Communication
doi.org/10.1002/chem.202100960
Chemistry—A European Journal
hypervalent iodine in presence of hexafluoroisopropanol.[8] Very
recently, Powers and co-workers addressed this challenge using
iodine precursors as a redox mediator for CÀ N bond formations.
Here the selective anodic oxidation of iodine catalyst is carried
out in presence of the substrate and hence identified as in cell
method of CÀ H amination.[9] The electrochemistry with amidyl
radical demonstrate new advancements and many novel trans-
formations were discovered.[10] While the generation of nitre-
nium ion intermediates is a key step in different chemical
transformations, their electrochemical generation and applica-
tions in the synthesis of N-heterocycles are rare.[11]
To our knowledge, the only example so far is a characteristic
two-step oxidation of acetanilide derivatives reported by
Waldvogel and co-workers. They demonstrated that amidoaryl
substrates could be oxidized electrochemically to N-acyl radicals
and then to the corresponding nitrenium ion intermediates
leading to the corresponding benzoxazoles (Scheme 1c).[12]
Herein, we report a transition metal-free direct electrolytic
approach for C(sp2)À H amination, involving an electrochemically
generated nitrenium ion intermediate in the presence of an
in situ generated supporting electrolyte in substoichiometric
quantities (Scheme 1d). The attempts to reduce the use of
additional supporting electrolytes has been a key area of
research in electrochemistry as it considerably compliments the
concept of green and sustainable chemistry.[13] We investigated
the direct electrolysis of 2-acetamidobiphenyl (1a) in 1,1,1,3,3,3-
hexafluoroisopropanol (Table 1). The reaction did not proceed
to give the desired product (2a), instead we observed the
formation of the NÀ N dimer of 1a (entry 1). Previous reports
suggested that such products are formed by radical-radical
couplings.[14] This encouraged us to evaluate the effect of using
graphite electrodes for electrolysis because of their known
preference for two electron oxidations over the single electron
oxidation pathway (entry 2). To our delight, constant current
electrolysis using graphite electrodes in presence of potassium
tert-butoxide yielded 57% of the desired product 2a (entry 3).
Interestingly, the omission of tetrabutylammonium tetrafluor-
oborate from the reaction did not affect the outcome to a large
extent and did not interrupt the electrolysis with a higher
resistance as well (entry 4). Further screening of different
solvents, inorganic and organic bases (entries 5–10) revealed
sodium ethoxide as the better candidate under our electrolytic
conditions (entry 11). It is noteworthy to mention that we
consistently observed the formation of HFIP adducts of 1a as
side products throughout our optimization studies (see Sup-
porting Information for details).
Afterwards we evaluated the substrate scope of the electro-
oxidative intramolecular CÀ H amination using different 2-
amidobiaryl derivatives. The substitutions on different positions
of both rings were tolerated (scheme 2). Especially, different
substitutions on 4-position of the aniline ring (2c–2h) as well as
electron neutral and electron donating substituents on para
position of the phenyl ring (2l–2p) were well compatible under
our reaction conditions. Notably, for the first time, N-formyl-2-
aminobiphenyl substrate was transformed to the corresponding
carbazole derivative (2b) without the formation of a six
membered ring (phenanthridin-6-one) as reported in previous
studies.[15]
Substitution at 3’ position leads to a mixture of regioiso-
meric products in a ratio of 2.3:1 (2i and 2i’). In addition,
biphenyl substrates with 5-chloro or 2’-methyl substitutions
were transformed to the corresponding carbazoles (2j and 2k)
albeit in lower yields. To our delight, the substrates with a
polyaromatic ring as well as substitutions on both rings yielded
the corresponding carbazoles with moderate yields (2q and 2r).
The general trend in substrate scope and observations
made during the reaction studies (see Supporting Information
for details) indicated the electro-oxidative formation of a
nitrenium ion intermediate (Scheme 3). Such cationic nitrogen
intermediates can be observed in hypervalent iodine mediated
amination reactions.[6–7] A detailed cyclovoltammetric study of
anilide moieties had measured two distinct oxidation peaks
based on which a diyl mechanism was delineated before.[12]
Here, we speculated that the anodic oxidation of substrate 1a
produces a highly acidic cation radical A. Proton abstraction of
this cation radical by 1,1,1,3,3,3-hexafluoropropan-2-olate gen-
erated at cathode results in N-acyl radical intermediate B
formation. It is important to mention that a direct proton
abstraction from substrate 1a is not possible considering the
pKa value of the 1,1,1,3,3,3-hexafluoropropan-2-olate. This N-
acyl radical B further undergoes a second oxidation at the
anode with formation of nitrenium ion C. The rearomatization
of the intermediate D formed by nucleophilic attack of the aryl
ring to the nitrenium ion C afforded carbazole 2a. At this point,
another reaction possibility is a competitive formation of the
side product 6a. The added base in the reaction reacts with
hexafluoroisopropanol to form the salt which helps to eliminate
the requirement of an additional supporting electrolyte for
electrolysis.[16] This was confirmed by carrying out the reaction
Table 1. Optimization of reaction conditions.[a]
Entry
Base (equiv.)
Solvent
Yield[b]
1[c][d]
2[c]
3[c]
4
5
6
7
8
9
–
–
HFIP
HFIP
HFIP
HFIP
TFE
MeCN
HFIP
HFIP
HFIP
HFIP
HFIP
n.d.
trace
57
KOtBu (2)
KOtBu (1)
KOtBu (1)
KOtBu (1)
LiOtBu (1)
Et3N (2)
DBU (2)
NaOEt (1)
NaOEt (0.75)
52
n.d.
n.d.
59
56
45
60
63
10
11[e]
[a] Reaction conditions: constant current electrolysis (5 mA) for 3 h (~3.2 F/
mol) using graphite electrodes: 1a (0.2 mmol), solvent (0.06 M). [b] Isolated
yield. [c] n-Bu4NBF4 (0.2 mmol, 1 equiv.) as supporting electrolyte.
[d] Glassy carbon anode and platinum plate cathode. [e] 3 mA current
and 2.8 F/mol charge passed in 5 h. n.d.=not detected.
Chem. Eur. J. 2021, 27, 8008–8012
8009
© 2021 The Authors. Published by Wiley-VCH GmbH
Puthanveedu, Mahesh
