- Near-Ambient-Temperature Dehydrogenative Synthesis of the Amide Bond: Mechanistic Insight and Applications
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The current existing methods for the amide bond synthesis via acceptorless dehydrogenative coupling of amines and alcohols all require high reaction temperatures for effective catalysis, typically involving reflux in toluene, limiting their potential practical applications. Herein, we report a system for this reaction that proceeds under mild conditions (reflux in diethyl ether, boiling point 34.6 °C) using ruthenium PNNH complexes. The low-temperature activity stems from the ability of Ru-PNNH complexes to activate alcohol and hemiaminals at near-ambient temperatures through the assistance of the terminal N-H proton. Mechanistic studies reveal the presence of an unexpected aldehyde-bound ruthenium species during the reaction, which is also the catalytic resting state. We further utilize the low-temperature activity to synthesize several simple amide bond-containing commercially available pharmaceutical drugs from the corresponding amines and alcohols via the dehydrogenative coupling method.
- Kar, Sayan,Xie, Yinjun,Zhou, Quan Quan,Diskin-Posner, Yael,Ben-David, Yehoshoa,Milstein, David
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p. 7383 - 7393
(2021/06/30)
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- Practical Synthesis of Amides via Copper/ABNO-Catalyzed Aerobic Oxidative Coupling of Alcohols and Amines
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A modular Cu/ABNO catalyst system has been identified that enables efficient aerobic oxidative coupling of alcohols and amines to amides. All four permutations of benzylic/aliphatic alcohols and primary/secondary amines are viable in this reaction, enabling broad access to secondary and tertiary amides. The reactions exhibit excellent functional group compatibility and are complete within 30 min-3 h at rt. All components of the catalyst system are commercially available.
- Zultanski, Susan L.,Zhao, Jingyi,Stahl, Shannon S.
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supporting information
p. 6416 - 6419
(2016/06/09)
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- Metal-free, hydroacylation of CC and NN bonds via aerobic C-H activation of aldehydes, and reaction of the products thereof
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In this report, a thorough evaluation of the use of aerobically initiated, metal-free hydroacylation of various CC and NN acceptor molecules with a wide range of aldehydes is presented. The aerobic-activation conditions that have been developed are in sharp contrast to previous conditions for hydroacylation, which tend to use transition metals, peroxides that require thermal or photochemical degradation, or N-heterocyclic carbenes. The mildness of the conditions enables a number of reactions involving sensitive reaction partners and, perhaps most significantly, allows for α-functionalised chiral aldehydes to undergo radical-based hydroacylation with complete retention of optical purity. We also demonstrate how the resulting hydroacylation products can be transformed into other useful intermediates, such as γ-keto- sulfonamides, sultams, sultones, cyclic N-sulfonyl imines and amides.
- Chudasama, Vijay,Akhbar, Ahmed R.,Bahou, Karim A.,Fitzmaurice, Richard J.,Caddick, Stephen
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p. 7301 - 7317
(2013/10/22)
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- XtalFluor-E, an efficient coupling reagent for amidation of carboxylic acids
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Amides were produced from carboxylic acids and amines by using XtalFluor-E as an activator. Even poorly reactive carboxylic acids can be transformed to amides. In addition, optically active amines and/or carboxylic acids were not epimerized/racemized during the process.
- Orliac, Aurélie,Gomez Pardo, Domingo,Bombrun, Agnès,Cossy, Janine
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supporting information
p. 902 - 905
(2013/03/29)
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- Defining the structural parameters that confer anticonvulsant activity by the site-by-site modification of (R)-N′-benzyl 2-amino-3-methylbutanamide
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Primary amino acid derivatives (PAADs) (N′-benzyl 2-substituted 2-amino acetamides) are structurally related to functionalized amino acids (FAAs) (N′-benzyl 2-substituted 2-acetamido acetamides) but differ by the absence of the terminal N-acetyl group. Both classes exhibit potent anticonvulsant activities in the maximal electroshock seizure animal model, and the reported structure-activity relationships (SARs) of PAADs and FAAs differ in significant ways. Recently, we documented that PAAD efficacy was associated with a hydrocarbon moiety at the C(2)-carbon, while in the FAAs, a substituted heteroatom one atom removed from the C(2)-center was optimal. Previously in this issue, we showed that PAAD activity was dependent upon the electronic properties of the 4′-N′-benzylamide substituent, while FAA activity was insensitive to electronic changes at this site. In this study, we prepared analogues of (R)-N′-benzyl 2-amino-3-methylbutanamide to identify the structural components for maximal anticonvulsant activity. We demonstrated that the SAR of PAADs and FAAs diverged at the terminal amide site and that PAADs had considerably more structural latitude in the types of units that could be incorporated at this position, suggesting that these compounds function according to different mechanism(s).
- King, Amber M.,De Ryck, Marc,Kaminski, Rafal,Valade, Anne,Stables, James P.,Kohn, Harold
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p. 6432 - 6442
(2011/12/01)
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- Functionalisation of aldehydes via aerobic hydroacylation of azodicarboxylates 'on' water
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Herein we report the functionalisation of aldehydes via hydroacylation of azodicarboxylates. A range of functionalised aldehydes are employed as the limiting reagent including chiral non-racemic aldehydes bearing α-stereocentres which are functionalised giving access to enantiomerically pure products. The resultant hydrazides can be employed as acyl donors in the synthesis of amides.
- Chudasama, Vijay,Ahern, Jenna M.,Dhokia, Dipti V.,Fitzmaurice, Richard J.,Caddick, Stephen
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p. 3269 - 3271
(2011/05/02)
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- Lipase-catalyzed synthesis of chiral amides. A systematic study of the variables that control the synthesis
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A systematic study of the aminolysis of esters catalyzed by different lipases from different origins was carried out. A factorial analysis showed that the main variables that control the amide synthesis are: temperature, hydrophobicity of the solvent, reaction volume and amount of water added to the reactor medium. Besides, several undescribed interactions of variables are significative in the control of the process, too. The resolution of racemic esters or amines was analyzed. Lipascs from Rhizopus niveus, Candida antarctica B and PPL gave the best enantioselectivities in the resolution of chiral esters while C. rugosa and P. cepacia lipases were the less interesting lipases. α-Chymotrypsin shows lower enantioselectivity and yield than Rhizopus niveus, C. antarctica B and PPL lipases in the resolution of racemic esters. This protease needs a large excess of acyl donor in respect to the amine and works at a lower temperature than lipases due to its low thermostability. Ail the tested lipases showed R-enantiopreference in the aminolysis of esters using (R,S) 1-phenyl-ethylamine. In this reaction, the lipase A from C. antarctica, (SP526) and Rhizopus niveus lipase are good catalysts for the synthesis. On the other, PS and PPL are less interesting biocatalysts. Therefore, the optimum biocatalyst is different if we want to resolve (R,S) esters or (R,S) amines. The aminolysis is interesting for the resolution of racemic amines but not for the resolution of racemic esters. The immobilization does not alter the enantiopreference of the lipases.
- De Castro, Maria Soledad,Sinisterra Gago, Jose V.
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p. 2877 - 2892
(2007/10/03)
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- The asymmetric Favorskii rearrangement: A synthesis of optically active α-alkyl amides from aldehydes and (-)-1-chloroalkyl p-tolyl sulfoxide
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The first asymmetric Favorskii rearrangement is described. Optically active α-alkyl amides of enantiomeric excess up to 94% were realized from aldehydes and optically active (-)-1-chloroalkyl p-tolyl sulfoxides via the Favorskii rearrangement of optically
- Satoh,Motohashi,Kimura,Tokutake,Yamakawa
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p. 4823 - 4826
(2007/10/02)
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- Lipase-catalyzed synthesis of optically active amides in organic media
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Lipases from Candida cylindracea and Candida antarctica catalyze the aminolysis of activated and nonactivated esters respectively. The degree of enantioselectivity depends on the amine.
- Quiros,Sanchez,Brieva,Rebolledo,Gotor
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p. 1105 - 1112
(2007/10/02)
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- Acylation reactions mediated by tantalum carboxylates
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Facile nucleophilic attack on coordinated carboxylate ligaods is reported: complexes of tantalum(V) react rapidly with amines and amino acid esters to give the corresponding amides. Cyclopentadienyltantalum(V) amino acid carboxylate complexes have been pr
- Joshi, Kiran,Bao, Jiang,Goldman, Alan S.,Kohn, Joachim
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p. 6649 - 6652
(2007/10/02)
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