Palladium-catalyzed cross-coupling of 1,4-disubstituted 5-iodo-1,2,3-triazoles with organotin reagents

Article abstract of DOI:10.1055/s-0032-1318112

In a new synthetic approach for building systems bearing a 1,2,3-triazole moiety, we report here the first Stille cross-coupling reaction of 1,4-disubstituted 5-iodo-1,2,3-triazoles with a range of stannyl derivatives to give the corresponding 5-vinyl-1,2,3-triazoles. Georg Thieme Verlag Stuttgart. New York.

Full text of DOI:10.1055/s-0032-1318112

PAPER
▌633
paper
Palladium-Catalyzed Cross-Coupling of 1,4-Disubstituted 5-Iodo-1,2,3-tri-
azoles with Organotin Reagents
1,4-Disubstituted 5-Vinyl-1,2,3-triazoles
Yvan Carcenac,a Franck David-Quillot,b Mohamed Abarbri,a Alain Duchêne,a Jérôme Thibonnet*a
a
Laboratoire d’Infectiologie et Santé Publique (UMR UFR/INRA 1282), Equipe ‘Recherche et Innovation en Chimie Médicinale’ Université
François Rabelais, Faculté des Sciences et Techniques, Parc de Grandmont, 37200 Tours, France
Fax +33(2)47367073 ; E-mail: jerome.thibonnet@univ-tours.fr
b
CEA Le Ripault, 37260 Monts, France
Received: 31.10.2012; Accepted after revision: 27.12.2012
Metal-catalyzed transition sp2–sp2 or sp–sp2 carbon–
Abstract: In a new synthetic approach for building systems bearing
carbon bond formation has attracted much attention over
a 1,2,3-triazole moiety, we report here the first Stille cross-coupling
the last three decades.12 The palladium–catalyzed cross-
reaction of 1,4-disubstituted 5-iodo-1,2,3-triazoles with a range of
coupling reaction (Suzuki–Miyaura, Hiyama, Kharasch,
Negishi, Kumada, Liebeskind–Srogl, and Stille) is one of
the most efficient methods for the construction of C–C
bonds.13 These reactions are frequently employed in the
synthesis of numerous natural products, biologically ac-
tive molecules, heterocycles, molecular electronics, den-
drimers, and conjugated polymers or nanostructures.14
The reactivity of the halide of 4- or 5-halotriazoles has
been widely studied with arylboronic acids, alkenes, and
terminal alkynes via Suzuki, Heck, Sonogashira, and even
palladium-catalyst-free reactions.15,16 To the best of our
knowledge, Stille-like coupling17 has been reported on tri-
azol-4-yltin substrates for the synthesis of 1H-1,2,4-
triazole18 and triazol-5-yltin19 substrates to reach 1H-
1,2,4-triazoles. Other works report the use of the palladi-
um–copper catalyst system with 4- and 5-halotriazole.20
We report here a convenient two-step route for efficient
preparation of 1,4,5-trisubstituted 1,2,3-triazoles from io-
dotriazole by the Stille cross-coupling reaction.
stannyl derivatives to give the corresponding 5-vinyl-1,2,3-tri-
azoles.
Key words: 1,2,3-triazoles, click chemistry, palladium catalyst,
Stille cross-coupling reaction, vinyltin reagents
Although the 1,2,3-triazole core has not been found in nat-
ural products to date, this aromatic heterocycle family is
very appealing.1–3 1,2,3-Triazoles are widely applied in
numerous areas of science and they also have industrial
uses; they are interesting units for biotechnology. Active
1,2,3-triazoles have been reported in the literature, such as
anti-HIV4 or anti-microbial agents.5 Other areas including
biological conjugation,6 catalyst design7 or materials sci-
ence and polymer chemistry2,8 are also impacted.
In this study, we focused on 1,4,5-trisubstituted 1,2,3-tri-
azoles that we planned to access via cross-coupling reac-
tions of 1,4-disubstituted 5-iodo-1,2,3-triazoles. Various
strategies have been published for the synthesis of tri-
azoles (Scheme 1). These strategies can be summarized as
two general routes based on copper-catalyzed azide–
alkyne cycloaddition (CuAAC) reactions.9 The first route
(method A) consists of trapping the copper(I) triazolide
intermediate I (Scheme 1) with an electrophilic halogena-
tion reagent.10
Azides 1 were generated from organic halides and sodium
azide, while the corresponding 5-iodo-1,2,3-triazoles 3a–i
were obtained by method A. Under the optimized click
chemistry reaction conditions described by Wu et al.,10a
azides 1 underwent a copper(I)-catalyzed cycloaddition
reaction with various terminal alkynes 2; the results are
reported in Scheme 2. Reaction of ferrocenylacetylene
yielded a mixture (70:30) of 5-iodotriazole 3c and 5H-tri-
azole. In the case of ethyl propiolate, a mixture (67:33) of
5-iodo and 4-iodo regioisomers 3g was obtained. In all
other cases, the desired 5-iodo-1,2,3-triazoles were ob-
tained as the exclusive products, in moderate to good
yields. Purification of compound 3d′ by silica gel column
chromatography led to partial cleavage of the acetal
(Scheme 3). Subsequent acidic treatment of the acetal/
aldehyde mixture led to 73% overall yield of 3d. The
same treatment with 3a afforded the triazole 3b.
method A: X = H
CuI, ICl (ref. 10a)
CuI, NBS (ref. 10b)
R1 N3
+
N
N
N
N
NaI, Cu(ClO4)2 (ref. 10c)
N
N
R2
R1
R2
R1
R2
X
method B: X = I
CuI, TTTA (ref. 11)
I
Cu-Ln
I
Scheme 1 General methods for the preparation of 5-iodotriazoles
Method B uses a haloalkyne instead of a terminal alkyne.
This second route generally allows rapid, and more con-
trolled synthesis of 5-iodotriazoles.11
To introduce the vinyl group, the reaction was performed
with 1.2 equivalents of vinyltin reagent under Stille con-
ditions in the presence of a catalytic amount (6%) of
dichlorobis(acetonitrile)palladium(II). Tributyl(vi-
nyl)stannane reagents 4 for use in the Stille cross-cou-
pling of 3 were prepared by transmetalation21 or by
SYNTHESIS 2013, 45, 0633–0638
Advanced online publication: 01.02.2013
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0032-1318112; Art ID: SS-2012-Z0849-OP
© Georg Thieme Verlag Stuttgart · New York

634
Y. Carcenac et al.
PAPER
silica column chromatography in order to remove stannic
residues.22
I
R2
Et3N, THF
R1
N3
+
R2
N
N
CuI, ICl, r.t.
Table 1 Stille Coupling of 5-Iodo-1,2,3-triazoles
2
1
N
R1
3a–i
R3
R4
PdCl2(MeCN)2 (6 mol%)
DMF, 40 °C, 12 h
I
R2
R2
R3
EtO
I
CHO
I
Fc
R4
I
OEt
N
N
+
SnBu3
N
N
N
N
R1
N
N
N
N
N
4
3
R1
N
N
N
5
N
Ph
Ph
Ph
3a (83%)
3b (76%)a
3c (60%)
Entrya Vinylstannane
Product 5
Yieldb (%)
I
CHO
I
Ph
I
Ph
Me3Si
CHO
N
N
N
N
N
N
4a
N
N
N
1
N
N
55
R3 = H; R4 = SiMe3
MeO2C
MeO2C
N
3d (73%)a
3e (55%)
3f (63%)
MeO2C
5a
OEt
I
CO2Et
I
Ph
I
Me3Si
CHO
OEt
N
N
N
N
N
N
N
N
N
N
N
2
3
4a
77
59
Ph
Ph
Ph
3h (77%)
3i (85%)
N
3g (60%)
Ph
Scheme 2 Synthesis of 5-iodo-1,2,3-triazoles: a After treatment with
5b
1 M HCl.
Me3Si
Fc
EtO
N
N
4a
R1
N3
I
CHO
N
I
OEt
Ph
OEt
i
+
+
N
N
5c
N
N
N
OEt
ii
N
R1
CHO
R1
3a/3b R1 = Ph 83% (100:0)
3d'/3d R1 = CO2Me 96% (27:73)
N
N
4b
4
5
6
81
75
70
N
R3 = R4 = H
I
CHO
3b R1 = Ph 76%
Ph
5d
3d R1 = CO2Me 73%
N
N
N
CHO
R1
N
N
Scheme 3 Reactions with 3,3-diethoxyprop-1-yne. Reagents and
conditions: (i) CuI (1 equiv), ICl (1 equiv), Et3N (1.2 equiv), THF, r.t.;
(ii) 1. CuI (1 equiv), ICl (1 equiv), Et3N (1.2 equiv), THF, r.t.; 2. 1 M
HCl, THF, 30 min. The proportions of acetal/aldehyde are given in
brackets.
4b
4b
N
MeO2C
5e
Ph
N
N
hydrostannylation22 of the corresponding alkynes with tri-
butyltin hydride at 80 °C without any solvent. Compounds
4a and 4c were obtained as mixtures of E- and Z-diaste-
reomers (E/Z 9:1) and used without separation, because
the Stille cross-coupling always yields the thermodynam-
ically more stable E-isomers.23 The results of Stille reac-
tion of 1,4-disubstituted 5-iodo-1,2,3-triazoles 3 are
summarized in Table 1. The reaction proceeded with
moderate to good yields. In most cases, E stereochemistry
was observed for the C=C bond in the products (Table 1,
entries 1–3, 7; 5a: JH,H = 19.6 Hz; 5b: JH,H = 19.4 Hz; 5c:
JH,H = 19.7 Hz; 5g: JH,H = 19.6 Hz). Purification of the de-
sired compounds was achieved by potassium carbonate–
N
MeO2C
5f
Me3Si
Ph
N
N
7
4a
70
N
MeO2C
5g
Synthesis 2013, 45, 633–638
© Georg Thieme Verlag Stuttgart · New York

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1,4-Disubstituted 5-Vinyl-1,2,3-triazoles
635
Table 1 Stille Coupling of 5-Iodo-1,2,3-triazoles (continued)
Melting points were recorded on a Stuart SMP3 melting point appa-
ratus and are uncorrected. IR spectra were obtained (neat) using a
Perkin-Elmer Spectrum-One. NMR spectra were recorded on a
Bruker AC 300 MHz spectrometer relative to TMS. HRMS were
measured with a Shimadzu QP2010 instrument (ESI mode). Analyt-
ical TLC was carried out using pre-coated silica gel 60 F254 plates,
which were developed using standard visualizing agents: UV light
or KMnO4. Purification by flash chromatography was performed
using silica gel (230–400 mesh) as the stationary phase and mix-
tures of pentane and EtOAc as the mobile phase. Alkynes 3,3-
diethoxyprop-1-yne and ethynylferrocene were prepared according
to literature procedures.25 Vinyltributyltin was prepared from vinyl-
magnesium bromide and bis(tributyltin) oxide.21 Tributyl[2-(tri-
methylsilyl)vinyl]stannane and tributyl(styryl)stannane were
prepared by hydrostannation of (trimethysilyl)acetylene and ethy-
nylbenzene, respectively.26,23a
R3
R4
PdCl2(MeCN)2 (6 mol%)
DMF, 40 °C, 12 h
I
R2
R2
R3
R4
N
N
+
SnBu3
N
N
N
N
R1
4
3
R1
5
Entrya Vinylstannane
Product 5
Yieldb (%)
Ph
Ph
4c
8
N
N
98
R3 = H; R4 = Ph
N
5-Iodo-1,2,3-triazoles; General Procedure
5h
A mixture of azide (10 mmol), terminal alkyne (10 mmol), Et3N (12
mmol), THF (100 mL), ICl (10 mmol), and CuI (10 mmol) was
stirred at r.t. under an argon atmosphere for 60 h. The solvent was
removed by distillation under reduced pressure and the crude resi-
due was purified by column chromatography (silica gel, pentane–
EtOAc, 100:0 to 80:20).
Ph
N
N
9
10
11
12
4b
89
80
98
98
N
Ph
5i
1-Benzyl-4-(diethoxymethyl)-5-iodo-1H-1,2,3-triazole (3a)
Yellowish oil; yield: 3.21 g (83%).
Ph
IR (neat): 3065, 3033, 2976, 2929, 2881, 1497, 1456, 1443, 1222,
1121, 1062, 913, 729 cm–1.
1H NMR (300 MHz, CDCl3): δ = 1.25 (t, J = 7.1 Hz, 6 H), 3.62 (dq,
J = 9.5, 7.1 Hz, 2 H), 3.70 (dq, J = 9.5, 7.1 Hz, 2 H), 5.60 (s, 2 H),
5.66 (s, 1 H), 7.24–7.38 (m, 5 H).
13C NMR (75 MHz, CDCl3): δ = 15.1, 53.9, 61.8, 77.6, 96.5, 127.8,
128.4, 128.8, 134.2, 148.7.
HRMS (ESI): m/z [M + H]+ calcd for C14H19IN3O2: 388.0517;
found: 388.0514; m/z [M + Na]+ calcd for C14H18IN3NaO2:
410.0336; found: 410.0334.
4d
N
N
N
R3 = Me; R4 = H
N
N
Ph
5j
CO2Et
N
4b
4c
Ph
5k
Ph
1-Benzyl-5-iodo-1H-1,2,3-triazole-4-carbaldehyde (3b)
Yellow solid; yield: 2.38 g (76%); mp 122–123 °C.
CO2Et
N
N
IR (neat): 2846, 1696, 1494, 1439, 1358, 1240, 1137, 1079, 823,
761, 723 cm–1.
1H NMR (300 MHz, CDCl3): δ = 5.67 (s, 2 H), 7.27–7.40 (m, 5 H),
N
Ph
5l
10.11 (s, 1 H).
OEt
OEt
13C NMR (75 MHz, CDCl3): δ = 54.1, 82.3, 128.0, 128.9, 129.0,
133.3, 147.6, 184.1.
HRMS (ESI): m/z [M + H]+ calcd for C10H9IN3O: 313.9785; found:
313.9782; m/z [M + Na]+ calcd for C10H8IN3NaO: 335.9604; found:
335.9602.
N
N
13
4b
85
N
Ph
5m
1-Benzyl-4-ferrocenyl-5-iodo-1H-1,2,3-triazole (3c)
a Reaction conditions: iodotriazole 3 (1.0 mmol), vinylstannane (1.2
mmol), PdCl2(MeCN)2 (0.06 mmol), DMF (2 mL), 40 °C, under ar-
Orange solid; yield: 2.81 g (60%); mp 160–162 °C (dec.).
IR (neat): 3100, 2924, 1646, 1567, 1495, 1455, 1410, 1221, 1103,
1052, 880, 825, 720 cm–1.
1H NMR (300 MHz, CDCl3): δ = 4.10 (s, 5 H), 4.33 (t, J = 1.8 Hz,
2 H), 5.03 (t, J = 1.8 Hz, 2 H), 5.61 (s, 2 H), 7.21–7.38 (m, 5 H).
gon, 12 h.
b Isolated yield.
In summary, we have developed an efficient two-step
route to 1,4,5-trisubstituted 1,2,3-triazoles using Stille-
like methodology. The reaction was easy to implement, as
was recovery of the desired compounds. The potential ap-
plications of these new compounds are currently under in-
vestigation in our laboratory.
13C NMR (75 MHz, CDCl3): δ = 54.0, 67.0, 68.8, 69.5, 70.1, 74.6,
127.5, 128.3, 128.8, 134.5, 150.0.
HRMS (ESI): m/z [M + H]+ calcd for C19H17FeIN3: 468.9733;
found: 468.9732.
Methyl 2-(4-Formyl-5-iodo-1H-1,2,3-triazol-1-yl)acetate (3d)
Yellow solid; yield: 2.15 g (73%); mp 112–113 °C.
IR (neat): 2992, 2956, 2924, 2857, 2781, 1741, 1699, 1504, 1437,
1416, 1372, 1234, 1145, 1087, 972, 835, 750 cm–1.
© Georg Thieme Verlag Stuttgart · New York
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636
Y. Carcenac et al.
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1H NMR (300 MHz, CDCl3): δ = 3.77 (s, 3 H), 5.24 (s, 2 H), 10.04
(s, 1 H).
13C NMR (75 MHz, CDCl3): δ = 50.8, 53.4, 84.3, 147.6, 165.4,
184.0.
HRMS (ESI): m/z [M + H]+ calcd for C6H7IN3O3: 295.9527; found:
295.9526; m/z [M + Na]+ calcd for C6H6IN3NaO3: 317.9346; found:
317.9345.
Methyl (E)-2-{4-Formyl-5-[2-(trimethylsilyl)vinyl]-1H-1,2,3-
triazol-1-yl}acetate (5a)
Brown oil; yield: 147 mg (55%).
IR (neat): 2957, 2841, 1755, 1694, 1534, 1439, 1367, 1249, 1216,
988, 841, 724 cm–1.
1H NMR (300 MHz, CDCl3): δ = 0.16 (s, 9 H), 3.79 (s, 3 H), 5.22
(s, 2 H), 6.83 (d, J = 19.6 Hz, 1 H), 7.13 (d, J = 19.6 Hz, 1 H), 10.18
(s, 1 H).
Methyl 2-(5-Iodo-4-phenyl-1H-1,2,3-triazol-1-yl)acetate (3e)
White solid; yield: 1.88 g (55%); mp 150–151 °C.
13C NMR (75 MHz, CDCl3): δ = –1.8, 49.7, 53.3, 124.8, 138.6,
143.5, 146.6, 166.0, 185.3.
IR (neat): 2961, 1743, 1436, 1422, 1366, 1344, 1238, 1073, 982,
801, 769, 714, 689 cm–1.
1H NMR (300 MHz, CDCl3): δ = 3.81 (s, 3 H), 5.27 (s, 2 H), 7.36–
7.54 (m, 3 H), 7.96 (d, J = 7.2 Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 51.4, 53.1, 77.9, 127.4, 128.6,
128.7, 129.9, 150.1, 166.1.
HRMS (ESI): m/z [M + H]+ calcd for C11H11IN3O2: 343.9891;
found: 343.9888; m/z [M + Na]+ calcd for C11H10IN3NaO2:
365.9710; found: 365.9708.
HRMS (ESI): m/z [M + H]+ calcd for C11H18N3O3Si: 268.1112;
found: 268.1111; m/z [M + Na]+ calcd for C11H17N3NaO3Si:
290.0931; found: 290.0930.
(E)-1-Benzyl-5-[2-(trimethylsilyl)vinyl]-1H-1,2,3-triazole-4-
carbaldehyde (5b)
Colorless oil; yield: 220 mg (77%).
IR (neat): 3034, 2955, 2839, 1694, 1533, 1467, 1430, 1248, 989,
840, 712, 692 cm–1.
1H NMR (300 MHz, CDCl3): δ = 0.08 (s, 9 H), 5.61 (s, 2 H), 6.76
(d, J = 19.4 Hz, 1 H), 7.15 (m, 2 H), 7.25 (d, J = 19.4 Hz, 1 H),
7.28–7.36 (m, 3 H), 10.17 (s, 1 H).
1-Allyl-5-iodo-4-phenyl-1H-1,2,3-triazole (3f)
Pale yellow solid; yield: 1.96 g (63%); mp 97–98 °C.
IR (neat): 3079, 3033, 2988, 2931, 1646, 1606, 1578, 1471, 1448,
1345, 1230, 1155, 1066, 986, 915, 763, 692 cm–1.
13C NMR (75 MHz, CDCl3): δ = –1.9, 52.7, 124.8, 127.2, 128.7,
129.1, 134.1, 138.1, 143.9, 146.4, 185.3.
1H NMR (300 MHz, CDCl3): δ = 5.09 (dt, J = 5.6, 1.5 Hz, 2 H),
5.22 (br d, J = 17.0 Hz, 1 H), 5.35 (br d, J = 10.3 Hz, 1 H), 6.01 (ddt,
J = 17.0, 10.3, 5.6 Hz, 1 H), 7.36–7.51 (m, 3 H), 7.95 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 53.2, 76.5, 119.9, 127.5, 128.6,
128.7, 130.3, 130.8, 150.0.
HRMS (ESI): m/z [M + H]+ calcd for C11H11IN3: 311.9992; found:
311.9985.
HRMS (ESI): m/z [M + H]+ calcd for C15H20N3OSi: 286.1370;
found: 286.1367.
(E)-1-Benzyl-4-ferrocenyl-5-[2-(trimethylsilyl)vinyl]-1H-1,2,3-
triazole (5c)
Red oil; yield: 260 mg (59%).
IR (neat): 3085, 2952, 1655, 1455, 1243, 990, 841, 808, 714, 691
cm–1.
1H NMR (300 MHz, CDCl3): δ = 0.12 (s, 9 H), 4.10 (s, 5 H), 4.30
(t, J = 1.9 Hz, 2 H), 4.72 (t, J = 1.9 Hz, 2 H), 5.56 (s, 2 H), 6.34 (d,
J = 19.7 Hz, 1 H), 6.75 (d, J = 19.7 Hz, 1 H), 7.15 (m, 2 H), 7.27–
7.37 (m, 3 H).
13C NMR (75 MHz, CDCl3): δ = –1.6, 52.5, 67.4, 68.7, 69.4, 76.0,
127.1, 128.1, 128.2, 128.9, 131.0, 135.4, 139.8, 143.9.
Ethyl 1-Benzyl-5-iodo-1H-1,2,3-triazole-4-carboxylate (3g)27
[CAS Reg. No. 1262782-91-1]
Yellow solid; yield: 2.14 g (60%).
1-Benzyl-5-iodo-4-phenyl-1H-1,2,3-triazole (3h)27
[CAS Reg. No. 860002-66-0]
HRMS (ESI): m/z [M + H]+ calcd for C24H28FeN3Si: 442.1390;
found: 442.1385; m/z [M + Na]+ calcd for C24H27FeN3NaSi:
464.1216; found: 464.1218.
Yellow solid; yield: 2.78 g (77%).
1-Benzyl-4-(2,2-diethoxyethyl)-5-iodo-1H-1,2,3-triazole (3i)
Orange solid; yield: 3.41 g (85%); mp 45–46 °C.
1-Benzyl-5-vinyl-1H-1,2,3-triazole-4-carbaldehyde (5d)
Yellow solid; yield: 173 mg (81%); mp 50–51 °C.
IR (neat): 3086, 3060, 3014, 2975, 2925, 2873, 1604, 1513, 1435,
1352, 1214, 1131, 1025, 898, 803, 727, 706 cm–1.
1H NMR (300 MHz, CDCl3): δ = 5.65 (s, 2 H), 5.82 (dd, J = 11.3,
1.4 Hz, 1 H), 6.59 (dd, J = 17.6, 1.4 Hz, 1 H), 6.72 (dd, J = 17.6,
11.3 Hz, 1 H), 7.17 (m, 2 H), 7.26–7.37 (m, 3 H), 10.19 (s, 1 H).
13C NMR (75 MHz, CDCl3): δ = 52.0, 119.0, 126.7, 127.2, 128.4,
128.9, 133.8, 143.7, 185.1.
1H NMR (300 MHz, CDCl3): δ = 1.14 (t, J = 7.1 Hz, 6 H), 3.01 (d,
J = 5.9 Hz, 2 H), 3.48 (dq, J = 9.3, 7.1 Hz, 2 H), 3.72 (dq, J = 9.3,
7.1 Hz, 2 H), 4.88 (t, J = 5.9 Hz, 1 H), 5.60 (s, 2 H), 7.22–7.26 (m,
2 H), 7.30–7.38 (m, 3 H).
13C NMR (75 MHz, CDCl3): δ = 5.3, 31.7, 54.2, 62.4, 80.4, 102.1,
HRMS (ESI): m/z [M + H]+ calcd for C12H12N3O: 214.0975; found:
214.0972; m/z [M + Na]+ calcd for C12H11N3NaO: 236.0794; found:
236.0791.
127.6, 128.4, 128.8, 134.5, 148.4.
HRMS (ESI): m/z [M + H]+ calcd for C15H21IN3O2: 402.0678;
found: 402.0673.
Methyl 2-(4-Formyl-5-vinyl-1H-1,2,3-triazol-1-yl)acetate (5e)
Stille Reaction; General Method
Yellowish oil; yield: 146 mg (75%).
A mixture of triazole (1.0 mmol), vinylstannane (1.2 mmol), and
PdCl2(MeCN)2 (0.06 mmol) in DMF (2 mL) was stirred overnight
at 40 °C under an argon atmosphere for 12 h. The mixture was
poured into EtOAc (10 mL), filtered, washed with sat. NH4Cl
(3 × 10 mL) and brine (10 mL), dried (MgSO4), and concentrated
under reduced pressure. The crude product was purified by column
chromatography (10% w/w anhyd K2CO3–silica gel, pentane–
EtOAc, 100:0 to 60:40).
IR (neat): 2958, 2921, 2852, 1745, 1691, 1544, 1459, 1364, 1218,
987, 835 cm–1.
1H NMR (300 MHz, CDCl3): δ = 3.69 (s, 3 H), 5.17 (s, 2 H), 5.80
(dd, J = 11.4, 1.1 Hz, 1 H), 6.43 (dd, J = 17.6, 1.1 Hz, 1 H), 6.59
(dd, J = 17.6, 11.4 Hz, 1 H), 10.06 (s, 1 H).
13C NMR (75 MHz, CDCl3): δ = 49.5, 53.3, 119.2, 127.6, 138.1,
143.6, 166.2, 185.3.
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1,4-Disubstituted 5-Vinyl-1,2,3-triazoles
637
HRMS (ESI): m/z [M + H]+ calcd for C8H10N3O3: 196.0717; found:
196.0717; m/z [M + Na]+ calcd for C8H9N3NaO3: 218.0536; found:
218.0534.
13C NMR (75 MHz, CDCl3): δ = 22.4, 51.9, 122.2, 126.5, 127.6,
127.9, 128.2, 128.7, 128.9, 131.2, 133.7, 134.7, 135.7, 143.6.
HRMS (ESI): m/z [M + H]+ calcd for C18H18N3: 288.1495; found:
288.1488.
Methyl 2-(4-Phenyl-5-vinyl-1H-1,2,3-triazol-1-yl)acetate (5f)
Colorless oil; yield: 170 mg (70%).
Ethyl 1-Benzyl-5-vinyl-1H-1,2,3-triazole-4-carboxylate (5k)
Orange oil; yield: 252 mg (98%).
IR (neat): 2962, 1750, 1438, 1352, 1219, 992, 818, 779, 717, 696
cm–1.
1H NMR (300 MHz, CDCl3): δ = 3.75 (s, 3 H), 5.16 (s, 2 H), 5.58
(dd, J = 17.9, 0.7 Hz, 1 H), 5.63 (dd, J = 11.7, 0.7 Hz, 1 H), 6.60
(dd, J = 17.9, 11.7 Hz, 1 H), 7.28–7.43 (m, 3 H), 7.72 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 49.5, 53.0, 122.1, 123.3, 127.6,
128.2, 128.6, 130.9, 131.6, 144.8, 167.0.
IR (neat): 2982, 1713, 1540, 1456, 1341, 1240, 1175, 1058, 1026,
944, 849, 731, 695 cm–1.
1H NMR (300 MHz, CDCl3): δ = 1.42 (t, J = 7.1 Hz, 3 H), 4.43 (q,
J = 7.1 Hz, 2 H), 5.64 (s, 2 H), 5.74 (dd, J = 12.0, 0.8 Hz, 1 H), 5.95
(dd, J = 18.0, 0.8 Hz, 1 H), 6.84 (dd, J = 18.0, 12.0 Hz, 1 H), 7.12
(m, 2 H), 7.29–7.38 (m, 3 H).
HRMS (ESI): m/z [M + H]+ calcd for C13H14N3O2: 244.1081; found:
244.1077; m/z [M + Na]+ calcd for C13H13N3NaO2: 266.0900;
found: 266.0897.
13C NMR (75 MHz, CDCl3): δ = 14.4, 52.6, 61.4, 120.7, 125.6,
126.9, 128.6, 129.2, 134.5, 136.8, 138.0, 161.5.
HRMS (ESI): m/z [M + H]+ calcd for C14H16N3O2: 258.1237; found:
258.1232.
Methyl (E)-2-{4-Phenyl-5-[2-(trimethylsilyl)vinyl]-1H-1,2,3-tri-
azol-1-yl}acetate (5g)
Ethyl (E)-1-Benzyl-5-styryl-1H-1,2,3-triazole-4-carboxylate
Colorless oil; yield: 220 mg (70%).
(5l)
IR (neat): 2954, 1754, 1606, 1439, 1354, 1248, 1215, 994, 864, 842,
772, 697 cm–1.
1H NMR (300 MHz, CDCl3): δ = 0.15 (s, 9 H), 3.78 (s, 3 H), 5.20
(s, 2 H), 6.36 (d, J = 19.7 Hz, 1 H), 6.77 (d, J = 19.7 Hz, 1 H), 7.34
(m, 1 H), 7.42 (m, 2 H), 7.74 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = –1.7, 49.7, 52.9, 127.6, 128.0,
128.1, 128.6, 131.1, 132.6, 141.2, 144.6, 166.9.
HRMS (ESI): m/z [M + H]+ calcd for C16H22N3O2Si: 316.1476;
found: 316.1474; m/z [M + Na]+ calcd for C16H21N3NaO2Si:
338.1295; found: 338.1292.
Brown paste; yield: 327 mg (98%).
IR (neat): 2986, 2902, 1711, 1542, 1444, 1248, 1163, 1111, 1052,
976, 753, 727, 691 cm–1.
1H NMR (300 MHz, CDCl3): δ = 1.43 (t, J = 7.1 Hz, 3 H), 4.44 (q,
J = 7.1 Hz, 2 H), 5.70 (s, 2 H), 7.13–7.40 (m, 12 H).
13C NMR (75 MHz, CDCl3): δ = 14.4, 52.8, 61.3, 111.1, 126.9,
127.2, 128.6, 128.9, 129.3, 129.5, 134.7, 135.6, 136.6, 138.3, 139.4,
161.7.
HRMS (ESI): m/z [M + H]+ calcd for C20H20N3O2: 334.1550; found:
334.1544.
(E)-1-Allyl-4-phenyl-5-styryl-1H-1,2,3-triazole (5h)
Yellow paste; yield: 281 mg (98%).
1-Benzyl-4-(2,2-diethoxyethyl)-5-vinyl-1H-1,2,3-triazole (5m)
Yellow oil; yield: 256 mg (85%).
IR (neat): 3026, 2935, 1644, 1603, 1485, 1440, 1358, 1238, 1072,
975, 915, 771, 756, 718, 702, 691 cm–1.
1H NMR (300 MHz, CDCl3): δ = 5.11 (dt, J = 5.3, 1.7 Hz, 2 H),
5.21 (br d, J = 17.1 Hz, 1 H), 5.38 (br d, J = 10.4 Hz, 1 H), 6.12 (ddt,
J = 17.1, 10.4, 5.3 Hz, 1 H), 6.98 (d, J = 16.7 Hz, 1 H), 7.01 (d,
J = 16.7 Hz, 1 H), 7.31–7.49 (m, 8 H), 7.80 (m, 2 H).
IR (neat): 3064, 3033, 2975, 2931, 2879, 1633, 1456, 1373, 1224,
1058, 926, 837, 729, 695 cm–1.
1H NMR (300 MHz, CDCl3): δ = 1.14 (t, J = 7.0 Hz, 6 H), 3.08 (d,
J = 5.8 Hz, 2 H), 3.49 (dq, J = 9.3, 7.0 Hz, 2 H), 3.73 (dq, J = 9.3,
7.0 Hz, 2 H), 4.90 (t, J = 5.8 Hz, 1 H), 5.48 (dd, J = 11.7, 1.0 Hz, 1
H), 5.55 (s, 2 H), 5.82 (dd, J = 17.8, 1.0 Hz, 1 H), 6.46 (dd, J = 17.8,
11.7 Hz, 1 H), 7.10–7.16 (m, 2 H), 7.27–7.37 (m, 3 H).
13C NMR (75 MHz, CDCl3): δ = 51.1, 112.6, 118.8, 126.8, 127.9,
128.2, 128.8, 129.0, 129.1, 131.0, 131.5, 132.0, 135.9, 136.3, 145.2.
HRMS (ESI): m/z [M + H]+ calcd for C19H18N3: 276.1495; found:
13C NMR (75 MHz, CDCl3): δ = 15.3, 31.6, 52.2, 62.9, 103.1,
121.2, 121.8, 126.9, 128.2, 128.9, 132.7, 135.2, 141.7.
276.1489.
HRMS (ESI): m/z [M + H]+ calcd for C17H24N3O2: 302.1869; found:
302.1873.
1-Benzyl-4-phenyl-5-vinyl-1H-1,2,3-triazole (5i)
Orange liquid; yield: 232 mg (89%).
IR (neat): 3062, 3032, 1687, 1606, 1496, 1455, 1350, 1239, 1073,
993, 919, 778, 732, 694 cm–1.
1H NMR (300 MHz, CDCl3): δ = 5.56 (dd, J = 11.6, 0.9 Hz, 1 H),
5.57 (dd, J = 18.0, 0.9 Hz, 1 H), 5.62 (s, 2 H), 6.59 (dd, J = 18.0,
11.6 Hz, 1 H), 7.20 (m, 2 H), 7.30–7.47 (m, 6 H), 7.76 (m, 2 H).
Acknowledgment
We thank the ‘Service d’analyse chimique du Vivant de Tours’ for
recording NMR and HRMS spectra. Johnson Matthey is thanked for
a generous gift of palladium metal salts.
13C NMR (75 MHz, CDCl3): δ = 52.3, 122.1, 123.0, 127.0, 127.8,
128.2, 128.3, 128.7, 129.1, 131.0, 131.3, 135.3, 145.3.
HRMS (ESI): m/z [M + H]+ calcd for C17H16N3: 262.1339; found:
262.1333.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis. Included
are copies of 1H and 13C NMR spectra of compounds 3 and 5.SnoIufropig
m
iotSrat
ungIifop
r
t
1-Benzyl-4-phenyl-5-(prop-1-en-2-yl)-1H-1,2,3-triazole (5j)
Orange solid; yield: 220 mg (80%); mp 63–64 °C.
References
IR (neat): 2988, 2957, 2903, 1712, 1641, 1576, 1543, 1446, 1423,
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1H NMR (300 MHz, CDCl3): δ = 1.72 (dd, J = 1.4, 1.0 Hz, 3 H),
5.18 (m, 1 H), 5.54 (s, 2 H), 5.56 (m, 1 H), 7.22 (m, 2 H), 7.28–7.35
(m, 4 H), 7.40 (m, 2 H), 7.84 (m, 2 H).
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Synthesis 2013, 45, 633–638
© Georg Thieme Verlag Stuttgart · New York