Selective arylation/annulation cascade reactions of 2-alkynylanilines with diaryliodonium salts

Article abstract of DOI:10.1016/S1872-2067(16)62522-6

An efficient Cu catalyzed selective arylation/annulation cascade reaction of 2-alkynylanilines with diaryliodonium salts was developed. This reaction was selective to N-arylation instead of C-arylation, which provides a simple synthetic method for N-aryl indoles.

Full text of DOI:10.1016/S1872-2067(16)62522-6

Chinese Journal of Catalysis 37 (2016) 1837–1840
a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m
j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / c h n j c
Communication
Selective arylation/annulation cascade reactions of
2‐alkynylanilines with diaryliodonium salts
YingDuan a,b,*, YanliangYang b, XiaoyuDai b, DongmiLi b
a College of Food and Drug, Luoyang Normal University, Luoyang 471934, Henan, China
b College of Chemistry and Chemical Engineering, Henan Key Laboratory of Function‐Oriented Porous Materials, Luoyang Normal University, Luoyang
471934, Henan, China
A R T I C L E I N F O
A B S T R A C T
Article history:
An efficient Cu catalyzed selective arylation/annulation cascade reaction of 2‐alkynylanilines with
diaryliodonium salts was developed. This reaction was selective to N‐arylation instead of
C‐arylation, which provides a simple synthetic method for N‐aryl indoles.
© 2016, Dalian Institute of Chemical Physics, Chinese Academy of Sciences.
Published by Elsevier B.V. All rights reserved.
Received 16 July 2016
Accepted 13 September 2016
Published 5 November 2016
Keywords:
Selective arylation
Annulation
Diaryliodonium salt
2‐Alkynylaniline
N‐Aryl indole
Cascade reaction
Diaryliodonium salts are used in versatile organic transfor‐
mations because of their highly electron‐deficient nature and
excellent leaving‐group ability [1]. As mild, nontoxic, and selec‐
tive reagents, they are competent arylating agents in organic
synthesis [2,3], especially in constructing C−C [4–13] and C−X
[14–17] bonds. Among these, nucleophilic substitution reac‐
tions between diaryliodonium salts with nitrogen nucleophiles
have received much attention [18–21]. Recently, Guant’s group
[7] reported aromatic electrophile equivalents generated from
the combination of diaryliodonium salts and copper catalysts
via the intermediacy of Cu(III)–aryl species. These active spe‐
cies were considered to be responsible for the high activity of
the diaryliodonium salts in Cu catalyzed reactions.
cally important compounds [22]. Consequently, much attention
has been paid to their preparation, which is a major research
area in organic synthesis and many methods have been devel‐
oped [23]. Meanwhile, the cyclization of 2‐alkynylaniline deriv‐
atives has long been exploited for the construction of indoles
[24,25].
Although diaryliodonium salts have been applied to a num‐
ber of arylation reactions with substrates possessing single
nucleophilic group, the selective arylation of the substrates
with two or more nucleophilic groups is still a challenging sub‐
ject [4,6]. For example, it was disclosed that although
C‐arylation and N‐arylation can be achieved by diaryliodonium
salts, the selectivity is still a challenge. The key to solving this is
how to exploit the difference in the nucleophilic groups. Here,
we reported an example of a selective N‐arylation reaction of
2‐alkynylanilines with diaryliodonium salts where subse‐
Indoles are one of the most ubiquitous heterocycles found in
nature. Owing to their significant biological activity, indoles are
central structural motifs in making numerous pharmacologi‐
* Corresponding author. Tel/Fax: +86‐379‐68618516; E‐mail: duanying7@163.com
This work was supported by the Intercollegiate Key Scientific Research Projects of Henan Province (15A150018).
DOI: 10.1016/S1872‐2067(16)62522‐6 | http://www.sciencedirect.com/science/journal/18722067 | Chin. J. Catal., Vol. 37, No. 11, November 2016

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YingDuan et al. / Chinese Journal of Catalysis 37 (2016) 1837–1840
tion was also examined. The result showed that DCE was the
best choice while a decreased yield of the desired product was
observed in solvents such as toluene, CH2Cl2, CHCl3 and THF
(Table 1, entries 13–16). The counter‐ions of the diphenylio‐
donium salt were also evaluated. The result showed that di‐
phenyliodonium traflate was superior to diphenyliodonium
chloride, diphenyliodonium hexafluorophosphate and diphe‐
nyliodonium tetrafluoroborate (Table 1, entries 17–19).
With these optimized reaction conditions in hand, we next
elucidated the substrate scope of the cascade reaction. First,
various o‐alkynylanilines 1 with diphenyliodonium triflate (2a)
were employed in the reaction. The results are compiled in
Scheme 2. Generally, the reactions proceeded smoothly to af‐
ford the corresponding indoles 3 in isolated yields of
79%–97%. The reaction went well when R1 = aryl group while
the electronic nature of the substituent on the benzene ring of
R1 was varied. Both electron‐withdrawing and elec‐
tron‐donating groups were tolerated. Notably, it was found that
alkynes bearing alkenyl (R1 = alkenyl group) or alkyl groups (R1
= alkyl group) on the alkyne terminus were also compatible,
providing the products 3e–3g in good to excellent yields of
79%–92%. Substitution with 4‐Me or 4‐Cl functionalities on the
parent aryl ring also afforded 3h and 3i in high yields of 89%
and 97%, respectively.
The scope of the reaction was also investigated by varying
the diaryliodonium triflate. The results are summarized in
Scheme 3. Interestingly, the sterically demanding
di(o‐methylpheny)liodonium triflate 2b gave product 4b in
good yield (82%). Higher yields (4c–4f) were obtained with
less sterically demanding diaryliodonium triflates. Also, the
substituent nature of R1 has some influence on the reaction (4f
vs 4g). Substrates with substituent on the benzene ring (1h)
reacted with diaryliodonium triflate to afford 4h with good to
excellent yields (82% and 98%, respectively).
Scheme 1. Reaction of 2‐alkynylaniline (1a) and diphenyliodonium salt
(2a).
quently the untouched C‐nucleophile behaved as another reac‐
tive site to complete arylation‐annulation cascade reactions to
afford N‐aryl indoles [26–28] (Scheme 1).
We first examined the reaction of 2‐(phenylethynyl)aniline
(1a) and diphenyliodonium triflate (2a). First, to overcome the
possible competition of N‐arylindoles and C‐arylation,
1,2‐dichloroethane (DCE) was placed on the top of the solvent
list because it has been demonstrated to favor N‐aryltaion [4].
No reaction occurred when the metal catalyst was omitted. A
Cu catalyst system has been shown to be effective in both the
arylation and annulation of 2‐alkynylanilines [29]. Both cop‐
per(I) and copper(II) salts were effective for this reaction, and
the use of 10 mol% Cu(OCOC8H17)2 (copper 2‐ethylhexoate)
gave the desired product 3a in 93% yield. Meanwhile, the use
of CuCl, CuBr, CuI, CuSCN and Cu(OTf)2 resulted in decreased
yields (Table 1, entries 1–8). Then the screening of the base
exhibited that N,N‐diisopropylethylamine (DIPEA) was more
effective than the other bases (Et3N, K2CO3, KOtBu and K3PO4,
Table 1, entries 9–12). The influence of the solvent on the reac‐
Table 1
Optimization of the reaction conditions.
The reaction of 1a and unsymmetric diaryliodonium salt 2i
was also evaluated. Aryl with a lesser steric effect could be
transferred to 1a, and 4i was obtained in 80% yield (Scheme
4).
Entry
1
2
3
4
5
6
7
8
[Cu]
—
CuCl
CuBr
Base
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
Et3N
Solvent Yield a (%)
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
<5
56
61
67
67
80
61
93
69
<5
26
<5
69
56
35
20
22
48
43
CuI
CuSCN
CuBF4(MeCN)4
Cu(OTf)2
Cu(OCOC8H17)2
Cu(OCOC8H17)2
Cu(OCOC8H17)2
Cu(OCOC8H17)2
Cu(OCOC8H17)2
Cu(OCOC8H17)2
Cu(OCOC8H17)2
Cu(OCOC8H17)2
Cu(OCOC8H17)2
Cu(OCOC8H17)2
Cu(OCOC8H17)2
Cu(OCOC8H17)2
9
10
11
12
13
14
15
16
17 b
18 c
19 d
K2CO3
KOtBu
K3PO4
DIPEA Toluene
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
CH2Cl2
CHCl3
THF
DCE
DCE
DCE
Reaction conditions: 1a (0.2 mmol), 2a (0.4 mmol), [Cu] (10 mol%),
base (0.4 mmol), solvent (2.0 mL), 1 h. a Isolated yields. b Diphenylio‐
donium chloride used. c Diphenyliodonium hexafluorophosphate used.
d Diphenyliodonium tetrafluoroborate used.
Scheme 2. Synthesis of N‐phenyl indoles (3a–3i). Reaction conditions:
1 (0.2 mmol), 2a (0.4 mmol), Cu(OCOC8H17)2 (10 mol%), DIPEA (0.4
mmol), solvent (2.0 mL), 1 h.

YingDuan et al. / Chinese Journal of Catalysis 37 (2016) 1837–1840
1839
Scheme 6. Mechanism of the cascade reaction.
were tolerated to afford a large scope of N‐aryl indoles with
good to excellent yield. The reaction was shown to be the selec‐
tive N‐arylation first and then heteroannulation.
Scheme 3. Synthesis of N‐arylindole (4b–4h). Reaction conditions: 1
(0.2 mmol), 2 (0.4 mmol), Cu(OCOC8H17)2 (10 mol%), DIPEA (0.4 mmol)
solvent (2.0 mL), 1 h.
Acknowledgments
The authors thank Prof. Yonggui Zhou and Dr. Wenxue
Huang for chemical reagents and helpful discussions.
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YingDuan et al. / Chinese Journal of Catalysis 37 (2016) 1837–1840
Graphical Abstract
Chin. J. Catal., 2016, 37: 1837–1840 doi: 10.1016/S1872‐2067(16)62522‐6
Selective arylation/annulation cascade reactions of
2‐alkynylanilines with diaryliodonium salts
Ying Duan *, Yanliang Yang, Xiaoyu Dai, Dongmi Li
Luoyang Normal University
An efficient Cu catalyzed selective arylation/annulation cascade re‐
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