Synthesis of saturated nitrogen heterocycles by Strecker reaction – nucleophilic cyclization

Grygorenko, Oleksandr O.

doi:10.1016/j.tetlet.2020.151645

Cited by 11 publications

(31 citation statements)

References 55 publications

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“…Nevertheless, synthesis of the title primary alcohols Martin periodinane (DMP) followed by reaction with the commercially available Ohira-Bestmann reagent. [41,42] In addition to that, an alternative approach to amino acids 13 a,b based on the tandem Strecker reaction -intramolecular nucleophilic cyclization (STRINC) sequence (that worked well for the parent 2,4-methanoproline) [19] was evaluated. In particular, alcohol 6 a was tosylated and then subjected to alkene cleavage with RuCl 3 À NaIO 4 to give ketone 24 (81 % yield) (Scheme 6).…”

Section: Resultsmentioning

confidence: 99%

“…Column chromatography was performed using Kieselgel Merck 60 (230-400 mesh) as the stationary phase. 1 H, 13 C and 19 F NMR spectra were recorded on a Agilent ProPulse 600 spectrometer (at 600 MHz for 1 H NMR, 151 MHz for 13 C NMR), Bruker 170 Avance 500 spectrometer (at 500 MHz for 1 H NMR, 126 MHz for 13 C NMR and 470 MHz for 19 F NMR) and Varian Unity Plus 400 spectrometer (at 400 MHz for 1 H NMR, 101 MHz for 13 C NMR and 376 MHz for 19 F NMR). NMR chemical shifts are reported in ppm (δ scale) downfield from TMS as an internal standard and are referenced using residual NMR solvent peaks at 7.26 and 77.16 ppm for 1 H and 13 C in CDCl 3 , 2.50 and 39.52 ppm for 1 H and 13 C in DMSO-d 6 .…”

Section: Methodsmentioning

confidence: 99%

“…13 C NMR (151 MHz, CDCl 3 ) δ 168.2, 114.2 (dd, J = 4.9, 0.6 Hz), 110.9 (t, J = 252.3 Hz), 70.7 (dd, J = 28.5, 26.4 Hz), 20.5, 17.6 (t, J = 2.8 Hz). 19 F NMR (470 MHz, CDCl 3 ) δ À 127.3 (dd, J = 288, 55.6 Hz), À 132.9 (dd, J = 288, 55. 6…”

Section: Methodsmentioning

confidence: 99%

“…13 C NMR (151 MHz, CDCl 3 ) δ 137.1, 118.5 (t, J = 4.7 Hz), 113.8 (t, J = 247 Hz), 111.0, 37.6 (t, J = 3.6 Hz), 34.9 (t, J = 23.5 Hz). 19 F NMR (470 MHz, CDCl 3 ) δ À 124.9 (d, J = 55. 3…”

Section: -(Difluoromethyl)-3-methylenecyclobutane-1-carbonitrile (7 B)mentioning

confidence: 99%

“…In particular, this framework is a part of a naturally occurring non-proteinogenic amino acid -2,4-methanoproline, a target for numerous synthetic studies. [17][18][19][20][21][22][23][24][25][26] Relevance of the 2,4-methanopyrrolidine scaffold to medicinal chemistry was also outlined. [20,[27][28][29] It is widely recognized that introducing fluorinated substituents into potential biologically active compounds can finetune their physico-chemical parameters, improve metabolic stability, and provide additional opportunities for interactions with a biological target.…”

Section: Introductionmentioning

confidence: 99%

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4‐(Di‐/Trifluoromethyl)‐2‐heterabicyclo[2.1.1]hexanes: Advanced Fluorinated Phenyl Isosteres and Proline analogues

et al. 2021

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A gram-scale synthesis, physico-chemical characterization, and lead-likeness assessment of 4-di/trifluoromethyl-2-heterabicyclo [2.1.1]hexanes as fluorinated bicyclic proline analogues and phenyl isosteres are disclosed. The key step of the synthesis included iodocyclization of fluorinated 3-hydroxy-/3aminomethyl methylenecyclobutanes; with the amino derivatives, the reaction was accompanied with carboxylation and further cyclization. Apart from the corresponding 4-di/ trifluoromethyl-2,4-methanoprolines, a series of fluorinated oxabicyclo[2.1.1]hexane-derived building blocks relevant to medicinal chemistry (i. e. primary iodides, carboxylic acids, alcohols, azides, primary amines, sulfonyl chlorides, and alkynes) were prepared. For representative derivatives of the resulting fluorinated 2-oxabicyclo[2.1.1]hexanes, pK a and logP values were measured to clarify their potential as the possible phenyl isosteres. Apart from the somewhat increased acidity, finetuned lipophilicity intermediate between that of non-fluorinated or aromatic counterparts was observed. Finally, the potential of the title building blocks was demonstrated by generation of virtual compound libraries using the LLAMA software. The resulting libraries fitted perfectly the lead-like chemical space, had higher three-dimensionality, and showed lower mean lead-likeness penalty as compared to those obtained from either non-fluorinated or aromatic derivatives.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: -(Difluoromethyl)-3-methylenecyclobutane-1-carbonitrile (7 B)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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4‐(Di‐/Trifluoromethyl)‐2‐heterabicyclo[2.1.1]hexanes: Advanced Fluorinated Phenyl Isosteres and Proline analogues

et al. 2021

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Cyclization Through Dual C(sp³)−H Functionalization

Sadeghi

2024

Adv Synth Catal

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C(sp3)–H functionalization methods have been widely employed in many organic transformations such as cyclization reactions, heterocycle synthesis, cross‐coupling protocols, and photochemical transformations. Among these transformations, cyclization reaction through C(sp3)–H functionalization offers a direct route to convert simple linear substrates to complex products. There are three modes of utilizing C(sp3)–H bonds in cyclization reactions including single, double, and dual C(sp3)–H functionalization. As the most challenging mode, dual C(sp3)–H functionalization refers to converting two separate C(sp3)–H bonds in one molecule into desired C–Z bonds which can be employed in cyclization reactions. Cyclization reaction via dual functionalization of C(sp3)–H can be classified based on the C(sp3)–H reactivities. Therefore, these reactions can be categorized into three classes based on the types of C(sp3)–H bonds including activated‐activated, activated‐unactivated, and unactivated‐unactivated C(sp3)–H bonds. Most published reports for cyclization reactions via dual C(sp3)–H functionalization involve activated‐activated C(sp3)–H bonds. However, the number of reported papers on the other two classes has been growing. This review focuses on the dual C(sp3)–H functionalization protocols used for cyclization reactions and categorizes the published papers based on the types of C(sp3)–H bonds.

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Salicylaldehydes in Strecker Reaction: Synthesis of Tricyclic Benzofuro[2,3‐b]pyrazin‐2(1H)‐ones via One‐Pot Seven Domino Reactions

Hosseinpour,

Sarvary,

Habibzadeh

2023

Eur J Org Chem

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The current study reports the first Strecker reaction with salicylaldehydes as carbonyl compounds. This pseudo‐five‐component reaction involved two moles of salicylaldehyde, two moles of cyanide, and one mole of amine, which reacted together in ethanol at reflux conditions, resulting in the tricyclic products benzofuro[2,3‐b]pyrazin‐2(1H)‐one (4a‐v). The benzofuro[2,3‐b]pyrazin‐2(1H)‐one products were formed via one‐pot seven Domino reactions including the Strecker reaction/ intramolecular cyclization/ tautomerization of imine to enamine/ Strecker reaction/ intramolecular cyclization/ conversion of amidine to amide/ and aerobic oxidation.

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Synthesis of saturated nitrogen heterocycles by Strecker reaction – nucleophilic cyclization

Cited by 11 publications

References 55 publications

4‐(Di‐/Trifluoromethyl)‐2‐heterabicyclo[2.1.1]hexanes: Advanced Fluorinated Phenyl Isosteres and Proline analogues

4‐(Di‐/Trifluoromethyl)‐2‐heterabicyclo[2.1.1]hexanes: Advanced Fluorinated Phenyl Isosteres and Proline analogues

Cyclization Through Dual C(sp³)−H Functionalization

Salicylaldehydes in Strecker Reaction: Synthesis of Tricyclic Benzofuro[2,3‐b]pyrazin‐2(1H)‐ones via One‐Pot Seven Domino Reactions

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Synthesis of saturated nitrogen heterocycles by Strecker reaction – nucleophilic cyclization

Cited by 11 publications

References 55 publications

4‐(Di‐/Trifluoromethyl)‐2‐heterabicyclo[2.1.1]hexanes: Advanced Fluorinated Phenyl Isosteres and Proline analogues

4‐(Di‐/Trifluoromethyl)‐2‐heterabicyclo[2.1.1]hexanes: Advanced Fluorinated Phenyl Isosteres and Proline analogues

Cyclization Through Dual C(sp3)−H Functionalization

Salicylaldehydes in Strecker Reaction: Synthesis of Tricyclic Benzofuro[2,3‐b]pyrazin‐2(1H)‐ones via One‐Pot Seven Domino Reactions

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Cyclization Through Dual C(sp³)−H Functionalization