Electrochemical Formation of N-Acyloxy Amidyl Radicals and Their Application: Regioselective Intramolecular Amination of sp² and sp³ C–H Bonds

Abstract

Electrochemical generation of N-acyloxy amidyl radicals via an inner-sphere electron-transfer process is described for the first time. With NaBr as the catalyst and electrolyte, the in situ generated amidyl radicals undergo intramolecular C(sp/sp)-H aminations to give lactams with unprecedented regio- and chemoselectivities. Moreover, the synthetic utility of current method is demonstrated by the synthesis of PJ34 and Phenaglaydon.

Electrochemical Synthesis of 5‐Aryl‐phenanthridin‐6‐one by Dehydrogenative N,C Bond Formation

“…Recently, Zeng et al. reported a protocol to construct phenanthredin‐6‐one by employing a constant current setup in undivided cells with the aid of an anodically generated reagent (mediator) in order to facilitate the cyclization reaction, limited only to N ‐acetyl or N ‐pivaloyl functionalities (Scheme , middle part) . A leastwise stoichiometric amount of the mediator (NaBr), depending on the setup, and in special cases also Na 2 CO 3 as additive are required.…”

“…with the aid of an anodically generatedr eagent (mediator) in order to facilitate the cyclization reaction, limited only to Nacetyl or N-pivaloyl functionalities (Scheme 1, middlep art). [13] A leastwise stoichiometric amount of the mediator (NaBr), depending on the setup, and in special cases also Na 2 CO 3 as additive are required. With ac urrent efficiency of 0.4 (platinum electrodes) this process consumes unusual large amountso f appliedc harge.…”

Hexafluoro‐2‐Propanol‐Promoted Electro‐Oxidative [3+2] Annulation of 1,3‐Dicarbonyl Compounds and Alkenes

“…Electrosynthesis, which can avoid the external oxidants by employing the electrons to achieve the redox reaction, is considered as a versatile and eco‐friendly synthetic strategy and has experienced remarkable renaissance in recent years . The electrochemical alkene difunctionalization is emerging as a approach to construct C−C, C−N, C−O, C−Cl and so on .…”

Merging Photochemistry with Electrochemistry: Functional‐Group Tolerant Electrochemical Amination of C(sp3)−H Bonds

“…[5] The Hofmann-Lçffler-Freytag (HLF) reaction is ap ioneering example of such reactivity, [6,7] and numerous variations of the HLF reaction have emerged for C À Hh alogenation and nitrogen-heterocycle synthesis. [14,15] Each of these examples exhibits limited functional-group compatibility owing to the requirement for high anode potentials ( Figure 1B). [14,15] Each of these examples exhibits limited functional-group compatibility owing to the requirement for high anode potentials ( Figure 1B).…”

“…[8][9][10][11] Electrochemical methods, summarized in Figure 1, have been explored as am eans to bypass the use of undesirable stoichiometric oxidants or pregeneration of N À Xc ompounds,b oth of which compromise the atom-economy and other appealing features of these methods.S everal distinct mechanistic approaches have been investigated in these electrochemical HLF-type reactions ( Figure 1A): i) stepwise ET-PT-ET to generate ab enzyl cation, which reacts with an appended nitrogen nucleophile, [12] ii)proton-coupled electron transfer (PCET) to generate an itrogen-centered radical that promotes 1,5-HAT, similar to the key C À Hactivation step in the HLF reaction, [13] and iii)bromide-mediated formation of an N-bromo intermediate that undergoes thermal NÀBr homolysis to achieve the key 1,5-HATs tep. [14,15] Each of these examples exhibits limited functional-group compatibility owing to the requirement for high anode potentials ( Figure 1B). These issues could be addressed by using am ediator that undergoes regeneration at lower potentials.Anumber of modified HLF reactions have been reported with stoichiometric chemical oxidants,c atalytic I 2 ,a nd visible-light illumination, [11] raising the possibility that iodide could be used as an electrochemical mediator ( Figure 1A iv ).…”