Aminoxyl-Catalyzed Electrochemical Diazidation of Alkenes Mediated by a Metastable Charge-Transfer Complex

Abstract

We report the development of a new aminoxyl radical catalyst, CHAMPO, for the electrochemical diazidation of alkenes. Mediated by an anodically generated charge-transfer complex in the form of CHAMPO−N 3 , radical diazidation was achieved across a broad scope of alkenes without the need for a transition metal catalyst or a chemical oxidant. Mechanistic data support a dual catalytic role for the aminoxyl serving as both a single-electron oxidant and a radical group transfer agent. The discovery of reactions mediated by organic radicals continues to provide solutions to challenging synthetic problems in traditional two-electron chemistry. 1 In this context, design and implementation of new catalytic strategies have both expanded the toolbox available for accessing new synthetic targets and transformed the fundamental understanding of reactions involving open-shell pathways. 2 For example, persistent aminoxyl radicals [e.g., (2,2,6,6tetramethylpiperidin-1-yl)oxyl (TEMPO)] have been extensively explored in catalytic oxidation reactions with both conventional chemical 3 and electrochemical techniques, 4 which has given rise to synthetically useful processes for small-molecule and polymer syntheses. Despite significant advances, we contend that the scope of TEMPO chemistry remains to be fully explored. TEMPO and related N-oxyl radicals can undergo one-electron redox processes, granting access to three discrete oxidation states. 4 This feature distinguishes these radicals from common organic compounds and likens them to many transition metal complexes. In this fashion, TEMPO has been shown to enable single-electron oxidation events in an inner-sphere manner via the formation of metastable closed-shell intermediates. 5,6 Nevertheless, the systematic use of the "metallic" character of N-oxyls in catalyst development remains meager. 7 To date, reactions catalyzed by N-oxyls are largely confined to oxidations of alcohols, 8 aldehydes, 9 amines, 10 (thio)amides, 11 and peroxyl radicals. 12 In *

Electrooxidation enables highly regioselective dearomative annulation of indole and benzofuran derivatives

“…Electrochemical oxidation offers a mild and efficient alternative to the use of hazardous chemical oxidants and demonstrates unique reaction selectivity compared with the results under thermal conditions [45][46][47][48][49][50][51][52][53][54][55][56][57][58][59] . With sufficient potential bias, organic substrates can lose one electron at the anode to generate highly reactive intermediates [60][61][62][63] .…”

Photochemical Transformations with Iodine Azide after Release from an Ion‐Exchange Resin

“…Alternatively, the azide radical ( 6 ) can be generated from PhI(OAc) 2 and sodium azide which also leads to H radical abstraction from the solvent THF . As suggested for bulky TEMPO derivatives, TEMPO–azide adducts can form, serving as an azide radical in a “resting state” . A sample taken from a reaction mixture consisting of polymer 3 d and TEMPO in acetonitrile was analyzed by HPLC‐MS after 2 h and a signal at m / z= 199.2 (M + +1) was detected which could be TEMPO‐N 3 16 .…”

“… Radical 1,2‐addition of azide and TEMPO to alkenes and formation of 17 – 24 by photochemical activation of polymer‐bound reagent 3 d ; structure of TEMPO azide 16 ( 16 was also described to be a salt).…”

“…The structure of 24 was determined by X‐ray crystallographic analysis (see the Supporting Information) . This result is consistent with the observations of Lin and co‐workers, who found that aminoxyl radicals are able to catalyze the anti ‐diazidation of alkenes, likely with 16 serving as an azide radical reservoir . This alternative outcome of the reaction is fostered by increasing steric hindrance around the alkene moiety and the aminoxyl radical.…”

Photochemische Transformationen mit Iodazid nach Freisetzung von einem Ionenaustauscherharz

“… Radikalische 1,2‐Addition von Azid und TEMPO an Alkene und Bildung von 17 – 24 durch photochemische Aktivierung des polymergebundenen Reagens 3 d ; Struktur von TEMPO‐Azid 16 ( 16 wurde auch als Salz beschrieben).…”