Electrocatalytic Access to Azetidines via Intramolecular Allylic Hydroamination: Scrutinizing Key Oxidation Steps through Electrochemical Kinetic Analysis

Abstract

Azetidines are prominent structural scaffolds in bioactive molecules, medicinal chemistry, and ligand design for transition metals. However, state-of-the-art methods cannot be applied to intramolecular hydroamination of allylic amine derivatives despite their underlying potential as one of the most prevalent synthetic precursors to azetidines. Herein, we report an electrocatalytic method for intramolecular hydroamination of allylic sulfonamides to access azetidines for the first time. The merger of cobalt catalysis and electricity enables the regioselective generation of key carbocationic intermediates, which could directly undergo intramolecular C–N bond formation. The mechanistic investigations including electrochemical kinetic analysis suggest that either the catalyst regeneration by nucleophilic cyclization or the second electrochemical oxidation to access the carbocationic intermediate is involved in the rate-determining step (RDS) of our electrochemical protocol and highlight the ability of electrochemistry in providing ideal means to mediate catalyst oxidation.

Co-Catalyzed Hydrofluorination of Alkenes: Photocatalytic Method Development and Electroanalytical Mechanistic Investigation

“…However, it can subsequently be oxidized to Co IV –alkyl, which constitutes a masked, stabilized carbocation that undergoes selective nucleophilic substitution. Indeed, the formation of Co IV –alkyl complexes from the corresponding Co III –alkyl has recently been interrogated by Zhu, Ohmiya, Kim, Zhang, Pronin, Holland, and Shigehisa to enable nucleophilic substitution to form C–O, C–N, and C–C bonds. We envision that this reactivity may be extended to fluorination using F – as the nucleophile.…”

Mechanism of Alkene Hydrofunctionalization by Oxidative Cobalt(salen) Catalyzed Hydrogen Atom Transfer

“…A variety of silanes have been used in oxidative MHAT catalysis, including PhSiH 3 , PhMeSiH 2 , Et 2 SiH 2 , and (Me 2 SiH) 2 O. − The oxidant is usually an N -fluoro-2,4,6-trimethylpyridinium ( N -fluorocollidinium) salt, but some methodologies utilize other oxidants such as N -fluorobenzenesulfonimide (NFSI), peroxybenzoates, or iodine­(III) reagents. ,− Oxidative MHAT catalysis most often employs intramolecular nucleophiles, which are typically neutral O- and N-donor Lewis bases. These intramolecular reactions can afford epoxides, aziridines, lactones, lactams, ethers, pyrrolidines, and even benzocyclic compounds. ,,− Intermolecular reactions can add greater diversity to the products, and a few examples have been reported with alcohols, secondary amines, triazoles, or benzoic acids serving as the nucleophilic coupling partners. ,,,− Many solvents and functional groups are compatible with the reaction, and oxidative MHAT catalysis seldom requires temperatures above 25 °C, making it quite facile.…”

Electrohydrogenation of Nitriles with Amines by Cobalt Catalysis

“…Using earth-abundant cobalt-hydride as an example, the Co III À H could be generated by electroreduction of Co(II) precatalyst to low valent Co(I) and followed by protonation in an acidic medium. [6] Related to this strategy, Hisaeda, [7] Baran, [8] Lin [9] and others [10] demonstrated that this electrogenerated Co III À H could be intercepted by a hydrogen atom transfer (HAT) pathway, reacting with an alkene or alkyne to achieve hydrogenations and hydrofunctionalizations. [11] In addition to non-polar unsaturated bonds, the selective electroreduction of polar unsaturated bonds, such as carbonyl compounds is also highly demanded.…”