Tin‐Free Radical Alkoxyamine Addition and Isomerization Reactions by Using the Persistent Radical Effect: Variation of the Alkoxyamine Structure

Abstract

Various C-centered radicals can efficiently be generated through thermal C-O-bond homolysis of alkoxyamines. This method is used to perform environmentally benign radical cyclization and intermolecular addition reactions. These alkoxyamine isomerizations and intermolecular carboaminoxylations are mediated by the persistent radical effect (PRE). In the paper, the effect of the variation of the alkoxyamine structure--in particular steric effects in the nitroxide moiety--on the outcome of the PRE mediated radical reactions will be discussed. Fourteen different nitroxides were used in the studies. It will be shown that reaction times can be shortened about 100 times upon careful tuning of the alkoxyamine structure. Activation energies for the C-O-bond homolysis of the various alkoxyamines are provided. The kinetic data are used to explain the reaction outcome of the PRE-mediated processes.

Nitroxides: Applications in Synthesis and in Polymer Chemistry

“…[211] It was found that replacing the TEMPO moiety in the starting alkoxyamine with sterically more hindered nitroxides provides compounds which undergo thermal radical carboaminoxylation with 1-octene in higher yields (up to 86 % yield) in a much shorter reaction time (1.5 h). [212] The reaction time for the radical carboaminoxylation of 1-octene with alkoxyamine 102 to give 103 was reduced to ten minutes by switching to microwave heating. [213,214] More recently, microflow radical carboaminoxylations of 1-octene and other olefins by using the sterically highly hindered alkoxyamine 104 were reported.…”

Nitroxide decomposition: Implications toward nitroxide design for applications in living free‐radical polymerization

“…These unusual properties have led to a wide range of applications spanning their use in biology as spin labels [1][2][3][4][5][6] to the development of organomagnetic materials. 7 In organic chemistry, nitroxides have been used in kinetic studies, [8][9][10][11] as oxidizing species in the form of the corresponding N-oxo ammonium salts, [12][13][14][15][16][17][18][19][20][21][22][23] as temporary caps for transient carbon radicals, [24][25][26][27][28][29][30][31] and as probes for stereocontrol with prochiral carbon radicals. [32][33][34][35][36] In polymer chemistry, nitroxide-mediated polymerization (NMP) [37][38][39][40][41][42][43][44][45][46][47] has become popular as a method for preparing living polymers ...…”

Radicals in organic synthesis. Part 1

“…142 The activation energy for C-O bond homolysis depends upon the stability of both radicals and the structure of the nitroxide. Increasing the steric bulk of the nitroxide results in a far more efficient C-O bond homolysis; 2,6-di-tert-butyl nitroxide reacts over 4-fold faster than the standard TEMPO nitroxide, whilst one of the most effective nitroxides is the ethyl derivative 151 (Fig.…”