aromatic CꢀH bond to generate aryl gold(III) species.8
Several AuCl3-catalyzed CꢀC bond-forming reactions
have been suggested to follow the direct auration
pathway.9 We have recently reported a highly efficient
AuCl3-catalyzed halogenation of aromatics by N-halo-
succinimide.10 To account for the extraordinary high
catalytic efficiency of this reaction, a dual activation mode
has been proposed. Herein we further demonstrate that
AuCl3 is also a highly efficient catalyst in the direct
acetoxylation of arenes with iodobenzene diacetate.11,12
A dual activation process may also operate with direct
auration of aromatic substrates and activation of PhI-
(OAc)2 through complexation.
At the outset of the investigation, mesitylene 1a was
employed as the substrate to react with PhI(OAc)2 in the
presence of AuCl3 (2 mol %) in 1,2-dichloroethane at
different temperatures. We observed that the reaction was
highly sensitive to temperature (Table 1, entries 1, 2). At
60 °C, only a trace amount of product could be detected,
while, at 80 °C, we could isolate the acetoxylation product
in moderately high yield (entry 2). However, di- and
triacetoxylation products were also observed. The over-
acetoxylation problem could be easily circumvented by
employing an excess amount of aromatic substrates
(entries 4ꢀ7). It was also observed that the reaction time
could be significantly shortened by carrying it out at 110 °C.
Reducing the Au(III) catalyst loading to 1 mol %
resulted in a longer reaction time and slightly diminished
yield (entry 8). The solvents were found to significantly
affect the reaction, and the initially used DCE provided the
optimal results (entries 9ꢀ11). Finally, for comparison we
also carried out the reaction under Fe(III)- and Pd(II)-
catalyzed conditions, and under strong acidic conditionsas
well. None of them afforded the expected acetoxylation
products(entries 12ꢀ17). Thecontrol experiment indicates
thatnoreactionoccursin the absenceofcatalyst(entry17).
With the optimal reaction conditions in hand, we pro-
ceeded to extend the scope of the reaction, and the results
are summarized in Table 2. The reaction is general for
electron-rich aromatics. For the substrates bearingthree or
more methyl groups, the acetoxylation all worked well
with 2 mol % AuCl3 catalyst, even for the substrates
bearing halogen substituents or an acetyl group (entries
4ꢀ6). When the strong electron-withdrawing group CN
was present, a slightly higher catalyst loading was required
(entry 7). The aromatic substrates bearing only two methyl
substituents require a higher catalyst loading and the
reaction took a longer time (entry 8). The diminished yield
in this case was due to the formation of homocoupling of
p-xylene.13,14 Interestingly, the acetoxylation also worked
with toluene derivatives bearing electron-withdrawing
substituents (entries 11, 12). However, an acetoxylation
product could not be identified with toluene itself as
substrate.
The AuCl3-catalyzed conditions could also be applied
to the aromatic substrates bearing methoxy groups,
although a slightly higher catalyst loading was required.
It was also observed that the reaction showed excellent
regioselectivities. Thus, the reaction with anisole provided
the product with an acetoxy group introduced to the para
position. For all other substituted anisole substrates, the
regioselectivity of the acetoxylation is dominated by the
methoxy substituent.
To gain insight into the reaction mechanism, kinetic
isotope effect (KIE) experiments have been carried out in
both an inter- and intramolecular manner. For the inter-
molecular experiment, an inverse KIE of 0.92 was ob-
served (eq 1), while the corresponding intramolecular
experiment afforded an inverse KIE of 0.83 (eq 2). For
Table 1. AuCl3-Catalyzed Reaction of Mesitylene 1a and
PhI(OAc)2
a
catalyst
(mol %)
temp
t
yield
(%)b
entry
ratio
solvent
(°C)
(h)
1
1:1.2
1:1.2
1:1.5
1.5:1
2.0:1
2.5:1
3.0:1
2.5:1
2.5:1
2.5:1
2.5:1
1.5:1
1.5:1
2.5:1
2.5:1
2.5:1
2.5:1
AuCl3(2)
AuCl3(2)
AuCl3(2)
AuCl3(2)
AuCl3(2)
AuCl3(2)
AuCl3(2)
AuCl3(1)
AuCl3(5)
AuCl3(5)
AuCl3(5)
FeCl3(20)
FeBr3(20)
Pd(OAc)2(5)
AcOH(200)
H2SO4(200)
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DMF
CH3CN
AcOH
DCE
DCE
DCE
DCE
DCE
AcOH
60
80
24
24
24
12
12
12
12
24
24
12
24
24
24
24
24
24
24
trace
56c
68c
61c
72
2
3
80
4
110
110
110
110
110
110
110
110
80
5
6
75
7
69
(9) (a) Li, Z.; Capretto, D. A.; Rahaman, R. O.; He, C. J. Am. Chem.
Soc. 2007, 129, 12058. (b) Shi, Z.; He, C. J. Org. Chem. 2004, 69, 3669. (c)
Shi, Z.; He, C. J. Am. Chem. Soc. 2004, 126, 5964. (d) Shi, Z.; He, C.
J. Am. Chem. Soc. 2004, 126, 13596. (e) Reetz, M. T.; Sommer, K. Eur. J.
Org. Chem. 2003, 3485. (f) Dyker, G.; Muth, E.; Hashmi, A. S. K.; Ding,
L. Adv. Synth. Catal. 2003, 345, 1247. (g) Hashmi, A. S. K.; Schwarz, L.;
Choi, J. H.; Frost, T. M. Angew. Chem., Int. Ed. 2000, 39, 2285. (h) Luo,
Y.; Li, C.-J. Chem. Commun. 2004, 1930. (i) Sun, X.; Sun, W.; Fan, R.;
Wu, J. Adv. Synth. Catal. 2007, 349, 2151.
(10) (a) Mo, F.; Yan, J. M.; Qiu, D.; Li, F.; Zhang, Y.; Wang, J.
Angew. Chem., Int. Ed. 2010, 49, 2028. (b) Qiu, D.; Mo, F.; Zheng, Z.;
Zhang, Y.; Wang, J. Org. Lett. 2010, 12, 5474.
(11) For a recent report on AuCl3-catalyzed direct amination of
arenes, see: Gu, L.; Neo, B. S.; Zhang, Y. Org. Lett. 2011, 13, 1872.
(12) For a review on hypervalent iodine, see: Zhdankin, V. V.; Stang,
P. J. Chem. Rev. 2008, 108, 5299.
8
61
9
0
10
11
12
13
14
15
16
17
<5
53
0
80
0
110
110
110
110
trace
0
trace
trace
d
ꢀ
a Reaction conditions: mesitylene 1a, PhI(OAc)2 (1 mmol), solvent
(2 mL). The reaction was monitored by GC-MS. The ratio refers to 1a/
PhI(OAc)2. b Isolated yield based on PhI(OAc)2. c Di- and triacetoxyla-
tion products were observed. d No catalyst was used. DCE = 1,2-
dichloroethane, DMF = N,N-dimethylformamide.
(13) Kar, A.; Mangu, N.; Kaiser, H. M.; Tse, M. K. J. Organomet.
Chem. 2009, 694, 524.
(14) For detailed discussion on the acetoxylation and homocoupling,
see Supporting Information.
Org. Lett., Vol. 13, No. 19, 2011
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