Multicomponent Reaction of <i>Z</i>-Chlorooximes, Isocyanides, and Hydroxylamines as Hypernucleophilic Traps. A One-Pot Route to Aminodioximes and Their Transformation into 5-Amino-1,2,4-oxadiazoles by Mitsunobu–Beckmann Rearrangement

Mercalli, Valentina; Massarotti, Alberto; Varese, Monica; Giustiniano, Mariateresa; Meneghetti, Fiorella; Novellino, Ettore; Tron, Gian Cesare

doi:10.1021/acs.joc.5b01676

Cited by 23 publications

(7 citation statements)

References 43 publications

(35 reference statements)

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“…In particular, Isocyanide-based Multicomponent Reactions (IMCRs) [1][2][3][4], have been proven to be an ideal tool to provide in one single step medium-complexity molecular skeletons, usually accessible only via a multistep approach. Most of MCR chemistry is performed with isocyanides and is related to the Ugi reaction [5,6], a four-component transformation (4CR) described in 1959 by Professor Ivar Ugi. In the reaction, an acid component, like a carboxylic acid, reacts with an oxo-component (a ketone or an aldehyde), a primary amine, and an isocyanide.…”

Section: Introductionmentioning

confidence: 99%

α-Amino Acids as Synthons in the Ugi-5-Centers-4-Components Reaction: Chemistry and Applications

et al. 2019

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Since the first reports, the Ugi four-component reaction (U-4CR) has been recognized as a keystone transformation enabling the synthesis of peptide mimetics in a single step and with high atom economy. In recent decades, the U-4CR has been a source of inspiration for many chemists fascinated by the possibility of identifying new efficient organic reactions by simply changing one of the components or by coupling in tandem the multicomponent process with a huge variety of organic transformations. Herein we review the synthetic potentialities, the boundaries, and the applications of the U-4CR involving α-amino acids, where the presence of two functional groups—the amino and the carboxylic acids—allowed a 5-center 4-component Ugi-like reaction, a powerful tool to gain access to drug-like multi-functionalized scaffolds.

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Section: Introductionmentioning

confidence: 99%

α-Amino Acids as Synthons in the Ugi-5-Centers-4-Components Reaction: Chemistry and Applications

et al. 2019

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“…The formation of the carbonyl is accompanied by the loss of the thiocyanate unit. Water attacks the C=N carbon in 11 c leading to the formation of a diol and an imine in 11 d , further rearrangement results in the final product 11 .…”

Section: Resultsmentioning

confidence: 99%

A New Synthetic Method for Tetraazatricyclic Derivatives and Evaluation of Their Biological Properties

et al. 2018

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A new method for the synthesis of tetraazatricyclic compounds by a reaction of benzoyl isothiocyanates with 2‐aminobenzimidazole is presented and a possible mechanism proposed. The new base‐catalyzed degradation of the tetraazatricyclic ring has been carried out. A reaction of benzoyl isothiocyanate with 2‐aminobenzoxazole, however, resulted in the formation of 3‐benzoyl‐1‐(2‐hydroxyphenyl)urea while a reaction with 2‐aminobenzothiazole gave 3‐(1,3‐benzothiazol‐2‐yl)‐1‐(benzoyl)thiourea. Density functional theory computed reaction mechanism for the formation of tetraazaatricyclic compounds is discussed. Biological screening of the compounds against Plasmodium falciparium and HIV‐1 protease showed very little activity but they were moderately active against Trypanosoma brucei with an IC50 of 19.71 μM for 11‐(3‐methoxyphenyl)‐1,8,0,12‐tetraazatricyclo [7.4.0.02,7]trideca‐2(7),3,5,9,11‐pentaene‐13‐thione (4).

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“…34 After optimization of the reaction conditions, we obtained the aminodioxime 44 in 72% yield just by mixing (Z)phenylchloroxime (14), pentyl isocyanide (25), and hydroxylamine (43) in dichloromethane at room temperature, using sodium hydrogen carbonate as the base (Scheme 9). 35…”

Section: Scheme 8 Two-step Synthesis Of 12-benoxazole-3-carboxamidesmentioning

confidence: 99%

“…Results showed that mechanism C was the most energetically favorable in comparison with mechanisms A and B, and with the energy barrier of the direct attack of the third nucleophile to the nitrile N-oxide species. 35…”

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Nitrile N-Oxides and Nitrile Imines as New Fuels for the Discovery of Novel Isocyanide-Based Multicomponent Reactions

2016

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With this short review we would like to describe our work on isocyanide-mediated multicomponent reactions using the 1,3-dipolar species nitrile N-oxides and nitrile imines as electrophilic inputs. Our goal is to show the potentiality of these transformations, elucidate the mechanisms of the reactions, demonstrate the versatility, and highlight the potentiality of this chemistry.\ud 1 Introduction\ud 2 (Z)-ChloroximesasElectrophilicPartnersforIsocyanides\ud 2.1 Precedents for the Reaction Between Nitrile N-Oxides and Iso-\ud cyanides\ud 2.2 Reaction between (Z)-Chloroximes, Isocyanides, and Carboxylic\ud Acids (or Amines)\ud 2.3 The Use of Other Nucleophiles as the Third Partner\ud 2.4 General Mechanism\ud 3 Nitrile Imines as Electrophilic Partners for Isocyanides\ud 4 Conclusions and Future Outloo

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Multicomponent Reaction of Z-Chlorooximes, Isocyanides, and Hydroxylamines as Hypernucleophilic Traps. A One-Pot Route to Aminodioximes and Their Transformation into 5-Amino-1,2,4-oxadiazoles by Mitsunobu–Beckmann Rearrangement

Cited by 23 publications

References 43 publications

α-Amino Acids as Synthons in the Ugi-5-Centers-4-Components Reaction: Chemistry and Applications

α-Amino Acids as Synthons in the Ugi-5-Centers-4-Components Reaction: Chemistry and Applications

A New Synthetic Method for Tetraazatricyclic Derivatives and Evaluation of Their Biological Properties

Nitrile N-Oxides and Nitrile Imines as New Fuels for the Discovery of Novel Isocyanide-Based Multicomponent Reactions

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