Selective C(8)-H Activation of Imidazopyridines Mediated by Cooperative Nickel-Aluminum Catalysis

Article abstract of DOI:10.1055/s-0035-15661438

A catalytic paradigm is described featuring a synergistic interaction between nickel, aluminum and different ligands to impart a rather remote C-H alkenylation of imidazo[1,5-a]pyridines at the C-8 position without the necessity of installing a directing group. The scope of the direct C-H activation reactions of various 5-aryl- and 3-arylimidazopyridines is established using different sterically hindered alkynes.

Full text of DOI:10.1055/s-0035-15661438

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2016, 48, A–H
A
special topic
C.-Y. Liu et al.
Special Topic
Synthesis
Selective C(8)–H Activation of Imidazopyridines Mediated by
Cooperative Nickel–Aluminum Catalysis
Cheng-Yuan Liua
Ying-Ho Chena
5-substituted imidazopyridine
IMes
N
Chih-Hao Chena,b
Ming-Shiuan Yua
Fu-Yu Tsai*b
N
N
Ni-Al
N
R
R
28 examples
17–98% yield
ligands
R3P
Ni(cod)2 (5 mol%)
ligand (5–20 mol%)
60–100 °C
Tiow-Gan Ong*a,c
AlMe3 (20–100 mol%)
a Institute of Chemistry, Academia Sinica, Nangang, Taipei,
11529, Taiwan, ROC
tgong@gate.sinica.edu.tw
b Department of Molecular Science and Engineering, National
Taipei University of Technology, Taipei, 10608, Taiwan, ROC
c Department of Applied Chemistry, National Chiao Tung
University, HsinChu, Taiwan, ROC
N
N
N
N
Ar
3-arylimidazopyridine
Ar
C–H activation at C8
This work is dedicated to the victims of the recent Tainan earthquake.
Received: 23.02.2016
Accepted after revision: 17.03.2016
Published online: 15.06.2016
DOI: 10.1055/s-0035-15661438; Art ID: ss-2016-c0130-st
previous work
NI
N
C3-selective
N
1
3
Abstract A catalytic paradigm is described featuring a synergistic in-
teraction between nickel, aluminum and different ligands to impart a
rather remote C–H alkenylation of imidazo[1,5-a]pyridines at the C-8
position without the necessity of installing a directing group. The scope
of the direct C–H activation reactions of various 5-aryl- and 3-arylimid-
azopyridines is established using different sterically hindered alkynes.
current focus
3
N
8
N
5
NI-Al
+
N
N
N
C5-selective
n-Pr
n-Pr
N
5
5
Key words C–H activation, nickel, aluminum, imidazopyridines, coop-
erative catalysis
trace amount
C5 and C8
Scheme 1 C–H derivatizations of imidazo[1,5-a]pyridine
Over the past decade, transition-metal-promoted C–H
bond activation has emerged as a powerful and pervasive
catalytic synthetic strategy, avoiding additional steps asso-
ciated with prefunctionalized coupling partners.1 Never-
theless, research concerning C–H activation of imidazo[1,5-
a]pyridines remains surprisingly under-represented, in
spite of the importance of these compounds as electronic
and photo-responsive materials,2 carbene-like ancillary li-
gands3 and bioactive agents.4 So far, the majority of C–H
functionalizations of imidazo[1,5-a]pyridines have been es-
tablished exclusively at the more acidic regions, namely the
C-3 and C-1 positions.5
divergent C–H alkenylation of imidazo[1,5-a]pyridine at the
C-5 and C-3 positions (Scheme 1).9 Such highly regioselec-
tive C–H reactions at these positions are enabled by the co-
operative interaction between Ni and Al. During the course
of this work, we also obtained, unexpectedly, a trace
amount of a side product in which C–H functionalization
with the alkyne had occurred at the rather remote C-8 posi-
tion simultaneously with the C-5 position. So far, no single
example of the direct C-8 functionalization of imidazo[1,5-
a]pyridine has been reported. Thus, a new strategy for se-
lective C(8)–H bond activation of imidazopyridine would be
an obvious choice to pursue for synthetic curiosity as well
as to increase the synthetic utility of nickel catalysis.
Previously, our group,6 as well as those of Nakao and
Hiyama7 and Chatani8 have embraced the cooperative catal-
ysis paradigm based on nickel and aluminum to promote
and control one particular unique C–H derivatization in
pyridines or azoles with high precision. More recently, we
developed a general approach featuring a controlled regio-
To test our initial hypothesis for remote C–H activation
at the C-8 position (Table 1), we selected the alkenylation of
5-phenylimidazo[1,5-a]pyridine (1a) with 4,4-dimethyl-2-
pentyne (2a) in the presence of Ni(cod)2 (5 mol%) in toluene
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

B
C.-Y. Liu et al.
Special Topic
Synthesis
at 60 °C as a model system. Two regioisomeric products,
3aa (C8-H) and 4aa (C1-H) were obtained under these reac-
tion conditions in yields of 32% and 6%, respectively, with
low selectivity. The addition of AlMe3 (10 mol%) not only
had a beneficial effect upon the yield of the reaction (68%),
but also essentially promoted exclusive selectivity for C–H
functionalization at the C-8 position. Finally, the yield of the
reaction could be further optimized to 95% by increasing
the amount of AlMe3 to 20 mol%. It is also noteworthy that
the reaction between 1a and the unsymmetrical alkyne
was highly selective, giving the corresponding E-configured
stereoisomeric adduct bearing the smaller methyl substitu-
ent on the same side as the imidazopyridine.
t-Bu
Me
Ni(cod)2 (5 mol%)
IMes (5 mol%)
N
Me
t-Bu
+
N
N
N
AlMe3 (20 mol%)
toluene, 60 °C, 6 h
2a
(1.2 equiv)
R
R
1
3
(0.5 mmol)
major
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
Me
Me
Me
Me
Me
N
N
N
N
N
N
N
N
N
N
Me
Table 1 Optimization of the Process
Me
F
OMe
3ca, 96% 3da, 67% (90%)a,b 3ea, 11% (43%)a,b
3aa, 95%
t-Bu
3ba, 82%
t-Bu
t-Bu
t-Bu
Me
Ni(cod)2 (5 mol%)
IMes (5 mol%)
Me
t-Bu
Me
Me
t-Bu
t-Bu
+
N + Me
t-Bu
Me
Me
Me
N
additive
N
N
2a
toluene, 60 °C
N
N
(1.2 equiv)
N
N
Ph
N
N
N
1a
Ph
4aa
N
Ph
3aa
N
N
N
N
(0.5 mmol)
TMS
tBu
C5H11
Entry
Additive
(mol%)
Time
(h)
Yield of 3aa Yield of 4aa E/Z
(%)a
(%)a
(3aa)b
CO2Et
CF3
3fa, 63% (87%)a,b 3ga, 88%a,b
3ha, 74%a,b
3ia, 88%
3ja, 98%a,c
1c
2
–
17
6
32
68
95
6
–
–
99:1
99:1
99:1
Scheme 2 C8-Alkenylation of various imidazopyridines 1 with 2a. Re-
agents and conditions: 1 (0.5 mmol), 2a (0.6 mmol), Ni(cod)2 (5 mol%),
IMes (5 mol%), toluene (2 mL), AlMe3 (20 mol%), 60 °C; E/Z ratio = 99:1.
AlMe3 (10)
AlMe3 (20)
3
6
a AlMe3 (0.6 equiv). b 100 °C, 12 h. c 24 h.
a Yield of isolated product.
b Determined by 1H NMR spectroscopy.
c Reaction temperature was 100 °C.
To further illustrate the catalytic utility of this protocol,
we expanded the scope to different alkynes (Scheme 3). A
good yield (70%) with high C-8 selectivity was observed
with phenyl(tert-butyl)-alkyne 2b, albeit a higher tempera-
ture of 100 °C was required along with an increased Lewis
acid loading (60 mol%) compared to several of the previous
cases in Scheme 2. An electron-donating methyl substituent
at different positions of phenyl alkynes 2c–e afforded C-8
alkenylated products 3ac–ae selectively, and in good to
moderate yields. Alternatively, a similar type of alkyne de-
rivative bearing an electron-withdrawing CF3 group (2f)
was also suitable for this reaction. The yield and regioselec-
tivity were both good, demonstrating the non-sensitivity of
the reaction toward electronic perturbation of the phenyl
group. Unfortunately, symmetrical oct-4-yne (2g) experi-
enced rather sluggish reactivity (17%), but still maintained
a favorable regioselectivity for C-8. We attributed the poor
yield to a lack of steric hindrance in the alkyne, with the
other competing alkyne cyclotrimerization process prevail-
ing. Again, increasing the steric demand of the alkyne had a
beneficial effect on the yield of the reaction, as witnessed in
the cases of 2h and 2i containing larger isopropyl and
trimethylsilyl groups, respectively. Finally, it should be
mentioned that styrene and other olefinic substrates were
not compatible with this reaction protocol.
With optimized reaction conditions in hand, we next
examined the scope of the process with various 5-substi-
tuted imidazo[1,5-a]pyridines 1 (Scheme 2). Electron-do-
nating functional groups such as methyl at different posi-
tions (1b,c) afforded C8-alkenylation products in superior
yields (~90%), with the exception that a methoxy group (1d)
gave an average yield of 67%. Nevertheless, the yield of this
reaction could be increased to 90% by elevating the tem-
perature of the reaction to 100 °C in the presence of AlMe3
(60 mol%). 5-Arylimidazopyridines possessing electron-
withdrawing groups such as CF3 (1f) and CO2Et (1g) were
also feasible substrates producing high yields of the corre-
sponding alkenylated products 3fa and 3ga. However, fluo-
ro derivative 1e was a less impressive substrate in terms of
the isolated yield of the alkenylated product 3ea. Notably,
this procedure could also be extended to long-chain and
sterically hindered 5-alkylimidazopyridines 1h–j leading to
good conversions.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

C
C.-Y. Liu et al.
Special Topic
Synthesis
ucts 6bb and 6cb, respectively. In contrast, substrates pos-
sessing electron-withdrawing components 5d–g furnished
rather lower yields (~45%) in this reaction, but still main-
tained high selectivity toward C(8)–H activation. Finally,
hydroheteroarylation of alkyne 2b could also be performed
with 3-tert-butylimidazopyridine (5h) to afford a good
yield of product 6hb.
R2
R1
Ni(cod)2 (5 mol%)
IMes (5 mol%)
N
R1
R2
+
N
N
AlMe3 (60 mol%)
toluene, 100 °C, 12 h
2
N
Ph
(1.2 equiv)
Ph
1a
(0.5 mmol)
3
Me
t-Bu
t-Bu
t-Bu
R2
Ph
Me
R1
Ni(cod)2 (5 mol%)
PCy3 (20 mol%)
R1
R2
N
+
N
N
N
N
N
AlMe3 (1.0 equiv)
toluene, 100 °C, 6 h
N
N
N
2
N
R3
(1.1 equiv)
Ph
3ab, 70%
Ph
3aa, 95%
Ph
3ac, 62%
R3
5
6
(0.5 mmol)
F3C
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
Ph
n-Pr
Me
t-Bu
t-Bu
Ph
n-Pr
Me
Me
Ph
N
N
N
N
N
N
N
N
N
N
N
N
N
N
Ph
Ph
3ad, 85%
Ph
3af, 79%
N
N
3ae, 87%
Ph
Ph
Ph
TMS
i-Pr
n-Pr
Me
n-Bu
OMe
Me
n-Pr
6aa, 46%
t-Bu
6ab, 83%
t-Bu
6ag, 44%b
t-Bu
6bb, 83%
t-Bu
6cb, 68%
t-Bu
N
N
N
N
N
Ph
Ph
N
Ph
Ph
Ph
3ah, 71%
Ph
3ai, 90%
Ph
Ph
3ag,17%
N
N
N
N
N
N
N
N
N
t-Bu
Scheme 3 C8-Alkenylation of 1a with different alkynes. Reagents and
conditions: 1a (0.5 mmol), 2 (0.6 mmol), Ni(cod)2 (5 mol%), IMes (5
mol%), toluene (2 mL), AlMe3 (60 mol%), 100 °C; E/Z ratio = 99:1.
N
F
CF3
Ph
F
6db, 36%
6eb, 30%
6fb, 43%
6gb, 38%
6hb, 59%
At this stage, we also wanted to further examine the vi-
ability of this catalytic reaction with various 3-phenylimid-
azo[1,5-a]pyridines 5, which might perhaps be valuable for
the future study of photosensitive compounds (Scheme 4).
Using Ni(cod)2 (5 mol%), PCy3 (20 mol%) and AlMe3 (1
equiv) as the additive, we found that alkyne 2b (6ab, 83%)
was more reactive than the less bulky alkynes 2a (6aa, 46%)
and 2g (6ag, 44%). These results again stressed the need for
bulky alkynes in order to avoid the possible competing
alkyne cyclotrimerization reaction. Interestingly, we also
found that the 1,3-dimesitylimidazolium (IMes) ligand was
not the suitable for the reaction of 3-phenylimidazopyri-
dine 5a, affording an isolated yield of 8%.10 We speculated
that the electronic difference between the topologies of 3-
phenyl- and 5-phenylimidazopyridine derivatives might
dictate the reactivity based on the nature of the ligand as a
strong σ-donor or π-acceptor. In this regard, a π-acceptor li-
gand such as phosphine is a more effective scaffold than
IMes to mediate the C–H activation of 3-phenylimidazopyr-
idine.10 Next, we systematically investigated the influence
of different 3-arylimidazopyridine derivatives. Substrates
with methyl (5b) and methoxy (5c) functional groups were
converted in good 83% and 68% yields into the final prod-
Scheme 4 C8-Alkenylation with 3-imidazopyridines 5. Reagents and
conditions: 5 (0.5 mmol), 2 (5.5 mmol), Ni(cod)2 (5 mol%), PCy3 (20
mol%), toluene (2 mL), AlMe3 (1.0 equiv), 100 °C; E/Z ratio = 99:1.
a 130 °C, alkyne 2g (1.5 equiv).
In summary, without resorting to installing a directing
group on the imidazopyridine, we have established a new
method for the C–H bond functionalization of imidazo[1,5-
a]pyridines. The catalytic paradigm features a synergistic
interaction between Ni, Al and different ligands to impart
rather remote C–H activation via alkenylation at the C-8 po-
sition of the substrate, which is considered to be unprece-
dented. Ongoing work seeks to gain a detailed mechanistic
understanding of the behavior of the C–H activation occur-
ring at the C-8 position.
Dry solvents were obtained by purification methods according to the
literature.11 IMes,12 IPr,12a,13 and imidazo[1,5-a]pyridines14 were pre-
pared according to literature procedures. Unless otherwise noted, all
other reagents were purchased from Acros, Alfa Aesar, Merck, Sigma-
Aldrich and Strem and were used without purification. All air-sensi-
tive manipulations were performed under an atmosphere of nitrogen
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

D
C.-Y. Liu et al.
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Synthesis
using Schlenk techniques or in a glovebox. 1H and 13C NMR spectra
were recorded using Bruker 300 MHz or 400 MHz spectrometers. The
residual proton of the deuterated solvent (CDCl3, 1H NMR: 7.24 ppm)
or the carbon of the solvent (CDCl3, 13C NMR: 77.0 ppm) were used as
references. Data are reported in the following order: chemical shift
(δ); multiplicity [s (singlet), d (doublet), t (triplet), q (quartet), sext
(sextet), m (multiplet)]; coupling constant, J (Hz); integration. High-
resolution mass spectra were obtained with a JEOL, JMS-700 spec-
trometer.
13C NMR (75 MHz, CDCl3): δ = 141.2, 138.7, 136.0, 133.8, 133.1, 130.6,
130.0, 128.8, 128.6, 126.9, 125.0, 121.0, 116.4, 112.9, 32.8, 30.6, 21.2,
17.4.
HRMS (APCI): m/z [M + H]+ calcd for C21H25N2: 305.2018; found:
305.2010.
(E)-8-(4,4-Dimethylpent-2-en-2-yl)-5-(4-methoxyphenyl)imid-
azo[1,5-a]pyridine (3da)
The reaction was performed according to general procedure A, with
the exception that 0.6 equiv of AlMe3 were used at 100 °C for 12 h.
C8-Alkenylation of 5-Substituted Imidazo[1,5-a]pyridines; Gener-
al Procedure A
Yield: 144 mg (90%); yellow oil.
1H NMR (300 MHz, CDCl3): δ = 8.16 (s, 1 H), 7.56–7.47 (m, 3 H), 7.01
(d, 3JHH = 8.7 Hz, 2 H), 6.60 (d, 3JHH = 6.9 Hz, 1 H), 6.41 (d, 3JHH = 6.9 Hz,
1 H), 5.97–5.93 (m, 1 H), 3.86 (s, 3 H), 2.18 (d, 3JHH = 0.9 Hz, 3 H), 1.23
(s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 160.4, 141.4, 136.0, 133.0, 130.9, 130.8,
129.6, 127.0, 126.4, 121.1, 116.6, 114.5, 112.9, 55.4, 33.0, 30.8, 17.6.
In a glovebox, a vial (20 mL) was charged with Ni(cod)2 (7 mg, 5
mol%), IMes (7.7 mg, 5 mol%) and 1 (0.5 mmol) in dry toluene (2 mL).
The mixture was stirred for 5 min, followed by the addition of AlMe3
(0.1 mL, 1.0 M in toluene, 20 mol%). After stirring for 5 min, alkyne 2
(1.2 equiv) was added. The vial was screw-capped and taken outside
the glovebox. Following 6 h of stirring at 60 °C, the reaction mixture
was added to CH2Cl2, stirred under air for 10 min, filtered through a
pad of Celite and then concentrated in vacuo. The residue was puri-
fied by flash chromatography on silica gel (EtOAc–hexane, 1:1) to af-
ford the product.
HRMS (APCI): m/z [M + H]+ calcd for C21H25N2O: 321.1967; found:
321.1960.
(E)-8-(4,4-Dimethylpent-2-en-2-yl)-5-(4-fluorophenyl)imid-
azo[1,5-a]pyridine (3ea)
(E)-8-(4,4-Dimethylpent-2-en-2-yl)-5-phenylimidazo[1,5-a]pyri-
dine (3aa)
The reaction was performed according to general procedure A, with
the exception that 0.6 equiv of AlMe3 were used at 100 °C for 12 h.
The reaction was performed according to general procedure A.
Yield: 66 mg (43%); yellow oil.
Yield: 138 mg (95%); yellow solid.
1H NMR (300 MHz, CDCl3): δ = 8.09 (s, 1 H), 7.62–7.54 (m, 2 H), 7.51
1H NMR (300 MHz, CDCl3): δ = 8.16 (s, 1 H), 7.64–7.45 (m, 6 H), 6.62
(s, 1 H), 7.25–7.16 (m, 2 H), 6.61 (d, 3JHH = 6.8 Hz, 1 H), 6.43 (d, 3JHH
=
3
(d, 3JHH = 6.8 Hz, 1 H), 6.47 (d, JHH = 6.8 Hz, 1 H), 5.98–5.95 (m, 1 H),
6.8 Hz, 1 H), 5.97–5.94 (m, 1 H), 2.18 (d, 3JHH = 1.1 Hz, 3 H), 1.24 (s, 9
2.19 (d, 3JHH = 1.1 Hz, 3 H), 1.25 (s, 9 H).
H).
13C NMR (75 MHz, CDCl3): δ = 141.2, 136.2, 133.8, 132.9, 130.7, 130.6,
129.3, 128.9, 128.0, 126.8, 121.0, 116.4, 113.0, 32.8, 30.6, 17.4.
HRMS (APCI): m/z [M + H]+ calcd for C20H23N2: 291.1861; found:
291.1862.
13C NMR (75 MHz, CDCl3): δ = 163.2 (d, 1JCF = 248.3 Hz), 141.6, 136.7,
132.0, 131.0, 130.7, 130.3 (d, 3JCF = 8.2 Hz), 126.8, 121.4, 116.4 (d, 2JCF
=
21.5 Hz), 113.4, 33.1, 30.8, 17.6.
HRMS (APCI): m/z [M + H]+ calcd for C20H22N2F: 309.1767; found:
309.1766.
(E)-8-(4,4-Dimethylpent-2-en-2-yl)-5-(p-tolyl)imidazo[1,5-a]pyri-
dine (3ba)
(E)-8-(4,4-Dimethylpent-2-en-2-yl)-5-[4-(trifluoromethyl)phe-
nyl]imidazo[1,5-a]pyridine (3fa)
The reaction was performed according to general procedure A, but re-
duced to 0.1 mmol scale.
The reaction was performed according to general procedure A, with
the exception that 0.6 equiv of AlMe3 were used at 100 °C for 12 h.
Yield: 25 mg (82%); yellow oil.
1H NMR (300 MHz, CDCl3): δ = 8.17 (s, 1 H), 7.49 (d, 3JHH = 7.9 Hz, 3 H),
7.31 (d, 3JHH = 8.0 Hz, 2 H), 6.61 (d, 3JHH = 7.0 Hz, 1 H), 6.44 (d, 3JHH = 6.9
Hz, 1 H), 5.97–5.94 (m, 1 H), 2.43 (s, 3 H), 2.19 (d, 3JHH = 1.1 Hz, 3 H),
1.24 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 141.4, 139.6, 136.2, 133.2, 131.2, 130.9,
130.8, 129.8, 128.1, 127.0, 121.1, 116.6, 113.0, 33.0, 30.8, 21.3, 17.6.
Yield: 156 mg (87%); yellow oil.
1H NMR (300 MHz, CDCl3): δ = 8.12 (s, 1 H), 7.80–7.69 (m, 4 H), 7.53
3
3
(s, 1 H), 6.62 (d, JHH = 6.8 Hz, 1 H), 6.47 (d, JHH = 6.9 Hz, 1 H), 5.97–
5.94 (m, 1 H), 2.18 (d, 3JHH = 1.1 Hz, 3 H), 1.23 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 141.8, 137.5 (d, 3JCF = 13.8 Hz), 131.4 (q,
2JCF = 33.0 Hz), 131.4, 130.9, 130.5, 128.6, 126.6, 126.2 (d, 4JCF = 3.3 Hz),
123.7 (q, 1JCF = 270.8 Hz), 121.7, 116.3, 114.1, 33.0, 30.7, 17.5.
HRMS (APCI): m/z [M + H]+ calcd for C21H25N2: 305.2018; found:
305.2012.
HRMS (ESI): m/z [M + H]+ calcd for C21H22N2F3: 359.1735; found:
359.1743.
(E)-8-(4,4-Dimethylpent-2-en-2-yl)-5-(m-tolyl)imidazo[1,5-a]pyr-
idine (3ca)
Ethyl (E)-4-{8-(4,4-Dimethylpent-2-en-2-yl)imidazo[1,5-a]pyri-
din-5-yl}benzoate (3ga)
The reaction was performed according to general procedure A.
Yield: 146 mg (96%); yellow oil.
The reaction was performed according to general procedure A, with
the exception that 0.6 equiv of AlMe3 were used at 100 °C for 12 h.
1H NMR (300 MHz, CDCl3): δ = 8.17 (s, 1 H), 7.50 (s, 1 H), 7.45–7.37
(m, 3 H), 7.32–7.25 (m, 1 H), 6.61 (d, 3JHH = 6.9 Hz, 1 H), 6.45 (d, 3JHH
=
Yield: 159 mg (88%); yellow oil.
6.9 Hz, 1 H), 5.98–5.94 (m, 1 H), 2.42 (s, 3 H), 2.19 (d, 3JHH = 1.5 Hz, 3
H), 1.25 (s, 9 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

E
C.-Y. Liu et al.
Special Topic
Synthesis
3
1H NMR (300 MHz, CDCl3): δ = 8.21–8.14 (m, 3 H), 7.68 (d, JHH = 8.3
1H NMR (300 MHz, CDCl3): δ = 8.17 (s, 1 H), 7.59 (s, 1 H), 7.58–7.42
(m, 5 H), 7.34–7.25 (m, 5 H), 6.45–6.34 (m, 3 H), 1.03 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 142.8, 140.0, 135.4, 134.2, 133.9, 133.2,
130.9, 130.0, 129.5, 129.1, 128.1, 127.7, 127.1, 127.0, 121.6, 119.1,
113.0, 34.3, 31.1.
Hz, 2 H), 7.52 (s, 1 H), 6.61 (d, 3JHH = 6.9 Hz, 1 H), 6.50 (d, 3JHH = 6.9 Hz,
1 H), 5.95 (s, 1 H), 4.40 (q, JHH = 7.1 Hz, 2 H), 2.18 (s, 3 H), 1.40 (t,
3
3JHH = 7.2 Hz, 3 H), 1.23 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 165.7, 141.8, 138.2, 137.2, 132.0, 131.4,
130.9, 130.6, 130.4, 128.1, 126.8, 121.6, 116.4, 114.0, 61.2, 33.0, 30.8,
17.6, 14.3.
HRMS (ESI): m/z [M + H]+ calcd for C25H25N2: 353.2018; found:
353.2010.
HRMS (APCI): m/z [M + H]+ calcd for C23H27N2O2: 363.2073; found:
363.2071.
(E)-8-[3,3-Dimethyl-1-(p-tolyl)but-1-en-1-yl]-5-phenylimid-
azo[1,5-a]pyridine (3ac)
(E)-8-(4,4-Dimethylpent-2-en-2-yl)-5-octylimidazo[1,5-a]pyri-
dine (3ha)
The reaction was performed according to general procedure A, with
the exception that 0.6 equiv of AlMe3 were used at 100 °C for 12 h.
The reaction was performed according to general procedure A, with
the exception that 0.6 equiv of AlMe3 were used at 100 °C for 12 h.
Yield: 114 mg (62%); yellow solid.
1H NMR (400 MHz, CDCl3): δ = 8.22 (s, 1 H), 7.64–7.62 (m, 3 H), 7.57–
7.51 (m, 3 H), 7.25–7.18 (m, 4 H), 6.47–6.42 (m, 3 H), 2.42 (s, 3 H),
1.10 (s, 9 H).
13C NMR (100 MHz, CDCl3): δ = 142.6, 139.8, 137.2, 135.5, 134.3,
133.9, 133.1, 131.0, 130.6, 129.4, 129.0, 128.1, 127.8, 127.5, 127.1,
126.9, 121.5, 119.0, 113.0, 34.2, 31.1, 21.3.
Yield: 121 mg (74%); yellow oil.
1H NMR (300 MHz, CDCl3): δ = 8.04 (s, 1 H), 7.47 (s, 1 H), 6.49 (d,
3JHH = 6.9 Hz, 1 H), 6.30 (d, 3JHH = 6.9 Hz, 1 H), 5.88–5.85 (m, 1 H), 2.78
3
3
(t, JHH = 7.6 Hz, 2 H), 2.12 (d, JHH = 1.2 Hz, 3 H), 1.82–1.67 (m, 2 H),
1.50–1.10 (m, 19 H), 0.90–0.79 (m, 3 H).
13C NMR (75 MHz, CDCl3): δ = 141.1, 135.0, 132.9, 130.8, 130.5, 125.4,
121.0, 116.2, 110.3, 32.8, 31.7, 31.3, 30.7, 29.3, 29.2, 29.1, 25.6, 22.5,
17.6, 14.0.
HRMS (ESI): m/z [M + H]+ calcd for C26H27N2: 367.2169; found:
367.2166.
HRMS (ESI): m/z [M + H]+ calcd for C22H35N2: 327.2800; found:
327.2792.
(E)-8-[3,3-Dimethyl-1-(m-tolyl)but-1-en-1-yl]-5-phenylimid-
azo[1,5-a]pyridine (3ad)
The reaction was performed according to general procedure A, with
the exception that 0.6 equiv of AlMe3 were used at 100 °C for 12 h.
(E)-8-(4,4-Dimethylpent-2-en-2-yl)-5-(4,4-dimethylpentyl)imid-
azo[1,5-a]pyridine (3ia)
Yield: 156 mg (85%); yellow solid.
The reaction was performed according to general procedure A.
1H NMR (400 MHz, CDCl3): δ = 8.21 (s, 1 H), 7.64–7.59 (m, 3 H), 7.54–
7.48 (m, 3 H), 7.28–7.23 (m, 1 H), 7.15–7.13 (m, 3 H), 6.45–6.40 (m, 3
H), 2.38 (s, 3 H), 1.08 (s, 9 H).
13C NMR (100 MHz, CDCl3): δ = 142.6, 139.8, 137.2, 135.5, 134.3,
133.9, 133.1, 131.0, 130.6, 129.4, 129.0, 128.1, 127.8, 127.5, 127.1,
126.9, 121.5, 119.0, 113.0, 34.2, 31.1, 21.3.
Yield: 138 mg (88%); yellow oil.
1H NMR (300 MHz, CDCl3): δ = 8.02 (s, 1 H), 7.46 (s, 1 H), 6.48 (d, 3JHH
=
3
6.8 Hz, 1 H), 6.30 (d, JHH = 6.8 Hz, 1 H), 5.87–5.83 (m, 1 H), 2.73 (t,
3
3JHH = 7.6 Hz, 2 H), 2.10 (d, JHH = 0.9 Hz, 3 H), 1.78–1.63 (m, 2 H),
1.35–1.10 (m, 11 H), 0.83 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 141.0, 135.0, 132.9, 130.7, 130.4, 125.3,
120.9, 116.1, 110.2, 43.8, 32.8, 32.0, 30.7, 30.2, 29.1, 20.8, 17.5.
HRMS (ESI): m/z [M + H]+ calcd for C21H33N2: 313.2644; found:
HRMS (ESI): m/z [M + H]+ calcd for C26H27N2: 367.2169; found:
367.2166.
313.2644.
(E)-8-[3,3-Dimethyl-1-(o-tolyl)but-1-en-1-yl]-5-phenylimid-
azo[1,5-a]pyridine (3ae)
(E)-8-(4,4-Dimethylpent-2-en-2-yl)-5-(trimethylsilyl)imidazo[1,5-
a]pyridine (3ja)
The reaction was performed according to general procedure A, with
the exception that 0.6 equiv of AlMe3 were used at 100 °C for 12 h.
The reaction was performed according to general procedure A, with
the exception that 0.6 equiv of AlMe3 were used for 24 h.
Yield: 159 mg (87%); yellow solid.
1H NMR (400 MHz, CDCl3): δ = 8.23 (s, 1 H), 7.80 (s, 1 H), 7.61–7.59
Yield: 140 mg (98%); black oil.
(m, 2 H), 7.53–7.50 (m, 3 H), 7.32–7.20 (m, 4 H), 6.99 (s, 1 H), 6.36 (d,
1H NMR (300 MHz, CDCl3): δ = 8.17 (s, 1 H), 7.46 (s, 1 H), 6.66 (d, 3JHH
=
3JHH = 7.2 Hz, 1 H), 6.30 (d, JHH = 6.8 Hz, 1 H), 2.16 (s, 3 H), 1.04 (s, 9
3
3
6.6 Hz, 1 H), 6.48 (d, JHH = 6.8 Hz, 1 H), 5.92–5.89 (m, 1 H), 2.15 (d,
H).
3JHH = 1.1 Hz, 3 H), 1.22 (s, 9 H), 0.41 (s, 9 H).
13C NMR (100 MHz, CDCl3): δ = 142.8, 139.3, 136.6, 134.3, 133.9,
133.2, 133.0, 131.0, 130.9, 130.0, 129.5, 129.1, 128.1, 127.5, 127.1,
124.8, 121.6, 118.7, 113.1, 34.4, 30.5, 19.9.
13C NMR (75 MHz, CDCl3): δ = 141.3, 138.2, 133.5, 130.7, 129.5, 128.7,
121.4, 120.2, 115.1, 32.8, 30.6, 17.3, –2.3.
HRMS (ESI): m/z [M + H]+ calcd for C17H27N2Si: 287.1944; found:
HRMS (ESI): m/z [M + H]+ calcd for C26H27N2: 367.2169; found:
287.1947.
367.2166.
(E)-8-(3,3-Dimethyl-1-phenylbut-1-en-1-yl)-5-phenylimidazo[1,5-
a]pyridine (3ab)
(E)-8-{3,3-Dimethyl-1-[4-(trifluoromethyl)phenyl]but-1-en-1-yl}-
5-phenylimidazo[1,5-a]pyridine (3af)
The reaction was performed according to general procedure A, with
the exception that 0.6 equiv of AlMe3 were used at 100 °C for 12 h.
The reaction was performed according to general procedure A, with
the exception that 0.6 equiv of AlMe3 were used at 100 °C for 12 h.
Yield: 123 mg (70%); yellow solid.
Yield: 166 mg (79%); yellow solid.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

F
C.-Y. Liu et al.
Special Topic
Synthesis
1H NMR (300 MHz, CDCl3): δ = 8.20 (s, 1 H), 7.63–7.42 (m, 10 H), 6.47
the glovebox. Following 6 h of stirring at 100 °C, the reaction mixture
was added to CH2Cl2, stirred under air for 10 min, filtered through a
pad of Celite and then concentrated in vacuo. The residue was puri-
fied by flash chromatography on silica gel (EtOAc–hexane, 1:9) to af-
ford compounds 6 as the major products.
(s, 1 H), 6.42 (d, 3JHH = 7.5 Hz, 1 H), 6.33 (d, 3JHH = 6.9 Hz, 1 H), 1.04 (s, 9
H).
13C NMR (125 MHz, CDCl3): δ = 143.94, 143.89, 134.1, 133.6, 133.7,
3
133.5, 130.8, 130.4, 129.6, 129.4, 129.2, 128.2, 127.2, 124.8 (d, JCF
=
3.8 Hz), 124.1 (q, 1JCF = 270.4 Hz), 121.5, 119.4, 112.9, 34.4, 32.2.
(E)-8-(4,4-Dimethylpent-2-en-2-yl)-3-phenylimidazo[1,5-a]pyri-
dine (6aa)
HRMS (ESI): m/z [M + H]+ calcd for C26H24F3N2: 421.1886; found:
421.1884.
The reaction was performed according to general procedure B.
Yield: 67 mg (46%); yellow solid.
(E)-8-(Oct-4-en-4-yl)-5-phenylimidazo[1,5-a]pyridine (3ag)
The reaction was performed according to general procedure A, with
the exception that 0.6 equiv of AlMe3 were used at 100 °C for 12 h.
1H NMR (300 MHz, CDCl3): δ = 8.15–8.07 (m, 1 H), 7.79–7.73 (m, 2 H),
7.55 (s, 1 H), 7.49 (t, JHH = 7.5 Hz, 2 H), 7.40 (t, JHH = 7.3 Hz, 1 H),
6.55–6.49 (m, 2 H), 5.93 (d, 3JHH = 1.1 Hz, 1 H), 2.18 (d, 3JHH = 1.0 Hz, 3
H), 1.24 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 141.5, 138.5, 138.1, 131.3, 130.8, 130.6,
128.9, 128.4, 128.0, 121.1, 119.4, 115.8, 113.2, 33.0, 33.8, 17.7.
3
3
Yield: 26 mg (17%); yellow solid.
1H NMR (300 MHz, CDCl3): δ = 8.17 (s, 1 H), 7.67–7.43 (m, 6 H), 6.63
(d, 3JHH = 6.8 Hz, 1 H), 6.46 (d, 3JHH = 6.9 Hz, 1 H), 5.91 (t, 3JHH = 7.3 Hz,
1 H), 2.52 (t, 3JHH = 7.1 Hz, 2 H), 2.32–2.16 (m, 2 H), 1.60–1.30 (m, 4 H),
0.98 (t, 3JHH = 7.4 Hz, 3 H), 0.88 (t, 3JHH = 7.3 Hz, 3 H).
HRMS (ESI): m/z [M + H]+ calcd for C20H23N2: 291.1861; found:
291.1862.
13C NMR (75 MHz, CDCl3): δ = 136.8, 134.1, 133.9, 133.1, 131.6, 131.4,
129.5, 129.1, 128.2, 126.9, 121.2, 116.9, 113.2, 32.1, 30.3, 22.9, 21.8,
13.9.
HRMS (ESI): m/z [M + H]+ calcd for C21H25N2: 305.2018; found:
305.2018.
(E)-8-(3,3-Dimethyl-1-phenylbut-1-en-1-yl)-3-phenylimidazo[1,5-
a]pyridine (6ab)
The reaction was performed according to general procedure B.
Yield: 146 mg (83%); yellow solid.
3
1H NMR (300 MHz, CDCl3): δ = 8.09 (d, JHH = 7.1 Hz, 1 H), 7.77–7.71
(E)-8-(4-Methylpent-2-en-2-yl)-5-phenylimidazo[1,5-a]pyridine
(3ah)
3
(m, 2 H), 7.60 (s, 1 H), 7.53–7.25 (m, 8 H), 6.44 (t, JHH = 6.9 Hz, 1 H),
The reaction was performed according to general procedure A, with
the exception that 0.6 equiv of AlMe3 were used at 100 °C for 12 h.
6.38 (s, 1 H), 6.31 (d, 3JHH = 6.6 Hz, 1 H), 1.02 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 143.1, 140.1, 138.6, 136.0, 135.6, 131.5,
130.6, 130.1, 129.0, 128.6, 128.1, 127.9, 127.3, 121.5, 119.7, 118.5,
113.1, 34.4, 31.3.
Yield: 98 mg (71%); yellow solid.
1H NMR (300 MHz, CDCl3): δ = 8.12 (s, 1 H), 7.63–7.43 (m, 6 H), 6.64
(d, 3JHH = 6.9 Hz, 1 H), 6.45 (d, JHH = 6.8 Hz, 1 H), 5.90–5.82 (m, 1 H),
HRMS (ESI): m/z [M + H]+ calcd for C25H25N2: 353.2018; found:
3
2.85–2.65 (m, 1 H), 2.11–2.07 (m, 3 H), 1.07 (d, 3JHH = 6.7 Hz, 6 H).
353.2012.
13C NMR (75 MHz, CDCl3): δ = 139.0, 134.5, 134.0, 133.1, 130.7, 129.4,
129.3, 129.1, 128.2, 127.0, 121.3, 116.5, 113.2, 27.7, 22.7, 16.2.
(E)-8-(Oct-4-en-4-yl)-3-phenylimidazo[1,5-a]pyridine (6ag)
HRMS (ESI): m/z [M + H]+ calcd for C19H21N2: 277.1705; found:
277.1707.
The reaction was performed according to general procedure B, with
the exception that 1.5 equiv of the alkyne were used at 130 °C.
Yield: 67 mg (44%); yellow solid.
1H NMR (400 MHz, CDCl3): δ = 8.12 (d, 3JHH = 6.2 Hz, 1 H), 7.77 (d, 3JHH
= 7.6 Hz, 2 H), 7.56 (s, 1 H), 7.49 (t, 3JHH = 7.5 Hz, 2 H), 7.40 (t, 3JHH = 7.3
(E)-5-Phenyl-8-[1-(trimethylsilyl)hex-1-en-2-yl]imidazo[1,5-
a]pyridine (3ai)
The reaction was performed according to general procedure A, with
the exception that 0.6 equiv of AlMe3 were used at 100 °C for 12 h.
Hz, 1 H), 6.56–6.47 (m, 2 H), 5.88 (t, 3JHH = 7.3 Hz, 1 H), 2.51 (t, 3JHH
=
7.6 Hz, 2 H), 2.23 (q, 3JHH = 7.3 Hz, 2 H), 1.50 (sext, 3JHH = 7.3 Hz, 2 H),
1.37 (sext, 3JHH = 7.4 Hz, 2 H), 0.98 (t, 3JHH = 7.4 Hz, 3 H), 0.88 (t, 3JHH
=
Yield: 157 mg (90%); yellow solid.
7.3 Hz, 3 H).
1H NMR (400 MHz, CDCl3): δ = 8.19 (s, 1 H), 7.64–7.62 (m, 2 H), 7.54–
13C NMR (100 MHz, CDCl3): δ = 138.5, 136.9, 135.6, 131.9, 131.6,
130.7, 128.9, 128.5, 128.1, 121.0, 119.5, 116.2, 113.2, 32.2, 30.3, 22.9,
21.8, 14.0, 13.9.
HRMS (ESI): m/z [M + H]+ calcd for C21H25N2: 305.2018; found:
305.2017.
3
3
7.47 (m, 4 H), 6.67 (d, JHH = 7.2 Hz, 1 H), 6.48 (d, JHH = 6.8 Hz, 1 H),
3
6.00 (s, 1 H), 2.64 (t, JHH = 7.2 Hz, 2 H), 1.37–1.30 (m, 4 H), 0.86 (t,
3JHH = 6.8 Hz, 3 H), 0.23 (s, 9 H).
13C NMR (100 MHz, CDCl3): δ = 154.1, 134.6, 134.0, 133.6, 131.1,
130.6, 129.6, 129.2, 128.3, 127.0, 121.4, 116.4, 113.1.
HRMS (ESI): m/z [M + H]+ calcd for C22H29N2Si: 349.2095; found:
349.2091.
(E)-8-(3,3-Dimethyl-1-phenylbut-1-en-1-yl)-3-(p-tolyl)imid-
azo[1,5-a]pyridine (6bb)
The reaction was performed according to general procedure B.
C8-Alkenylation of 3-Substituted Imidazo[1,5-a]pyridines; Gener-
Yield: 152 mg (83%); yellow solid.
al Procedure B
3
In a glovebox, a vial (20 mL) was charged with Ni(cod)2 (7 mg, 5
mol%), PCy3 (28 mg, 20 mol%) and 5 (0.5 mmol) in dry toluene (2 mL).
The mixture was stirred for 5 min, followed by the addition of AlMe3
(0.5 mL, 1.0 M in toluene, 100 mol%). After stirring for 5 min, alkyne 2
(1.1 equiv) was added. The vial was screw-capped and taken outside
1H NMR (300 MHz, CDCl3): δ = 8.06 (d, JHH = 7.1 Hz, 1 H), 7.63 (d,
3JHH = 8.1 Hz, 2 H), 7.57 (s, 1 H), 7.33–7.27 (m, 7 H), 6.42 (t, 3JHH = 7.0
Hz, 1 H), 6.37 (s, 1 H), 6.28 (d, 3JHH = 6.5 Hz, 1 H), 2.40 (s, 3 H), 1.02 (s,
9 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

G
C.-Y. Liu et al.
Special Topic
Synthesis
13C NMR (75 MHz, CDCl3): δ = 142.8, 140.0, 138.5, 138.3, 135.7, 135.4,
131.1, 129.9, 129.4, 127.8, 127.7, 127.5, 127.1, 121.1, 119.5, 118.2,
112.8, 34.2, 31.1, 21.2.
HRMS (ESI): m/z [M + H]+ calcd for C26H27N2: 367.2174; found:
367.2178.
13C NMR (75 MHz, CDCl3): δ = 163.0 (d, 1JCF = 245.2 Hz), 143.3, 140.0,
137.1, 136.1, 135.4, 132.5 (d, JCF = 8.3 Hz), 131.7, 130.5 (d, JCF = 8.4
Hz), 130.0, 127.8, 127.3, 123.5, 121.7, 119.4, 118.7, 115.4 (d, 2JCF = 21.0
Hz), 114.9 (d, 2JCF = 22.8 Hz), 113.5, 34.4, 31.2.
3
3
HRMS (ESI): m/z [M + H]+ calcd for C25H24N2F: 371.1924; found:
371.1920.
(E)-8-(3,3-Dimethyl-1-phenylbut-1-en-1-yl)-3-(4-methoxyphe-
nyl)imidazo[1,5-a]pyridine (6cb)
(E)-3-([1,1′-Biphenyl]-4-yl)-8-(3,3-dimethyl-1-phenylbut-1-en-1-
yl)imidazo[1,5-a]pyridine (6gb)
The reaction was performed according to general procedure B.
The reaction was performed according to general procedure B.
Yield: 130 mg (68%); yellow solid.
Yield: 81 mg (38%); yellow solid.
3
1H NMR (300 MHz, CDCl3): δ = 8.01 (d, JHH = 7.1 Hz, 1 H), 7.70–7.63
3
(m, 2 H), 7.55 (s, 1 H), 7.32–7.26 (m, 5 H), 7.05–6.99 (m, 2 H), 6.41 (t,
3JHH = 6.9 Hz, 1 H), 6.37 (s, 1 H), 6.30–6.24 (m, 1 H), 3.85 (s, 3 H), 1.01
(s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 159.7, 142.8, 140.0, 138.3, 135.7, 135.4,
130.9, 130.0, 129.4, 127.7, 127.1, 122.8, 120.9, 119.5, 118.1, 114.2,
112.7, 55.2, 34.2, 31.1.
1H NMR (300 MHz, CDCl3): δ = 8.16 (d, JHH = 7.1 Hz, 1 H), 7.84 (d,
3
3JHH = 8.3 Hz, 2 H), 7.73 (d, JHH = 8.2 Hz, 2 H), 7.68–7.61 (m, 3 H),
3
7.51–7.26 (m, 8 H), 6.47 (t, JHH = 6.9 Hz, 1 H), 6.39 (s, 1 H), 6.33 (d,
3JHH = 6.8 Hz, 1 H), 1.03 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 143.1, 141.1, 140.3, 140.0, 138.2, 135.9,
135.4, 131.5, 130.0, 129.4, 128.8, 128.3, 128.1, 127.8, 127.5, 127.2,
127.0, 121.6, 119.7, 118.4, 113.1, 34.3, 31.1.
HRMS (ESI): m/z [M + H]+ calcd for C26H27N2O: 383.2123; found:
383.2122.
HRMS (ESI): m/z [M + H]+ calcd for C31H29N2: 429.2331; found:
429.2325.
(E)-8-(3,3-Dimethyl-1-phenylbut-1-en-1-yl)-3-(4-fluorophe-
nyl)imidazo[1,5-a]pyridine (6db)
(E)-3-(tert-Butyl)-8-(3,3-dimethyl-1-phenylbut-1-en-1-yl)imid-
azo[1,5-a]pyridine (6hb)
The reaction was performed according to general procedure B.
The reaction was performed according to general procedure B.
Yield: 67mg (36%); yellow solid.
Yield: 98 mg (59%); yellow solid.
3
1H NMR (400 MHz, CDCl3): δ = 7.99 (d, JHH = 7.1 Hz, 1 H), 7.74–7.69
3
(m, 2 H), 7.57 (s, 1 H), 7.35–7.25 (m, 5 H), 7.18 (t, JHH = 8.7 Hz, 2 H),
1H NMR (400 MHz, CDCl3): δ = 7.88 (d, 3JHH = 7.4 Hz, 1 H), 7.41 (s, 1 H),
3
6.44 (t, 3JHH = 6.9 Hz, 1 H), 6.36 (s, 1 H), 6.31 (d, 3JHH = 6.7 Hz, 1 H), 1.02
7.32–7.21 (m, 5 H), 6.37 (t, JHH = 7.0 Hz, 1 H), 6.31 (s, 1 H), 6.20 (d,
(s, 9 H).
3JHH = 6.8 Hz, 1 H), 1.52 (s, 9 H), 0.98 (s, 9 H).
13C NMR (100 MHz, CDCl3): δ = 162.7 (d, 1JCF = 247.4 Hz), 143.1, 140.0,
137.5, 136.0, 135.4, 131.4, 129.9 (d, 3JCF = 8.3 Hz), 127.8, 127.2, 126.7,
121.4, 119.3, 118.4, 116.0 (d, 2JCF = 21.8 Hz), 113.2, 34.3, 31.1.
13C NMR (75 MHz, CDCl3): δ = 145.2, 142.8, 140.2, 136.0, 135.5, 131.5,
130.0, 127.7, 127.0, 120.9, 118.8, 116.8, 111.6, 34.3, 33.3, 31.1, 28.0.
HRMS (ESI): m/z [M + H]+ calcd for C23H29N2: 333.2331, found:
333.2338.
HRMS (ESI): m/z [M + H]+ calcd for C25H24N2F: 371.1924; found:
371.1916.
(E)-8-(3,3-Dimethyl-1-phenylbut-1-en-1-yl)-3-[4-(trifluorometh-
yl)phenyl]imidazo[1,5-a]pyridine (6eb)
Acknowledgment
This work is financially supported by the Ministry of Science & Tech-
nology of Taiwan (MOST-104-2628-M-001-005-MY4 grant) and by an
Academia Sinica Career Development Award (104-CDA-M08). We are
grateful to Dr. Mei-Chun Tseng for the mass spectrometric analyses.
The reaction was performed according to general procedure B.
Yield: 63 mg (30%); yellow solid.
3
1H NMR (400 MHz, CDCl3): δ = 8.11 (d, JHH = 7.2 Hz, 1 H), 7.90 (d,
3JHH = 8.1 Hz, 2 H), 7.75 (d, 3JHH = 8.3 Hz, 2 H), 7.61 (s, 1 H), 7.36–7.25
(m, 5 H), 6.52 (t, 3JHH = 6.9 Hz, 1 H), 6.38 (d, 3JHH = 6.7 Hz, 1 H), 6.35 (s,
1 H), 1.03 (s, 9 H).
Supporting Information
13C NMR (100 MHz, CDCl3): δ = 143.4, 139.9, 136.9, 136.2, 135.4,
134.0, 132.1, 130.0, 128.0, 127.9, 127.3, 125.9 (d, 3JCF = 3.3 Hz), 122.1,
119.3, 118.9, 113.8, 34.4, 31.1.
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1561438.
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u
p
p
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rmoaitn
HRMS (APCI): m/z [M + H]+ calcd for C26H24N2F3: 421.1892; found:
421.1883.
References
(1) For selected reviews, see: (a) Wang, D. H.; Engle, K. M.; Shi, B. F.;
Yu, J.-Q. Science 2010, 327, 315. (b) Chen, X.; Engle, K. M.; Wang,
D. H.; Yu, J.-Q. Angew. Chem. Int. Ed. 2009, 48, 5094. (c) Daugulis,
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(E)-8-(3,3-Dimethyl-1-phenylbut-1-en-1-yl)-3-(3-fluorophe-
nyl)imidazo[1,5-a]pyridine (6fb)
The reaction was performed according to general procedure B.
Yield: 80 mg (43%); yellow solid.
1H NMR (300 MHz, CDCl3): δ = 8.09 (d, 3JHH = 7.1 Hz, 1 H), 7.58 (s, 1 H),
7.57–7.40 (m, 3 H), 7.35–7.25 (m, 5 H), 7.14–7.05 (m, 1 H), 6.49 (t,
3JHH = 7.0 Hz, 1 H), 7.37–7.32 (m, 2 H), 1.02 (s, 9 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

H
C.-Y. Liu et al.
Special Topic
Synthesis
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H