The Reaction of N-Trimethylsilyl-Substituted Heteroarylamines with Esters and Thioesters: An Efficient Protocol To Access Diheteroarylamides

Synthesis ◽  
2019 ◽  
Vol 51 (08) ◽  
pp. 1779-1790
Author(s):  
Ana Koperniku ◽  
Maryam Zamiri ◽  
David Grierson
Keyword(s):  
Parallel Synthesis ◽  
Amide Bond ◽  
Coupling Reactions ◽  
Trimethylsilyl Derivative ◽  
Vacuum Filtration ◽  
Bond Forming ◽  
Compound Libraries ◽  
Amide Coupling ◽  
Derivatives Of

The S-benzyl thioester and methyl ester derivatives of a representative 4-pyridinone-based carboxylic acid were sufficiently activated to react efficiently in amide coupling reactions with the amide anion generated in situ from the N-trimethylsilyl derivative of different weakly nucleophilic heteroarylamines. In acetonitrile as solvent, the precipitated diheteroarylamide products were isolated in pure form by vacuum filtration. This simple amide bond forming protocol can be readily adapted to the parallel synthesis of compound libraries.

scholarly journals Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications

2014 ◽  
Vol 10 ◽  
pp. 1919-1932 ◽  
Author(s):  
Mahesh K Lakshman ◽  
Manish K Singh ◽  
Mukesh Kumar ◽  
Raghu Ram Chamala ◽  
Vijayender R Yedulla ◽  
...  
Keyword(s):  
Amide Bond ◽  
Coupling Agents ◽  
Cyclic Ketones ◽  
Substitution Reactions ◽  
Facile Synthesis ◽  
Reaction Conditions ◽  
Peptide Coupling ◽  
Acyclic Nucleoside ◽  
Derivatives Of

(1H-Benzo[d][1,2,3]triazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP), 1H-benzo[d][1,2,3]triazol-1-yl 4-methylbenzenesulfonate (Bt-OTs), and 3H-[1,2,3]triazolo[4,5-b]pyridine-3-yl 4-methylbenzenesulfonate (At-OTs) are classically utilized in peptide synthesis for amide-bond formation. However, a previously undescribed reaction of these compounds with alcohols in the presence of a base, leads to 1-alkoxy-1H-benzo- (Bt-OR) and 7-azabenzotriazoles (At-OR). Although BOP undergoes reactions with alcohols to furnish 1-alkoxy-1H-benzotriazoles, Bt-OTs proved to be superior. Both, primary and secondary alcohols undergo reaction under generally mild reaction conditions. Correspondingly, 1-alkoxy-1H-7-azabenzotriazoles were synthesized from At-OTs. Mechanistically, there are three pathways by which these peptide-coupling agents can react with alcohols. From 31P{1H}, [18O]-labeling, and other chemical experiments, phosphonium and tosylate derivatives of alcohols seem to be intermediates. These then react with BtO− and AtO− produced in situ. In order to demonstrate broader utility, this novel reaction has been used to prepare a series of acyclic nucleoside-like compounds. Because BtO− is a nucleofuge, several Bt-OCH2Ar substrates have been evaluated in nucleophilic substitution reactions. Finally, the possible formation of Pd π–allyl complexes by departure of BtO− has been queried. Thus, alpha-allylation of three cyclic ketones was evaluated with 1-(cinnamyloxy)-1H-benzo[d][1,2,3]triazole, via in situ formation of pyrrolidine enamines and Pd catalysis.

scholarly journals Branching out at C-2 of septanosides. Synthesis of 2-deoxy-2-C-alkyl/aryl septanosides from a bromo-oxepine

2012 ◽  
Vol 8 ◽  
pp. 522-527 ◽  
Author(s):  
Supriya Dey ◽  
Narayanaswamy Jayaraman
Keyword(s):  
Suzuki Reaction ◽  
Ring Expansion ◽  
Protecting Groups ◽  
Coupling Reactions ◽  
Sonogashira Coupling ◽  
Alkyl Aryl ◽  
Organometallic Reactions ◽  
Bond Forming ◽  
Derivatives Of ◽  
Cyclopropane Derivatives

This paper deals with the synthesis of 2-deoxy-2-C-alkyl/aryl septanosides. A range of such septanoside derivatives was synthesized by using a common bromo-oxepine intermediate, involving C–C bond forming organometallic reactions. Unsaturated, seven-membered septanoside vinyl bromides or bromo-oxepines, obtained through a ring expansion methodology of the cyclopropane derivatives of oxyglycals, displayed a good reactivity towards several acceptor moieties in C–C bond forming Heck, Suzuki and Sonogashira coupling reactions, thus affording 2-deoxy-2-C-alkyl/aryl septanosides. Whereas Heck and Sonogashira coupling reactions afforded 2-deoxy-2-C-alkenyl and -alkynyl derivatives, respectively, the Suzuki reaction afforded 2-deoxy-2-C-aryl septanosides. Deprotection and reduction of the 2-deoxy-2-alkenyl derivative afforded the corresponding 2-deoxy-2-C-alkyl septanoside free of protecting groups. The present study illustrates the reactivity of bromo-oxepine in the synthesis of hitherto unknown septanosides, branching out at C-2, through C–C bond formation with alkyl and aryl substituents.

scholarly journals A protocol for amide bond formation with electron deficient amines and sterically hindered substrates

2016 ◽  
Vol 14 (2) ◽  
pp. 430-433 ◽  
Author(s):  
Maria E. Due-Hansen ◽  
Sunil K. Pandey ◽  
Elisabeth Christiansen ◽  
Rikke Andersen ◽  
Steffen V. F. Hansen ◽  
...  
Keyword(s):  
Elevated Temperature ◽  
Bond Formation ◽  
Amide Bond ◽  
Standard Methods ◽  
Amide Bond Formation ◽  
Amide Coupling ◽  
Sterically Hindered

A protocol for amide coupling by in situ formation of acyl fluorides and reaction with amines at elevated temperature has been developed and found to be efficient for coupling of sterically hindered substrates and electron deficient amines where standard methods failed.

scholarly journals Ultrasound-Accelerated Amide Coupling Reactions Directed toward the Synthesis of 1-Acetyl-3-carboxamide-β-carboline Derivatives of Biological Importance

SynOpen ◽  
2017 ◽  
Vol 01 (01) ◽  
pp. 0008-0010 ◽  
Author(s):  
N. Sharma ◽  
P. Kumari ◽  
P. Sharma ◽  
N. Bhagat ◽  
S. Bhagat
Keyword(s):  
Reaction Time ◽  
Carboxylic Acid ◽  
Aromatic Amines ◽  
Coupling Reactions ◽  
Biological Importance ◽  
Amide Coupling ◽  
Derivatives Of

Several biologically important 1-acetyl-3-carboxamide-β-carboline derivatives were rapidly synthesized by ultrasound-promoted amide coupling of 1-acetyl-9H-pyrido[3,4-b]indole-3-carboxylic acid with substituted aromatic amines. The major advantages of the proposed method are that use of ultrasound irradiations afforded the desired products in a drastically reduced reaction time and in excellent yields compared with conventional stirring.

scholarly journals Ni-Electrocatalytic C(sp3)–C(sp3) Doubly Decarboxylative Coupling

2021 ◽  
Author(s):  
benxiang zhang ◽  
yang gao ◽  
yuta hioki ◽  
martins oderinde ◽  
jennifer qiao ◽  
...  
Keyword(s):  
Organic Synthesis ◽  
Present Method ◽  
Bond Formation ◽  
Amide Bond ◽  
Bond Forming ◽  
Amide Bond Formation ◽  
Redox Active ◽  
Decarboxylative Coupling ◽  
The 19Th Century

This work presents a modern spin on one of the oldest known Csp3–Csp3 bond forming reactions in synthetic chemistry: the Kolbe electrolysis. This reaction holds incredible promise for synthesis, yet its use has been near non-existent in mainstream organic synthesis. In contrast to the strongly oxidative electrolytic protocol employed traditionally since the 19th century, the present method utilizes in situ generated redox-active esters (RAEs) which are combined with a mildly reductive Ni-electrocatalytic cycle. It can be used to heterocouple 1o, 2o, and even certain 3o RAEs with a protocol reminiscent of amide bond formation in terms of simplicity. Due to its mild nature the reaction tolerates a range of functional groups, is scalable, and was strategically enlisted for the synthesis of 25 known compounds to reduce overall step-counts by 74%.

Hindered rotation around the amide bond in a series of derivatives of 2-acetamidothiophenes

1991 ◽  
Vol 88 ◽  
pp. 689-707 ◽  
Author(s):  
P Andriamadio ◽  
D Nicole ◽  
A Cartier ◽  
M Wierzbicki ◽  
G Kirsch
Keyword(s):  
Amide Bond ◽  
Hindered Rotation ◽  
Derivatives Of

Synthetic Strategies to Access Heteroatomic Spirocentres Embedded in Natural Products

Synthesis ◽  
2021 ◽  
Author(s):  
Michael P. Badart ◽  
Bill C. Hawkins
Keyword(s):  
Natural Products ◽  
Heterocyclic Compound ◽  
Chemical Space ◽  
Three Dimensional ◽  
Coupling Reactions ◽  
Conjugate Additions ◽  
Biological Targets ◽  
Compound Libraries ◽  
The Common ◽  
Significant Attention

AbstractThe spirocyclic motif is abundant in natural products and provides an ideal three-dimensional template to interact with biological targets. With significant attention historically expended on the synthesis of flat-heterocyclic compound libraries, methods to access the less-explored three-dimensional medicinal-chemical space will continue to increase in demand. Herein, we highlight by reaction class the common strategies used to construct the spirocyclic centres embedded in a series of well-studied natural products.1 Introduction2 Cycloadditions3 Palladium-Catalysed Coupling Reactions4 Conjugate Additions5 Imines, Aminals, and Hemiaminal Ethers6 Mannich-Type Reactions7 Oxidative Dearomatisation8 Alkylation9 Organometallic Additions10 Conclusions

scholarly journals The Fluoride Anion-Catalyzed Sulfurization of Thioketones with Elemental Sulfur Leading to Sulfur-Rich Heterocycles: First Sulfurization of Thiochalcones

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 822
Author(s):  
Grzegorz Mlostoń ◽  
Jakub Wręczycki ◽  
Katarzyna Urbaniak ◽  
Dariusz M. Bieliński ◽  
Heinz Heimgartner
Keyword(s):  
Elemental Sulfur ◽  
Fluoride Anion ◽  
Ring Size ◽  
Mild Conditions ◽  
Tetrabutylammonium Fluoride ◽  
Cesium Fluoride ◽  
Secondary Reactions ◽  
Derivatives Of

Fluoride anion was demonstrated as a superior activator of elemental sulfur (S8) to perform sulfurization of thioketones leading to diverse sulfur-rich heterocycles. Due to solubility problems, reactions must be carried out either in THF using tetrabutylammonium fluoride (TBAF) or in DMF using cesium fluoride (CsF), respectively. The reactive sulfurizing reagents are in situ generated, nucleophilic fluoropolysulfide anions FS(8−x)−, which react with the C=S bond according to the carbophilic addition mode. Dithiiranes formed thereby, existing in an equilibrium with the ring-opened form (diradicals/zwitterions) are key-intermediates, which undergo either a step-wise dimerization to afford 1,2,4,5-tetrathianes or an intramolecular insertion, leading in the case of thioxo derivatives of 2,2,4,4-tetramethylcyclobutane-1,3-dione to ring enlarged products. In reactions catalyzed by TBAF, water bounded to fluoride anion via H-bridges and forming thereby its stable hydrates is involved in secondary reactions leading, e.g., in the case of 2,2,4,4-tetramethyl-3-thioxocyclobutanone to the formation of some unexpected products such as the ring enlarged dithiolactone and ring-opened dithiocarboxylate. In contrast to thioketones, the fluoride anion catalyzed sulfurization of their α,β-unsaturated analogues, i.e., thiochalcones is slow and inefficient. However, an alternative protocol with triphenylphosphine (PPh3) applied as a catalyst, offers an attractive approach to the synthesis of 3H-1,2-dithioles via 1,5-dipolar electrocyclization of the in situ-generated α,β-unsaturated thiocabonyl S-sulfides. All reactions occur under mild conditions and can be considered as attractive methods for the preparation of sulfur rich heterocycles with diverse ring-size.

scholarly journals Site-specific Umpolung amidation of carboxylic acids via triplet synergistic catalysis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yunyun Ning ◽  
Shuaishuai Wang ◽  
Muzi Li ◽  
Jie Han ◽  
Chengjian Zhu ◽  
...  
Keyword(s):  
Carboxylic Acids ◽  
Functional Group ◽  
Amide Bond ◽  
Coupling Reagents ◽  
Complex Molecules ◽  
Bond Forming ◽  
Synergistic Catalysis ◽  
Wide Range ◽  
Amidation Reaction ◽  
Forming Methods

AbstractDevelopment of catalytic amide bond-forming methods is important because they could potentially address the existing limitations of classical methods using superstoichiometric activating reagents. In this paper, we disclose an Umpolung amidation reaction of carboxylic acids with nitroarenes and nitroalkanes enabled by the triplet synergistic catalysis of FeI2, P(V)/P(III) and photoredox catalysis, which avoids the production of byproducts from stoichiometric coupling reagents. A wide range of carboxylic acids, including aliphatic, aromatic and alkenyl acids participate smoothly in such reactions, generating structurally diverse amides in good yields (86 examples, up to 97% yield). This Umpolung amidation strategy opens a method to address challenging regioselectivity issues between nucleophilic functional groups, and complements the functional group compatibility of the classical amidation protocols. The synthetic robustness of the reaction is demonstrated by late-stage modification of complex molecules and gram-scale applications.

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