Chemically triggered C–ON bond homolysis in alkoxyamines. Part 7. Remote polar effect

Audran, Gérard; Ibanou, Matisse Bim Batsiandzy; Brémond, Paul; Marque, Sylvain R. A.; Obame, Germain; Roubaud, Valérie; Siri, Didier

doi:10.1002/poc.3275

Cited by 6 publications

(8 citation statements)

References 35 publications

(71 reference statements)

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“…The remote polar effect (seven-bond range) is known . However, the benzylation of 6 with para-substituted benzyl bromide 5 (Figure ) affords a clear 4-fold increase in k d , as exemplified by W = NMe 2 (σ P = −0.83) to W = NO 2 (σ P = 0.78) . Obviously, groups as far as 10 bonds from the reactive center still display a significant effect even for an aromatic ring isolated by a methylene group (Figure ).…”

Section: Discussionmentioning

confidence: 99%

Smart Alkoxyamines: A New Tool for Smart Applications

2020

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In 1986, Rizzardo et al. discovered the nitroxide-mediated polymerization which relies on the reversibility of homolysis of the C−ON bond of alkoxyamine R 1 R 2 NOR 3 , a unique property of these molecules. This discovery has generated a tremendous endeavor in the field of polymer chemistry. Alkoxyamines have been used as initiators/controllers for nitroxidemediated polymerization. Moreover, photoexcitable alkoxyamines that dissociate under light at different wavelengths have also been developed for polymer chemistry. Over the past few years, alkoxyamines have started to be used in materials sciences. In many cases (e.g., self-healing polymers), the development of smart materials requires the use of smart building blocks, that is, molecules or systems whose properties and/or structures change upon external stimuli. Alkoxyamines exhibit a unique property: reversible homolysis (i.e., homolysis of the C−ON bond into alkyl R 3 • and nitroxyl R 1 R 2 NO• radicals and reformation via the coupling of these two species). Until now, this property has been controlled only by changes in temperatures or by light irradiation. Chemical and/or biochemical control of the homolysis event would open new gates for the application of these molecules in different fields such as biology and medicine. Thus, the concept of smart alkoxyamines is discussed and exemplified via the activation of alkoxyamines using chemical or/and biochemical changes amplifying the polar, steric, and stabilization effects. In situ activation is also discussed. It is shown that (i) increasing the electron-withdrawing properties of the alkyl fragment weakens the C−ON bond and thus favors homolysis but is opposite for the nitroxyl fragment; (ii) increasing the steric hindrance on the nonactive site affords dramatic conformation changes which weaken the C−ON bond; and (iii) increasing the stabilization of the released alkyl radical weakens the C−ON bond. Solvent effects and intramolecular hydrogen bonding are also discussed. Reactions used to highlight our purpose are either reversible or nonreversible and used under conditions that are as mild as possible (temperatures below 40 °C and atmospheric pressure). For example, a several (thousands of millions of) millions of orders of magnitude enhancement of the homolysis rate constant is observed upon enzymatic hydrolysis at 37 °C, meaning that a shift from a stable alkoxyamine (t 1/2 = 42 000 milleniums) to a highly labile alkoxyamine (t max = 1500 s for 35% conversion) is achieved. Applications of this concept are discussed for safe NMP initiators and for theranostic agents.

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Section: Discussionmentioning

confidence: 99%

Smart Alkoxyamines: A New Tool for Smart Applications

2020

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“…Purifications were performed on chromatography columns with silica gel grade 60 (230-400 mesh). 1 H, 13 C, and 31 P NMR spectra were recorded in CDCl 3 on a 300 or 400 MHz spectrometer. Chemical shifts (δ) in ppm were reported using residual nondeuterated solvents as internal references for 1 H and 13 C-NMR spectra, and 85% H 3 PO 4 for 31 P-NMR spectra.…”

Section: Methodsmentioning

confidence: 99%

“…: 110 °C (decomp. ); R f = 0.46 (DCM/acetone 7 : 3); 1 H NMR (400 MHz, CDCl 3 ) δ: 7.11 (d, J = 8.3 Hz, 2H), 6.64 (d, J = 8.3 Hz, 2H), 4.91 (q, J = 6.5 Hz, 1H), 3.92-4.40 (m, 4H), 3.34 (d, J H-P = 25.3 Hz, 1H), 1.57 (d, J = 6.8 Hz, 3H), 1.33 (t, J = 6.8 Hz, 3H), 1.32 (t, J = 7.0 Hz, 3 H), 1.24 (s, 9H), 0.85 (s, 9H); 13 Methyl 4-(1-((tert-butyl(1-(diethoxyphosphoryl)-2,2-dimethylpropyl)amino)oxy)ethyl)benzoate (RS/SR-4d and RR/SS-4d). To a degassed solution of CuBr (1.18 g, 8.3 mmol) and Cu (1.05 g, 16.5 mmol) in benzene, N,N,N′,N″,N″-pentamethyldiethylenetriamine (1.72 mL, 8.3 mmol) was added dropwise, and the solution was kept under argon bubbling for another 30 min.…”

Section: General Procedures For the Preparation Of 4bh-jmentioning

confidence: 99%

“…2) either by a carboxylic group in the case of alkoxyamine 2 12 or by a methylene group, in the case of alkoxyamine 3. 13 Taking into account that the nitroxyl fragment based on 1 • is prone to enhancing the effect of polar substituents on the alkyl fragment, the effect of the para-substituents on the aryl group in alkoxyamines 4 (Fig. 2) on the homolysis rate constant k d is investi- ( 1 H, 13 C NMR spectra) of compounds 4b,d,e,g-j, procedure for kinetic and pK a measurements.…”

Section: Introductionmentioning

confidence: 99%

“…13 Taking into account that the nitroxyl fragment based on 1 • is prone to enhancing the effect of polar substituents on the alkyl fragment, the effect of the para-substituents on the aryl group in alkoxyamines 4 (Fig. 2) on the homolysis rate constant k d is investi- ( 1 H, 13 C NMR spectra) of compounds 4b,d,e,g-j, procedure for kinetic and pK a measurements. CCDC 1441553 for (RS/SR)-4b, 1441554 for (RR/SS)-4d and 1452314 for (SR/RS)-4h.…”

Section: Introductionmentioning

confidence: 99%

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C–ON bond homolysis in alkoxyamines. Part 12: the effect of the para-substituent in the 1-phenylethyl fragment

et al. 2016

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The application of alkoxyamines as initiators/controllers in nitroxide mediated polymerization and as agents for theranostics requires the development of switchable (from stable one to labile one) alkoxyamines. One way to achieve this is to tune the polarity of various groups carried by either the alkyl fragment or the nitroxyl fragment. Thus, the effect of protonation/deprotonation of the para-functionalized aryl moiety carried by the alkyl fragment in diethyl(2,2-dimethyl-1-((1,1-dimethylethyl)(1-para-subsitutedphenylethoxy)amino)propyl)phosphonate is investigated. An increase in kd is observed with increasing localized electrical effect, i.e., in the presence of electron withdrawing groups at the para position of the phenyl ring. A striking effect of the intimate ion pair on kd is also observed.

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