Angewandte
Communications
Chemie
acyclic amine and six-membered piperidine was inefficient
under standard conditions. Thus modified conditions were
provided to perform the arylation (Scheme 2, 3v–3w).
Tertiary aliphatic amines were also viable substrates and
their selective arylation, thus further highlighted the synthetic
utility of this electrochemical approach, although satisfactory
yields were not obtained (Scheme 2, 3x–3ad). Direct aryla-
tion of triethylamine furnished 3x in 44% yield. Compound
3
y was also produced as a 4:1 mixture of regioisomers. It is
worth noting that an aryl group was regioselectively incorpo-
rated into N-benzyl aliphatic amines while the benzylic
methylene remained intact (Scheme 2. 3z–3ab). For cyclic
aliphatic amines, the arylation occurred preferentially at the
tetrahydropyrrole ring, as illustrated by 3ab–3ad.
Additionally, the scope with respect to analogues of 2a as
the aromatic partner was tested. Dicyano aromatic com-
pounds, including 1,4-dicyanobenzene, 2,5-dicyanotoluene,
and 4,4’-biphenyldicarbonitrile, readily underwent the cou-
pling with 1a to furnish corresponding products in moderate
to good yields (Scheme 2. 3ae–3ag). Since the elimination of
À
CN in 2,5-dicyanotoluene lacks regioselectivity, 3af is
produced as a 1:1 mixture of the two isomers. Benzonitriles
bearing ester and amide groups are also suitable substrates in
this electrochemical arylation (Scheme 2. 3ah–3ai). However,
some electron-deficient heteroaromatic compounds, such as
4
-cyanopyridine, 1-isoquinolinecarbonitrile, 2-chlorobenzox-
azole, and 2-chlorobenzothiazole, were not compatible with
this convergent paired electrolysis (see the Supporting
Information for details).
Figure 1. Cyclic voltammetry studies in 3 mL DMA (A) and CH CN (B,
3
À1
C, D, E; 0.1m nBu NClO ). A) 0.06 mmol 2a, 100 mVs ;
4 4
À1
B) 0.06 mmol 1m, 0.03 mmol I, 0.06 mmol 2,6-lutidine, 20 mVs
C) 0.06 mmol 1q, 0.03 mmol I, 0.06 mmol 2,6-lutidine, 20 mVs
D) 0.06 mmol 1m, 0.03 mmol I; E) 0.06 mmol 1q, 0.03 mmol I.
;
Compared with normal electrolysis, convergent paired
electrolysis is more dependent on mass transfer of reactive
species from the surface of electrodes to bulk solution. This
became the crucial factor in scale-up experiments. In order to
increase the concentration of a-amino radicals at the anode
and the collision frequency of anodic and cathodic inter-
mediates, a three-electrode system RVC(+)-RVC(À)-RVC-
À1
;
a similar interaction between 1q and TEMPO was also
detected at the same scanning rate (Figure 1C). However, the
cathodic peak gradually appeared as the scanning rate
À1
(+) was used and the distance between each electrode was as
increased from 10 to 200 mVs (Figure 1D). By contrast,
close as possible. In this way, the gram-scale electrochemical
arylation was performed on a 10 mmol scale and gave 1.52 g
the cathodic peak did not appear even at a scanning rate of
200 mVs when testing the interaction between TEMPO
À1
+
3
a in synthetically useful yield (see the Supporting Informa-
and 1m (Figure 1E). We thus presumed that the reaction rate
+
tion for details).
of TEMPO with 1q is much lower than that with the 1m
[
12]
In order to investigate the anodic and cathodic processes,
a series of cyclic voltammetry (CV) studies were conducted.
First, the electrochemical behavior of 2a was studied in 0.1m
DCB anion radical.
To further assess the convergent process of the electrolysis
reaction, a divided-cell experiment was carried out. Com-
pound 3a was not detected in the anode or cathode chambers.
However, the dimerization occurred and gave 8 in the anode
chamber (Scheme 3a). Next, under the standard conditions,
the electrolysis was carried out in the presence of 2.0 equiv of
9, which is used as a radical acceptor. This led to the formation
of 10 in 17% yield and impeded the generation of 3a
(Scheme 3b), thus indicating the existence of a-amino radical
À1
nBu NClO /DMA at 100 mVs . A couple of reversible redox
4
4
peaks were observed at À1.65 V, which corresponds to the
reduction of 2a to anion radical species 5, and À1.34 V, which
corresponds to the oxidation of anion radical species 5 to 2a
(
Figure 1A).
Then the CV curves of TEMPO and 1m were recorded.
The anodic peak of TEMPO was slightly increased but the
cathodic peak disappeared with the inclusion of 1m (Fig-
ure 1B), thus demonstrating that anodic formed TEMPO
reacted with 1m to generate the amino radical cation 6. The
involvement of 2,6-lutidine, which facilitates the deprotona-
tion of amino radical cation 6, shifted the electron transfer
equilibrium to TEMPO and greatly increased the catalytic
current (Figure 1F). The important role of 2,6-lutidine was
also shown in Table 1, entry 6. As depicted in Figure 1C,
[
13]
7. In the absence of anion radical 5, a-amino radical 7 could
be oxidized to iminium ion 12, which reacted with enamine
+
[
14]
intermediate to afford 8.
On the basis of the experimental studies above, a plausible
mechanism for the TEMPO-catalyzed arylation of a-amino
3
sp CÀH was proposed (Scheme 4). TEMPO is known to
[
5d]
+ [7e–g]
undergo single-electron oxidation to afford TEMPO ,
which reversibly oxidizes the tertiary arylamine to TEMPO
Angew. Chem. Int. Ed. 2019, 58, 1 – 6
ꢀ 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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