Knoevenagel Condensation between 2-Methyl-thiazolo[4,5-b]pyrazines and Aldehydes

We report the first total synthesis of (+)-granatumine A, a limonoid alkaloid with PTP-1B inhibitory activity, in 10 steps. Over the course of this study, two key methodological advances were made: a cost effective procedure for ketone alpha,beta-dehydrogenation using allyl-Pd catalysis, and a Pd-catalyzed protocol to convert epoxyketones to 1,3-diketones. The central tetrasubstituted pyridine is formed by a convergent Knoevenagel condensation and carbonyl-selective electrocyclization cascade, which was followed by a direct transformation of a 2H-pyran to a pyridine. These studies have led to the structural revision of two members of this family.

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Knoevenagel Condensation Reactions of Cyano Malononitrile-Derivatives Under Microwave Radiation

Current Organic Chemistry ◽

10.2174/1385272822666180123145819 ◽

2018 ◽

Vol 22 (6) ◽

pp. 519-532 ◽

Cited By ~ 6

Author(s):

Lucas Lima Zanin ◽

David Esteban Quintero Jimenez ◽

Luis Pina Fonseca ◽

Andre Luiz Meleiro Porto

Keyword(s):

Microwave Radiation ◽

Knoevenagel Condensation ◽

Condensation Reactions

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O-AcylTEMPOs, a Modified and Fundamental, but Unexplored Carboxylic Derivative: Recent Progress in Synthetic Applications

Current Organic Chemistry ◽

10.2174/1385272823666191019102511 ◽

2019 ◽

Vol 23 (19) ◽

pp. 2102-2121

Author(s):

Hiroyuki Kawafuchi ◽

Lijian Ma ◽

Md Imran Hossain ◽

Tsutomu Inokuchi

Keyword(s):

Organic Synthesis ◽

Recent Progress ◽

Knoevenagel Condensation ◽

Acid Synthesis ◽

Amino Acid Synthesis ◽

Electrophilic Amination ◽

Weinreb Amides ◽

Anionic Species ◽

Diastereoselective Addition ◽

Carbonyl Function

O-Acylated 2,2,6,6-tetramethylpiperidine-N-oxyls (abbr. O-AcylTEMPOs) are easily available and stable carboxylic derivatives, but their utility in organic synthesis is unexplored in contrast to analogues, such as the N-methoxy-N-methylamides, known as Weinreb amides. Especially, the O–N unit of the O-acylTEMPOs dictates a fairly electronwithdrawing character for the carbonyl function. This enhances the reactivity and stability of the resulting enolate ions. Accordingly, O-acylTEMPOs allow various transformations and this review encompasses seven topics: (1) Reactivity of O-acylTEMPOs towards nucleophiles and chemoselective transformations, (2) Reactivity of anionic species derived from O-acylTEMPOs, (3) E-Selective Knoevenagel condensation of acetoacetylTEMPOs and synthesis of furans, (4) Electrocyclization of 2,4-dienones derived from acetoacetic derivatives and 2-substituted enals, (5) Diastereoselective addition of amide anion to O-(2-alkenoyl)TEMPOs and β-amino acid synthesis, (6) Thermolysis of O-acylTEMPOs, and (7) Applications for Umpolung reactions using O-benzoylTEMPOs, useful for the electrophilic amination of alkenes and alkynes.

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Temperature Dependent Green Synthesis of 3-Carboxycoumarins and 3,4-unsubstituted Coumarins

Current Organic Synthesis ◽

10.2174/1570179415666180924124134 ◽

2019 ◽

Vol 16 (1) ◽

pp. 130-135 ◽

Cited By ~ 3

Author(s):

Jack van Schijndel ◽

Dennis Molendijk ◽

Luiz Alberto Canalle ◽

Erik Theodorus Rump ◽

Jan Meuldijk

Keyword(s):

Knoevenagel Condensation ◽

Ammonium Bicarbonate ◽

Solvent Free ◽

Temperature Dependent ◽

Step Procedure ◽

Synthetic Routes ◽

High Yields ◽

Temperature Optima ◽

Solvent Free Synthesis ◽

Full Conversion

Aim and Objective: Because of the low abundance of 3,4-unsubstituted coumarins in plants combined with the complex purification process required, synthetic routes towards 3,4-unsubstituted coumarins are especially valuable. In the present work, we explore the possibilities of a solvent-free Green Knoevenagel condensation on various 2-hydroxybenzaldehyde derivatives and malonic acid without the use of toxic organocatalysts like pyridine and piperidine but only use ammonium bicarbonate as the catalyst. Materials and Methods: To investigate the scope of the Green Knoevenagel condensation for the synthesis of 3,4-unsubstituted coumarins, various 2-hydroxybenzaldehyde derivatives were screened as starting material in the optimized two-step procedure developed for 2-hydroxybenzaldehyde. Results: This study shows that the intramolecular esterification and the decarboxylation are in competition, but show different temperature optima. In order to suppress premature decarboxylation and maximize the yield of coumarin, a two-step procedure was adopted. The reaction mixture containing ammonium bicarbonate is initially kept at 90ºC for 1 hour. After completion of the cyclization, the temperature of the reaction mixture is increased to 140ºC for 2 hours. Following this protocol, coumarin could be isolated with a yield of 95%. Conclusion: A two-step procedure for the solvent-free synthesis of several 3,4-unsubstituted coumarins was developed using ammonium bicarbonate, resulting in high yields of the desired products. Moreover, this procedure has a low E-factor and is, therefore an environmental friendly reaction in line with the principles of Green Chemistry. It was shown that by initially capping the temperature at 90ºC, premature decarboxylation can be suppressed. After full conversion to the intermediate 3-carboxycoumarin, the temperature can be increased to 140ºC finalizing the reaction. Ammonium bicarbonate was shown to catalyze both the Green Knoevenagel condensation and the decarboxylation step.

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New Substituted Difurylchalcones

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19922203 ◽

1992 ◽

Vol 57 (10) ◽

pp. 2203-2207 ◽

Cited By ~ 1

Author(s):

Katarína Špirková ◽

Štefan Stankovský

Keyword(s):

Nmr Spectra ◽

Knoevenagel Condensation ◽

Secondary Amines ◽

H Nmr ◽

Nucleophilic Reactions

Preparation of 1-(5-substituted-2-furyl)-2-phenylsulfonyl-2-furoyl ethylenes (IIa-IId) using the Lehnert modification of Knoevenagel condensation, as well as substitution nucleophilic reactions of the 1-(5-bromo-2-furoyl)-2-phenylsulfonyl-2-furoyl derivative (IIa) with the corresponding phenolate, thiophenolate and secondary amines are described. IR, UV and 1H NMR spectra of final products are presented.

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