Absolute Kinetics of Amidyl Radical Reactions

Abstract

An absolute kinetic scale for amidyl radical reactions was established by a combination of direct laser flash photolysis (LFP) and indirect competition kinetic studies. Six amidyl radicals were studied by LFP. Arrhenius parameters were determined for 6-exo cyclizations of the N-butyl-6,6-diphenyl-5-hexenamidyl radical (2) and the N-butyl-6-(trans-2-phenylcyclopropyl)-5-hexenamidyl radical (5) and for 1,5-hydrogen transfer in the N- (6,6-diphenyl-5-hexenyl)acetamidyl radical (3); rate constants for these reactions at 20 °C are 3.0 × 10 7 s -1 (2), 5.5 × 10 6 s -1 (3), and 1 × 10 7 s -1 (5). Kinetic limits were established by LFP for the fast cyclizations of the N-methyl-5,5-diphenyl-4-pentenamidyl radical (1) and the N-methyl-5-(trans-2-phenylcyclopropyl)-4-pentenamidyl radical (4) (k > 2 × 10 8 s -1 at ambient temperature) and for the slow fragmentation of the N-(2,2-diphenylethyl)acetamidyl radical (6) (k ) 2 × 10 4 s -1 at 48 °C). Rate constants for amidyl radical reactions with Bu 3 SnH and PhSH were determined by competition kinetics; respective rate constants are 1.3 × 10 9 M -1 s -1 at 20 °C and 9 × 10 7 M -1 s -1 at 23 °C. Cyclizations of simple amidyl radicals were determined from competition kinetic studies by employing Bu 3 SnH and N-(phenylthio)amide radical precursors using data from the literature and from studies in this work. Rate constants at 65 °C for 5-exo cyclizations of the N-butyl-4-pentenamidyl radical and the N-(4-pentenyl)butanamidyl radical and for 6-exo cyclization of the N-ethyl-5-hexenamidyl radical are 3 × 10 9 s -1 , 7 × 10 8 s -1 , and 1.0 × 10 7 s -1 , respectively. The kinetic values determined in this work can be employed in synthetic planning involving amidyl radicals, and the simple amidyl radical clocks can be used for measuring rate constants of bimolecular reactions. A compilation of the kinetics of nitrogen-centered radical cyclizations and bimolecular reactions of nitrogen radicals with Bu 3 SnH and PhSH is presented.

Catalytic alkylation of remote C–H bonds enabled by proton-coupled electron transfer

“…The motivation to develop amide homolysis protocols stems from the synthetic utility of the resulting amidyl radicals, which engage in a variety of synthetically useful transformations, including olefin amination 6–11 and directed C-H bond functionalization. 12–16 The latter process, a subset of the well-known Hofmann-Löffler-Freytag (HLF) reaction, relies on a favorable bond strength differential to enable amidyls to abstract H• from unactivated aliphatic C-H bonds (Figure 1b). 17–21 While powerful, these transforms typically require oxidative N- prefunctionalization of the amide starting materials to achieve efficient amidyl generation.…”

Mechanistic Perspectives on Stereocontrol in Lewis Acid-Mediated Radical Polymerization

“…66,67 Analogous polar effects have also been noted in transfer reactions. 68,69 The importance of polar effects in radical reactions is exemplified by the copolymerization of styrene (STY) and maleic anhydride. 70,71 This copolymerization affords highly alternating copolymer, as the relatively nucleophilic styrene radical reacts preferentially with the highly electrophilic maleic anhydride monomer and vice versa.…”

Hydrogen Atom Transfer in Model Reactions

“…[45]). In addition, the intermolecular reaction of amidyl radicals with thiophenol (PhSH) proceeds with k ¼ 9 Â 10 7 M À1 s À1 [46]. Representative kinetic data were obtained by laser flash photolysis for the intramolecular hydrogen transfer (1,5-H-shift) in the N-(6,6-diphenyl-5-hexenyl)acetamidyl radical 1 (Reaction (3.12); k 12 ¼ 5:5 Â 10 6 s À1 [46]).…”