Synthesis of Aziridine-2,2-dicarboxylates via 1,4-Addition of <i>N</i>,<i>O</i>-(Bistrimethylsilyl)hydroxylamine to α,β-Unsaturated Malonates

Cardillo, Giuliana; Gentilucci, Luca; Gianotti, Massimo; Perciaccante, Rossana; Tolomelli, Alessandra

doi:10.1021/jo015907+

Cited by 33 publications

(19 citation statements)

References 18 publications

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“…Lehnert himself used TiCl 4 without molecular sieves in his Knoevenagel condensations. [15] The limited role of molecular sieves in the investigated reactions indicates that another species that traps water is present in the reaction mixture, probably a titanium species.…”

Section: à ð1þmentioning

confidence: 99%

“…This reaction was first performed by Lehnert between aldehydes or ketones and a wide range of methylene active compounds. [14] It has been used to synthesise some natural products [15] and its stereochemistry has also been studied. [16,17] However, neither experimental nor theoretical studies have ever been performed to explain the role of titanium in this reaction.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Condensation of β‐Diester Titanium Enolates with Carbonyl Substrates: A Combined DFT and Experimental Investigation

Marrone

Renzetti

Maria

et al. 2009

Chemistry A European J

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The condensation of dialkyl beta-diesters with various aldehydes promoted by TiCl4 has been studied by DFT approaches and experimental methods, including NMR, IR and UV/Vis spectroscopy. Various possible reaction pathways have been investigated and their energy profiles evaluated to find out a plausible mechanism of the reaction. Theoretical results and experimental evidence point to a three-step mechanism: 1) Ti-induced formation of the enolate ion; 2) aldol reaction between the enolate ion and the aldehyde, both coordinated to titanium; and 3) intramolecular elimination that leads to a titanyl complex. The presented mechanistic hypothesis allows one to better understand the pivotal role of titanium(IV) in the reaction.

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Section: à ð1þmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Condensation of β‐Diester Titanium Enolates with Carbonyl Substrates: A Combined DFT and Experimental Investigation

Marrone

Renzetti

Maria

et al. 2009

Chemistry A European J

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“…As a consequence, the Knövenagel reaction was performed using TiCl 4 /pyridine affording the alkyne-protected alkylidene acetoacetate 11 in 83% yield as 1/4 mixture of Z/E isomers as well and confirming the previous hypothesis of alkyne side reactivity (Scheme 1, path B). Reaction conditions for the addition of bis-(N,O)-trimethylsilylhydroxylamine to 2 and 11 were optimized on the basis of our previous experience 21,22 , in order to avoid the formation of oxime by-product as a result of the undesired 1,2-addition process 23 . According to these considerations, the reaction was performed in DCM in the presence of a catalytic amount (5%) of ytterbium triflate as Lewis acid.…”

Section: Resultsmentioning

confidence: 99%

Side chain effect in the modulation of αvβ3/α5β1 integrin activity via clickable isoxazoline-RGD-mimetics: development of molecular delivery systems

Ferrazzano

Corbisiero

Potenza

et al. 2020

Sci Rep

Self Cite

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Construction of small molecule ligand (SML) based delivery systems has been performed starting from a polyfunctionalized isoxazoline scaffold, whose α v β 3 and α 5 β 1 integrins' potency has been already established. The synthesis of this novel class of ligands was obtained by conjugation of linkers to the heterocyclic core via Huisgen-click reaction, with the aim to use them as "shuttles" for selective delivery of diagnostic agents to cancer cells, exploring the effects of the side chains in the interaction with the target. Compounds 17b and 24 showed excellent potency towards α 5 β 1 integrin acting as selective antagonist and agonist respectively. Further investigations confirmed their effects on target receptor through the analysis of fibronectin-induced ERK1/2 phosphorylation. In addition, confocal microscopy analysis allowed us to follow the fate of EGFP conjugated α 5 β 1 integrin and 17b FITCconjugated (compound 31) inside the cells. Moreover, the stability in water solution at different values of pH and in bovine serum confirmed the possible exploitation of these peptidomimetic molecules for pharmaceutical application.

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“…Mitomycin C is an aziridine-containing antibiotic [5,6]. Cardillo and co-workers [9] reported the synthesis of aziridine-2,2-dicarboxylates 7 via the conjugate addition of N,O-bis(trimethylsilyl) hydroxylamine (TMSN HOTMS) 5 to alkylidene malonates, to give adducts 6 followed by cyclization as shown in Scheme 3. Cardillo and co-workers [9] reported the synthesis of aziridine-2,2-dicarboxylates 7 via the conjugate addition of N,O-bis(trimethylsilyl) hydroxylamine (TMSN HOTMS) 5 to alkylidene malonates, to give adducts 6 followed by cyclization as shown in Scheme 3.…”

Section: Methodsmentioning

confidence: 99%

“…Conjugate addition is an important bond-forming strategy utilized in organic synthesis. Cardillo and her co-workers [9] carried out the 1,4-addition of N,Obis(trimethylsilyl)hydroxyl-amine to a variety of dimethyl malonate olefins simply by stirring the components in CH 2 Cl 2 for 18h at room temperature and in the absence of catalyst. Cardillo and her co-workers [9] carried out the 1,4-addition of N,Obis(trimethylsilyl)hydroxyl-amine to a variety of dimethyl malonate olefins simply by stirring the components in CH 2 Cl 2 for 18h at room temperature and in the absence of catalyst.…”

Section: Methodsmentioning

confidence: 99%

Utilities of Some Carbon Nucleophiles in Heterocyclic Synthesis

Madkour¹,

Elgazwy

2007

COC

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New developments in the utilities of some carbon nucleophiles in heterocyclic synthesis are reviewed. General synthetic routes based on the utilization of carbon nucleophiles of active methylene are discussed. The major methods and modifications are analyzed. Heterocycles are ubiquitous in all kind of compounds of interest, and among all the possible synthetic methods of achieving their introduction into a structure, probably the use of a carbon nucleophile analogues are the most direct one. The present review deals with the generation and synthetic of carbon nucleophile, which uses as scaffold for the heterocyclic synthesis, and can be considered as an update review. Therefore the only references published upon the second quarter of 2003 are included, and the same restrictions to the literature coverage apply.

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Synthesis of Aziridine-2,2-dicarboxylates via 1,4-Addition of N,O-(Bistrimethylsilyl)hydroxylamine to α,β-Unsaturated Malonates

Cited by 33 publications

References 18 publications

Condensation of β‐Diester Titanium Enolates with Carbonyl Substrates: A Combined DFT and Experimental Investigation

Condensation of β‐Diester Titanium Enolates with Carbonyl Substrates: A Combined DFT and Experimental Investigation

Side chain effect in the modulation of αvβ3/α5β1 integrin activity via clickable isoxazoline-RGD-mimetics: development of molecular delivery systems

Utilities of Some Carbon Nucleophiles in Heterocyclic Synthesis

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