CL-150535
Received: June 2, 2015 | Accepted: June 27, 2015 | Web Released: July 4, 2015
Facile Synthesis of Diverse Multisubstituted ortho-Silylaryl Triflates via C-H Borylation
Suguru Yoshida, Ken Shimomori, Takako Nonaka, and Takamitsu Hosoya*
Laboratory of Chemical Bioscience, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University,
2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062
(E-mail: thosoya.cb@tmd.ac.jp)
Diverse multisubstituted ortho-silylaryl triflates were effi-
ciently synthesized from simple ortho-silylaryl triflates via
iridium-catalyzed regioselective C-H borylation and subsequent
deborylative functionalizations. An azidoaryne precursor syn-
thesized by this method served as a useful bis-reactive platform
molecule, thus demonstrating the utility of the method for
preparing diverse aromatic compounds.
triflates would be a practical approach (Figure 1C). Herein,
we demonstrate a facile method of synthesizing diverse multi-
substituted ortho-silylaryl triflates via the C-H borylation of
simple ortho-silylaryl triflates.
Our initial attempts to modify 3-methoxy-2-(trimethyl-
silyl)phenyl triflate (1a) directly by classical electrophilic
substitution reactions were unsuccessful. For example, neither
bromination nor Friedel-Crafts acylation of 1a efficiently
afforded 2a or 2b, and the cleavage of the C-Si bond proceeded
instead, providing predominantly 3 or 4 (Scheme 1).
With the increasing demands of chemical libraries that
facilitate efficient drug discovery, new synthetic methodologies
such as “diversity-oriented synthesis”1 and “multicomponent
reactions,”2 which enable expeditious preparation of vast
numbers of diversified compounds, are growing increasingly
important. An aryne serves as a favorable platform intermediate
for this purpose because it is capable of transforming into a wide
range of aromatic compounds via various types of reactions, i.e.,
cycloadditions with arynophiles or reactions with nucleophiles
and electrophiles (Figure 1A).3,4 Several methods for generating
arynes, including precursors, have been developed and applied
to the synthesis of a diverse array of aromatic compounds. ortho-
Silylaryl triflate 1 is one of the most widely used precursors
because of the mild conditions required for aryne generation,
which has prompted the development of numerous transforma-
tions mediated by an aryne.5 However, the preparation of
multisubstituted ortho-silylaryl triflates is not always easy,
particularly for substrates with a base-sensitive function, because
representative synthetic methods require multiple steps, includ-
ing a silylation step via a carbanion species (Figure 1B).6 To
render multisubstituted ortho-silylaryl triflates more accessible,
we hypothesized that derivatization of simple ortho-silylaryl
After several attempts, we determined that iridium-catalyzed
Smith/Miyaura-Ishiyama-Hartwig C-H borylation7 suited our
purpose. The reaction of ortho-silylaryl triflate 1a with
bis(pinacolato)diboron in the presence of a catalytic amount of
iridium complex and 4,4¤-di-tert-butyl-2,2¤-bipyridyl (dtbpy)
afforded borylated ortho-silylaryl triflate 5a in excellent yield
(Scheme 2). In common with reported examples, the borylation
proceeded regioselectively at a sterically unhindered position of
1a without damaging the silyl or the triflyloxy group. However,
borylation of ortho-iodoaryl triflate 6, another type of aryne
precursor,8 did not proceed under the same conditions and
starting material 6 was recovered.
The borylation conditions were applicable to various 3- or
6-substituted 2-(trimethylsilyl)phenyl triflates 1 (Table 1). Elec-
tron-donating methyl- and trimethylsilyl-substituted ortho-silyl-
aryl triflates were borylated to afford 5b and 5c, respectively, in
high yields, demonstrating that the substitution positions of the
OMe
OMe
NBS
SiMe3
OTf
Br
(1.5 equiv)
+
CH2Cl2
rt, 2 h
OTf
OMe
Br
2a
3
SiMe3
OTf
17%
77%
R'
cyclo-
addition
OR'
OR''
A
OMe
OMe
PhCOCl (1.0 equiv)
AlCl3 (1.5 equiv)
1a
SiMe3
OTf
H
NR''
O
SiMe3
OTf
O
F–
R
R
R
R'
+
R
R
R
CH2Cl2
A wide variety of products
OTf
Ph
E
0 °C to rt
30 min
O
R
aryne
O
O
R
O
2b
4
1
R''
NR'2
R''
R'
OR''
Nu–
E+
0%
95%
Nu
P(NR')2
O
R
R
O
Scheme 1. Initial attempts to modify ortho-silylaryl triflate 1a by
classical electrophilic substitution reactions. NBS: N-bromosuccin-
imide.
B
Representative approaches
H
C
R
This work
R
SiMe3
OTf
SiMe3
diversification
SiMe3
OH
Br
(pinB)2 (1.5 equiv)
[Ir(OMe)(cod)]2 (2.5 mol %)
dtbpy (4.0 mol %)
R
R
OMe
OMe
under
mild conditions
OTf
R'
OTf
X
R
X
simple
multisubstituted
- multi-step synthesis
- via carbanion species
OH
hexane
rt, 12 h
pinB
OTf
OTf
1a: X = SiMe3
6 : X = I
5a: X = SiMe3 97%
7 : X = I 0%
Figure 1. (A) Generation of arynes from ortho-silylaryl triflates
and examples of available products via diverse transformations. (B)
Representative synthetic methods for ortho-silylaryl triflate. (C)
The strategy used in this work. Tf: CF3SO2, Nu: nucleophile, E:
electrophile.
Scheme 2. Borylation of aryne precursors 1a and 6 using an
iridium catalyst. Bpin: 4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl,
cod: 1,4-cyclooctadiene, dtbpy: 4,4¤-di-tert-butyl-2,2¤-bipyridyl.
© 2015 The Chemical Society of Japan
Yoshida, Suguru
