CL-190223
Received: March 20, 2019 | Accepted: April 13, 2019 | Web Released: May 25, 2019
Facile Synthesis of Diverse o-Iodoaryl Triflates from o-Silylaryl Triflates by
Aluminum-mediated Desilyliodination
Suguru Yoshida,* Yuki Hazama, Kazuya Kanemoto, Yu Nakamura, and Takamitsu Hosoya*
Laboratory of Chemical Bioscience, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU),
2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan
E-mail: s-yoshida.cb@tmd.ac.jp (S. Yoshida), thosoya.cb@tmd.ac.jp (T. Hosoya)
A convenient method for preparing diverse o-iodoaryl
triflates by the desilyliodination of o-silylaryl triflates has been
developed. The treatment of o-silylaryl triflates with 1,3-diiodo-
5,5-dimethylhydantoin (DIH) in the presence of aluminum
trichloride efficiently afforded the corresponding o-iodoaryl
triflates, including those with multiple 1-iodo-2-(triflyloxy)arene
moieties. Various multisubstituted o-iodoaryl triflates were
easily prepared by the iridium-catalyzed C-H borylation of
readily available, simple o-silylaryl triflates, followed by
deborylative transformations and subsequent desilyliodinaton.
arynophile
Me3SiCH2MgCl
A
A
B
aryne
transformation
I
FG
FG
FG
coupling
partner
cat. Pd
coupling
partner
cat. Pd
OTf
FG
A
A
B
sequential
cross-coupling
OTf
FG
B
Previous work
(pinB)2
cat. [Ir(OMe)(cod)]2
cat. dtbpy
OMe
OMe
OMe
SiMe3
SiMe3
OTf
DIH
SiMe3
Keywords: Desilyliodination
| Aluminum trichloride |
n-hexane
rt, 12 h
97%
OTf
pinB
FG
OTf
1a
1b
Aryne precursor
FG = Br, OH, N3, etc.
Me3SiOTf
CH2Cl2
rt, 4 h; 87%
o-Iodoaryl triflates are multipotent intermediates that are
beneficial for preparing various aromatic compounds via aryne
chemistry1-4 and sequential cross-coupling reactions.5 Hence, o-
iodoaryl triflates demonstrate wide applications for the synthesis
of natural products6 and organic materials.5b,7 In particular, the
transformations of arynes generated from o-iodoaryl triflates
have been widely employed for the synthesis of diverse multi-
substituted arenes. Recently, our group has reported a silyl-
methyl Grignard reagent as an efficient activator for generating a
wide range of arynes from o-iodoaryl triflates under mild
conditions.3 This method for generation of arynes exhibited
broad functional group tolerance, significantly expanding the
synthesizable aromatics via aryne intermediates (Figure 1A).
Although simple o-iodoaryl triflates have been easily prepared
from the corresponding phenol derivatives,8 the availability of
multisubstituted o-iodoaryl triflates is still limited. Herein, we
report a facile method for preparing various o-iodoaryl triflates
by the desilyliodination of o-silylaryl triflates.
O
I
N
(pinB)2
cat. [Ir(OMe)(cod)]2
cat. dtbpy
N
I
OMe
I
OMe
I
O
DIH
n-hexane
rt, 12 h
0%
OTf
pinB
OTf
2a
2b
C
DIH (1.5 equiv)
Me3SiOTf (1.5 equiv)
SiMe3
I
OTf
OTf
CH2Cl2
rt, 2 h
X
X
1c
2c 27%
Br 2d 36%
X = Cl
X = Cl
Br 1d
Figure 1. Transformations involving o-iodoaryl triflates. (A)
Synthesis of diverse arenes from o-iodoaryl triflates via aryne
intermediates and sequential cross-coupling. (B) Diversification
of simple o-silylaryl triflate 1a. (C) Initial attempts of
desilyliodination of o-silylaryl triflates 1c and 1d.
Previously, our group developed a facile method for
preparing diverse o-silylaryl triflates by the iridium-catalyzed
C-H borylation of simple o-silylaryl triflates such as 1a
(Figure 1B).9 During that study, we unexpectedly found that
the treatment of borylated o-silylaryl triflate 1b with 1,3-diiodo-
5,5-dimethylhydantoin (DIH) in the presence of trimethylsilyl
triflate selectively afforded o-iodoaryl triflate 2b in high yield,
leaving the boryl group untouched. In contrast, the iridium-
catalyzed C-H borylation of o-iodoaryl triflate 2a did not afford
2b. Based on these results, we anticipated that a wide variety of
o-iodoaryl triflates would be prepared by the C-H borylation of
o-silylaryl triflates followed by the desilyliodination. However,
our initial attempts of the desilyliodination of more electron-
deficient o-silylaryl triflates 1c and 1d compared to 1a using
DIH and trimethylsilyl triflate afforded the desired o-iodoaryl
triflates 2c and 2d in low yields (Figure 1C).
and the results revealed that aluminum trichloride (AlCl3) most
efficiently promotes the iodination using DIH most efficiently
among several of the tested Lewis acids (Table 1). The treatment
of 1c with 1.5 equiv each of DIH and AlCl3 in dichloromethane
at room temperature afforded 2-chloro-6-iodophenyl triflate
(2c) in high yield (Entry 1). Several other conditions reported
for desilyliodination using electrophilic iodination reagents10
with Lewis acids were less effective or ineffective except for
the combination of iodine monochloride and AlCl3 (Entry 9).
Considering the instability of iodine monochloride, a more user-
friendly DIH was selected as the iodinating reagent for the
desilyliodination of o-silylaryl triflates in subsequent studies.
The optimized conditions were successfully applied to
the desilyliodination of a wide variety of o-silylaryl triflates
(Figure 2). Not only unsubstituted o-iodophenyl triflate (2e) but
also o-iodoaryl triflates bearing methoxy (2a and 2h), triflyloxy
(2f),11 morpholino (2g), methyl (2i and 2j), and bromo groups
(2d) were efficiently prepared from the corresponding o-silylaryl
The reaction conditions for the desilyliodination were
screened using 2-chloro-6-(trimethylsilyl)phenyl triflate (1c),
© 2019 The Chemical Society of Japan
Yoshida, Suguru
