A Mild Multi-Component Reaction for the Synthesis of 4,5-Disubstituted 1 H -1,2,3-Triazoles from Phosphonium Salts, Aldehydes, and Sodium Azide

Article abstract of DOI:10.1055/s-0037-1609720

A mild and metal-free multi-component reaction to synthesize 4,5-disubstituted 1 H -1,2,3-triazoles from phosphonium salts, aldehydes, and sodium azide is described. The process undergoes an organocatalyzed coupling of formyl group with phosphonium to for

Full text of DOI:10.1055/s-0037-1609720

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2018, 50, A–G
paper
A
en
G.-L. Wu, Q.-P. Wu
Paper
Synthesis
A Mild Multi-Component Reaction for the Synthesis of 4,5-Disub-
stituted 1H-1,2,3-Triazoles from Phosphonium Salts, Aldehydes,
and Sodium Azide
Guang-Long Wu
+
R2
R1
+
Qin-Pei Wu*
R2CHO, NaN3
L-proline, r.t.
PPh3
Br–
R1
R2
PPh3
R1
NH
N
School of Chemistry and Chemical Engineering, Beijing
Institute of Technology, 5 South Zhongguancun Street,
Haidian District, Beijing 100081, China
qpwu@bit.edu.cn
N
23 examples, up to 81% yield
Received: 25.01.2018
Accepted after revision: 27.03.2018
Published online: 08.05.2018
cycles;6f by-product separation,6g and stereo- and regiose-
lective olefination.6h,i We envisioned that phosphonium salt
could also couple with aldehyde to form olefinic phospho-
nium salt, which is followed by a [3+2] cycloaddition with
azide to produce a triazole ring as do acrylonitriles5a and α-
haloacrylates (Scheme 1).5g
DOI: 10.1055/s-0037-1609720; Art ID: ss-2018-h0049-op
Abstract A mild and metal-free multi-component reaction to synthe-
size 4,5-disubstituted 1H-1,2,3-triazoles from phosphonium salts, alde-
hydes, and sodium azide is described. The process undergoes an or-
ganocatalyzed coupling of formyl group with phosphonium to form a
key intermediate, olefinic phosphonium salt, which is followed by the
[3+2] cycloaddition of the azide to the activated alkene. A series of rep-
resentative 4,5-disubstituted 1H-1,2,3-triazoles were prepared.
Wittig reaction:
+
R1
+
X–
R2CHO
PPh3
base
PPh3
–
R2
R1
R1
– O=PPh3
Key words phosphonium salt, triazole, organic catalyst, multicompo-
nent reaction, cycloaddition
This work:
+
R1
N
R2
NH
+
PPh3
X–
R2CHO
catalyst
NaN3
1,2,3-Triazoles are an important class of heterocyclic
compounds, which have been widely used in organic syn-
thesis,1 medicinal chemistry,2 and the development of new
materials.3 Therefore, many methods have been developed
to synthesize 1,2,3-triazoles till now.4 Among these devel-
oped approaches, most are for N-substituted 1,2,3-tri-
azoles, and only a few are for N-unsubstituted 1,2,3-tri-
azoles, which also have wide applications.5 Construction of
4,5-disubstituted 1H-1,2,3-triazoles can be achieved via a
tandem three-component reaction, involving the coupling
of Julia reagent,5h nitroalkene,5e,j,k or cyanocarbonyl com-
pounds5i with aldehyde, followed by cycloaddition with so-
dium azide. In this paper, we report a mild method to syn-
thesize 4,5-disubstituted 1H-1,2,3-triazoles by a multi-
component reaction from commercially inexpensive phos-
phonium salts, aldehydes, and sodium azide.
PPh3
R1
– PPh3
R1
R2
N
Scheme 1 Reactions of phosphonium salts
Olefinic sulfur salt intermediates are formed via the
coupling of sulfur salts with aldehydes in the presence of
L-proline.7 Thus, our initial experiment was performed with
(ethoxycarbonylmethyl)triphenylphosphonium
bromide
(1a), benzaldehyde (2a), and NaN3 catalyzed by L-proline.
The mixture was stirred in DMSO solution at room tem-
perature for 24 hours and the expected product, triazole 3a,
was obtained in a 75% isolated yield. The Wittig product 4a
was collected in an 11% yield (Table 1, entry 1). When the
reaction was performed at 80 °C, the yield for the triazole
product was reduced to 50%, and the yield of the by-prod-
uct, olefin, increased to 25% (entry 2). Thus, high tempera-
ture does not favor triazole formation. When DMSO was re-
placed with EtOH, MeOH, or MeCN as the solvent, all the re-
actions were negative (entries 3–5). In DMF solution, the
yield of the main product, triazole, was moderate (51%, en-
Phosphonium salts are usually deprotonated with a
strong base to form phosphorus ylides, which have been
studied intensively ever since the Wittig reaction became
popular in the 1950s (Scheme 1)6a,b including new methods
for the generation of phosphorus ylides,6b,c,j the synthesis of
modified nucleosides,6d vinyl isocyanides,6e and macro-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–G

B
G.-L. Wu, Q.-P. Wu
Paper
Synthesis
Table 1 Optimization of the Reaction Conditionsa
obtained in 81% and 13% yields and trace triazole product
was observed when K2CO3 was used in 100 mol% and 10
mol%, respectively (entries 15 and 16), indicating that
strong bases promote the formation of the Wittig product.9
p-Toluenesulfonic acid was unsuitable for the formation of
triazole or olefins (entry 17). In the control experiment, no
product was formed in the absence of L-proline or amines
(entry 18).
CO2Et
COOEt
Ph
PPh3
NaN3
Br
PhCHO
+
+
CO2Et
catalyst, solvent
NH
N
Ph
N
1a
2a
3a
4a
Entry
Solvent
Catalyst
(mol%)
Yield of 3a Yield of 4a
(%)b
(%)b
With the optimized conditions, the scope of aldehydes
in this multistep reaction was screened (Scheme 2). The re-
sults indicated that electron-donating groups (Me, MeO,
MeS, or NMe2) or weakly electron-withdrawing groups (F,
Cl, Br, or CF3) on the aromatic aldehydes favored the genera-
tion of the corresponding triazoles in yields of 63–81%
(compounds 3b–j). However, strong electron-withdrawing
groups (CN, NO2, and CO2Me) did not favor this tandem re-
action (yields: 31–45%, 3l–n). 4,5-Disubstituted 1H-1,2,3-
triazole 3k containing a phenol hydroxyl group was formed
in a much lower yield (28%). Compared with thiophen-2-yl
aldehyde, pyridine-3-yl aldehyde gave rise to a much lower
yield (yield: 35% and 63% for compounds 3o and 3p, respec-
tively). Furthermore, butyraldehyde produced the corre-
sponding triazole 3q in a 71% yield, similar to the results for
aromatic aldehydes with an electron-donating group (com-
pounds 3a–d).
Besides the (ethoxycarbonylmethyl)triphenylphospho-
nium bromide (1a) described above, phosphonium salts
prepared by the quaternization of triphenylphosphine with
bromomethyl ketone compounds were also examined un-
der mild conditions (Scheme 3). The results indicated that
the electron-withdrawing phenyl ketone produced α-keto
1H-1,2,3-triazoles in lower yields (5c vs 5a and 5b) than the
cyclopropyl bromomethyl ketone. Under similar conditions,
(cyanomethyl)triphenylphosphonium bromide showed
good reactivity in the formation of a few corresponding 1H-
1,2,3-triazoles 5d–f. (Benzyl)triphenylphosphonium bro-
mide failed to be transformed to the corresponding triazole
product 5g possibly because of the failure in the coupling of
benzaldehyde with the phosphonium salt under these mild
conditions. However, acylmethyl and cyanomethylphos-
phonium salts can generate 4,5-disubstituted 1H-1,2,3-tri-
azoles through their sequential coupling with aldehyde and
NaN3 under these mild metal-free conditions.
1
2c
3
DMSO
DMSO
MeOH
EtOH
Proline (10)
Proline (10)
Proline (10)
Proline (10)
Proline (10)
Proline (10)
Proline (10)
Proline (10)
Proline (10)
Proline (10)
Morpholine (10)
Piperidine (10)
Glycine (10)
Serine (10)
K2CO3 (100)
K2CO3 (10)
TsOH (20)
75
50
11
25
trace
trace
4
trace
trace
51
trace
trace
15
5
MeCN
6
DMF
7
THF
trace
trace
trace
32
61
8
1,4-Dioxane
H2O
52
9
trace
40
10
11
12
13
14
15
16
17
18
DMSO/H2O (9:1)
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
71
16
68
18
67
15
71
13
trace
trace
NR
81
13
NR
NR
–
NR
a Reagents and conditions: 1a (345 mg, 0.8 mmol), PhCHO (2a; 128 mg,
1.2 mmol), NaN3 (79 mg, 1.2 mmol), catalyst, and solvent (5 mL), r.t., 24 h.
NR: No reaction.
b Isolated yields.
c The reaction was performed at 80 °C for 24 h.
try 6). In a weak polar solvent, tetrahydrofuran or 1,4-diox-
ane, only the olefin product was produced in a yield of 61%
or 52%, respectively, which is the Wittig reaction, and was
probably attributable to the insolubility of NaN3 (entries 7
and 8). Neither triazole 3a nor olefin 4a was observed in the
water solution (entry 9). However, in a solution of DMSO/
H2O (9:1, v/v), triazole 3a and olefin 4a were obtained in
isolated yields of 32% and 40%, respectively (entry 10).
The catalytic activities of both morpholine and piperi-
dine were also examined and both proved to be effective in
selectively producing the triazole product 3a in yields of
71% and 68%, respectively (Table 1, entries 11 and 12). Oth-
er amino acids like glycine and serine were also examined
and good yields were observed (entries 13 and 14). Notably,
the amount of L-proline or amines used in this procedure
was only 10 mol% of the phosphonium salt, rather than the
stoichiometric amount of a base that is usually involved in
the Wittig reaction.8 Additionally, Wittig product 3a was
To clarify the mechanism, LC-MS was used to monitor
the reaction of (ethoxycarbonylmethyl)triphenylphospho-
nium bromide (1a) with 4-methylthiobenzaldehyde, and
NaN3 for triazole 3h. The mass spectrum (positive ESI)
showed a peak at m/z = 263.1, exactly matching the calcu-
lated value for the molecular weight of protonated triphen-
ylphosphine (C18H15P–H+, m/z = 263.9).10 Moreover, in the
absence of NaN3, a peak at m/z = 483.1 is observed, which
exactly matches the calculated value for the molecular
weight of the olefinic triphenylphosphonium ion II
(C30H28O2SP+, m/z = 483.1) (vide infra, Scheme 4).10 In the
31P NMR spectra for the by-product, a strong signal at –5.41
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–G

C
G.-L. Wu, Q.-P. Wu
Paper
Synthesis
ppm should also be assigned to triphenylphosphine.10
Triphenylphosphine oxide, however, is a well-known by-
product of the Wittig reaction.11 In addition, the possibility
of the addition of azides to electron-deficient olefins like 4a
was examined by coupling ethyl cinnamate (4a) with sodi-
um azide under similar conditions. A negative result was
observed (Scheme 5), which indicates that 4a is not an in-
termediate for triazole product but a by-product (Table 1).
Accordingly, a plausible pathway for the formation of Ph3P
and the triazole product is described in Scheme 4. In the
presence of L-proline and sodium azide, phosphonium salt I
couples with protonated aldehyde to form the olefinic
phosphorus salt II.12,13 A [3+2] cycloaddition between II and
the azide anion generates the 4,5-disubstituted triazole
product,14 and triphenylphosphine15 is released via the aro-
matization-promoted elimination.
CO2Et
+
R
PPh3
L-proline (10 mol%)
R1CHO
Br–
Me
+
NH
N
NaN3, DMSO, r.t., 24 h
CO2Et
N
2
1a
3b–q
Br
MeO
CO2Et
NH
CO2Et
NH
CO2Et
MeO
CO2Et
NH
N
N
NH
N
N
N
N
N
N
+
+
3d (75%)
Br–
3b (79%)
3c (78%)
Ph3P
3e (80%)
PPh3
L-proline
MeS
Cl
Me2N
Br–
RCHO
F
+
R
CO2Et
NaN3
CO2Et
II
Knoevenagel condensation
CO2Et
NH
CO2Et
NH
I
CO2Et
NH
CO2Et
NH
N
N
N
N
N
N
N
N
3f (65%)
3g (63%)
3h (81%)
3i (65%)
–N
PPh3
NaBr
MeO2C
CO2Et
NC
N+
HO
F3C
+
N–
N
N
Ph3P
R
CO2Et
CO2Et
NH
HN
CO2Et
NH
R
CO2Et
CO2Et
Br–
NH
N
N
NH
N
N
N
N
N
III
N
3m (38%)
3j (78%)
3k (28%)
N
3l (45%)
Scheme 4 Proposed mechanism for sequentially coupling phosphoni-
um salt with aldehyde and sodium azide
O2N
CO2Et
NH
S
CO2Et
NH
CO2Et
NH
CO2Et
NH
N
N
CO2Et
NH
Ph
N
N
N
N
N
NaN3, DMSO
N
Ph
CO2Et
3n (31%)
3o (35%)
3p (63%)
3q (71%)
N
L-proline (10 mol%)
r.t., 24 h
no reaction
N
Scheme 2 Triazoles generated from various aldehydes
3a
4a
Scheme 5 No Reaction between 4a and sodium azide
R2
R1
N
+
Br–
PPh3
L-proline (10 mol%)
R1CHO
+
NH
In conclusion, a multi-component reaction to construct
4,5-disubstituted 1H-1,2,3-triazoles by sequentially cou-
pling phosphonium salts with aldehydes and azide has
been developed. This method features mild and metal-free
conditions. Starting from commercial and readily available
reagents, it provides an easy access to diversely functional-
ized 4,5-disubstituted 1H-1,2,3-triazoles. Notably, the ole-
finic triphenylphosphonium salt was previously demon-
strated to be generated via the coupling of phosphonium
salts with aldehydes.
R2
NaN3, DMSO, r.t., 24 h
N
2
1
5a–g
Me
O
O
O
NH
N
NH
N
NH
N
N
N
N
5a (43%)
5b (38%)
5c (56%)
O
F
Me
CN
NH
CN
NH
CN
NH
NH
N
N
N
N
All reactions were performed under air. All reagents were used with-
out further purification. Column chromatography was used for isolat-
ing the product and performed using 200–300 mesh silica gel with
the proper solvent system according to TLC analysis using KMnO4
stain and UV light to visualize the reaction components. NMR spectra
N
N
N
N
5d (56%)
5g (0%)
5e (67%)
5f (61%)
Scheme 3 Triazoles generated from various phosphonium salts and al-
dehydes
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–G

D
G.-L. Wu, Q.-P. Wu
Paper
Synthesis
were recorded in CDCl3, CD3OD or DMSO-d6, with proton and carbon
resonances at 300 or 400 and 75 MHz, respectively, and are refer-
enced to the residual solvent signal at δ = 7.28 (CDCl3), 4.89 (CD3OD),
2.50 ppm (DMSO-d6) for 1H and δ = 77.27 (CDCl3), 47.82 (CD3OD),
40.17 ppm (DMSO-d6) for 13C. Data for 1H are reported as follows:
chemical shift (δ ppm), multiplicity (standard abbreviations), cou-
pling constant, and integration. Data for 13C NMR are reported in
terms of chemical shift. MS and HRMS were measured in ESI mode,
and the mass analysis mode of the HRMS was TOF.
Ethyl 4-(2-Methoxyphenyl)-1H-1,2,3-triazole-5-carboxylate (3d)17
Eluent: EtOAc/PE (1:2); yield: 129 mg (75%); white solid; mp 123–
125 °C; Rf = 0.53 (PE/EtOAc 1:1).
1H NMR (300 MHz, CD3OD): δ = 7.62–7.28 (m, 2 Harom), 7.28–6.82 (m,
2 Harom), 4.23 (q, J = 7.1 Hz, 2 H, OCH2CH3), 3.77 (s, 3 H, OCH3), 1.18 (t,
J = 7.1 Hz, 3 H, OCH2CH3).
13C NMR (75 MHz, CD3OD): δ = 161.6, 157.3, 139.9, 135.7, 131.4,
131.0, 120.2, 116.3, 110.9, 60.9, 54.9, 13.2.
HRMS (ESI): m/z calcd for C12H14N3O3 [M + H]+: 248.1030; found:
248.1026.
4,5-Disubstituted 1,2,3-Triazoles; Ethyl 4-Phenyl-1H-1,2,3-tri-
azole-5-carboxylate (3a);16
Ethyl 4-(4-Bromophenyl)-1H-1,2,3-triazole-5-carboxylate (3e)5d
Typical Procedure
Eluent: EtOAc/PE (1:2); yield: 169 mg (80%); white solid; mp 169–
171 °C; Rf = 0.56 (PE/EtOAc 1:1).
To a reaction flask equipped with a magnetic stir bar was added
(ethoxycarbonylmethyl)triphenylphosphonium bromide (1a; 345 mg,
0.8 mmol), benzaldehyde (2a; 128 mg, 1.2 mmol), NaN3 (79 mg, 1.2
mmol), and L-proline (9 mg, 0.08 mmol). The mixture was dissolved
in DMSO (5 mL) and stirred at r.t. for 24 h. After completion of the
reaction, the mixture was poured into ice-water and extracted with
EtOAc (4 × 20 mL). The combined organic layers were dried (Na2SO4),
and the solvent was concentrated in vacuo. The residue was isolated
by chromatography on silica gel with EtOAc/PE (1:2) as eluent to af-
ford the product 3a; yield: 131 mg (75%); white solid; mp 92–94 °C;
Rf = 0.55 (PE/EtOAc 1:1).
1H NMR (300 MHz, DMSO-d6): δ = 7.74 (d, J = 8.5 Hz, 2 Harom), 7.68 (d,
J = 8.6 Hz, 2 Harom), 4.28 (q, J = 7.1 Hz, 2 H, OCH2CH3), 1.25 (t, J = 7.1 Hz,
3 H, OCH2CH3).
13C NMR (75 MHz, DMSO-d6): δ = 161.4, 145.1, 131.9, 131.8, 131.5,
128.4, 123.4, 61.5, 14.6.
HRMS (ESI): m/z calcd for
298.0009; found: 296.0029, 298.0006.
C11H11BrN3O2 [M +
H]+: 296.0029,
Ethyl 4-(4-Fluorophenyl)-1H-1,2,3-triazole-5-carboxylate (3f)5e
1H NMR (300 MHz, CDCl3): δ = 7.87–7.85 (m, 2 Harom), 7.48–7.47 (m, 3
Eluent: EtOAc/PE (1:2); yield: 126 mg (65%); colorless oil; Rf = 0.55
(PE/EtOAc 1:1).
H
arom), 4.45 (q, J = 7.1 Hz, 2 H, OCH2CH3), 1.38 (t, 3 H, J = 7.1 Hz,
1H NMR (300 MHz, CDCl3): δ = 7.91 (dd, J1 = 5.6 Hz, J2 = 8.4 Hz, 2 Harom),
7.15–7.2 (m, 2 Harom H), 4.45 (q, J = 7.2 Hz, 2 H, OCH2CH3), 1.40 (t, J =
7.2 Hz, 3 H, OCH2CH3).
OCH2CH3).
13C NMR (75 MHz, CDCl3): δ = 161.1, 146.2, 134.1, 129.7, 129.3, 128.3,
127.7, 61.7, 14.1.
13C NMR (75 MHz, CDCl3): δ = 165.4 (d, J = 248 Hz), 161.2, 146.8,
134.2, 131.6 (d, J = 7.4 Hz), 124.5, 115.8 (d, J = 22.6 Hz), 62.2, 14.4.
HRMS (ESI): m/z calcd for C11H12N3O2 [M + H]+: 218.0924; found:
218.0916.
HRMS (ESI): m/z calcd for C11H11FN3O2 [M + H]+: 236.0830; found:
236.0826.
Ethyl 4-(p-Tolyl)-1H-1,2,3-triazole-5-carboxylate (3b)5d
Eluent: EtOAc/PE (1:2); yield: 185 mg (79%); white solid; mp 129–
130 °C; Rf = 0.55 (PE/EtOAc 1:1).
Ethyl 4-(3-Chlorophenyl)-1H-1,2,3-triazole-5-carboxylate (3g)5e
1H NMR (300 MHz, CDCl3): δ = 7.73 (d, J = 8.1 Hz, 2 Harom), 7.16 (d, J =
8.1 Hz, 2 Harom), 4.40 (q, J = 7.1 Hz, 2 H, OCH2CH3), 2.40 (s, 3 H, ArCH3),
1.33 (t, J = 7.1 Hz, 3 H, OCH2CH3).
13C NMR (75 MHz, CDCl3): δ = 161.3, 146.2, 140.1, 134.1, 129.3, 129.3,
124.8, 61.9, 21.6, 14.3.
Eluent: EtOAc/PE (1:2); yield: 153 mg (63%); white solid; mp 101–
103 °C; Rf = 0.56 (PE/EtOAc 1:1).
1H NMR (400 MHz, CD3OD): δ = 7.90 (s, 1 Harom), 7.81–7.70 (m, 1 Harom),
7.54–7.42 (m, 2 Harom), 4.39 (q, J = 7.1 Hz, 2 H, OCH2CH3), 1.36 (t, J = 7.1
Hz, 3 H, OCH2CH3).
13C NMR (75 MHz, CD3OD): δ = 160.8, 144.7, 133.9, 130.6, 129.7,
HRMS (ESI): m/z calcd for C12H14N3O2 [M + H]+: 232.1081; found:
129.2, 129.1, 127.6, 127.5, 61.3, 13.2.
232.1074.
HRMS (ESI): m/z calcd for C11H11ClN3O2 [M + H]+: 252.0534; found:
252.0524.
Ethyl 4-(4-Methoxyphenyl)-1H-1,2,3-triazole-5-carboxylate (3c)17
Eluent: EtOAc/PE (1:2); yield: 133 mg (78%); white solid; mp 122–
125 °C; Rf = 0.54 (PE/EtOAc 1:1).
Ethyl 4-[4-(Methylthio)phenyl]-1H-1,2,3-triazole-5-carboxylate
(3h)
1H NMR (300 MHz, CDCl3): δ = 7.77 (d, J = 8.8 Hz, 2 Harom), 6.92 (d, J =
8.9 Hz, 2 Harom), 4.36 (q, J = 7.1 Hz, 2 H, OCH2CH3), 3.82 (s, 3 H, OCH3),
1.30 (t, J = 7.1 Hz, 3 H, OCH2CH3).
Eluent: EtOAc/PE (1:2); yield: 152 mg (81%); white solid; mp 118–
120 °C; Rf = 0.51 (PE/EtOAc 1:1).
1H NMR (300 MHz, CDCl3): δ = 7.78 (d, J = 8.4 Hz, 2 Harom), 7.29 (d, J =
8.4 Hz, 2 Harom), 4.40 (q, J = 7.1 Hz, 2 H, OCH2CH3), 2.51 (s, 3 H, SCH3),
1.33 (t, J = 7.1 Hz, 3 H, OCH2CH3).
13C NMR (75 MHz, CDCl3): δ = 161.6, 160.88, 145.3, 133.7, 130.9,
119.7, 113.9, 61.7, 55.5, 14.3.
HRMS (ESI): m/z calcd for C12H14N3O3 [M + H]+: 248.1030; found:
248.1027.
13C NMR (75 MHz, CDCl3): δ = 161.3, 141.3, 129.7, 129.7, 125.8, 124.3,
124.1, 62.0, 15.5, 14.3.
HRMS (ESI): m/z calcd for C12H14N3O2S [M + H]+: 264.0801; found:
264.0793.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–G

E
G.-L. Wu, Q.-P. Wu
Paper
Synthesis
Ethyl 4-[4-(Dimethylamino)phenyl]-1H-1,2,3-triazole-5-carboxyl-
HRMS (ESI): m/z calcd for C12H11N4O2 [M + H]+: 243.0877; found:
243.0866.
ate (3i)18
Eluent: EtOAc/PE (2:3), yield: 183 mg (65%); white solid; mp 124–
126 °C; Rf = 0.43 (PE/EtOAc 1:1).
Ethyl 4-(4-Nitrophenyl)-1H-1,2,3-triazole-5-carboxylate (3n)18
1H NMR (400 MHz, CD3OD): δ = 7.68 (d, J = 8.9 Hz, 2 Harom), 6.83 (d, J =
8.9 Hz, 2 Harom), 4.38 (q, J = 7.1 Hz, 2 H, OCH2CH3), 3.04 [s, 6 H,
N(CH3)2], 1.37 (t, J = 7.1 Hz, 3 H, OCH2CH3).
13C NMR (75 MHz, CD3OD): δ = 161.6, 151.8, 143.8, 130.0, 128.7,
113.7, 111.5, 60.9, 39.2, 13.3.
Eluent: EtOAc/PE (1:1); yield: 157 mg (31%); white solid; mp 178–
180 °C; Rf = 0.45 (PE/EtOAc 1:1).
1H NMR (300 MHz, CD3OD): δ = 8.29 (d, J = 9.0 Hz, 2 Harom), 8.10 (d, J =
9.0 Hz, 2 Harom), 4.37 (q, J = 7.1 Hz, 2 H, OCH2CH3), 1.34 (t, J = 7.1 Hz, 3
H, OCH2CH3).
13C NMR (75 MHz, CD3OD): δ = 160.6, 148.3, 145.1, 145.1, 135.6,
HRMS (ESI): m/z calcd for C13H16N4O2 [M + H]+: 261.1346; found:
130.2, 123.1, 61.6, 13.2.
261.1344.
HRMS (ESI): m/z calcd for C11H11N4O4 [M + H]+: 263.0775; found:
Ethyl 4-[4-(Trifluoromethyl)phenyl]-1H-1,2,3-triazole-5-carboxyl-
263.0768.
ate (3j)17
Eluent: EtOAc/PE (1:2); yield: 147 mg (78%); white solid; mp 151–
Ethyl 4-(Pyridin-3-yl)-1H-1,2,3-triazole-5-carboxylate (3o)19
152 °C; Rf = 0.51 (PE/EtOAc 1:1).
Eluent: EtOAc/PE (1:1); yield: 171 mg (35%); white solid; mp 158–
1H NMR (400 MHz, CD3OD): δ = 8.04 (d, J = 8.2 Hz, 2 Harom), 7.79 (d, J =
8.2 Hz, 2 Harom), 4.39 (q, J = 7.1 Hz, 2H, OCH2CH3), 1.35 (t, J = 7.1 Hz, 3
H, OCH2CH3).
160 °C; Rf = 0.48 (PE/EtOAc 1:1).
1H NMR (300 MHz, CD3OD): δ = 9.61 (s, 1 Hpyridyl), 9.33 (d, J = 4.8 Hz, 1
H
pyridyl), 8.86 (d, J = 7.8 Hz, 1 Hpyridyl), 8.22–8.18 (m, 1 Hpyridyl), 4.97 (q,
13C NMR (75 MHz, CD3OD): δ = 160.8, 145.1, 132.9, 130.7, 129.8,
126.1, 124.9 (q, J = 204 Hz), 122.5, 61.4, 13.2.
HRMS (ESI): m/z calcd for C12H11F3N3O2 [M + H]+: 286.0798; found:
J = 7.1 Hz, 2 H, OCH2CH3), 1.92 (t, J = 7.1 Hz, 3 H, OCH2CH3).
13C NMR (75 MHz, CD3OD): δ = 161.2, 151.0, 150.7, 150.1, 137.3,
137.0, 125.6, 123.9, 61.6, 14.6.
HRMS (ESI): m/z calcd for C10H11N4O2 [M + H]+: 219.0877; found:
286.0788.
219.0870.
Ethyl 4-(4-Hydroxyphenyl)-1H-1,2,3-triazole-5-carboxylate (3k)17
Eluent: EtOAc/PE (1:1); yield: 106 mg (28%); white solid; mp 164–
Ethyl 4-(Thiophen-2-yl)-1H-1,2,3-triazole-5-carboxylate (3p)5h
166 °C; Rf = 0.40 (PE/EtOAc 1:1).
Eluent: EtOAc/PE (1:2); yield: 118 mg (63%); white solid; mp 144–
1H NMR (400 MHz, CD3OD): δ = 7.64 (d, J = 8.7 Hz, 2 Harom), 6.90 (d, J =
8.7 Hz, 2 Harom), 4.36 (q, J = 7.1 Hz, 2 H, OCH2CH3), 1.35 (t, J = 7.1 Hz, 3
H, OCH2CH3).
146 °C; Rf = 0.50 (PE/EtOAc 1:1).
1H NMR (400 MHz, CD3OD): δ = 7.97 (d, J = 3.8 Hz, 1 Hthiophenyl), 7.56 (d,
J = 4.9 Hz, 1 Hthiophenyl), 7.14 (dd, J = 4.9, 3.8 Hz, 1 Hthiophenyl), 4.42 (q, J =
7.1 Hz, 2 H, OCH2CH3), 1.40 (t, J = 7.1 Hz, 3 H, OCH2CH3).
13C NMR (75 MHz, CD3OD): δ = 161.4, 159.1, 144.0, 130.7, 125.5,
13C NMR (75 MHz, CD3OD): δ = 160.8, 138.6, 136.3, 130.5, 129.5,
127.9, 127.3, 61.4, 13.3.
118.0, 115.0, 61.0, 13.3.
HRMS (ESI): m/z calcd for C11H12N3O3 [M + H]+: 234.0873; found:
HRMS (ESI): m/z calcd for C9H10N3O2S [M + H]+: 224.0488; found:
234.0867.
224.0482.
Ethyl 4-[4-(Methoxycarbonyl)phenyl]-1H-1,2,3-triazole-5-carbox-
ylate (3l)17
Ethyl 4-Propyl-1H-1,2,3-triazole-5-carboxylate (3q)20
Eluent: EtOAc/PE (1:2); yield: 107 mg (45%); white solid; mp 108–
110 °C; Rf = 0.50 (PE/EtOAc 1:1).
Eluent: EtOAc/PE (1:1); yield: 104 mg (71%); white solid; mp 93–
95 °C; Rf = 0.46 (PE/EtOAc 1:1).
1H NMR (400 MHz, CD3OD): δ = 8.12 (d, J = 8.5 Hz, 2 Harom), 7.95 (d, J =
8.5 Hz, 2 Harom), 4.39 (d, J = 7.1 Hz, 2 H, OCH2CH3), 3.96 (s, 3 H, OCH3),
1.35 (t, J = 7.1 Hz, 3 H, OCH2CH3).
13C NMR (75 MHz, CD3OD): δ = 166.7, 160.9, 145.1, 133.3, 130.6,
129.2, 129.1, 126.4, 61.4, 51.6, 13.3.
1H NMR (300 MHz, CDCl3): δ = 4.41 (q, J = 7.1 Hz, 2 H, OCH2CH3), 3.04
(t, J = 7.5 Hz, 2 H, CH2CH2CH3), 1.79-1.67 (m, 2 H CH2CH2CH3), 1.35 (t,
J = 7.1 Hz, 3 H, OCH2CH3), 0.94 (t, J = 7.4 Hz, 3 H, CH2CH2CH3).
13C NMR (75 MHz, CDCl3): δ = 161.9, 146.3, 135.2, 61.4, 26.2, 22.4,
14.4, 13.9.
HRMS (ESI): m/z calcd for C13H14N3O4 [M + H]+: 276.0979; found:
276.0969.
HRMS (ESI): m/z calcd for C8H14N3O2 [M + H]+: 184.1081; found:
184.1077.
Ethyl 4-(4-Cyanophenyl)-1H-1,2,3-triazole-5-carboxylate (3m)17
Phenyl(4-phenyl-1H-1,2,3-triazol-5-yl)methanone (5a)21
Eluent: EtOAc/PE (1:1), yield: 135 mg (38%); white solid; mp 119–
122 °C; Rf = 0.47 (PE/EtOAc 1:1).
Eluent: EtOAc/PE (1:3); yield: 162 mg (43%); white solid; mp 117–
120 °C; Rf = 0.62 (PE/EtOAc 1:1).
1H NMR (301 MHz, CD3OD): δ = 8.01 (d, J = 8.4 Hz, 2 Harom), 7.79 (d, J =
8.4 Hz, 2 Harom), 4.34 (q, J = 7.1 Hz, 2 H, OCH2CH3), 1.31 (t, J = 7.1 Hz, 3
H, OCH2CH3).
13C NMR (75 MHz, CD3OD): δ = 160.6, 145.2, 133.8, 132.2, 131.9,
130.0, 118.2, 112.6, 61.5, 13.2.
1H NMR (300 MHz, CDCl3): δ = 8.34–7.97 (m, 2 Harom), 7.97–6.94 (m, 8
H
arom).
13C NMR (75 MHz, CDCl3): δ = 188.4, 171.6, 146.2, 133.8, 130.8, 130.4,
130.0, 129.1, 128.8, 128.7, 128.6.
HRMS (ESI): m/z calcd for C15H12N3O [M + H]+: 250.0975; found:
250.0963.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–G

F
G.-L. Wu, Q.-P. Wu
Paper
Synthesis
Phenyl[4-(p-tolyl)-1H-1,2,3-triazol-5-yl]methanone (5b)22
Funding Information
Eluent: EtOAc/PE (1:3); yield: 149 mg (38%); white solid; mp 138–
140 °C; Rf = 0.62 (PE/EtOAc 1:1).
1H NMR (300 MHz, DMSO-d6): δ = 8.11 (d, J = 7.6 Hz, 2 Harom), 7.67–
7.59 (m, 3 Harom), 7.48 (t, J = 7.6 Hz, 2 Harom), 7.22 (d, J = 7.9 Hz, 2 Harom),
2.39 (s, 3 H, ArCH3).
13C NMR (75 MHz, DMSO-d6): δ = 188.5, 145.1, 141.3, 139.7, 137.9,
133.9, 130.8, 129.7, 129.2, 129.1, 125.9.
HRMS (ESI): m/z calcd for C16H14N3O [M + H]+: 264.1131; found:
This work was financially supported by the National Science Founda-
tion of China (Grant No. 21172019).
N
oaitn
a
l
Secince
F
o
u
n
d
oaitn
of
C
h
n
i
a
2(
1
1
7
2
0
1
9)
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1609720.
S
u
p
p
o
nrtogI
f
rmoaitn
S
u
p
p
ortiInfogrmoaitn
264.1130.
References
Cyclopropyl(4-phenyl-1H-1,2,3-triazol-5-yl)methanone (5c)
(1) (a) Meldal, M.; Tornøe, C. W. Chem. Rev. 2008, 108, 2952.
(b) Wacharasindhu, S.; Bardhan, S.; Wan, Z. K.; Tabei, K.;
Mansour, T. S. J. Am. Chem. Soc. 2009, 131, 4174. (c) Liu, Y.; Yan,
W.; Chen, Y.; Petersen, J. L.; Shi, X. Org. Lett. 2008, 10, 5385.
(d) Katritzky, A. R.; Bobrov, S.; Kirichenko, K.; Ji, Y.; Steel, P. J.
J. Org. Chem. 2003, 68, 5713. (e) Reid, A. K.; McHugh, C. J.; Richie,
G.; Graham, D. Tetrahedron Lett. 2006, 47, 4201. (f) Verma, A. K.;
Singh, J.; Chaudhary, R. Tetrahedron Lett. 2007, 48, 7199. (g) Dai,
Q.; Gao, W.; Liu, D.; Kapzes, L. M.; Zhang, X. J. Org. Chem. 2006,
71, 3928. (h) Jin, T.; Kamijo, S.; Yamamoto, Y. J. Org. Chem. 2004,
69, 3789.
Eluent: EtOAc/PE (1:2). Yield: 120 mg (56%); white solid; mp 113–
116 °C; Rf = 0.59 (PE/EtOAc 1:1).
1H NMR (300 MHz, CDCl3): δ = 7.82–7.54 (m, 2 Harom), 7.54–7.19 (m, 3
H
arom), 3.08–3.01 (m, 1 H, CH), 1.24–1.23 (m, 2 H, CH2), 1.05–1.01(m, 2
H, CH2).
13C NMR (75 MHz, CDCl3): δ = 195.9, 144.1, 141.8, 133.9, 130.4, 130.1,
129.4, 128.6, 127.5, 29.9, 19.5, 12.9.
HRMS (ESI): m/z calcd for C12H12N3O [M + H]+: 214.0975; found:
214.0968.
(2) (a) Kolb, H. C.; Sharpless, K. B. Drug Discov. Today 2003, 8, 1128.
(b) Manetsch, R.; Krasiski, A.; Radi, Z.; Raushel, J.; Taylor, P.;
Sharpless, K. B.; Kolb, H. C. J. Am. Chem. Soc. 2004, 126, 12809.
(c) Whiting, M.; Muldoon, J.; Lin, Y. C.; Silverman, S. M.;
Lindstrom, W.; Olson, A. J.; Kolb, H. C.; Finn, M. G.; Sharpless, K.
B.; Elder, J. H.; Fokin, V. V. Angew. Chem. Int. Ed. 2006, 45, 1435.
(d) Wang, J.; Sui, G.; Mocharla, V. P.; Lin, R. J.; Phelps, M. E.; Kolb,
H. C.; Tseng, H. R. Angew. Chem. Int. Ed. 2006, 45, 5276.
(e) Sugawara, A.; Sunazuka, T.; Hirose, T.; Nagai, K.; Yamaguchi,
Y.; Hanaki, H.; Sharpless, K. B.; Omura, S. Bioorg. Med. Chem.
Lett. 2007, 17, 6340. (f) Chen, H.; Taylor, J. L.; Abrams, S. R.
Bioorg. Med. Chem. Lett. 2007, 17, 1979. (g) Moorhouse, A. D.;
Moses, J. E. ChemMedChem 2008, 3, 715. (h) Tron, G. C.; Pirali, T.;
Billington, R. A.; Canonico, P. L.; Sorba, G.; Genazzani, A. A. Med.
Res. Rev. 2008, 28, 278.
4-(4-Fluorophenyl)-1H-1,2,3-triazole-5-carbonitrile (5d)23
Eluent: EtOAc/PE (1:1); yield: 163 mg (56%); white solid; mp 190–
192 °C; Rf = 0.37 (PE/EtOAc 1:1).
1H NMR (300 MHz, CD3OD): δ = 7.97 (dd, J1 = 6.8 Hz, J2 = 11.6 Hz, 2
H
arom), 7.41–7.15 (m, 2 Harom).
13C NMR (75 MHz, CD3OD): δ = 165.7 (d, J = 247.6 Hz), 147.1, 129.1 (d,
J = 8.6 Hz), 123.4, 116.9, 116.3 (d, J = 22.2 Hz), 112.7.
HRMS (ESI): m/z calcd for C9H6FN4 [M + H]+: 189.0571; found:
189.0565.
Spectral data match with those previously reported in the literature.14
4-(p-Tolyl)-1H-1,2,3-triazole-5-carbonitrile (5e)23
Eluent: EtOAc/PE (1:1); yield: 133 mg (67%); white solid; mp 173–
(3) (a) Wu, P.; Feldman, A. K.; Nugent, A. K.; Hawker, C. J.; Scheel, A.;
Voit, B.; Pyun, J.; Fre’chet, J. M. J.; Sharpless, K. B.; Fokin, V. V.
Angew. Chem. Int. Ed. 2004, 43, 3928. (b) Aucagne, V.; Ha’nni, K.
D.; Leigh, D. A.; Lusby, P. J.; Walker, D. B. J. Am. Chem. Soc. 2006,
128, 2186. (c) Ye, C. F.; Gard, G. L.; Winter, R. W.; Syvret, R. G.;
Twamley, B.; Shreeve, J. M. Org. Lett. 2007, 9, 3841. (d) Liu, Q. C.;
Zhao, P.; Chen, Y. M. J. Polym. Sci., Part A: Polym. Chem. 2007, 45,
3330. (e) Nandivada, H.; Jiang, X. W.; Lahann, J. Adv. Mater.
2007, 19, 2197. (f) Angelos, S.; Yang, Y. W.; Patel, K.; Stoddart, J.
F.; Zink, J. I. Angew. Chem. Int. Ed. 2008, 45, 1435.
175 °C; Rf = 0.38 (PE/EtOAc 1:1).
1H NMR (400 MHz, CD3OD): δ = 7.81 (d, J = 8.2 Hz, 2 Harom), 7.38 (d, J =
8.0 Hz, 2 Harom), 2.43 (s, 3 H, ArCH3).
13C NMR (75 MHz, CD3OD): δ = 147.0, 141.0, 130.0, 126.5, 123.3,
116.5, 112.9, 20.2.
HRMS (ESI): m/z calcd for C10H9N4 [M + H]+: 185.0822; found:
185.0813.
4-(4-Methoxyphenyl)-1H-1,2,3-triazole-5-carbonitrile (5f)23
(4) Selected examples of methods for synthesizing 1,2,3-triazoles:
(a) Journet, M.; Cai, D.; Kowal, J. J.; Larsen, R. D. Tetrahedron Lett.
2001, 42, 9117. (b) Coats, S. J.; Link, J. S.; Gauthier, D.; Hlasta, D.
Org. Lett. 2005, 7, 1469. (c) Gracias, V.; Darczak, D.; Gasiecki, A.
F.; Djuric, S. W. Tetrahedron Lett. 2005, 46, 9053. (d) Majireck,
M.; Weinreb, S. M. J. Org. Chem. 2006, 71, 8680. (e) Aucagne, V.;
Leigh, D. A. Org. Lett. 2006, 8, 4505. (f) Boren, B. C.; Narayan, S.;
Rasmussen, L. K.; Zhang, L.; Zhao, H.; Lin, Z.; Jia, G.; Fokin, V.
J. Am. Chem. Soc. 2008, 130, 8923.
Eluent: EtOAc/PE (1:1); yield: 166 mg (61%); white solid; mp 197–
200 °C; Rf = 0.33 (PE/EtOAc 1:1).
1H NMR (300 MHz, CD3OD): δ = 7.85 (d, J = 8.8 Hz, 2 Harom), 7.09 (d, J =
8.9 Hz, 2 Harom), 3.86 (s, 3 H, OCH3).
13C NMR (75 MHz, CD3OD): δ = 161.8, 128.2, 118.3, 116,1, 114.6,
113.0, 89.8, 54.8.
HRMS (ESI): m/z calcd for C10H9N4O [M + H]+: 201.0771; found:
201.0775.
(5) (a) Journet, M.; Cai, D.; Kowal, J. J. Tetrahedron Lett. 2001, 42,
9117. (b) Zefirov, N. S.; Chapovskaya, N. K.; Kolesnikov, V. V.
J. Chem. Soc., Chem. Commun. 1971, 1001. (c) Quiclet-Sire, B.;
Zard, S. Z. Synthesis 2005, 3319. (d) Wang, T.; Hu, X. C.; Huang,
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–G

G
G.-L. Wu, Q.-P. Wu
Paper
Synthesis
X. J. J. Braz. Chem. Soc. 2012, 23, 1119. (e) Hu, Q.; Liu, Y.; Deng, X.
Adv. Synth. Catal. 2016, 358, 1689. (f) Gao, Y.; Lam, Y. Org. Lett.
2006, 8, 3283. (g) Augustine, J. K.; Boodappa, C.; Venkatachaliah,
S. Org. Biomol. Chem. 2014, 12, 2280. (h) Chai, H.; Guo, R.; Yin,
W. ACS Comb. Sci. 2015, 17, 147. (i) Ponpandian, T.;
Muthusubramanian, S. Tetrahedron Lett. 2012, 53, 59. (j) Wu, L.;
Wang, X.; Chen, Y. Synlett 2016, 27, 437. (k) Thomas, J.; John, J.;
Parekh, N.; Dehaen, W. Angew. Chem. Int. Ed. 2014, 53, 10155.
(6) (a) Wittig, G.; Geissler, G. Justus Liebigs Ann. Chem. 1953, 580,
44. (b) Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89, 863.
(c) Cattelan, L.; Noe, M.; Selva, M.; Demitri, N.; Perosa, A. Chem-
SusChem 2015, 8, 3963. (d) Lémaire, S.; Houpis, I.;
Wechselberger, R.; Langens, J.; Vermeulen, W. A. A.; Smets, N.;
Nettekoven, U.; Wang, Y.; Xiao, T.; Qu, H.; Liu, R.; Jonckers, T. H.
M.; Raboisson, P.; Vandyck, K.; Nilsson, K. M.; Farina, V. J. Org.
Chem. 2011, 76, 297. (e) Spallarossa, M.; Wang, Q.; Riva, R.; Zhu, J.
Org. Lett. 2016, 18, 1622. (f) Mysĺiwiec, D.; Lis, T.; Gregoliński, J.;
Stępień, M. J. Org. Chem. 2015, 80, 6300. (g) Xia, X.; Toy, P. H.
Synlett 2015, 26, 1737. (h) Cachatra, V.; Almeida, A.; Sardinha, J.;
Lucas, S. D.; Gomes, A.; Vaz, P. D.; Florêncio, M. H.; Nunes, R.;
Vila-Viçosa, D.; Calhorda, M. J.; Rauter, A. P. Org. Lett. 2015, 17,
5622. (i) Sengupta, S.; Duan, H.; Lu, W.; Petersen, J. L.; Shi, X.
Org. Lett. 2008, 10, 1493. (j) Schirmer, M. L.; Adomeit, S.;
Werner, T. Org. Lett. 2015, 17, 3078.
(10) The LCMS data for monitoring the reaction of synthesizing com-
pound 3h and the 31P NMR spectrum of the triphenylphosine
by-product are provided in the Supporting Information.
(11) (a) Li, A. H.; Dai, L. X. Chem. Rev. 1997, 97, 2341. (b) Xie, P.;
Huang, Y. Org. Biomol. Chem. 2015, 13, 8578.
(12) (a) Northtrup, A. B.; MacMillan, D. W. C. J. Am. Chem. Soc. 2002,
124, 6798. (b) Storer, R. I.; MacMillan, D. W. C. Tetrahedron 2004,
60, 7705.
(13) (a) Byrne, P. A.; Gilheany, D. G. Chem. Soc. Rev. 2013, 42, 6670.
(b) Sugiura, M.; Ashikari, Y.; Nakaijima, M. J. Org. Chem. 2015,
80, 8830.
(14) (a) Augustine, J. K.; Boodappa, C.; Venkatachaliah, S. Org. Biomol.
Chem. 2014, 12, 2280. (b) Ye, L. W.; Han, X.; Sun, X. L.; Tang, Y.
Tetrahedron 2008, 64, 1487.
(15) (a) Du, Y.; Lu, X.; Zhang, C. Angew. Chem. Int. Ed. 2003, 42, 1035.
(b) Xie, P.; Huang, Y. Org. Biomol. Chem. 2015, 13, 8578.
(c) Zhou, R.; He, Z. Eur. J. Org. Chem. 2016, 11, 1937.
(16) Rolf, H. P.; Pasquale, R. Aust. J. Chem. 1994, 47, 1375.
(17) Amantini, D. F.; Piermatti, O.; Pizzo, F.; Zunino, E.; Vaccaro, L.
J. Org. Chem. 2005, 70, 6526.
(18) Berestovitskaya, V. M.; Baichurin, R. I.; Aboskalova, N. I.;
Baichurina, L. V.; Trukhin, E. V.; Fel’gendler, A. V.;
Gensirovskaya, M. A. Russ. J. Gen. Chem. 2016, 86, 1266.
(19) Chen, Y.; Hu, Q.; Liu, Y. Faming Zhuanli Shenqing 2016,
105541796. Chem. Abstr. 2016, 164, 602163.
(7) Wu, G.-L.; Wu, Q.-P. Adv. Synth. Catal. 2018, 360, in press, DOI:
10.1002/adsc.201701587.
(20) Shin, C.; Yonezawa, Y.; Yoshimura, J. Tetrahedron Lett. 1974, 15,
7.
(21) Li, J.; Wang, D.; Zhang, Y.; Li, J.; Chen, B. Org. Lett. 2009, 11,
3024.
(22) Zhu, Y.; Li, J.; Liu, R. Huaxue Shiji 2016, 38, 565. Chem. Abstr.
2016, 165, 416564.
(23) Cheng, Z.; Li, W.; He, F.; Zhou, J.; Zhu, X. Bioorg. Med. Chem.
2007, 15, 1533.
(8) (a) Taber, D. F.; Sheth, R. B. J. Org. Chem. 2008, 73, 8030.
(b) Leung, P. S. W.; Teng, Y.; Toy, P. H. Org. Lett. 2010, 12, 4996.
(9) (a) El-Batta, A.; Jiang, C.; Zhao, W.; Anness, R.; Cooksy, A. L.;
Bergdahl, M. J. Org. Chem. 2007, 72, 5244. (b) Bazhenov, D. N.;
Pevzner, M. S.; Ostrovsh Gindin, V. A.; Shcherbinin, N. B.;
Zhniaev, V. N. Zh. Org. Khim. 1994, 30, 791. (c) Hudson, R. F.;
Chopard, P. A. J. Org. Chem. 1963, 28, 2446.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–G