Reactions of the Cumyloxyl Radical with Secondary Amides. The Influence of Steric and Stereoelectronic Effects on the Hydrogen Atom Transfer Reactivity and Selectivity

Abstract

A time-resolved kinetic study of the hydrogen atom transfer (HAT) reactions from secondary alkanamides to the cumyloxyl radical was carried out in acetonitrile. HAT predominantly occurs from the N-alkyl α-C-H bonds, and a >60-fold decrease in kH was observed by increasing the steric hindrance of the acyl and N-alkyl groups. The role of steric and stereoelectronic effects on the reactivity and selectivity is discussed in the framework of HAT reactions from peptides.

Bimodal Evans−Polanyi Relationships in Hydrogen Atom Transfer from C(sp3)--H Bonds to the Cumyloxyl Radical. A Combined Time-Resolved Kinetic and Computational Study

“…Care was taken to select substrates containing equivalent aliphatic CH bonds or, in those containing non-equivalent aliphatic CH bonds, substrates from which HAT to CumO  predominantly or almost exclusively occurs from a single CH site or type of site. Previous studies clearly show that tert-alkoxyl radicals display very low reactivity toward the CH bonds of unactivated methyl groups (kH < 1  10 4 M 1 s 1 ), 32,33 and are essentially unreactive toward alkenyl and aryl C(sp 2 )H bonds. 33,34 HAT from primary and secondary amines and alcohols is known to occur predominantly at CH bonds α to the heteroatom rather than from the NH and OH bonds, respectively.…”

“…2,2-Dimethylbutane (2), 2,3-dimethylbutane (3), 2,2,3-trimethylbutane (4), cycloheptane (7), adamantane (9), toluene (10), ethylbenzene (11), cumene (12), diphenylmethane (13) Commercial samples of propylamine (29), hexylamine (31), octylamine (32), triallylamine (39), dichloromethane (52) and chloroform (53) were purified prior of use by filtration over neutral alumina. The purity of the substrates was checked by GC prior to the kinetic experiments and was in all cases > 99.5%.…”

Electronic and Torsional Effects on Hydrogen Atom Transfer from Aliphatic C–H Bonds: A Kinetic Evaluation via Reaction with the Cumyloxyl Radical

“…HAT from pentane, 1-pentanol, and pentylamine to CumO • has been previously investigated and discussed . By considering that unactivated methyl groups display an extremely low reactivity toward tert- alkoxyl radicals ( k H ≤ 1.3 × 10 4 M –1 s –1 per methyl group), the k H value measured for reaction of CumO • with pentane ( k H = 3.1 × 10 5 M –1 s –1 ) indicates that with this substrate HAT mostly occurs from the methylene groups.…”

Electronic control over site-selectivity in hydrogen atom transfer (HAT) based C(sp3)–H functionalization promoted by electrophilic reagents

“…Based on these precedents, a time-resolved kinetic study on HAT from the C-H bonds of an extended series of 1-Z-propyl and 1-Z-pentyl derivatives bearing different Z groups to CumO has been recently carried out, aimed at a quantitative evaluation of the role of electronic effects on these reactions (Table 2). 51 By considering that unactivated methyl groups display an extremely low reactivity toward tert-alkoxyl radicals (k H o 10 4 M À1 s À1 per methyl group), 52 and by taking into account the similar reactivity displayed by the methylene groups of pentane toward CumO , 53 and the measured k H value for this reaction (k H = 3.1 Â 10 5 M À1 s À1 ), a second-order rate constant k H E 1.0 Â 10 5 M À1 s À1 has been estimated for HAT from the methylene group of propane taken as the unsubstituted reference substrate for the 1-Z-propyl series. On the basis of this observation, the B10 and B100-fold increase (quantified by k rel in Table 2) in k H measured on going from propane to 1-propanol and propylamine respectively, is indicative of a-CH 2 activation determined by the presence of the electron-rich OH and NH 2 groups.…”