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.

Simultaneous Capture and Profile the Kinetic Changes of Short-Lived Reactive Electrochemical Reaction Intermediates by Time-Resolved Mass Spectrometry

“…29 electrosynthesis was reported (Figure 3a), but the reaction mechanism hasn't been fully illustrated due to the absence of the direct evidence of the key intermediates. 30 The proposed mechanism involving the two steps of electrooxidation and two steps of electroreduction on anode and cathode, respectively. 30 We envision that our platform using paired electrodes is quite suitable to study these electrochemical intermediates and processes of this reaction.…”

“…30 The proposed mechanism involving the two steps of electrooxidation and two steps of electroreduction on anode and cathode, respectively. 30 We envision that our platform using paired electrodes is quite suitable to study these electrochemical intermediates and processes of this reaction.…”

“…Then, the immediate reduction of A4 at the cathode to generate the final product 3 (Figure 3a). 30 As shown in Figure 3b and 3c, the nESTASI mass spectra of the reaction solution show only the peaks of ionized starting 4-alkoxy aniline 1 at m/z 292.1003 ([M+H] + , error 0.3 ppm), m/z 309.1273 4 ([M+NH4] + , error 1.9 ppm), m/z 314.0822 ([M+Na] + , error 0.3 ppm), and m/z 330.0562 ([M+K] + , error 0.3 ppm) when the EC power was off. However, the peaks of intermediates A1, A2, A3 and A4 were simultaneously observed at m/z 291.0926 (error 0.7 ppm), 290.0848 (error 1.0 ppm), 352.1214 (error 0.3 ppm), 320.0949 (error −0.6 ppm) at 0.4 min of electrochemical reaction, respectively, but the product 3 was hardly detected at this moment.…”

“…Electrosynthesis with alternating current (AC) is an emerging technology. [30][31][32] Given that this C−O/O−H cross-metathesis reaction was reported to have highly efficient when the AC was applied, we next used this transformative platform to study the process of this reaction in AC mode. To the best of our knowledge, this is the first time that the reactive intermediates of an AC-driven electrochemical reaction was studied by on-line mass spectrometry.…”