.
Angewandte
Communications
II
originally reported by Buchwald et al. were modified Table 2: Substrate scope for the Cu -catalyzed Chan–Lam coupling reaction of
aniline derivatives 1a–1l and electron-deficient aryl boronic acids 2a–2k under
visible-light-mediated photoredox catalysis.
slightly by introducing fac-[Ir(ppy) ]as a co-catalyst
3
[
a]
under blue LED irradiation, the desired N,N-diaryl
amine 3a was obtained in moderate yield (entry 1).
By screening various solvents (entries 2–6), we found
that the visible-light-mediated Chan–Lam reaction
occurred efficiently in nitrile-based solvents
(
entries 5–6). Furthermore, because of the difficul-
1
2
[b]
Entry
Ar
Ar
Product
Yield [%]
ties associated with removing benzonitrile, we re-
examined the solvents and found that a 1:1 mixture
of toluene and acetonitrile provided the desired
product 3a in excellent yield (entry 7). Finally, we
performed control experiments and determined that
the copper catalyst, the visible-light photoredox
catalyst, and blue LED irradiation were all essential
components of the aerobic oxidative CÀN coupling
1
2
3
4
5
6
7
8
9
Ph (1a)
4-Cl-C H (2a)
4-Cl-C H (2a)
6 4
4-Cl-C H (2a)
6 4
4-Cl-C H (2a)
6 4
3a
3b
3c
3d
3e
3 f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
93 (7)
100 (23)
95 (11)
100 (12)
43 (37)
91 (7)
100 (9)
71 (15)
42 (11)
47 (13)
72 (15)
55 (10)
79 (12)
89 (12)
85 (19)
43 (5)
6
4
4-Me-C H (1b)
6
4
3-Me-C H (1c)
6
4
2-Me-C H (1d)
6
4
4-MeO-C H (1e)
4-Cl-C H (2a)
6
4
6
4
4-Br-C
H
(1 f)
4-Cl-C
H
4
(2a)
6
4
6
4-Cl-C H (1g)
4-Cl-C H (2a)
6
4
6
4
4-CN-C H (1h)
4-Cl-C H (2a)
6
4
6
6
4
4
[
10]
4-CO
2
Et-C
6
H
4
(1i)
4-Cl-C
H
(2a)
reaction.
1
1
1
0
1
2
4-Ac-C H (1j)
4-Cl-C H (2a)
6
4
6
4
With the optimized conditions in hand, we
4-CF
3
-C
6
H
4
(1k)
4-Cl-C
6
H
4
(2a)
II
examined the substrate scope of the Cu -catalyzed
3,5-Cl -C H (1l)
4-Cl-C H (2a)
6 4
2
6
3
aerobic coupling reaction between primary aryl 13
amines 1a–1l with electron-deficient aryl boronic 14
acids 2a–2i under visible-light-mediated photoredox
conditions (Table 2). When aniline derivatives 1a–
Ph (1a)
4-F-C H (2b)
6
4
Ph (1a)
Ph (1a)
Ph (1a)
Ph (1a)
Ph (1a)
Ph (1a)
Ph (1a)
Ph (1a)
Ph (1a)
4-Br-C
H
4
(2c)
6
15
16
17
18
19
4-CF -C H (2d)
3 6 4
4-CN-C H (2e)
6
4
4-Ac-C H (2 f)
47 (18)
62 (19)
65 (17)
<5 (<2)
6
4
1
d, which bear slightly electron-donating substitu-
4-CO Me-C H (2g)
2
6
4
ents, were subjected to the Chan–Lam reaction with
3-Cl-C H (2h)
3s
3t
3u
3v
6
4
4
-chlorophenylboronic acid (2a), the desired N,N- 20
2-Cl-C H (2i)
6
4
[
c]
c]
[12]
diaryl amines 3a–3d were obtained in excellent 21
yields (entries 1–4). On the other hand, when para-
anisidine (1e) was utilized as a substrate, the yield
Ph (2j)
100
[
[8]
22
4-MeO-C H (2k)
76 (70)
6
4
[a] Reaction conditions: 1 (0.25 mmol), 2 (0.38 mmol), Cu(OAc) (0.025 mmol,
2
was moderate, and there was virtually no difference 10 mol%), myristic acid (0.050 mmol, 20 mol%), fac-[Ir(ppy) ] (0.0025 mmol,
3
between the visible-light-mediated conditions and 1 mol%), 2,6-lutidine (0.25 mmol), toluene/MeCN (1:1, 1.0 mL), 358C, 20 h, open
air, blue LED irradiation. [b] Yield of isolated products 3a–3v based on the amounts
of 1a–1l. Yields shown in parentheses are of the isolated products 3a–3t for the
the control reaction (entry 5). Whereas the halogen-
substituted aniline derivatives 1 f and 1g proved to
reactions performed in the absence of fac-[Ir(ppy) ] and blue LED irradiation.
3
be excellent coupling partners for the aerobic CÀN
[
c] Using 5 mol% of Cu(OAc) and 10 mol% of myristic acid.
2
bond-forming reaction (entries 6 and 7), the more
electron-deficient anilines 1h–1l provided the
desired products in moderate to good yields
[13]
(
entries 8–12). Next, we investigated different electron-defi-
Scheme 1. Initially, the Cu catalyst could undergo ligand
exchange and transmetalation with aromatic amine 1 and aryl
boronic acid 2 to generate Cu amide A. Concurrently, a light-
induced metal-to-ligand charge transfer of fac-[Ir(ppy)3]
would result in the formation of photoexcited complex 4
cient aryl boronic acids. We found that aryl boronic acids
substituted with halogens (2b and 2c) were viable substrates
to furnish the N,N-diaryl amines 3m and 3n in good to
excellent yields (entries 13 and 14). In contrast, visible-light-
mediated Chan–Lam reactions with the electron-poor aryl
boronic acids 2e and 2g were only moderately successful in
most cases (entries 15–18). We also examined the effect of
different chlorine substitution patterns and found that the
meta-substituted aryl boronic acid 2h provided the desired
product 3s in modest yield (entry 19), whereas 2-chlorophe-
nylboronic acid (2i) showed very poor reactivity (entry 20).
Although our studies had thus far focused on Chan–Lam
coupling reactions of aniline derivatives 1a–1l with the
electron-deficient aryl boronic acids 2a–2i, we also examined
the more electron-rich aryl boronic acids 2j and 2k and found
them to be viable substrates to provide the corresponding
N,N-diaryl amines 3u and 3v in good to excellent yields
IV/ III
[1e]
(E1/2
*
= À1.73 V vs. SCE), which could be oxidatively
[14]
quenched with O (E
the oxidizing Ir complex 5 and generate superoxide. Based
= À0.92 V vs. SCE) to produce
2
1/2red
[
11]
[15]
on our working hypothesis, this single-electron oxidant could
III
facilitate the oxidation of Cu amide A to the key Cu
[16]
intermediate B,
which regenerates the fac-[Ir(ppy) ] to
3
complete the photoredox catalytic cycle. Reductive elimina-
tion of B would furnish the desired cross-coupling product 3
I
and a Cu salt, which, upon oxidation by air, would regenerate
II
the Cu catalyst to complete the Cu catalytic cycle. Two
III
potential pathways to access the reactive Cu intermediate B
through single-electron oxidation by a photoexcited [Ir(ppy)3]
complex can be considered. In the first case, the direct
[
12]
II
(
entries 21 and 22).
A tentative mechanism for the fac-[Ir(ppy) ]-catalyzed
Chan–Lam coupling reaction of aromatic amines 1 and aryl
boronic acids 2 under blue LED irradiation is shown in
oxidation of Cu amide A by either the photoexcited
III/II
[Ir(ppy) ]* 4 (E *
= 0.31 V vs. SCE) or the oxidatively
3
3
1/2
+
IV/III
[1e]
quenched [Ir(ppy)3] 5 (E1/2
= 0.77 V vs. SCE)
is
III
possible to generate the key Cu intermediate B. Conversely,
2
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2015, 54, 1 – 5
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