectively).
- Kim, Yongju,Kim, Jonghoon,Park, Seung Bum
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supporting information; experimental part
p. 17 - 20
(2009/08/07)
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- A conventional new procedure for N-acylation of unprotected amino acids
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The preparation of amide derivatives (4) by N-acylation of unprotected α-amino acids is easily achieved via readily available benzotriazolyl carboxylates (2a-d) or succinimidyl carboxylates (2e-f). These intermediates (2) are prepared from reaction of carboxylic acids (1) with 1-hydroxybenzotriazole (HO-Bt) or N-hydroxysuccinimide (HO-Su) in the presence of equimolar amounts of 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (WSCI). The overall yields of the target compounds (4) were excellent, and this two-stage procedure could be applicable as an alternative procedure for one-pot reaction.
- Fujisaki, Fumiko,Oishi, Marumi,Sumoto, Kunihiro
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p. 124 - 127
(2007/10/03)
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- Solid phase reduction of oxazolones using BER-Ni2B-A simple synthesis of N-benzoylphenylalanines
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Borohydride exchange resin (BER)-Ni2B is successfully used as a reagent for the solid phase reduction of the C-4 exocyclic double bond of oxazolones to give the N-benzoylphenylalanines and hence the corresponding amino acids.
- Sikdar, Atul P.,Chetri, Ajoy B.,Das, Pranab J.
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p. 2878 - 2881
(2007/10/03)
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- The use of cellulose (chromatography paper) as a cheap, versatile and non-covalent support for organic molecules during multi-step synthesis
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Cellulose chromatography paper provides a novel non-covalent support for synthesis and in-situ purification of multi-dimensional arrays.
- Shanahan, Stephen E.,Byrne, Douglas D.,Inglis, Graham G. A.,Alam, Mahbub,Macdonald, Simon J. F.
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p. 2554 - 2555
(2007/10/03)
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- Tuning lipase enantioselectivity in organic media using solid-state buffers
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The enantioselectivity exhibited by Candida antarctica lipase B (CALB) in predominantly organic media has been studied for different enzyme protonation states. Alcoholysis of (±)-2-phenyl-4-benzyloxazol-5(4H)-one (1) using butan-1-ol as the nucleophile in low-water organic solvents was used as a model reaction. Using either organo-soluble bases or the newly introduced solid-state buffers of known pKa, the protonation state of the lipase was altered. By choice of the appropriate solid-state buffer or organic base, the enantioselectivity could be selectively tuned. Both Et3N and the solid-state buffer pair CAPSO/CAPSO.Na were found to increase the enantioselectivity of the reaction catalyzed by CALB and that of another lipase (Mucor miehei). Significant differences to both the enantioselectivity and catalytic rate were observed, especially under hydrated conditions where byproduct acid was formed.
- Quiros,Parker,Turner
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p. 5074 - 5079
(2007/10/03)
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- Rhodium-catalysed racemisation of N-acyl α-amino acids
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The first transition metal-catalysed racemisation of N-acyl α-amino acids, which is of importance for kinetic resolution processes, is described. Enantiomerically pure N-acyl α-amino acids were efficiently racemised under mild conditions using various rhodium complexes as catalysts, e.g. [Rh(cod)Cl]2, in the presence of phosphines. (C) 2000 Elsevier Science Ltd.
- Hateley, Martin J.,Schichl, Daniel A.,Kreuzfeld, Hans-J?rn,Beller, Matthias
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p. 3821 - 3824
(2007/10/03)
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- Palladium-catalyzed transfer hydrogenation in alkaline aqueous medium
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Catalytic transfer hydrogenation using palladium(II) chloride, formate and aqueous sodium hydroxide is effective for the reduction of unsaturated carboxylic acids, azalactones, and α-ketocarboxylic acids. This method is convenient, economical, avoids organic solvents, and uses a stable, nonpyrophoric catalyst. (C) 2000 Elsevier Science Ltd.
- Arterburn,Pannala,Gonzalez,Chamberlin
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p. 7847 - 7849
(2007/10/03)
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- Beauveria bassiana ATCC 7159 contains an L-specific α-amino acid benzamidase
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Biotransformation of a series of racemic N-benzoyl α-amino acids by the fungus Beauveria bassiana ATCC 7159 results in isolation of the corresponding D-amino acid benzamides in high enantiomeric purity and yield.
- Holland, Herbert L.,Andreana, Peter R.,Salehzadeh-Asl, Reza,Van Vliet, Aaron,Ihasz, Nancy J.,Brown, Frances M.
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p. 667 - 672
(2007/10/03)
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- Ring opening with kinetic resolution of azlactones by Ti-TADDOLates
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The kinetic resolution of azlactones by the Lewis, acid-mediated transfer of an isopropoxide ligand from the chiral ligand sphere of Ti- TADDOLate is described. The reactions proceed with in-situ racemization of the starting material to afford highly enantiomerically enriched N-benzoyl- amino acid isopropylesters (er > 95:5 after recrystallization). The absolute configuration of the major enantiomer of N-benzoyl-phenylalanine isopropyl ester and its analogs with other aromatic substituents was shown to be (S)- (+) when the (R,R)-Ti-TADDOLate was employed. Only benzyl-substituted azlactones can be opened enantioselectively by the method described here.
- Gottwald, Konstanze,Seebach, Dieter
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p. 723 - 738
(2007/10/03)
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- HETEROCYCLIC AMIDE COMPOUNDS AND PHARMACEUTICAL USE OF THE SAME
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Heterocyclic amide compounds of the formula (I) STR1 wherein each symbol is as defined in the specification, pharmacologically acceptable salts thereof, pharmaceutical compositions thereof and pharmaceutical use thereof. The heterocyclic amide compounds and pharmacologically acceptable salts thereof of the present invention have superior inhibitory activity against chymase groups in mammals inclusive of human, and can be administered orally or parenterally. Therefore, they are useful as chymase inhibitors and can be effective for the prophylaxis and treatment of various diseases caused by chymase, such as those caused by angiotensin II.
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- Palladium-catalyzed amidocarbonylation - A new, efficient synthesis of N-acyl amino acids
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For the first time palladium catalysts have been used successfully for the amidocarbonylation reaction. The activity of the cobalt catalysts that were used exclusively beforehand has now been exceeded by an order of magnitude, and the reaction can be performed under far milder conditions. Palladium-catalyzed amidocarbonylation reactions can now be used for the synthesis of a much wider range of N-acyl amino acids.
- Beller,Eckert,Vollmuller,Bogdanovic,Geissler
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p. 1494 - 1496
(2007/10/03)
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- Reactivity of the Amino Groups of α-Amino Acids and Dipeptides in Reaction with Benzoyl Chloride in a Dioxane-Water Solvent
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The kinetic characteristics (rate constants, activation energies, and entropies of activation) for the reaction of a series of α-amino acids and dipeptides with benzoyl chloride in aqueous dioxane are presented.The amino group in the investigated α-amino acids has high reactivity 4 liter/mole*sec>; the dipeptides have lower reactivity 3 liter/mole*sec>.
- Kuritsyn, L. V.,Kalinina, N. V.
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p. 767 - 770
(2007/10/02)
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- Enzymatic Asymmetric Synthesis of α-Amino Acids. Enantioselective Cleavage of 4-Substituted Oxazolin-5-ones and Thiazolin-5-ones
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A general enzymatic asymmetric synthesis of L-α-amino acids has been developed.This method entails the use of the Pseudomonas cepacia lipase (P-30) to catalyze the enantioselective methanolysis of a variety of 4-substituted 2-phenyloxazolin-5-one derivatives in a nonpolar organic solvent to furnish optically active N-benzoyl-L-α-amino acid methyl esters (ee = 66-98 percent), which in turn is subjected to a protease-catalyzed kinetic resolution yielding enantiomerically pure N-benzoyl-L-α-amino acids.This synergistic coupling of two enzymes allows the ready preparation of L-α-amino acids of high enantiopurity in yields greater than 50 percent, an inherent advantage over conventional resolution procedures.Two proteases were found to catalyze the enantioselective hydrolysis of a variety of 4-substituted 2-phenylthiazolin-5-one derivatives to give N-(thiobenzoyl)-L-α-amino acids of high optical purity.
- Crich, Joyce Z.,Brieva, Rosario,Marquart, Peer,Gu, Rui-Lin,Flemming, Steffen,Sih, Charles J.
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p. 3252 - 3258
(2007/10/02)
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- Composition containing a penem or carbapenem antibiotic and the use of the same
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Administration of an N-acylated amino acid in association with a penem or carbapenem antibiotic relieves or eliminates the renal problems associated with administration of the antibiotic alone. The amino acid derivative and antibiotic may be formulated together as a composition or administered separately, either simultaneously or sequentially.
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- Preparation process of N-acylphenylalanines
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A process for preparing an N-acylphenylalanine represented by the formula (II): STR1 wherein R3 and R4 mean individually a hydrogen atom or an alkyl, alkoxy, phenoxy, hydroxy or methylenedioxy group, and R denotes a methyl or phenyl group, which comprises catalytically reducing an N-acyl-β-phenylserine represented by the formula (I): STR2 wherein R1 and R2 mean individually a hydrogen atom or an alkyl, alkoxy, phenoxy, benzyloxy or methylenedioxy group, and R has the same meaning as defined in the formula (II), in the presence of a reducing catalyst or both reducing catalyst and acid, in a solvent.
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- Ruthenium-phosphine complex
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A ruthenium-phosphine complex represented by the formula (I) wherein R--BINAP represents tertiary phosphine represented by the formula (II) STR1 R which is the same represents hydrogen, methyl or t-butyl, S represents tertiary amine, y represents 0 or 1, and when y is 0, x represents 2, z represents 4 and p represents 1, and when y is 1, x represents 1, z represents 1 and p represents 0.
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- Electron transfer reactions. Reaction of Δ2-oxazoline-5-ones and related substrates with potassium
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The reaction of several Δ2-oxazolin-5-ones (1a-c, 12) and bioxazolinones (17, 26) with potassium in THF has been investigated.Treatment of 1a with potassium in THF gave a mixture of dibenzamide (11a), N-benzoyl-C-phenylglycine (6a), and C-phenylglycine (10a).A higher yield of 11a was obtained, together with benzoic acid (9), when the reaction of 1a wascarried out in THF saturated with oxygen.The reaction of 1b gave a mixture of β-phenylalanine (10b) and 9, whereas 1c gave a mixture of N-benzoyl-C,C-diphenylglycine (6c) and N-benzoyl-C,C-diphenylmethylamine (5c).Similarly, the reaction of 12 gave a mixture of α-benzamidocinnamic ac id (15) and 9.The reaction of the bioxazolinone 17 with potassium gave a mixture of 11a, 6a, and 10a, along with an appreciable yield of 2,3,5,6-tetraphenylpyrazine (25), whereas 26 under analogous conditions gave a mixture of 15, 6b, and benzamide (29).Reasonable mechanisms, involving the initial formation of radical anion intermediates and their subsequent transformation to give the observed products, have been suggested.Potassium superoxide oxidation of some of these substrates gives similar product mixtures.Cyclic voltammetric studies have been carried out to measure the reduction potentials of 1a-c, 12, 17, and 26 in the generation of their radical anions.The radical anions of these substrates were also generated pulse radiolytically in methanol and their spectra showed absorption maxima in the region 295-350 nm.
- Muneer, Mohammed,Tikare, Ravindra K.,Kamat, Prashant V.,George, Manapurathu V.
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p. 1624 - 1630
(2007/10/02)
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- DIISOPROPYLETHYLAMINE ELIMINATES DIPEPTIDE FORMATION DURING THE ACYLATION OF AMINO ACIDS USING BENZOYL CHLORIDE AND SOME ALKYL CHLOROFORMATES
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Acylation of amino acids using benzoyl chloride in aqueous alkali leads to benzoylamino acids containing one percent of benzoyldipeptide.Use of diisopropylethylamine instead of sodium hydroxide as base eliminates the side reaction responsible for the contaminant.Ethoxycarbonylamino acids are advantageously prepared in the same manner using ethyl chloroformate or diethyl dicarbonate.The latter gives rise to some N-substituted dipeptide when used in aqueous alkali.The method is unsatisfactory for the benzyloxycarbonylation of amino acids.Use of 9-fluorenylmethyl chloroformate and diisopropylethylamine gives the pure derivative of leucine in moderate yield.
- Chen, Francis M. F.,Benoiton, N. Leo
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p. 1224 - 1227
(2007/10/02)
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- Synthesis of Acylamino Acids and Acylamino Acid Amides by Simultaneous Reduction and Hydrolysis of Unsaturated 2,4-Disubstituted 2-Imidazolin-5-ones
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Twelve acylamino acids (II) and two acylamino acid amides (III) have been prepared by the simultaneous reduction and hydrolysis of unsaturated 2,4-disubstituted 2-imidazolin-5-ones (I) with a mixture of zinc dust and potassium hydroxide solution.
- Devasia, Ganapathiplackal M.,Shafi, P. Mohamed
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p. 204 - 206
(2007/10/02)
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- SYNTHESIS OF FLUORINATED α-AMINO KETONES PART I: α-BENZAMIDOALKYL MONO- DI- AND TRIFLUOROMETHYL KETONES
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2-Phenyl-5(4H)-oxazolones, obtained from α-amino acids, are reacted with di- and trifluoro acetic anhydride by a modified Dakin-West procedure to yield in a one-pot reaction α-benzamidoalkyl-di- and trifluoromethyl ketones in good yields.The monofluoromethyl analogues were also prepared from α-amino acids, however the use of the highly toxic fluoroacetic anhydride was avoided.The key step is the halogen exchange reaction on the corresponding bromomethyl ketone.
- Kolb, Michael,Barth, Jacqueline,Neises, Bernhard
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p. 1579 - 1582
(2007/10/02)
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- NEW SYNTHETIC ROUTE TO N-ACYL-α-AMINO ACIDS VIA AMIDOCARBONYLATION BY MEANS OF HOMOGENEOUS BINARY CATALYST SYSTEMS
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New catalytic processes which lead to the formation of N-acyl-α-amino acids promoted by homogeneous binary systems are described: (a) the isomerization-amidocarbonylation of allylic alcohols catalyzed by transition metal binary systems, e.g., Co-Rh, Co-Pd, Co-Fe, giving various aliphatic N-acyl-α-amino acids; (b) the isomerization-amidocarbonylation of oxiranes catalyzed by cobalt-Lewis acid systems giving N-acyl-α-amino acids; The process is extremely effective for the synthesis of N-acetylphenylalanine from styrene oxide and (c) the hydroformylation-amidocarbonylation of trifluoropropene catalyzed by cobalt-rhodium binary system giving N-acetyltrifluorovaline in excellent regioselectivity and yield.Possible mechanisms for these new processes are discussed.
- Hirai, Kenji,Fujita, Makoto,Fuchikami, Takamasa
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p. 203 - 214
(2007/10/02)
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- Process for production of N-acyl-α-amino acids
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A process for the production of an N-acyl-α-amino acid represented by the general formula STR1 wherein R1, R2, R3 and R4, independently from each other, represent a hydrogen atom, an alkyl or cycloalkyl group which may be substituted, or an aryl or heteroaromatic group selected from the group consisting of furyl, pyrrolyl, pyridinyl, thienyl and indolyl which may be substituted, which comprises reacting an oxirane represented by the general formula STR2 wherein R1 and R2 are as defined above, an amide compound represented by the general formula wherein R3 and R4 are as defined above, and carbon monoxide in the presence of hydrogen, a cobalt-containing catalyst, and a promoter composed of a compound containing a metal selected from Groups I, II, III and IV of the periodic table.
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- Components of the Chinese drug 'Ti-ku-'pi'. Isolation and establishment of structure of a new dipeptide, lyciumamide
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A new dipeptide, lyciumamide (1), was isolated from the Chinese crude drug 'Ti-ku-'pi', root bark of Lycium chinense MILL. (Solanaceae), and was shown by spectroscopy, chemical degradation, and synthesis to be N-benzoyl-L-phenylalanyl-L-phenylalaninol O-acetate (1).
- Noguchi,Mochida,Shingu,et al.
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p. 3584 - 3587
(2007/10/02)
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- 2,2'-BIS(DIPHENYLPHOSPHINO)-1,1'-BINAPHTHYL (BINAP). A NEW ATROPISOMERIC BIS(TRIARYL)PHOSPHINE. SYNTHESIS AND ITS USE IN THE Rh(I)-CATALYZED ASYMMETRIC HYDROGENATION OF α-(ACYLAMINO)ACRYLIC ACIDS
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Racemic 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl has been synthesized from 2,2'-dihydroxy-1,1'-binaphthyl in two steps and resolved into optically pure (R)-(+) and (S)-(-) enantiomers by the use of (+)-di-μ-chlorobis dipalladium.This new axially dissymmetric bis(triaryl)phosphine serves as an excellent ligand for Rh(I)-catalyzed asymmetric hydrogenations of α-(acylamino)acrylic acids or esters.Factors controlling the enantioselectivity and mechanistic aspects are discussed on the basis of the 31P-NMR measurements.
- Miyashita, A.,Takaya, H.,Souchi, T.,Noyori, R.
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p. 1245 - 1253
(2007/10/02)
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- PHOSPHORORGANISCHE VERBINDUNGEN 105. Synthese chiraler und achiraler ditertiaerer 1-Phosphino-2-Aminoethan-Derivate (=P-CH2-CHR-N=) und einige Anwendungen
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Primary amines with an optical active ligand add to vinyl- and propenylphosphonium salts according the reaction schemes (5) and (6), forming compounds of the type E and F.F contains a new asymmetric center in the bridge giving rise to the formation of a mixture of diastereomers, which can be resolved.Phosphonium salts of the type E and F with a benzyl group on the phosphonium center are cleaved reductively by alkali amalgams (Li/Hg; Na/Hg; K/Hg) forming tertiary phosphines with an aminogroup in the β-position.The reductive cleavage with alkali amalgams is superior to the cathodic cleavage.Application: The synthesis of Ni(0)- and Pd(0)-complexes of type J fails.Bis-phosphine complexes of type 21 are formed.The rate of the homogeneous hydrogenation of 1-hexene with Rh(I)-complexes (containing G as a ligand) has an optimum with respect to a Rh/Co-catalyst proportion of 1:2 to 1:1.6.The optical induction of the homogeneous hydrogenation of Z-N-Acylamino-cinnamic acid is lower than 5percent.
- Horner, Leopold,Dickerhof, Karlheinz
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p. 331 - 350
(2007/10/02)
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- Kinetics of Racemization and Hydrolysis of Oxazol-5(4H)-ones
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The kinetics of hydrolysis and ionization of three substrates, 4-benzyl-2-phenyl-, 4-methyl-2-phenyl- and 4-benzyl-2-methyl-oxazol-5(4H)-one have been investigated.Under neutral and basic conditions both reactions are buffer and hydroxide ion catalysed.In aqueous solution, ionization, leading to racemization of the optically active oxazolones, and ring opening occur competitively with similar rate constants.In solvents with lower dielectric constants, ionization becomes much faster than ring opening.An intermediate corresponding to a minor reaction pathway has been detected; it results probably from the addition of water to the C-N double bond.
- Daffe, Viviane,Fastrez, Jacques
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p. 783 - 788
(2007/10/02)
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- Von der basenkatalysierten Ringoeffnung von 2H-Azirinen zu einer α-Alkylierungsmethode von primaeren Aminen
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It is shown than fluorene-9'-spiro-2-(3-phenyl-2H-azirine) (1) on treatment with various alcohols in the presence of the corresponding alkoxide ions yields N-(9'-fluorenyl)benzimidates 2a-d (Scheme 1). 2,2,3-Triphenyl-2H-aziridine (3) reacts with methanol in a similar manner (Scheme 2).Benzimidates 2a (Scheme 3), 8 (Scheme 4) and 10 (Scheme 5) can easily be deprotonated by butyllithium (BuLi) or lithium diisopropylamide (LDA) in tetrahydrofuran (THF) to 1-methoxy-2-aza-allylanions, that can be alkylated, at C(3), exclusively, by various electrophiles (e.g.R-X (X = I, Br), RCHO or methyl acrylate (see also Scheme 6)).As the acidic hydrolyses (1 N HCl) of benzimidates 9 and 11 leads to the corresponding α-alkylated free amines 15 and 18 (Scheme 7 and 8), benzoyl derivatives 16 and 19 are obtained from the hydrolysis under basic conditions.On the other hand it is observed that a catalyzed Chapman rearrangement of 9 and 11 results in the formation of N-benzoyl-N-methyl derivatives 17 and 20 (Scheme 7 and 8).The described reactions offer a simple method for the α-alkylation of actived primary amines.
- Schulthess, Adrian Heinz,Hansen, Hans-Juergen
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p. 1322 - 1336
(2007/10/02)
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