Alternating Current Electrolysis Enabled Formal C−O/O−H Cross‐Metathesis of 4‐Alkoxy Anilines with Alcohols

Abstract

While multiple bond metathesis reactions, for example olefin metathesis, have seen considerable recent progress, direct metathesis of traditionally inert C−O single bonds is extremely rare and particularly challenging. Undoubtedly, metathesis reaction of C−O bonds is one of the most ideal routes for the value‐added upgrading of molecules involving C−O bonds. Reported here is a new protocol to achieve the formal C−O/O−H cross‐metathesis via alternating current electrolysis. Featuring mild reaction conditions, the protocol allows readily available 4‐alkoxy anilines and alcohols to be converted into a wide range of valuable products in highly regioselective and chemoselective manner. Moreover, the present strategy can be used in the late‐stage modification of pharmaceuticals as well as biologically active compounds, which demonstrated the potential application.

Controlling One- or Two-Electron Oxidation for Selective Amine Functionalization by Alternating Current Frequency

“…Tetrahydroisoquinoline alkaloids are an important class of bioactive natural products and display a myriad of biological activities. [26][27] N-aryl ring bearing electron-donating and electron-withdrawing groups such as methoxy, fluoro, dioxine, dimethyl, trifluoromethyl (20)(21)(22)(23)(24)(25)(26) and N-benzyl (27) all afforded arylated and cyanation products (20a-27a and 20b-27b). Under DC electrolysis, formation of cyanation product was predominantly observed in good yield 36-63% because the benzylic position is prone to overoxidation to form iminium cation.…”

“…More recently, AC electrolysis, where the flow of charge periodically changes direction, started to gain interest in the organic synthesis community. [13][14][15][16][17][18][19][20][21] One of the experimentally observed properties of AC electrolysis is its ability to reduce over-oxidation/reduction products without using any mediators relative to its direct current (DC) counterpart. 18 For example, Sattler et al 15 demonstrated that AC electrolysis solved the problem of the over-oxidation of disulfides to oxo species and over-reduction of disulfides to unidentified black precipitate in synthesizing unsymmetrical disulfides by an electrochemical sulfur-sulfur bond metathesis reaction.…”

Rapid identification of the short-lived intermediates in alternating-current electrolysis by mass spectrometry

“…30 Recently, the novel C–O/O–H cross-metathesis of 4-alkoxy anilines with alcohols under AC electrolysis was reported by Lei et al for late-stage modification of 4-alkoxy anilines. 14 A brief illustration of the proposed reaction mechanism is shown in Fig. 3.…”

“…10 Unlike direct-current (DC) electrolysis, the periodically polarityswitching feature of alternating-current (AC) electrolysis allows oxidation and reduction processes to take place sequentially on the same electrode. [11][12][13][14] The newly electrogenerated intermediates thus do not have to migrate between the two electrodes, enabling short-lived intermediates to react immediately upon the polarity reversal. In addition, AC electrolysis can also provide possibilities for unique chemoselectivity and high yields in certain circumstances via the fine-tuning of frequency, waveform, and potential along with other reaction parameters.…”

“…In addition, AC electrolysis can also provide possibilities for unique chemoselectivity and high yields in certain circumstances via the fine-tuning of frequency, waveform, and potential along with other reaction parameters. 15 Although it has been successfully applied to organic synthesis, 11,14,15 water splitting, 16 and electrochemiluminescence, 17,18 mechanistic insights into AC electrolysis remain largely unexplored due to the elusive lifetimes and ultrahigh reactivities of the electrogenerated intermediates. Cyclic voltammetry, electron paramagnetic resonance spectroscopy, and product analysis using various spectroscopic approaches have been extensively applied to gain mechanistic understandings on AC electrolysis.…”