Chemically triggered C–ON bond homolysis in alkoxyamines: regioselectivity and chemoselectivity

Abstract

Recently, we examplified the activation of the C-ON bond homolysis by protonation, alkylation, benzylation, acylation, oxidation and complexation with a Lewis acid of the nitrogen atom of the 1-(pyridin-4-yl)ethyl fragment (Chem. Commun., 2011, 4291 and Org. Lett., 2012, 358) and of the 1-(pyridin-2-yl)ethyl fragment (J. Org. Chem. ASAP Doi:10.1021/jo401674v) of (N-(2-methylpropyl)-N-(1-diethylphosphono-2,2-dimethylpropyl)-N-oxyl) SG1-based alkoxyamines. The quaternization of the 1-(pyridin-3-yl)ethyl fragment by the aforementioned reactions was investigated for the corresponding SG1-based alkoxyamines. In sharp contrast to the quaternization at ortho and para positions of the pyridyl moiety, the effect of the quaternization at the meta position was weak. The effects of quaternization at ortho, meta and para positions were investigated through natural bond orbital and Mulliken charges, HOMO-LUMO interactions in the starting materials and the radical stabilization energy of the released 1-puridylmethyl radicals using DFT calculations with the B3LYP/6-31G(d) and UBMK/6-311+G(3df,2p)//R(O)B3LYP/6-31G(d) methods, respectively.

Smart Control of Nitroxide-Mediated Polymerization Initiators’ Reactivity by pH, Complexation with Metals, and Chemical Transformations

“…The same has been observed during protonation of ortho -isomer 4 [26] and meta -isomer 5 [27] though the latter has manifested a smaller effect, as expected (vide infra). It should be noted that when terpyridine or bipyridine is the substituent of alkyl fragments (as in 6 and 7 ), the effect of protonation also enhances k d .…”

How intramolecular hydrogen bonding (IHB) controls the C–ON bond homolysis in alkoxyamines

“…Thus, estimated activation energies E′ a were determined (Table 4 and ESI †). Taking into account the small difference in polarity between the alkyl fragment carrying a pyridyl (σ I = 0.06) 50,51 or a phenyl (σ I = 0.07) 52 moiety, no significant difference was reported, 41 and the presence of the hydroxyl group capable of intraR IHB does not provide more than a 2-fold increase in k d , as highlighted by the couples 6/9 and 4/3. To unveil the effect of IHB on k d , the hydroxyl group was protected by silylation in 2 and 5, by methylation in 8, and by acylation in 7 and 10, to suppress the occurrence of IHB (see the ESI †).…”

“…13), and are given by the modified Hasselbach-Henderson equation (eqn (1), exemplified by 4/4H+, and Table 3). 40,41…”

How intramolecular coordination bonding (ICB) controls the homolysis of the C–ON bond in alkoxyamines

“…Alkoxyamines carrying regioisomer ortho (B); meta (C), and para (A) of pyridyl moiety have been oxidized into their corresponding N-oxide. Oxides of A 29 and B 30 exhibit a decrease of E a by 10 kJ mol −1 according to the non-oxidized regioisomer ( E a ≈ 124 kJ mol −1 ) whereas only a decrease by 3 kJ mol −1 ( ref. 31 ) is reported for the regioisomer meta .…”

“…The activation is mainly ascribed to the extra stabilization of the released radical in oxidized form (caused by nitroxide mesomeric form) in comparison the non-oxidized alkyl radical. [29][30][31] Thus, the increase in k d for the oxidized regio-isomer meta is ascribed to a small increase of the polarity. Then, the very close values of E a for 4 to 6 agree with the non-activating oxidation at the position meta.…”