Synthesis of 1H-indazoles by an electrochemical radical C_sp²–H/N–H cyclization of arylhydrazones

Abstract

The development of efficient and sustainable C-N bond-forming reactions to N-heterocyclic frameworks has been a long-standing interest in organic synthesis. In this work, we develop an electrochemical radical Csp2-H/N-H cyclization...

Electrochemical Amidation: Benzoyl Hydrazine/Carbazate and Amine as Coupling Partners

“…Benzyl amines such as 1-phenylethane-1-amine (17a, 71%), (3-(trifluoromethyl)phenyl)methanamine (18a, 72%), and furan-2-ylmethanamine (19a, 60%) provided their benzoylated products when reacted with benzoyl hydrazine (a). The 2-(aminomethyl)aniline (20) having two primary amino groups, one attached to the aryl moiety and the other at the benzylic position, preferentially benzoylated at the benzylic site giving product (20a) in 65% yield without affecting the aromatic amine. This methodology was equally successful for other primary alkyl amines having substituted aromatic (21−23) and heteroaromatic ( 24) pendants and all effectively underwent amidation giving their amides 21a (72%), 22a (69%), 23a (51%), and 24a (65%), respectively.…”

“…The solvent HFIP interacts via hydrogen bonding with the N-H of the benzoyl hydrazine (a). 20 Similarly, the amine morpholine (a) is activated via an Hbonding interaction with the HFIP, and subsequent anodic oxidation generates N-centered radical intermediate (E). 19a Finally, radical−radical cross-coupling between intermediates D and E afforded the amide 1a.…”

“…Amidic bonds have been successfully constructed using C-protected amino acids such as L-proline methyl ester (26) and L-phenylalanine methyl ester (27) giving amides 26a (70%) and 27a (75%) in good yields. The primary aromatic amine, such as aniline (28), failed to react, which is consistent with the selectivity observed for the substrate 2-(aminomethyl)aniline (20), where one of the amino groups was selectively benzoylated using benzoyl hydrazine (a). Besides aniline (28), other N-H containing heterocycles such as imidazole (29), tetrazole (30), indole (31), benzamide (32), and ammonia (33) were completely unsuccessful.…”

Recent Advances to Mediate Reductive Processes of Nitroarenes Using Single-Electron Transfer, Organomagnesium, or Organozinc Reagents

“…In 2021, Lei and co-workers published an electrochemical reductive method to access diaryl amines from aryl boronic acids and nitroarenes (Scheme 27 ). 87 The authors discovered that the optimal conditions for the reductive cross-coupling reaction employed a platinum plate anode and a carbon cloth cathode in an undivided cell under 10 mA constant current using an 80:1:1 mixture of HFIP, acetonitrile, and formic acid. Using a different cathode (e.g., nickel plate) or a different anode (e.g., carbon cloth) led to a diminished yield of diaryl amine 176a .…”

Metal-Free Synthesis of N-Heterocycles via Intramolecular Electrochemical C-H Aminations

“…The reported methods for the synthesis of 1H-indazoles are limited by the use of metal catalysts at high temperature or stoichiometric chemical oxidants such as Oxane. To circumvent these limitations, Lei and co-workers developed an electrochemical strategy for the synthesis of 1H-indazoles under metal-free conditions ( Wan et al, 2022 ). This intramolecular cyclization was carried out in an undivided cell with platinum plates as the electrodes and n -Bu 4 NBF 4 /DCM/HFIP as the electrolyte solution under CCE conditions.…”