- Catalytic Kinetic Resolution of Disubstituted Piperidines by Enantioselective Acylation: Synthetic Utility and Mechanistic Insights
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The catalytic kinetic resolution of cyclic amines with achiral N-heterocyclic carbenes and chiral hydroxamic acids has emerged as a promising method to obtain enantio-enriched amines with high selectivity factors. In this report, we describe the catalytic kinetic resolution of disubstituted piperdines with practical selectivity factors (s, up to 52) in which we uncovered an unexpected and pronounced conformational effect resulting in disparate reactivity and selectivity between the cis- and trans-substituted piperidine isomers. Detailed experimental and computational studies of the kinetic resolution of various disubstituted piperidines revealed a strong preference for the acylation of conformers in which the α-substituent occupies the axial position. This work provides further experimental and computational support for the concerted 7-member transition state model for acyl transfer reagents and expands the scope and functional group tolerance of the secondary amine kinetic resolution.
- Wanner, Benedikt,Kreituss, Imants,Gutierrez, Osvaldo,Kozlowski, Marisa C.,Bode, Jeffrey W.
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supporting information
p. 11491 - 11497
(2015/09/21)
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- Arene-ruthenium(II) complexes containing inexpensive tris(dimethylamino) phosphine: Highly efficient catalysts for the selective hydration of nitriles into amides
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The catalytic hydration of nitriles into amides, in water under neutral conditions, has been studied using a series of arene-ruthenium(II) derivatives containing the commercially available and inexpensive ligand tris(dimethylamino)phosphine. Among them, best results were obtained with the complex [RuCl2(η6-C6Me6) {P(NMe2)3}], which selectively provided the desired amides in excellent yields and short times (TOF values up to 11 400 h-1). The process was operative with both aromatic, heteroaromatic, aliphatic, and α,β-unsaturated organonitriles and showed a high functional group tolerance. The stability of [RuCl2(η6-C 6Me6){P(NMe2)3}] in water was evaluated, observing its progressive decomposition into the less-active dimethylamine-ruthenium(II) complex [RuCl2(η6-C 6Me6)(NHMe2)] by hydrolysis of the coordinated P(NMe2)3 ligand. The X-ray crystal structure determination of the toluene complex [RuCl2(η6-C6H 5Me){P(NMe2)3}] is also included.
- Garcia-Alvarez, Rocio,Diez, Josefina,Crochet, Pascale,Cadierno, Victorio
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experimental part
p. 5442 - 5451
(2011/12/13)
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- PREPARATION OF TRANDOLAPRIL
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A process for preparing trandolapril, (2S,3aR,7aS)-1-[(S)-N-[(S)-1-Carboxy-3-phenylpropyl]alanyl]hexahydro-2-indolinecarboxylic acid, 1-ethyl ester, and intermediates that are useful in the process.
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Page/Page column 12
(2010/11/28)
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- One-pot synthesis of ene-lactams via N-debenzylation of keto-containing N-2,4-dimethoxylbenzylamides
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A general method of ene-lactam preparation is described. Ene-lactams can be prepared efficiently from keto-containing N-2,4-dimethoxylbenzylamides in good to excellent yields. This method is applicable for the preparation of substituted δ-, γ-, and ε-ene-lactams and bicyclic ene-lactams.
- Kan, Wai Ming,Cheng, Ching-Lung,Chern, Ching-Yuh
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p. 4257 - 4264
(2007/10/03)
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- Cyclization of 2-ethylene ketal-cyclohexyl-1-propionamide in PPA-AcOH?
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All efforts made for the preparation of 2-oxocyclohexyl-1-propionamide 3, have led to the preparation of quinolone 4. 2-Ethylene ketal- cyclohexyl-1-propionamide 8 on reaction with PPA/AcOH affords a new quinolone 9, which on reduction with NaBH4 furnishes another reduced quinolone 10. All compounds have been characterised by their spectral data analysis.
- Srivastava,Kumar,Singh
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p. 1248 - 1250
(2007/10/03)
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- Ruthenium-Catalyzed Hydration of Nitriles and Transformation of δ-Ketonitriles to Ene-lactams: Total Synthesis of (-)-Pumiliotoxin C
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Hydration of nitriles with 1-2 equivalents of water can be performed efficiently by using RuH2(PPh3)4 catalyst to give the corresponding amides.Under the similar reaction conditions, δ-ketonitriles can be converted into the corresponding ene-lactams, which are versatile synthetic intermediates.The efficiency of the reaction is demonstrated by the short-step synthesis of (-)-pumiliotoxin C.
- Murahashi, Shun-Ichi,Sasao, Shigehiro,Saito, Eiichiro,Naota, Takeshi
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p. 8805 - 8826
(2007/10/02)
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- Ruthenium-Catalyzed Hydration of Nitriles and Transformation of δ-Keto Nitriles to Ene-Lactams
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Hydration of nitriles and transformation of δ-keto nitriles to ene-lactams can be performed efficiently by using RuH2(PPh3)4 catalyst under mild conditions.The effectiveness of the reaction is illustrated by the short-step synthesis of (-)-pumiliotoxin C.
- Murahashi, Shun-Ichi,Sasao, Shigehiro,Saito, Eiichiro,Naota, Takeshi
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p. 2521 - 2523
(2007/10/02)
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- Derivatives of bicyclic aminoacids agents containing these compounds and their use
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Disclosed are cis, exo- and trans-compounds of the formula I STR1 in which n denotes 0, 1 or 2, R1 denotes hydrogen, (C1 -C6)-alkyl which can optionally be substituted by amino, (C1 -C4)-acyl- or bezoylamino, (C2 -C6)-alkenyl, (C5 -C9)-cycloalkyl, (C5 -C9)-cycloalkenyl, (C5 -C7)-cycloalkyl-(C1 -C4)-alkyl, aryl or partially hydrogenated aryl, which can, in each case, be substituted by (C1 -C2)-alkyl, (C1 -C2)-alkoxy or halogen, aryl-(C1 -C4)-alkyl, /which can be substituted as defined previously in the aryl radical/, a monocyclic or bicyclic sulfur or nitrogen and/or nitrogen heterocyclic radical, or a side chain of naturally occurring aminoacid, R2 denotes hydrogen, (C1 -C6)-alkyl, (C2 -C6)-alkenyl or aryl-(C1 -C4)-alkyl, Y denotes hydrogen or hydroxyl, Z denotes hydrogen or Y and Z together denote oxygen, X denotes (C1 -C6)-alkyl, (C2 -C6)-alkenyl, (C6 -C9)-cycloalkyl or aryl which can be mono-, di- or tri- substituted by (C1 -C4)-alkyl, (C1 -C4)-alkoxy, hydroxyl, halogen, nitro, amino, (C1 -C4)-alkylamino, di-(C1 -C4 -alkylamino or methylenedioxy, or indol-3-yl, or physiologically acceptable salts thereof, a process of the preparation thereof, agents containing them, their use as a medicine and intermediates for the preparation thereof.
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- 13C NMR SPECTRA AND STEREOCHEMISTRY OF THE ANILS OF 2-(β-CYANOETHYL)CYCLOHEXANONE
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The conformations and configurations of the anils of 2-(β-cyanoethyl)cyclohexanone, which exist predominantly in the imine form in 50percent solutions in carbon tetrachloride, were studied by 13C NMR spectroscopy.The predominant conformer is the anti-equa
- Kayukova, L. A.,Chernova, N. V.,Manchuk, Z. N.,Erzhanov, K. B.
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p. 1389 - 1392
(2007/10/02)
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- Reaction of Schiff Bases with Acrylamides. Synthesis of 2-Oxotetrahydropyridines
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Ketimines react with acrylamide and methacrylamide in the presence of aluminium chloride to afford 2-oxotetrahydropyridines by a C-alkylation pathway.
- Barluenga, Jose,Muniz, Laudina,Palacios, Francisco,Gotor, Vicente
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- ENAMINE CHEMISTRY-XXIV. SYNTHESIS, THIATION, AND REDUCTION OF LACTAMS
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Enamines, 1, prepared from cyclohexanones or cyclopentanones are reacted with acrylamide to give lactams, the condensed 2-piperidones, 2.Ethyl 2-(1-pyrrolidinyl)-2-cyclohexene-1-propanoate, 3, when treated with primary amines, produces the corresponding N-substituted 2-piperidones, 4.Ethyl 2-(1-pyrrolidinyl)-2-cyclohexene-1-ethanoates and ethyl 2-(1-pyrrolidinyl)-2-cyclopentene-1-ethanoate, 5, react with primary amines to give condensed N-substituted 2-pyrrolidones, 6, and non-cyclic imines, 7.The starting enamines , 1, treated with 2-bromo acetamides only afford the N-alkylated compounds, 8 (2-pyrrolidino acetamides), and the regioselectivity of this reaction is rationalized in terms of the HSAB-principle.Compound 1 undergoes an exchange reaction (aminolysis) when reacted with primary amines to give the imines 9.Thiation of the lactams 2 and 6 with the Lawesson reagent (LR), affords the corresponding thiolactams, 10.Reduction of the lactams and thiolactams, 2, 6, and 10 by LAH gives the imines, 11, and the enamines, 16.Further reduction of 11 (LAH) affords the saturated amines, 15.The stereochemistry for the formation of 15 is discussed using the torsion angle notation and the principal of least torsional distortion.In a one-pot reaction using LAH-acetic anhydride the lactams, 2, and the thiolactams, 10, are transformed into the enamides, 14.Compound 14 was also obtained from 11 by direct acetylation with acetic anhydride in the presence of triethylamine.
- El-Barbary, A. A.,Carlsson, S.,Lawesson, S.-O.
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p. 405 - 412
(2007/10/02)
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- Selective Reduction of αβ-Olefinic Amides and Lactams by Magnesium and Methanol
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αβ-Olefinic amides with various substitution patterns at the carbon-carbon double bond and at nitrogen are all reduced to the corresponding saturated amides by magnesium and methanol.The same reducing system reduces N-benzyl-8-azabicyclonona-1(6),3-dien-7-ones at the conjugated double bond to give mixtures of the cis- and trans-dihydro-derivatives; the isolated, non-conjugated double bond is not reduced, even in the 3,4-diphenylsubstituted compound.Magnesium and methanol reduces quinolin-2(1H)-ones to their 3,4-dihydro-derivatives, and 5,6,7,8-tetrahydroquinolin-2(1H)-one to a mixture of two dihydro-derivatives.
- Brettle, Roger,Shibib, Sa'ad M.
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p. 2912 - 2919
(2007/10/02)
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