Cobalt-catalyzed alkenylation of thiazoles with alkynes via C-H bond functionalization

Article abstract of DOI:10.1055/s-0030-1260077

A cobalt-Xantphos catalyst has been developed for the syn addition of (benzo)thiazoles to internal alkynes via C-H bond functionalization. The reaction affords C2-alkenylated (benzo)thiazoles with high regio- and stereoselectivities under mild conditions. Georg Thieme Verlag Stuttgart. New York.

Full text of DOI:10.1055/s-0030-1260077

SPECIAL TOPIC
2561
Cobalt-Catalyzed Alkenylation of Thiazoles with Alkynes via C–H Bond
Functionalization
C
obalt-Catalyze
h
d
A
lkenylat
e
ion of
T
hia
z
n
oles hua Ding, Naohiko Yoshikai*
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University,
Singapore 637371, Singapore
Fax +65(6791)1961; E-mail: nyoshikai@ntu.edu.sg
Received 15 March 2011
(50 mol%) and was effective for the addition of (benz)ox-
Abstract: A cobalt–Xantphos catalyst has been developed for the
azole derivatives,2 poorly promoted the reaction (entry 1).
Throughout the screening of other ligands, Xantphos
syn addition of (benzo)thiazoles to internal alkynes via C–H bond
functionalization. The reaction affords C2-alkenylated (benzo)thia-
emerged as the ligand of choice, allowing the reaction to
proceed smoothly at 60 °C in tetrahydrofuran to afford the
alkenylation product 3a in 75% yield with exclusive syn
selectivity (entry 2). Note that Xantphos was a rather poor
ligand for the reaction of (benz)oxazole derivatives.2 Oth-
er bidentate phosphine ligands such as dppe, dppp, dppb,
and dppf were less effective (entries 3–6). The use of other
Grignard reagents such as methylmagnesium chloride and
2,2-dimethylpropylmagnesium bromide resulted in lower
yields (entries 7 and 8). The reaction did not take place at
all when the amount of (trimethylsilyl)methylmagnesium
chloride was reduced to 30 mol%. The product yield was
further improved to 90% when toluene was used as the
solvent instead of tetrahydrofuran (entry 9).
zoles with high regio- and stereoselectivities under mild conditions.
Key words: cobalt, C–H activation, heterocycles, hydroarylation,
alkynes
The prevalence of aromatic heterocycles in functional
molecules as well as increasing interest in C–H bond
functionalization as a viable synthetic strategy have driv-
en chemists to develop a variety of metal-catalyzed direct
functionalization reactions of heteroaromatic C–H
bonds.1 Among such transformations, insertion of an un-
saturated molecule into the C–H bond is particularly at-
tractive due to the intrinsically atom-economical process.
We recently reported a cobalt-catalyzed alkenylation re-
action of the C2 position of a (benz)oxazole derivative
with an internal alkyne that occurs at room temperature.2–4
This reaction represents a rare example of cobalt-cata-
lyzed heteroaromatic C–H bond functionalization, and
features the low cost of the cobalt catalyst5 and mild reac-
tion conditions. We report here an extension of this chem-
istry to (benzo)thiazole derivatives. Thus, a cobalt–
Xantphos catalyst has been developed for the C2-alkeny-
lation of a (benzo)thiazole with an internal alkyne with
high regio- and stereoselectivities (Scheme 1).6,7 The re-
ported reaction adds to the rapidly expanding repertoire of
cobalt catalysis for C–H bond functionalization.8–10
The optimized reaction conditions allowed C2-alkenyla-
tion of a variety of thiazole derivatives with oct-4-yne in
good yield with high syn stereoselectivity (Figure 1). 4-
Methylthiazole served as an excellent substrate, affording
the corresponding alkenylation product 3b in 85% yield,
while the reaction of unsubstituted thiazole was rather
Pr
N
S
R1
R2
Pr
Pr
N
S
Pr
BnO
3b R1 = Me, R2 = H, 85%
3c R1 = R2 = H, 23%
3d, 81%
R1
R1
N
S
N
S
Pr
cat. Co–Xantphos
toluene, 60 °C
N
Pr
N
S
+
H
R2
S
Pr
R2
Pr
Scheme 1 Co–Xantphos-catalyzed addition of (benzo)thiazole to
alkyne
R
R
3e R = H, 71% (E/Z = 23:1)
3f R = Me, 67%
3g R = OMe, 65% (E/Z = 15:1)
3h R = F, 85% (E/Z = 10:1)
3i R = CF3, 74% (E/Z = 11:1)
We chose 4,5-dimethylthiazole (1a) and oct-2-yne (2a) as
model reactants, and screened reaction conditions
(Table 1). The cobalt–DPEphos catalyst, which was gen-
erated from cobalt(II) bromide (10 mol%), DPEphos (10
mol%), and (trimethylsilyl)methylmagnesium chloride
Pr
N
S
Pr
Pr
N
S
Pr
NC
3j, 81%
3k, 75% (E/Z = 5:1)
SYNTHESIS 2011, No. 16, pp 2561–2566
Advanced online publication: 17.06.2011
DOI: 10.1055/s-0030-1260077; Art ID: C29411SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
1
1
Figure 1 Scope of thiazoles. Unless otherwise noted, the reaction
was performed under the conditions described in Table 1, entry 9, and
the E/Z ratio was >99:1. The yield of 3c was determined by GC.

2562
Z. Ding, N. Yoshikai
SPECIAL TOPIC
Table 1 Optimization of Reaction Conditionsa
bond formation took place exclusively at the position
proximal to the methyl group. Note that the regioselectiv-
ity trend observed for the unsymmetrical alkynes (3m, 3n,
and 3o) is the same as observed for the reaction of ox-
azoles catalyzed by Co–DPEphos.2 Terminal alkynes
failed to participate in the reaction.
CoBr2 (10 mol%)
H
Pr
ligand (10 mol%)
N
Pr
N
S
RMgX (50 mol%)
+
H
THF, 60 °C, 12 h
S
Pr
Pr
2a
1a
3a
(1.2 equiv)
Pr
N
S
n-Bu
n-Bu
N
PPh2
PPh2
S
NC
Fe
O
O
3l, 94%
3m, 71%
n
PPh2
PPh2
Ph2P
DPEphos
PPh2
Ph2P
Xantphos
PPh2
dppe (n = 2)
dppp (n = 3)
dppb (n = 4)
dppf
Ph
N
S
R
N
Entry
Ligand
DPEphos
Xantphos
dppe
RMgX
Yieldb (%)
S
NC
1
2
3
4
5
6
7
8
9
Me3SiCH2MgCl
Me3SiCH2MgCl
Me3SiCH2MgCl
Me3SiCH2MgCl
Me3SiCH2MgCl
Me3SiCH2MgCl
MeMgCl
2
75
12
64
34
29
51
58
90c
3n, 68%
3o R = Me, 42%
3p R = Ph, 36%
Figure 2 Scope of alkynes. Unless otherwise noted, the reaction
was performed under the conditions described in Table 1, entry 2, and
the E/Z ratio was > 99:1. 3m is the major regioisomer (regioselectivity
was 2:1). For 3o and 3p, the reaction was performed at 80 °C.
dppp
dppb
Because the optimum catalytic systems for the alkenyla-
tion of (benz)oxazoles and (benzo)thiazoles are different,
we became interested in the chemoselectivity of each sys-
tems. First, we performed competition experiments using
benzothiazole 1k and benzoxazole 4 [Scheme 2 (a)]. The
reaction of an equimolar mixture of 1k and 4 with oct-4-
yne (2a) in the presence of the Co–DPEphos catalyst ex-
pectedly resulted in exclusive formation of a benzoxazole
adduct 5 in 48% yield. On the other hand, it was rather un-
expected that the Co–Xantphos catalyst did not promote
the alkenylation of 1k, but afforded only a small amount
(3%) of 5. Apparently, benzoxazole seems to have inhib-
ited the reaction of benzothiazole, while the reason for the
inhibition is not clear at this stage.
dppf
Xantphos
Xantphos
Xantphos
t-BuCH2MgBr
Me3SiCH2MgCl
a Reaction was performed on a 0.3-mmol scale at 0.2 M concentration.
b GC yield.
c Toluene was used as the solvent. Isolated yield.
sluggish (3c). A related thiazole substrate bearing a ben-
zyloxy group also afforded the corresponding alkenyla-
tion product 3d in good yield. 5-Arylthiazole derivatives,
which could be readily synthesized by direct C5-arylation
of thiazole with the corresponding aryl bromides or io-
dides,11 also participated in the reaction to afford the alk-
enylation products 3e–j in moderate to good yields with
high stereoselectivities. The aryl group on the thiazole
ring could be either electron-rich (3f, 3g) or electron-with-
drawing (3h, 3i). The cobalt–Xantphos catalyst tolerated
the presence of a cyano group (3j), as did the cobalt–
DPEphos catalyst in the alkenylation of oxazole deriva-
tives.2 Benzothiazole also participated in the reaction
(3k).
Next, a substrate 6 bearing both oxazole and thiazole moi-
eties was subjected to the Co–DPEphos and Co–Xantphos
catalytic systems [Scheme 2 (b)]. While the reaction was
rather sluggish with both of the catalytic systems, we
noted a difference in the chemoselectivity. While the ox-
azole moiety was exclusively alkenylated with the Co–
DPEphos system, the Co–Xantphos system afforded a
mixture of products 7 and 8 resulting from activation of
the oxazolyl and thiazolyl C–H bonds, respectively. The
origin of this chemoselectivity difference is elusive at this
moment, while we consider that the Co–Xantphos- and
Co–DPEphos-catalyzed reactions share essentially the
same catalytic cycle consisting of (1) oxidative addition of
the C2–H bond to the cobalt center, (2) insertion of the
alkyne into the Co–H bond, and (3) reductive elimination
of the resulting diorganocobalt intermediate.2
Next, the scope of alkynes was studied (Figure 2). Ali-
phatic alkynes afforded the alkenylation products 3l–n in
moderate to good yields. Unsymmetrical alkynes such as
hex-2-yne and 4-methylpent-2-yne underwent C–C bond
formation preferentially at the less-hindered positions,
while the regioselectivity was modest (2:1) for the former
alkyne. The reactions of aromatic alkynes were sluggish
and required heating at 80 °C, affording the products 3o
and 3p in modest yields. For 1-phenylprop-1-yne, C–C
In summary, we have developed a cobalt–Xantphos cata-
lyst for activation of a (benzo)thiazole C2–H bond fol-
lowed by insertion of an internal alkyne, which affords the
Synthesis 2011, No. 16, 2561–2566 © Thieme Stuttgart · New York

SPECIAL TOPIC
Cobalt-Catalyzed Alkenylation of Thiazoles
2563
5-[2-(Trifluoromethyl)phenyl]thiazole; Typical Procedure
(a)
2-Iodobenzotrifluoride (0.70 mL, 5 mmol), thiazole (0.42 mL, 6
mmol), KOAc (0.59 g, 6 mmol), and Pd(OAc)2 (11.2 mg, 0.05
mmol) were dissolved in N,N-dimethylacetamide (15 mL), stirred at
130 °C for 18 h, and then quenched with H2O (10 mL). The result-
ing mixture was extracted with EtOAc (3 × 10 mL). The combined
organic layers were dried (Na2SO4), concentrated under reduced
pressure, and purified by chromatography (silica gel, hexane–
EtOAc, 10:1) to afford the product as a colorless oil; yield: 70%;
Rf = 0.13 (hexane–EtOAc, 10:1).
N
Pr
Pr
N
S
S
Pr
Pr
Pr
1k (1 equiv)
Co cat.
3k
+
N
N
Pr
2a
O
O
(1.2 equiv)
4 (1 equiv)
5
Co–DPEphos (20 °C, 12 h): 3k, 0%; 5, 48%
Co–Xantphos (60 °C, 12 h): 3k, 0%; 5, 3%
IR (NaCl): 3072, 1605, 1578, 1527, 1446, 1396, 1315, 1267, 1174,
1130, 1066, 1035, 869, 767 cm–1.
(b)
1H NMR (400 MHz, CDCl3): d = 8.88 (s, 1 H), 7.88 (s, 1 H), 7.80–
Pr
N
O
N
7.78 (m, 1 H), 7.61–7.51 (m, 2 H), 7.48–7.46 (m, 1 H).
13C NMR (100 MHz, CDCl3): d = 153.6, 142.9 (q, 4JC-F = 2.0 Hz),
134.0, 133.4, 131.6, 129.6 (q, 2JC-F = 30.0 Hz), 129.5, 128.9, 126.5
(q, 3JC-F = 5.3 Hz), 123.6 (q, 1JC-F = 272 Hz).
Pr
O
S
S
HRMS (ESI): m/z [M + H]+ calcd for C10H7NSF3: 230.0251; found:
230.0248.
N
N
7
6
Co cat.
N
+
5-(2-Fluorophenyl)thiazole
Following the typical procedure; yellow oil; yield: 75%; Rf = 0.52
(hexane–EtOAc, 3:1).
Pr
Pr
O
2a
(1.2 equiv)
Pr
S
N
IR (NaCl): 3080, 1718, 1577, 1523, 1483, 1473, 1450, 1390, 1247,
1222, 1122, 1103, 873, 812, 754 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.84 (s, 1 H), 8.25 (s, 1 H), 7.63–
7.59 (m, 1 H), 7.35–7.30 (m, 1 H), 7.22–7.16 (m, 2 H).
Pr
8
Co–DPEphos (60 °C, 12 h): 7, 20%; 8, 0%
Co–Xantphos (60 °C, 12 h): 7, 5%; 8, 7% (E/Z = 4:1)
13C NMR (100 MHz, CDCl3): d = 158.7 (d, 1JC-F = 249 Hz), 152.8
Scheme 2 Competition of benzothiazole and benzoxazole in cobalt-
catalyzed reaction with oct-4-yne. Co–DPEphos: CoBr2 (10 mol%),
DPEphos (10 mol%), Me3SiCH2MgCl (50 mol%), pyridine (80
mol%), THF; Co–Xantphos: CoBr2 (10 mol%), Xantphos (10 mol%),
Me3SiCH2MgCl (50 mol%), toluene.
4
3
3
(d, JC-F = 4.0 Hz), 141.4 (d, JC-F = 7.0 Hz), 131.8 (d, JC-F = 5.0
3
4
Hz), 129.5 (d, JC-F = 9.0 Hz), 129.0 (d, JC-F = 3.0 Hz), 124.5 (d,
4JC-F = 4.0 Hz), 118.9 (d, JC-F = 14.0 Hz), 116.2 (d, JC-F = 12.0
2
2
Hz).
HRMS (ESI): m/z [M + H]+ calcd for C9H7NSF: 180.0283; found:
180.0286.
corresponding alkenylation product in moderate to good
yield with high syn stereoselectivity. The present catalytic
(E)-4,5-Dimethyl-2-(oct-4-en-4-yl)thiazole (3a); Typical Proce-
system adds to the repertoire of direct C–H functionaliza- dure
To a Schlenk tube were added CoBr2 (6.6 mg, 0.03 mmol), Xant-
tion of aromatic heterocycles. The different reactivities of
the Co–Xantphos and Co–DPEphos catalysts toward thia-
zole and oxazole derivatives deserve further synthetic and
mechanistic investigations.
phos (17.9 mg, 0.03 mmol), and toluene (1.3 mL); to the resulting
soln was added Me3SiCH2MgCl (0.89 M in THF, 0.17 mL, 0.15
mmol) at 0 °C. After stirring for 30 min at this temperature, 4,5-
dimethylthiazole (34 mg, 0.30 mmol) and oct-4-yne (53 mL, 0.36
mmol) were added sequentially. The mixture was stirred at 60 °C
for 12 h, and then quenched with sat. aq NH4Cl soln (1.5 mL) at r.t.
The resulting mixture was extracted with EtOAc (3 × 5 mL). The
combined organic layers were dried (MgSO4), concentrated under
reduced pressure, and purified by chromatography (silica gel, hex-
ane–EtOAc, 100:1) to afford 3a (60 mg, 90%) as a yellow oil. The
spectral data showed good agreement with the literature data.3a
Spectral data for 3k has been reported previously.2
Melting points were determined using a capillary melting point ap-
paratus and are uncorrected. Column chromatography was per-
1
formed on silica gel 60 (Merck). H and 13C NMR spectra were
recorded on Bruker AV-400 (400 MHz) or Jeol ECX-400 (400
MHz) spectrometers using TMS (d = 0) and CHCl3 (d = 77.0) as in-
ternal standards, respectively. Gas chromatographic (GC) analysis
was performed on a Shimadzu GC-2010 system equipped with an
FID detector and a capillary column, DB-5 (Agilent J&W, 0.25 mm
i.d. × 30 m, 0.25 mm film thickness). HRMS were obtained with a
Q-Tof Premier LC HR mass spectrometer. Unless otherwise noted,
chemicals were commercial grade and were used as received. Tolu-
ene was distilled over CaH2. Grignard reagents except MeMgCl
were prepared from the corresponding halides and Mg turnings and
titrated before use. The following thiazole derivatives were pre-
pared according to the literature procedure, and their spectral data
showed good agreement with the reported data: 5-[2-(benzyl-
oxy)ethyl]-4-methylthiazole,12 5-phenylthiazole,11c 5-(4-tolyl)thia-
zole,11c 5-(4-methoxyphenyl)thiazole,11c and 4-(4-methylthiazol-5-
yl)benzonitrile.11a
(E)-4-Methyl-2-(oct-4-en-4-yl)thiazole (3b)
Yellow oil; yield: 85%; Rf = 0.50 (hexane–EtOAc, 10:1).
IR (NaCl): 2958, 2927, 2870, 1519, 1452, 1375, 1301, 1103, 977,
893 cm–1.
1H NMR (400 MHz, CDCl3): d = 6.69 (s, 1 H), 6.38 (t, J = 7.5 Hz,
1 H), 2.55 (t, J = 7.6 Hz, 2 H), 2.42 (s, 3 H), 2.23–2.17 (m, 2 H),
1.56–1.47 (m, 4 H), 0.96 (t, J = 7.4 Hz, 3 H), 0.94 (t, J = 7.5 Hz, 3
H).
13C NMR (100 MHz, CDCl3): d = 170.7, 152.8, 134.5, 132.9, 111.7,
31.5, 30.5, 22.5, 22.3, 17.4, 14.02, 13.99.
HRMS (ESI): m/z [M + H]+ calcd for C12H20NS: 210.1316; found:
210.1317.
Synthesis 2011, No. 16, 2561–2566 © Thieme Stuttgart · New York

2564
Z. Ding, N. Yoshikai
SPECIAL TOPIC
(E)-5-[2-(Benzyloxy)ethyl]-4-methyl-2-(oct-4-en-4-yl)thiazole
(3d)
Yellow oil; yield: 81%; Rf = 0.46 (hexane–EtOAc, 10:1).
IR (NaCl): 3020, 2956, 2927, 2870, 1629, 1575, 1521, 1475, 1452,
1402, 1377, 1257, 1219, 1168, 1105, 1076, 1037, 974, 935, 893,
864, 812, 752 cm–1.
IR (NaCl): 3028, 2958, 2927, 2868, 1722, 1680, 1544, 1454, 1377,
1359, 1269, 1103, 1028, 904, 734, 696 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.05 (s, 1 H), 7.59–7.55 (m, 1 H),
7.30–7.24 (m, 1 H), 7.19–7.12 (m, 2 H), 6.44 (t, J = 7.4 Hz, 1 H),
2.61 (t, J = 7.6 Hz, 2 H), 2.28–2.22 (m, 2 H), 1.64–1.50 (m, 4 H),
0.99 (t, J = 7.4 Hz, 3 H), 0.98 (t, J = 7.4 Hz, 3 H).
1H NMR (400 MHz, CDCl3): d = 7.35–7.24 (m, 5 H), 6.31 (t,
J = 7.4 Hz, 1 H), 4.53 (s, 2 H), 3.63 (t, J = 6.8 Hz, 2 H), 2.99 (t,
J = 6.8 Hz, 2 H), 2.54–2.50 (m, 2 H), 2.32 (s, 3 H), 2.21–2.16 (m, 2
H), 1.56–1.44 (m, 4 H), 0.95 (t, J = 7.3 Hz, 3 H), 0.94 (t, J = 7.3 Hz,
3 H).
13C NMR (100 MHz, CDCl3): d = 167.4, 148.5, 138.0, 134.5, 132.1,
128.3, 127.58, 127.57, 126.3, 73.0, 70.3, 31.3, 30.5, 27.2, 22.6,
22.3, 15.1, 14.0, 13.9.
5
13C NMR (100 MHz, CDCl3): d = 171.2 (d, JC-F = 3.0 Hz), 158.9
(d, 1JC-F = 248 Hz), 141.2 (d, 4JC-F = 8.0 Hz), 134.8, 134.1, 130.2 (d,
3JC-F = 5.0 Hz), 129.2 (d, 3JC-F = 11.0 Hz), 129.0 (d, 3JC-F = 4.0 Hz),
124.5 (d, 4JC-F = 4.0 Hz), 119.7 (d, 2JC-F = 13.0 Hz), 116.2 (d, 2JC-F
=
22.0 Hz), 31.1, 30.6, 22.5, 22.3, 14.1, 14.0.
HRMS (ESI): m/z [M + H]+ calcd for C17H21NFS: 290.1379; found:
290.1384.
HRMS (ESI): m/z [M + H]+ calcd for C21H30NOS: 344.2048; found:
344.2052.
(E)-2-(Oct-4-en-4-yl)-5-[2-(trifluoromethyl)phenyl]thiazole (3i)
Yellow oil; yield: 74%; Rf = 0.42 (hexane–EtOAc, 10:1).
(E)-2-(Oct-4-en-4-yl)-5-phenylthiazole (3e)
Colorless oil; yield: 71%; Rf = 0.45 (hexane–EtOAc, 10:1).
IR (NaCl): 2960, 2931, 2872, 1604, 1575, 1448, 1315, 1263, 1172,
1130, 1109, 1066, 1035, 765, 746 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.78–7.76 (m, 1 H), 7.66 (s, 1 H),
7.58–7.554 (m, 1 H), 7.51–7.47 (m, 2 H), 6.43 (t, J = 7.4 Hz, 1 H),
2.60 (t, J = 7.8 Hz, 2 H), 2.28–2.22 (m, 2 H), 1.65–1.48 (m, 4 H),
0.99 (t, J = 7.4 Hz, 6 H).
IR (NaCl): 3076, 3061, 3024, 2958, 2929, 2870, 1598, 1523, 1483,
1448, 1429, 1377, 1163, 1103, 1074, 756, 688 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.88 (s, 1 H), 7.56–7.54 (m, 2 H),
7.40–7.36 (m, 2 H), 7.32–7.29 (m, 1 H), 6.41 (t, J = 7.4 Hz, 1 H),
2.60 (t, J = 7.7 Hz, 2 H), 2.27–2.22 (m, 2 H), 1.61–1.49 (m, 4 H),
0.99 (t, J = 7.4 Hz, 3 H), 0.98 (t, J = 7.3 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 170.5, 138.2, 137.4, 134.9, 133.8,
131.7, 129.0, 127.9, 126.5, 31.1, 30.6, 22.6, 22.3, 14.1, 14.0.
HRMS (ESI): m/z [M + H]+ calcd for C17H22NS: 272.1473; found:
272.1476.
13C NMR (100 MHz, CDCl3): d = 172.2, 142.1, 134.7, 134.1, 133.3,
2
132.2, 131.5, 130.2, 129.4 (q, JC-F = 30.0 Hz), 128.5, 126.5 (q,
1
3JC-F = 5.3 Hz), 123.8 (q, JC-F = 272 Hz), 31.3, 30.6, 22.5, 22.2,
14.1, 14.0.
HRMS (ESI): m/z [M + H]+ calcd for C18H21NF3S: 340.1347; found:
340.1349.
(E)-2-(Oct-4-en-4-yl)-5-(4-tolyl)thiazole (3f)
Yellow solid; yield: 67%; mp 42–43 °C; Rf = 0.62 (hexane–EtOAc,
10:1).
(E)-4-[4-Methyl-2-(oct-4-en-4-yl)thiazol-5-yl]benzonitrile (3j)
White solid; yield: 81%; mp 86–87 °C; Rf = 0.43 (hexane–EtOAc,
10:1).
IR (NaCl): 3022, 2727, 1890, 1494, 1301, 1234, 1163, 1105, 1066,
968, 891, 852, 812, 746 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.84 (s, 1 H), 7.47–7.42 (m, 2 H),
7.22–7.17 (m, 2 H), 6.39 (t, J = 7.4 Hz, 1 H), 2.61–2.57 (m, 2 H),
2.36 (s, 3 H), 2.27–2.21 (m, 2 H), 1.63–1.49 (m, 4 H), 0.98 (t,
J = 7.3 Hz, 3 H), 0.97 (t, J = 7.3 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 170.0, 137.9, 137.8, 137.5, 135.0,
133.6, 129.6, 128.8, 126.4, 31.1, 30.6, 22.6, 22.3, 21.2, 14.1, 14.0.
HRMS (ESI): m/z [M + H]+ calcd for C18H24NS: 286.1629; found:
286.1634.
IR (NaCl): 3057, 2725, 2227, 1624, 1593, 1554, 1537, 1494, 1328,
1309, 1078, 1035, 983, 898, 844 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.69–7.67 (m, 2 H), 7.55–7.53 (m,
2 H), 6.44 (t, J = 7.5 Hz, 1 H), 2.56 (t, J = 7.6 Hz, 2 H), 2.51 (s, 3
H), 2.26–2.21 (m, 2 H), 1.62–1.49 (m, 4 H), 0.98 (t, J = 7.4 Hz, 3
H), 0.97 (t, J = 7.3 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 169.5, 149.4, 137.4, 134.4, 134.1,
132.3, 129.3, 128.4, 118.6, 110.7, 31.2, 30.6, 22.5, 22.3, 16.7, 14.0,
13.9.
HRMS (ESI): m/z [M + H]+ calcd for C19H23N2S: 311.1582; found:
311.1578.
(E)-5-(4-Methoxyphenyl)-2-(oct-4-en-4-yl)thiazole (3g)
White solid; yield: 65%; mp 44–45 °C; Rf = 0.28 (hexane–EtOAc,
10:1).
IR (NaCl): 1610, 1533, 1494, 1253, 1178, 1041, 827 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.77 (s, 1 H), 7.51–7.45 (m, 2 H),
6.93–6.89 (m, 2 H), 6.37 (t, J = 7.4 Hz, 1 H), 3.82 (s, 3 H), 2.59 (t,
J = 7.6 Hz, 2 H), 2.27–2.21 (m, 2 H), 1.60–1.47 (m, 4 H), 0.98 (t,
J = 7.3 Hz, 3 H), 0.97 (t, J = 7.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 169.6, 159.5, 137.27, 137.22,
135.0 133.4, 127.8, 124.3, 114.4, 55.3, 31.1, 30.6, 22.6, 22.3, 14.1,
13.9.
(E)-2-(Dec-5-en-5-yl)-4,5-dimethylthiazole (3l)
Yellow oil; yield: 94%; Rf = 0.64 (hexane–EtOAc, 10:1).
IR (NaCl): 2956, 2926, 2858, 1552, 1454, 1377, 1259, 1095, 1020,
800, 665 cm–1.
1H NMR (400 MHz, CDCl3): d = 6.25 (t, J = 7.5 Hz, 1 H), 2.53–
2.50 (m, 2 H), 2.31 (s, 3 H), 2.30 (s, 3 H), 2.22–2.17 (m, 2 H), 1.47–
1.32 (m, 8 H), 0.91 (t, J = 7.2 Hz, 3 H), 0.90 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 166.5, 148.1, 134.6, 131.8, 124.5,
31.5, 31.4, 29.2, 28.1, 22.7, 22.5, 14.8, 13.97, 13.96, 11.3.
HRMS (ESI): m/z [M + H]+ calcd for C15H26NS: 252.1786; found:
252.1792.
HRMS (ESI): m/z [M + H]+ calcd for C18H24NOS: 302.1579; found:
302.1578.
(E)-4-[2-(Hex-2-en-2-yl)-4-methylthiazol-5-yl]benzonitrile(3m)
and (E)-4-[2-(Hex-2-en-3-yl)-4-methylthiazol-5-yl]benzonitrile
(E)-5-(2-Fluorophenyl)-2-(oct-4-en-4-yl)thiazole (3j)
Yellow oil; yield: 85%; Rf = 0.51 (hexane–EtOAc, 10:1).
(3m¢)
Yellow solid; yield: 71%; mp 60–61 °C; Rf = 0.36 (hexane–EtOAc,
10:1).
Synthesis 2011, No. 16, 2561–2566 © Thieme Stuttgart · New York

SPECIAL TOPIC
Cobalt-Catalyzed Alkenylation of Thiazoles
2565
IR (NaCl): 3055, 2725, 2229, 1602, 1527, 1492, 1305, 1180, 1074,
1041, 979, 850, 833 cm–1.
13C NMR (100 MHz, CDCl3): d = 152.4, 150.9, 150.7, 139.4, 131.3,
127.7, 127.4, 125.0 (2 peaks are overlapped), 122.1.
1H NMR (400 MHz, CDCl3): d = 7.69 (d, J = 8.4 Hz, 2 H, 3m and
3m¢), 7.54 (d, J = 8.4 Hz, 2 H, 3m and 3m¢), 6.54 (q, J = 7.1 Hz, 1
H, 3m¢), 6.48 (t, J = 7.4 Hz, 1 H, 3m), 2.59–2.55 (m, 2 H, 3m¢), 2.51
(s, 3 H, 3m and 3m¢), 2.27–2.21 (m, 2 H, 3m), 2.13 (s, 3 H, 3m),
1.86 (d, J = 7.2 Hz, 3 H, 3m¢), 1.60–1.49 (m, 2 H, 3m and 3m¢), 0.97
(t, J = 7.3 Hz, 3 H, 3m and 3m¢).
HRMS (ESI): m/z [M + H]+ calcd for C12H9N2OS: 229.0436; found:
229.0437.
(E)-2-(Oct-4-en-4-yl)-5-[4-(thiazol-5-yl)phenyl]oxazole (7)
Yellow solid; yield: 20%; mp 183–184 °C; Rf = 0.20 (hexane–
EtOAc, 3:1).
13C NMR (100 MHz, CDCl3): d = 170.0, 169.4, 149.38, 149.34,
137.4, 137.3, 135.2, 133.8, 132.3, 129.7, 129.3, 129.25, 129.24,
128.42, 128.39, 128.34, 118.58, 118.56, 110.7, 110.6, 30.8, 30.7,
22.2, 22.0, 16.67, 16.64, 14.7, 14.2, 13.92, 13.85.
HRMS (ESI): m/z [M + H]+ calcd for C17H19N2S: 283.1269; found:
283.1266.
IR (NaCl): 2725, 2360, 2341, 1724, 1683, 1525, 1269, 1105, 1047,
966, 941, 871, 831, 721 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.78 (s, 1 H), 8.13 (s, 1 H), 7.70–
7.61 (m, 4 H), 7.37 (s, 1 H), 6.67 (t, J = 7.6 Hz, 1 H), 2.56 (t, J = 7.6
Hz, 2 H), 2.54–2.25 (m, 2 H), 1.62–1.52 (m, 4 H), 1.01 (t, J = 7.2
Hz, 3 H), 0.99 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 163.2, 152.2, 149.5, 145.1, 139.2,
135.4, 130.6, 128.22, 128.18, 127.3, 124.6, 123.6, 30.4, 29.4, 22.54,
22.50, 14.1, 14.0.
(E)-4,5-Dimethyl-2-(4-methylpent-2-en-2-yl)thiazole (3n)
Colorless oil; yield: 68%; Rf = 0.47 (hexane–EtOAc, 10:1).
IR (NaCl): 2960, 2924, 2866, 1635, 1519, 1454, 1402, 1375, 1361,
1301, 1244, 1232, 1222, 1176, 1132, 1049, 1024, 977, 858 cm–1.
1H NMR (400 MHz, CDCl3): d = 6.12 (d, J = 9.3 Hz, 1 H), 2.74–
2.65 (m, 1 H), 2.31 (s, 3 H), 2.30 (s, 3 H), 2.08 (s, 3 H), 1.05 (d,
J = 6.7 Hz, 6 H).
13C NMR (100 MHz, CDCl3): d = 167.11, 148.09, 138.59, 127.78,
124.62, 27.81, 22.53, 14.82, 14.72, 11.35.
HRMS (ESI): m/z [M + H]+ calcd for C20H23N2OS: 339.1531;
found: 339.1531.
(E)-5-{4-[2-(Oct-4-en-4-yl)thiazol-5-yl]phenyl}oxazole (8)
Yellow solid; yield: 7%; mp 189–190 °C; Rf = 0.22 (hexane–
EtOAc, 3:1).
IR (NaCl): 2723, 2669, 1724, 1681, 1303, 1220, 1116, 1062, 964,
948, 877, 831, 721, 665 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.94 (s, 1 H), 7.93 (s, 1 H), 7.70–
7.60 (m, 4 H), 7.39 (s, 1 H), 6.43 (t, J = 6.8 Hz, 1 H), 2.60 (t, J = 7.6
Hz, 2 H), 2.29–2.23 (m, 2 H), 1.59–1.50 (m, 4 H), 0.99 (t, J = 7.2
Hz, 3 H), 0.98 (t, J = 7.2 Hz, 3 H).
HRMS (ESI): m/z [M + H]+ calcd for C11H18NS: 196.1160; found:
196.1165.
(E)-4-[4-Methyl-2-(1-phenylprop-1-en-2-yl)thiazol-5-yl]ben-
zonitrile (3o)
Yellow solid; yield: 42%; mp 136–138 °C; Rf = 0.11 (hexane–
EtOAc, 10:1).
IR (NaCl): 2225, 1602, 1521, 1490, 1305, 1045, 835 cm–1.
13C NMR (100 MHz, CDCl3): d = 163.28, 163.25, 152.2, 149.5,
141.4, 139.2, 135.4, 130.7, 128.2, 127.3, 124.6, 123.6, 30.5, 29.4,
22.54, 22.50, 14.1, 14.0.
1H NMR (400 MHz, CDCl3): d = 7.72–7.70 (m, 2 H), 7.59–7.57 (m,
2 H), 7.50 (s, 1 H), 7.45–7.38 (m, 4 H), 7.32–7.30 (m, 1 H), 2.56 (s,
3 H), 2.42 (s, 3 H).
HRMS (ESI): m/z [M + H]+ calcd for C20H23N2OS: 339.1531;
found: 339.1537.
13C NMR (100 MHz, CDCl3): d = 169.9, 149.9, 137.2, 136.5, 132.5,
131.2, 130.8, 129.5, 129.4, 128.4, 127.6, 118.6, 111.0, 16.7, 16.5.
Acknowledgment
We thank Singapore National Research Foundation (NRF-RF2009-
05) and Nanyang Technological University for financial support.
HRMS (ESI): m/z [M + H]+ calcd for C20H17N2S: 317.1112; found:
317.1114.
(E)-4-[2-(1,2-Diphenylvinyl)-4-methylthiazol-5-yl]benzonitrile
(3p)
References
Yellow solid; yield: 36%; mp 174–175 °C; Rf = 0.10 (hexane–
EtOAc, 10:1).
IR (NaCl): 2225, 1602, 1490, 1305, 835, 665 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.85 (s, 1 H), 7.66–7.64 (m, 2 H),
7.51–7.49 (m, 2 H), 7.46–7.45 (m, 3 H), 7.39–7.37 (m, 2 H), 7.16–
7.14 (m, 3 H), 7.08–7.06 (m, 2 H), 2.59 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 170.0, 150.5, 138.3, 137.3, 135.5,
134.0, 132.4, 131.3, 130.2, 130.1, 130.0, 129.3, 129.2, 128.7, 128.2,
128.0, 118.5, 111.0, 16.8.
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Synthesis 2011, No. 16, 2561–2566 © Thieme Stuttgart · New York

2566
Z. Ding, N. Yoshikai
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Synthesis 2011, No. 16, 2561–2566 © Thieme Stuttgart · New York