Palladium-catalyzed oxidative alkynylation of arene C-H bond using the chelation-assisted strategy

Article abstract of DOI:10.1016/j.tet.2012.04.003

Palladium-catalyzed alkynylation of arene C-H bonds with (triisopropylsilyl)acetylene was developed for the first time under oxidative conditions in the present study. Among various type of directing groups examined, the N-phenyl-2-aminopyridine skeleton was shown to be most effective and selective for the Pd-catalyzed direct alkynylation reaction, and the desired alkynylated products were obtained in moderate to good yields.

Full text of DOI:10.1016/j.tet.2012.04.003

Tetrahedron 68 (2012) 5162e5166
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Palladium-catalyzed oxidative alkynylation of arene CeH bond using the
chelation-assisted strategy
*
Seok Hwan Kim, Sae Hume Park, Sukbok Chang
Department of Chemistry and Molecular-Level Interface Research Center, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
Palladium-catalyzed alkynylation of arene CeH bonds with (triisopropylsilyl)acetylene was developed
for the first time under oxidative conditions in the present study. Among various type of directing groups
examined, the N-phenyl-2-aminopyridine skeleton was shown to be most effective and selective for the
Pd-catalyzed direct alkynylation reaction, and the desired alkynylated products were obtained in
moderate to good yields.
Received 3 February 2012
Received in revised form 27 March 2012
Accepted 1 April 2012
Available online 19 April 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Dedicated to Professor Zhang-Jie Shi on his
receipt of the Tetrahedron Young In-
vestigator Award
Keywords:
CeH bond activation
Alkynylation
Palladium catalyst
Chelation-assistance
Oxidative coupling
1. Introduction
limitations still exist such as the requirement of certain types of
heterocycles or electronically controlled arenes as substrates. As
The fact that carbonecarbon triple bonds are an important
building block in a wide range of compounds1 has led to extensive
research efforts on the development of synthetic approaches to
install the acetylenyl moiety in different types of molecules.2
Among those protocols investigated, Sonogashira reaction has
been regarded as the most efficient and reliable method since its
development.3 Although a range of alkynes and electrophilic sub-
strates can be successfully applied, it is sometimes accompanied
with problems such as facile homodimerization of terminal al-
kynes, poor reactivity of electron-deficient alkynes, or low product
yields from sterically hindered aryl halides, thus leading to search
for alternative methods to overcome those difficulties.4
The recent advance in the direct CeH bond activation of low
reacting molecules5 has stimulated investigation of more
straightforward alkynylation procedures, and it has resulted in the
development of the ‘Reverse’ Sonogashira reaction6 and oxidative
alkynylation reaction.7 Despite these early achievements, some
a result, direct alkynylation of non-activated arenes via CeH bond
activation pathway is very rare.8
Along with our continuing efforts to develop efficient catalytic
systems for the direct CeH bond functionalizations,9 we sought to
establish new conditions, which enable the coupling between ter-
minal alkynes and non-activated arenes under oxidative condi-
tions.10 Based on the previous reports on the chelation-assisted CeH
bond activation,11 various directing groups were first examined in an
oxidative alkynylation of arenes bearing those moieties to react with
(triisopropylsilyl)acetylene (Scheme 1). Since silver salts are often
used as the effective oxidant in a wide range of CeH bond activation
chemistry, a catalyst system consisted of Pd(OAc)2, AgOTf, and K2CO3
was initially tested for the alkynylation. It was found that substrates
such as 2-phenylpyridine, benzo[h]quinoline, 2-pyridyl(sulfon)am-
ides, 2-pyridylphenylsilane, anilides, or amides, which are frequently
employed compounds in the chelation-assisted CeH bond func-
tionalization, were all ineffective, and the desired products were not
obtained, giving rise to only a dimeric dialkyne side product in most
cases. In contrast, when N-phenyl-2-aminopyridine was employed
under the initial conditions, the corresponding alkynyl product was
observed to form albeit in low yield (<10%).
* Corresponding author. E-mail address: sbchang@kaist.ac.kr (S. Chang).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.04.003

S.H. Kim et al. / Tetrahedron 68 (2012) 5162e5166
5163
While the reaction became much sluggish at 60 ꢀC (entry 11),
change of equivalents of two reactants gave marginally increased
yield (entry 12). Finally, when alkyne 2 was added into the reaction
mixture in two portions over 4 h, the highest product yield could be
obtained in benzene solvent (entry 13).
The substrate scope of the present Pd-catalyzed direct CeH
alkynylation reaction was next investigated with substrates having
the basic skeleton of N-phenyl-N-methyl-2-aminopyridine under
the optimized reaction conditions, in which alkyne 2 was added in
two portions over 4 h (Table 2). Substituents at the 4-position of the
phenyl side did not cause any problems in the alkynylation al-
though electron-withdrawing groups provided slightly lower
product yields (entries 1e5). Whereas substrates having two
methyl substituents at the 3- and 5-position underwent the alky-
nylation reaction smoothly (entry 6), positioning two electron-
withdrawing substituents at the same sites made the alkynylation
almost ineffective (entry 7). In addition, when a substrate bearing
an ortho-substituent such as N-(2-methylphenyl)-N-methyl-2-
aminopyridine was subjected to the reaction conditions, no de-
sired product was obtained presumably due to the steric crowd-
edness to inhibit the effective chelation (entry 8). With regard to N-
substituents, alkynylation of substrates having N-ethyl or N-benzyl
group afforded the desired products in lower yields when
Scheme 1. Preliminary results of the CeH bond alkynylation with substrates bearing
various types of directing groups.
2. Results and discussion
Encouraged by the above promising result, numerous reaction
conditions were subsequently screened by employing N-phenyl-N-
methyl-2-aminopyridine (1a) and (triisopropylsilyl)acetylene (2) as
model substrates (Table 1).12 Due to the fact that metallic oxidants
such as silver salts were found to lead to mainly a dimerization
pathway of alkyne rather than the desired coupling reaction, non-
metallic oxidants were consequently tested. In addition, additive
effect of acids instead of bases was also investigated since it turned
out that the use of either organic or inorganic bases did not improve
the reaction efficiency upon extensive screenings. When silver salts
or hypervalent iodine(III) species were used as the oxidant, negli-
gible product yields were observed (entries 1 and 2). While a re-
action with 1,4-benzoquinone (BQ) was also sluggish (entry 3), the
addition of catalytic amounts of p-toluenesulfonic acid gave a sig-
nificantly improved result albeit in unsatisfactory yield (entry 4).
Other frequently used acids such as acetic acid or trifluoroacetic
acid showed much lower additive effects when compared to TsOH
(entries 5 and 6). Screen of different palladium precursors revealed
that Pd(acac)2 exhibited higher catalytic activity than Pd(OAc)2
(entry 7). Interestingly, reaction at lower temperatures resulted in
a bit increased yield mainly due to the inhibition of dimerization
side pathway (entry 8). The use of a larger amount of BQ (2 equiv to
1a) afforded slightly improved yields in benzene (entries 9 and 10).
Table 2
Substrate scope of the chelation-assisted oxidative alkynylationa
Entry
1
Substrate (1)
R
Product
Yieldb (%)
68
H
3a
2
3
4
5
Me
OMe
F
3b
3c
3d
3e
64
60
51
51
Cl
Table 1
6
7
Me
CF3
3f
41
Optimization of the chelation-assisted oxidative alkynylationa
3g
<1
8
9
3h
3i
<1
Entry Catalyst
Oxidant
Additive
Solvent
Temp (ꢀC) Yieldb (%)
1
Pd(OAc)2 AgOTf
Pd(OAc)2 PhI(OAc)2
Pd(OAc)2 BQ
Pd(OAc)2 BQ
Pd(OAc)2 BQ
Pd(OAc)2 BQ
Pd(acac)2 BQ
Pd(acac)2 BQ
Pd(acac)2 BQ
Pd(acac)2 BQ
Pd(acac)2 BQ
Pd(acac)2 BQ
Pd(acac)2 BQ
d
d
d
Toluene 100
Toluene 100
Toluene 100
<5
<5
5
26
14
6
Et
30
2
3
4
5
6
7
8
10
11
CH2Ph
i-Pr
3j
3k
25
<5
TsOH/H2O Toluene 100
AcOH
CF3CO2H
TsOH/H2O Toluene 100
TsOH/H2O Toluene
TsOH/H2O Toluene
TsOH/H2O Benzene
TsOH/H2O Benzene
TsOH/H2O Benzene
TsOH/H2O Benzene
Toluene 100
Toluene 100
35
43
45
53
10
56
70
80
80
80
60
80
80
9c
10c
11c
12c,d
13c,e
12
13
3l
9
4-Me
3m
73
a
Reaction conditions: 1a (0.1 mmol),
2 (0.15 mmol), palladium catalyst
14
15
5-Me
6-Me
3n
3o
71
<5
(0.01 mmol), acid additive (0.01 mmol), and oxidant (0.1 mmol) in solvent (0.2 mL)
for 12 h.
b
a
NMR yield of 3a.
BQ (0.2 mmol) was used.
Substrate (1a, 0.15 mmol) and alkyne (2, 0.1 mmol) were used.
Reaction conditions:
1
(0.2 mmol),
2
(0.13 mmolꢁ2 over 4 h), Pd(acac)2
c
(0.02 mmol), TsOH/H2O (0.02 mmol), and BQ (0.4 mmol) in benzene (1 mL) at 80 ꢀ
for 12 h.
C
d
e
b
Alkyne 2 was added in two portions (0.075 mmol each) over 4 h.
Isolated yield.

5164
S.H. Kim et al. / Tetrahedron 68 (2012) 5162e5166
compared to 1a (entries 9 and 10). This decreased efficiency was
attributed again to the steric factors considering the observation
that a starting material having N-isopropyl group did not undergo
the desired reaction (entry 11). Analogously, N-(2-pyridyl)indoline
underwent the alkynylation rather in low efficiency (entry 12).
Reaction efficiency was also examined with substrates having
substituents at the pyridine side. Alkynylation took place smoothly
with substrates with a methyl substituent at the 4- or 5-position of
the pyridyl moiety to afford the desired products in high yields
(entries 13 and 14). However, not surprisingly, substitution at the 6-
position of the pyridine side resulted in sluggish alkynylation (en-
try 15). On the other hand, the use of other types of alkynes such as
aryl- or aliphatic-terminal acetylenes was not successful under the
standard conditions employed, mainly due to the formation of
undesired homodiynes.
supposed to take a role at this stage in that stabilization of the
partial positive charge of B could be achieved by equilibrating it
with B0. The observed KIE values (Scheme 2) suggest that the CeH
bond activation is most likely the rate-limiting step in overall cat-
alytic processes to generate a six-membered palladacycle C. Ligand
exchange by acetylene would be followed to provide an arylpalla-
dium acetylide intermediate D. Finally, reductive elimination of D
will release the alkynylation product to regenerate Pd(0) species,
which is re-oxidized to Pd(II) by the action of BQ and acid
additives.15
In order to gain a mechanistic insight of the present CeH alky-
nylation reaction, we carried out kinetic isotope effect (KIE) studies
(Scheme 2).13 Observed hydrogen/deuterium KIE was significant in
both intramolecular (kH/kD, 2.7) and intermolecular (kH/kD, 4.3)
reactions. These values indicate that the C(sp2)eH bond cleavage
may be related to the rate-determining step.
Scheme 4. Proposed mechanism.
Scheme 2. Kinetic isotope effect study.
3. Conclusion
As anticipated, reaction of N-methyldiphenylamine (4) was to-
tally ineffective under the presently developed standard conditions
to suggest that the postulated chelation-assistance is critical to
determine the alkynylation efficiency. In addition, when 2-
benzylpyridine (5) was subjected to the conditions, no conversion
was observed, implying that the presence of a nitrogen linkage
between pyridyl and phenyl moiety in substrates is also a key factor
to achieve high product yields (Scheme 3).
In conclusion, to the best of our knowledge, we herein presented
the first example of the palladium-catalyzed oxidative alkynylation
of arene C(sp2)eH bonds with (triisopropylsilyl)-acetylene. The key
to the success was the substrate design enabling the effective
chelation-assistance. Although substrate scope is rather narrow
and product yields are not very high at this stage, we believe that
this preliminary study will be an important clue for the subsequent
progresses toward the development of highly efficient and more
general alkynylation reactions.
4. Experimental section
4.1. General methods
Unless otherwise stated, all commercial reagents and solvents
were used without additional purification. Analytical thin layer
chromatography (TLC) was performed on Merck pre-coated silica
gel 60 F254 plates. Visualization on TLC was achieved by the use of
UV light (254 nm). Column chromatography was undertaken on
silica gel (400e630 mesh) using a proper eluent. 1H NMR was
recorded on FT AM 400 (400 MHz). Chemical shifts were quoted in
parts per million (ppm) referenced to the appropriate solvent peak
or 0.0 ppm for tetramethylsilane. The following abbreviations were
used to describe peak splitting patterns when appropriate:
br¼broad, s¼singlet, d¼doublet, t¼triplet, q¼quartet, dd¼doublet
of doublet, m¼multiplet. Coupling constants, J, were reported in
hertz unit (Hz). 13C NMR was recorded on FT AM 400 (100 MHz) and
was fully decoupled by broad band proton decoupling. Chemical
shifts were reported in parts per milllion referenced to the center
Scheme 3. The reaction of diphenylmethylamine and 2-benzylpyridine.
Based on these results and precedent studies,14 a mechanistic
proposal of the present alkynylation reaction is shown in Scheme 4.
It is assumed that the pyridyl nitrogen atom of substrates co-
ordinates to the Pd(II) metal center leading to a complex A in order
to start a catalytic cycle. Considering the observed low reactivity of
substrates bearing electron-deficient substituents, the subsequent
key CeH bond activation is presumed to proceed via an electro-
philic metalation pathway to form an arylpalladium
p-complex B.
The nitrogen linker between phenyl and 2-pyridyl moieties is

S.H. Kim et al. / Tetrahedron 68 (2012) 5162e5166
5165
line of a triplet at 77.0 ppm of chloroform-d. Infrared (IR) spectra
were recorded neat in 0.5 mm path length using a sodium chloride
cell. Frequencies are given in reciprocal centimeters (cmꢂ1) and
only selected absorbance is reported. Agilent 6980 series GC system
with Agilent 5974 network mass selective detector was used to
determine GC yields. HP-35MS (Crosslinked 35% PH ME siloxane)
was used as capillary column on GCeMS. High resolution mass
spectra were obtained from the Korea Basic Science Institute
(Daegu) by using EI or FAB methods.
J¼3.0 Hz, 1H), 6.92e6.89 (m, 1H), 6.50e6.48 (m, 1H), 6.14e6.11 (m,
1H), 3.81 (s, 3H), 3.40 (s, 3H), 0.95e0.93 (m, 21H); 13C NMR
(100 MHz, CDCl3)
d 158.7, 157.8, 147.5, 141.1, 136.4, 130.2, 124.3,
118.4, 116.5, 112.1, 108.1, 103.3, 95.7, 55.6, 37.7, 18.4, 11.1; IR (NaCl)
n
3005, 2966, 2913, 2859, 2155,1596,1439,1366,1233,1161, 980, 882,
763 cmꢂ1; HRMS (EI) m/z calcd for C24H34N2OSi [M]þ: 394.2440,
found: 394.2441.
4.3.4. Compound 3d. Blue liquid; 1H NMR (400 MHz, CDCl3)
d
8.15e8.13 (m,1H), 7.26e7.23 (m, 2H), 7.20e7.16 (m, 1H), 7.09e7.06
(m, 1H), 6.54e6.52 (m, 1H), 6.16e6.13 (m, 1H), 3.40 (s, 3H),
0.95e0.93 (m, 21H); 13C NMR (100 MHz, CDCl3)
161.8,159.3,158.4,
147.6, 144.3, 136.5, 130.8, 130.7, 125.2, 125.1, 120.8, 120.6, 117.3, 117.1,
4.2. General procedure for the preparation of substrates16
d
To a solution of 2-bromopyridine (1.0 mmol), N-alkylaniline
derivatives (1.05 mmol), and KO-t-Bu (1.5 mmol) in anhydrous 1,4-
dioxane (3 mL) were added in turn to a screw-capped vial equipped
with a Teflon septum and magnetic stirring bar charged with
Pd(dba)2 (2 mol %) and IPreHCl (2 mol %) under argon. After stir-
ring in a pre-heated oil bath at 100 ꢀC for 12 h, the mixture was
cooled to ambient temperature, filtered through a pad of Celite
washing with dichloromethane (10 mLꢁ3). The solvents were re-
moved under reduced pressure and the crude product was purified
by chromatography on silica gel to give a pure desired product.
To a solution of the above obtained N-(2-pyridyl)aniline de-
rivative (1 mmol) and KO-t-Bu (2 mmol) in anhydrous DMF (10 mL)
was added iodomethane (2 mmol) under water bath. Stirring of the
reaction mixture for 12 h was followed by addition of water (10 mL)
and EtOAc (10 mL). The separated water layer was extracted with
EtOAc (5 mLꢁ2) and combined organic layers were washed with
saturated aqueous NH4Cl solution (10 mLꢁ2). The organic layer was
dried over MgSO4 and the solvents were evaporated. The crude
reaction residue was purified by chromatography on silica gel.
112.6, 108.0, 102.2, 97.4, 37.8, 18.4, 11.1; IR (NaCl) n 2943, 2855, 2155,
1653, 1596, 1496, 1411, 1317, 1259, 1151, 981, 879 cmꢂ1; HRMS (EI)
m/z calcd for C23H31FN2Si [M]þ: 382.2241, found: 382.2242.
4.3.5. Compound 3e. Blue liquid; 1H NMR (400 MHz, CDCl3)
d
8.16e8.14 (m, 1H), 7.53 (d, J¼2.5 Hz, 1H), 7.33e7.24 (m, 2H), 7.16
(d, J¼8.4 Hz, 1H), 6.56e6.54 (m, 1H), 6.19 (d, J¼8.6 Hz, 1H), 3.41 (s,
3H), 0.94e0.92 (m, 21H); 13C NMR (100 MHz, CDCl3)
158.2, 147.6,
146.7, 136.6, 134.0, 131.9, 130.2, 130.1, 124.9, 112.8, 108.2, 102.1, 97.8,
d
37.7, 18.4, 11.1; IR (NaCl) n 2962, 2919, 2890, 2861, 2159, 1597, 1563,
1437, 1358, 1315, 1112, 1065, 981, 882, 737 cmꢂ1; HRMS (EI) m/z
calcd for C23H31ClN2Si [M]þ: 398.1945, found: 398.1944.
4.3.6. Compound 3f. Light yellow liquid; 1H NMR (400 MHz, CDCl3)
d
8.15e8.13 (m, 1H), 7.24e7.19 (m, 1H), 6.98e6.97 (m, 1H), 6.87 (m,
1H), 6.50e6.47 (m, 1H), 6.15e6.13 (m, 1H), 3.41 (s, 3H), 2.43 (s, 3H),
2.30 (s, 3H), 0.96e0.94 (m, 21H); 13C NMR (100 MHz, CDCl3)
158.5,
148.1, 147.5, 142.7, 139.6, 136.2, 128.8, 126.7, 120.4, 112.0, 108.3,
d
102.3, 99.1, 37.6, 21.3, 21.1, 18.5, 11.2; IR (NaCl)
n 2942, 2864, 2151,
4.3. General procedure for the chelation-assisted Pd-
catalyzed oxidative alkynylation
1656, 1559, 1486, 1322, 883, 767 cmꢂ1; HRMS (EI) m/z calcd for
C25H36N2Si [M]þ: 392.2648, found: 392.2648.
To an oven dried Schlenk tube were added 1 (0.2 mmol), 2
(0.13 mmol), Pd(acac)2 (10 mol %), TsOH/H2O (10 mol %), benzo-
quinone (0.4 mmol), and benzene (1 mL) under N2. The reaction
mixture was stirred in a pre-heated oil bath at 80 ꢀC for 4 h and
then 2 (0.13 mmol) was again added to the reaction mixture. After
stirring at 80 ꢀC for 12 h, the mixture was cooled to ambient tem-
perature, filtered through a pad of Celite washing with dichloro-
methane (10 mLꢁ3). The solvents were removed under reduced
pressure and the crude product was purified by chromatography on
silica gel to give a pure desired product.
4.3.7. Compound 3i. Yellow liquid; 1H NMR (400 MHz, CDCl3)
d
8.14e8.12 (m, 1H), 7.59e7.57 (m, 1H), 7.37e7.35 (m, 1H), 7.26e7.19
(m, 3H), 6.50e6.48 (m, 1H), 6.05 (d, J¼8.6 Hz, 1H), 4.01 (q, J¼7.2 Hz,
2H), 1.21 (t, J¼7.1 Hz, 3H), 0.94 (br, 21H); 13C NMR (100 MHz, CDCl3)
d
157. 9, 147.5, 146.2, 136.4, 134.5, 130.2, 129.8, 126.7, 124.4, 112.2, 108.3,
103.7, 96.0, 44.4, 18.5, 13.4, 11.2; IR (NaCl)
n 2964, 2919, 2891, 2859,
2157, 1589, 1560, 1486, 1429, 1312, 1282, 1137, 982, 883, 722 cmꢂ1
;
HRMS (EI) m/z calcd for C24H34N2Si [M]þ: 378.2491, found: 378.2495.
4.3.8. Compound 3j. Green liquid; 1H NMR (400 MHz, CDCl3)
d
8.16e8.15 (m, 1H), 7.57e7.56 (m, 1H), 7.33e7.31 (m, 2H), 7.25e7.18
(m, 6H), 7.02e7.03 (m, 1H), 6.56e6.53 (m, 1H), 6.14 (d, J¼8.6 Hz, 1H),
5.25 (br, 2H), 0.98e0.95 (m, 21H); 13C NMR (100 MHz, CDCl3)
158.3,
147.6, 146.1, 139.4, 136.6, 134.6, 130.1, 129.6, 128.1, 126.7, 126.6, 123.7,
4.3.1. Compound 3a. Brown liquid; 1H NMR (400 MHz, CDCl3)
d
8.16e8.15 (m, 1H), 7.58e7.55 (m, 1H), 7.36e7.33 (m,1H), 7.25e7.21
(m, 3H), 6.53e6.51 (m, 1H), 6.18e6.15 (m, 1H), 3.44 (s, 3H),
0.96e0.95 (m, 21H); 13C NMR (100 MHz, CDCl3)
158.4, 148.1, 147.5,
136.4, 134.4, 130.0, 129.0, 126.6, 123.4, 112.4, 108.3, 103.5, 96.0, 37.7,
d
d
112.9, 108.1, 103.7, 96.5, 52.8, 18.5, 11.2; IR (NaCl) n 2942, 2864, 2157,
1586, 1560, 1476, 1436, 1382, 1308, 1154, 883, 765 cmꢂ1; HRMS (EI)
18.5, 11.2; IR (NaCl)
n
2959, 2891, 2861, 2158, 1589, 1521, 1457, 1363,
m/z calcd for C29H36N2Si [M]þ: 440.2648, found: 440.2646.
1070, 883, 756 cmꢂ1; HRMS (EI) m/z calcd for C23H32N2Si [M]þ:
364.2335, found: 364.2336.
4.3.9. Compound 3l. Colorless liquid; 1H NMR (400 MHz, CDCl3)
d
8.27e8.25 (m, 1H), 7.45e7.43 (m, 1H), 7.27e7.24 (m, 1H), 7.17e7.15
4.3.2. Compound 3b. Brown liquid; 1H NMR (400 MHz, CDCl3)
(m,1H), 6.95e6.93 (m,1H), 6.84 (t, J¼7.5 Hz,1H), 6.76e6.74 (m, 1H),
d
8.15e8.13 (m, 1H), 7.38e7.37 (m, 1H), 7.24e7.08 (m, 3H),
6.51e6.48 (m, 1H), 6.16e6.14 (m, 1H), 3.41 (s, 3H), 2.33 (s, 3H),
0.96e0.94 (m, 21H); 13C NMR (100 MHz, CDCl3)
158.5,147.4,145.5,
136.5, 136.3, 134.7, 130.9, 128.8, 123.0, 112.2, 108.2, 103.6, 95.4, 37.7,
4.35e4.30 (m, 2H), 3.07e3.03 (m, 2H), 0.94e0.87 (m, 21H); 13C
NMR (100 MHz, CDCl3)
125.1, 121.5, 115.9, 112.9, 109.4, 104.3, 99.7, 53.8, 28.7, 18.5, 11.1; IR
d 155.9, 147.6, 146.0, 136.1, 134.8, 132.6,
d
(NaCl) n 2942, 2889, 2864, 2145, 1592, 1469, 1433, 1381, 1323, 1218,
20.8, 18.5, 11.2; IR (NaCl)
n
2967, 2909, 2858, 2151, 1594, 1483, 1361,
1152, 1066, 988, 772 cmꢂ1; HRMS (EI) m/z calcd for C24H32N2Si
1316, 1153, 1068, 981, 825, 664 cmꢂ1; HRMS (EI) m/z calcd for
[M]þ: 376.2335, found: 376.2333.
C24H34N2Si [M]þ: 378.2491, found: 378.2496.
4.3.10. Compound 3m. Light yellow liquid; 1H NMR (400 MHz,
CDCl3)
4.3.3. Compound 3c. Dark brown liquid; 1H NMR (400 MHz, CDCl3)
d 8.02e8.01 (m, 1H), 7.57e7.56 (m, 1H), 7.38e7.34 (m, 1H),
d
8.14e8.12 (m,1H), 7.24e7.20 (m,1H), 7.11 (d, J¼8.7 Hz,1H), 7.05 (d,
7.25e7.21 (m, 2H), 6.37e6.36 (m,1H), 5.99 (br,1H), 3.43 (s, 3H), 2.08

5166
S.H. Kim et al. / Tetrahedron 68 (2012) 5162e5166
(s, 3H), 0.95 (br, 21H); 13C NMR (100 MHz, CDCl3)
147.2, 134.4, 129.9, 128.9, 126.4, 123.4, 114.2, 108.5, 103.6, 95.9, 37.9,
d 158.7, 148.3,
5. (a) Dick, A. R.; Sanford, M. S. Tetrahedron 2006, 62, 2439; (b) Beccalli, E. M.;
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21.1, 18.5, 11.2; IR (NaCl) n 3059, 2970, 2906, 2885, 2854, 2158, 1610,
1554, 1491, 1396, 1308, 1134, 1076, 983, 883, 753 cmꢂ1; HRMS (EI)
m/z calcd for C24H34N2Si [M]þ: 378.2491, found: 378.2492.
4.3.11. Compound 3n. Orange liquid; 1H NMR (400 MHz, CDCl3)
d
7.97 (m, 1H), 7.55e7.53 (m, 1H), 7.36e7.32 (m, 1H), 7.24e7.18 (m,
2H), 7.09e7.06 (m, 1H), 6.15e6.13 (m, 1H), 3.42 (s, 3H), 2.13 (s, 3H),
0.97e0.95 (m, 21H); 13C NMR (100 MHz, CDCl3)
156.8,148.6,147.0,
137.5, 134.4, 129.9, 128.8, 126.2, 123.2, 121.2, 108.3, 103.7, 95.9, 37.9,
18.5, 17.3, 11.2; IR (NaCl) 2972, 2904, 2879, 2855, 2156, 1611, 1560,
d
8. (a) Kobayashi, K.; Arisawa, M.; Yamaguchi, M. J. Am. Chem. Soc. 2002, 124, 8528;
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Chatani, N. Org. Lett. 2012, 14, 354.
n
1500, 1447, 1385, 1313, 1251, 1130, 1071, 996, 883, 812, 753 cmꢂ1
;
9. (a) Cho, S. H.; Hwang, S. J.; Chang, S. J. Am. Chem. Soc. 2008, 130, 9254; (b)
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Am. Chem. Soc. 2010, 132, 10272; (f) Kim, J. Y.; Cho, S. H.; Joseph, J.; Chang, S.
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A.; Bergman, R. G.; Ellman, J. A. Chem. Rev. 2010, 110, 624; (e) Chiusoli, G. P.;
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111, 1315.
HRMS (EI) m/z calcd for C24H34N2Si [M]þ: 378.2491, found:
378.2494.
Acknowledgements
This research was supported by the Korea Research Foundation
Grant (KRF-2008-C00024, Star Faculty Program) and MIRC (NRF-
2011-0001322).
Supplementary data
These data include experimental procedure, spectroscopic data,
and copies of 1H and 13C NMR of compounds obtained in this study.
Supplementary data associated with this article can be found in the
online version, at doi:10.1016/j.tet.2012.04.003.
12. See the Supplementary data for details.
13. For the synthesis of N-(2-deuteriophenyl)-2-aminopyridine, see: Wang, H.;
Wang, Y.; Peng, C.; Zhang, J.; Zhu, Q. J. Am. Chem. Soc. 2010, 132, 13217.
14. (a) Campeau, L.-C.; Parisien, M.; Jean, A.; Fagnou, K. J. Am. Chem. Soc. 2006, 128,
581; (b) Potavathri, S.; Pereira, K. C.; Gorelsky, S. I.; Pike, A.; LeBris, A. P.; DeBoef,
B. J. Am. Chem. Soc. 2010, 132, 14676.
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