A stereocontrolled 1,2-addition reaction of tetrazoles with alkyl propiolates for the synthesis of highly functionalized enamines

Article abstract of DOI:10.1002/adsc.201200868

A stereocontrolled 1,2-addition reaction of 1-aryl-1H-tetrazoles with alkyl propiolates for the synthesis of highly functionalized enamines was developed. In the presence of silver oxide (Ag₂O), the 1,2-addition reaction generated (Z)-N-cyano enamines in good yields with exclusive formation of the Z-isomers. Meanwhile, the 1,2-addition reaction generated (E)-N-cyano enamines in the presence of Ag₂O and potassium carbonate (K₂CO ₃) with high stereoselectivity and yields. Copyright

Full text of DOI:10.1002/adsc.201200868

FULL PAPERS
DOI: 10.1002/adsc.201200868
A Stereocontrolled 1,2-Addition Reaction of Tetrazoles with
Alkyl Propiolates for the Synthesis of Highly Functionalized
Enamines
Kai Luo,a Lingguo Meng,b Yicheng Zhang,b Xiuli Zhang,a,c,* and Lei Wangb,c,*
a
Department of Chemistry, Anhui Agricultural University, Hefei, Anhui 230036, Peopleꢀs Republic of China
E-mail: zhxiuli@163.com
b
Department of Chemistry, Huaibei Normal University, Huaibei, Anhui 235000, Peopleꢀs Republic of China
Fax : (+86)-561-309-0518; phone: (+86)-561-380-2069; e-mail: leiwang@chnu.edu.cn
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
c
Sciences, Shanghai 200032, Peopleꢀs Republic of China
Received: September 26, 2012; Revised: December 7, 2012; Published online: February 25, 2013
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201200868.
Abstract: A stereocontrolled 1,2-addition reaction of erated (E)-N-cyano enamines in the presence of
1-aryl-1H-tetrazoles with alkyl propiolates for the Ag2O and potassium carbonate (K2CO3) with high
synthesis of highly functionalized enamines was de- stereoselectivity and yields.
veloped. In the presence of silver oxide (Ag2O), the
1,2-addition reaction generated (Z)-N-cyano enam-
ines in good yields with exclusive formation of the Keywords: 1,2-addition reaction; alkyl propiolates;
Z-isomers. Meanwhile, the 1,2-addition reaction gen- N-cyano enamines; silver catalysis; tetrazoles
Introduction
tion,[9] etc. Remarkable progress has been made in
the Ag-catalyzed reaction of alkynes in recent years
Enamines are key structural motifs in many natural because Ag could bind/activate p-systems,[10] but
products. And most importantly, functionalized enam- there are a few reports on stereoselective addition re-
ines are pharmaceuticals with biologically relevant actions controlled by an Ag catalyst.[11]
properties, and versatile and valuable intermediates in
Apart from the wide applications of 1-aryltetrazoles
a variety of functional group transformations.[1] The in rocket propellants and explosives,[12a–c] they are also
À
traditional approach for enamine synthesis is derived used for organic transformations via their C H bond
from the reaction of an aldehyde or ketone with a sec- functionalizations.[12d] 1-Aryltetrazoles are known to
ondary amine followed by loss of water.[2] However, it decompose into N-arylcyanamides in the presence of
is difficult to prepare the enamines from aromatic a strong base.[13] However, there is no example of the
amines through the above method owing to their application of tetrazole as a potential synthetic equiv-
weak nucleophilic properties.
alent of cyanamide.
As an alternative method, the addition of amines to
Herein, we wish to report a stereocontrolled 1,2-ad-
alkynes is one of the most powerful methods for en- dition reaction of tetrazoles with alkyl propiolates for
amine preparation.[3] In general, N C
G
À
ing reactions using electron-deficient alkynes as elec- (Scheme 1). The stereochemistry of the products de-
trophilic precursors have been developed. However, pended on the choice of different reaction conditions.
only the Z- or the E-configuration addition products In the presence of Ag2O, the 1,2-addition reaction
were obtained under the different reaction conditions generated (Z)-N-cyano enamines in good yields with
without any stereocontrol.[4]
Silver salts have increasingly received interest as 1,2-addition reaction generated (E)-N-cyano enam-
catalysts by virtue of their expanding reactivity pat- ines in the presence of Ag2O and K2CO3 with high
terns[5] and have covered many interesting reactions, stereoselectivity and yields. Although cyanamides are
such as cycloisomerization cycloaddition,[6] C H acti- highly versatile building blocks for a number of or-
À
vation,[7] domino reaction,[8] and alkynylation reac- ganic transformations, including the synthesis of
Adv. Synth. Catal. 2013, 355, 765 – 780
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
765

Kai Luo et al.
FULL PAPERS
Table 1. Optimization of the reaction conditions for the
model reaction.[a]
Entry Ag salt
Base
Solvent
3a [%][b] 4a [%][b]
1
Ag2CO3
–
THF
42
35
2
Ag2O
–
THF
92
92[c]
12
ND
ND
23
3
AgCl
–
THF
Scheme 1.
4
5
6
7
8
9
10
11
12
13
14
Ag2SO4
AgNO3
AgOAc
Ag2O
Ag2O
Ag2O
Ag2O
Ag2O
Ag2O
Ag2O
Ag2O
–
–
–
–
–
–
–
–
THF
THF
THF
EtOEt
DMSO
DMF
dioxane 21
CH2Cl2
CH3CN
31
14
ND
ND
56
53
34
ND
ND
ND
ND
ND
ND
ND
ND
ND
81
a number of heterocycles, guanidines, imidazolines
and arylation of cyanamides,[14] N-cyano enamines
have not been prepared from the reaction of cyana-
mides and alkyl propiolates according to retrosynthet-
ic analysis (Scheme 1). Moreover, it is noteworthy to
mention that the tetrazoles, as synthetic precursors,
are more stable and less poisonous as compared with
ND
ND
–
–
CH3NO2 ND
THF
K2CO3
(3)[d]
(3)[d]
(5)[d]
(4)[d]
(4)[d]
21
32
15
14
cyanACHTUNGTRENNUNGamides, and N-cyano enamines are potiential
pharmaceuticals with biological activity.
81[c]
69
47
36
45
13
36
31
15
16
17
18
19
20
21
Ag2O
Ag2O
Ag2O
Ag2O
Ag2O
Ag2O
Ag2O
K3PO4
KOH
NaOH
Na2CO3 THF
KF THF
t-BuOLi THF
Et3N THF
THF
THF
THF
Results and Discussion
In the initial exploration of the stereocontrolled 1,2-
addition reaction of tetrazoles to alkyl propiolates, 1-
phenyl-1H-tetrazole (1a) and ethyl propiolate (2a)
were chosen as the model substrates for our investiga-
tion and the results are shown in Table 1. Firstly, the
effect of Ag salts on the model reaction was exam-
ined. When the model reaction was performed in the
presence of AgCO3 (20 mol%) in THF at 1008C
(sealed tube) for 12 h, a mixture of (Z)-N-cyano en-
amine 3a (42% yield) and (E)-N-cyano enamine 4a
[a]
Reaction conditions: 1a (0.50 mmol), 2a (0.60 mmol), Ag
salt (0.10 mmol), base (2.0 equiv., if need), solvent
(2.0 mL) at 1008C (sealed tube) under air, 12 h.
Isolated yields.
Under a nitrogen atomsphere.
GC yields in parentheses. ND=not detected.
[b]
[c]
[d]
(35% yield) was isolated (Table 1, entry 1). To our de- forded 21–56% yields of 3a (Table 1, entries 7–10).
light, 3a was obtained as the exclusive product and its When the solvent was switched to CH2Cl2, CH3CN or
yield could be increased to 92% when Ag2O CH3NO2, no product was detected by TLC (Table 1,
(20 mol%) was used as catalyst (Table 1, entry 2). entries 11–13). In order to further investigate the ste-
With use of other Ag salts, such as AgCl, and reoselectivity of this 1,2-addition, a base was added to
Ag2SO4, the model reaction also produced a mixture the reaction system. Gratifyingly, when K2CO3
of the stereoisomeric enamines 3a and 4a in poor ste- (2.0 equiv.) was added into Ag2O-catalyzed model re-
reoselectivity (Table 1, entries 3 and 4). However, no action, an 81% yield of (E)-enamine 4a was obtained
addition product was detected when AgNO3 or in good E-stereoselectivity, along with 3% yield of its
AgOAc was used as catalyst in the reaction (Table 1, Z-isomer 3a (Table 1, entry 14). Other bases, such as
entries 5 and 6). Furthermore, when the model reac- K3PO4, KOH and NaOH, generated the E-configura-
tion was carried out in the presence of Ag2O, a signifi- tion addition product 4a in 36–69% yields and trace
cant solvent effect was observed. Among the solvents amount of 3a (Table 1, entries 15–17). Meanwhile,
tested, THF was found to be the best one. Diethyl when Na2CO3, KF, t-BuOLi, and Et3N as bases were
ether, DMSO, DMF and dioxane were inferior and af- added to the reaction, mixtures of 4a and 3a were ob-
766
asc.wiley-vch.de
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 765 – 780

A Stereocontrolled 1,2-Addition Reaction of Tetrazoles with Alkyl Propiolates
Table 2. Ag2O-catalyzed synthesis of (Z)-enamines.[a]
Entry
1
1, R; 2, R1
Product 3
Yield [%][b]
92
1a, H; 2a, Et
3a
3b
3c
3d
3e
3f
3g
3h
3i
2
1b, 4-Me; 2a, Et
1c, 4-Et; 2a, Et
1d, 4-(i-Pr); 2a, Et
1e, 4-F; 2a, Et
93
94
95
80
84
83
88
70
74
72
70
71
87
85
3
4
5
6
1f, 4-Cl; 2a, Et
7
1g, 4-Br; 2a, Et
1h, 4-I; 2a, Et
8
9
1i, 4-NO2; 2a, Et
1j, 4-CF3; 2a, Et
1k, 4-MeCO; 2a, Et
1l, 4-MeO; 2a, Et
1m, 4-EtO; 2a, Et
1n, 3-Me; 2a, Et
1o, 3-(iPr); 2a, Et
10
11
12
13
14
15
3j
3k
3l
3m
3n
3o
Adv. Synth. Catal. 2013, 355, 765 – 780
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
767

Kai Luo et al.
FULL PAPERS
Table 2. (Continued)
Entry
1, R; 2, R1
Product 3
Yield [%][b]
83
16
1p, 3-Cl; 2a, Et
3p
3q
3r
3s
3t
17
18
19
20
1q, 2-Me; 2a, Et
70
77
82
75
1r, 2,3-(Me)2; 2a, Et
1s, 3,4-(Me)2; 2a, Et
1t, 2,4-(Me)2; 2a, Et
21
1u, 2,5-(Me)2; 2a, Et
1a, H; 2b, Me
3u
74
22
23
3v
3w
3x
90
82
87
1a, H; 2c,CH2C6H4ACHTUNTRGNEUNG(p-Me)
24
1a, H; 2d, CH2C6H4ACHTGUNTERNNU(G p-Cl)
[a]
Reaction conditions: 1 (0.50 mmol), 2 (0.60 mmol), Ag2O (0.10 mmol), THF (2.0 mL) at 1008C, sealed tube, air, 12 h.
Isolated yields.
[b]
tained, leading to low stereoselectivity (Table 1, en- products 3b–d in excellent yields (Table 2, entries 2–
tries 18–21). It should be noted that the same results 4). On the other hand, the reactions of substrates
were obtained when the reactions were performed 1 with F, Cl, Br, I, NO2, CF3 or MeCO group attached
under an inert nitrogen atmosphere (Table 1, entries 2 on the benzene ring with 2a generated the corre-
and 14).
sponding products 3e–k in 70–88% yields (Table 2,
Inspired by the above observations, we first investi- entries 5–11). However, substrates 1 with MeO or
gated the scope of the Ag2O-catalyzed Z-selective EtO group at the para-position of benzene ring gave
1,2-addition reaction of tetrazoles and alkyl propiol- 3l and 3m in 70% and 71% yields, respectively
ACHTUNGTRENNUNGates under the optimized reaction conditions and the (Table 2, entries 12 and 13). Treatment of (3-tolyl)-,
results are listed in Table 2. A variety of 1-aryl-1H-tet- (3-isopropylphenyl)- and (3-chlorophenyl)-1H-tetra-
razoles (1) was subjected to the reaction. It was found zoles with 2a afforded the corresponding products
that reactions of 1 with ethyl propiolate (2a) gave the 3n–p in 83–87% yields (Table 2, entries 14–16). An
corresponding (Z)-enamines 3 in moderate to good ortho-position effect of the 1-aryl-1H-tetrazole was
yields with exclusive Z-isomers regardless of the sub- observed in the reaction of 1-(o-tolyl)-1H-tetrazole
stituted groups on the aromatic rings of 1. Clearly, with 2 (Table 2, entry 17). Notably, multi-substituted
a 1-aryl-1H-tetrazole with an electron-donating group 1-aryl-1H-tetrazoles with 2a could also be converted
on the aromatic ring gave a better yield than that to the anticipated products in 70–82% yields under
having an electron-withdrawing group on the aromat- standard conditions (Table 2, entries 18–21).
ic ring. For example, 1 with an electron-donating
The reactions of 1-phenyl-1H-tetrazole (1a) with
group, such as Me, Et or i-Pr at the para-position of methyl propiolate (2b), 4-methylbenzyl propiolate
benzene ring reacted with 2a, providing the desired (2c), and 4-chlorobenzyl propiolate (2d) generated
768
asc.wiley-vch.de
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 765 – 780

A Stereocontrolled 1,2-Addition Reaction of Tetrazoles with Alkyl Propiolates
Table 3. Ag2O-catalyzed synthesis of (E)-enamines in the presence of K2CO3.[a]
Entry
1
1, R; 2, R1
Product 4
Yield [%][b]
81
1a, H; 2a, Et
4a
4b
4c
4d
4e
4f
4g
4h
4i
2
1b, 4-Me; 2a, Et
1c, 4-Et; 2a, Et
1d, 4-(i-Pr); 2a, Et
1e, 4-F; 2a, Et
92
90
93
78
80
76
74
63
72
73
89
90
83
81
3
4
5
6
1f, 4-Cl; 2a, Et
7
1g, 4-Br; 2a, Et
1h, 4-I; 2a, Et
8
9
1i, 4-NO2; 2a, Et
1j, 4-CF3; 2a, Et
1k, 4-MeCO; 2a, Et
1l, 4-MeO; 2a, Et
1m, 4-EtO; 2a, Et
1n, 3-Me; 2a, Et
1o, 3-(i-Pr); 2a, Et
10
11
12
13
14
15
4j
4k
4l
4m
4n
4o
Adv. Synth. Catal. 2013, 355, 765 – 780
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
769

Kai Luo et al.
FULL PAPERS
Table 3. (Continued)
Entry
1, R; 2, R1
Product 4
Yield [%][b]
80
16
1p, 3-Cl; 2a, Et
4p
4q
4r
4s
4t
17
18
19
20
1q, 2-Me; 2a, Et
64
71
77
73
1r, 2,3-(Me)2; 2a, Et
1s, 3,4-(Me)2; 2a, Et
1t, 2,4-(Me)2; 2a, Et
21
1u, 2,5-(Me)2; 2a, Et
1a, H; 2b, Me
4u
70
22
23
4v
4w
4x
72
74
77
1a, H; 2c, CH2C6H4ACHTUNTRGNEUNG(p-Me)
24
1a, H; 2d, CH2C6H4ACHTGUNTERNNU(G p-Cl)
[a]
Reaction conditions: 1 (0.50 mmol), 2 (0.60 mmol), Ag2O (0.10 mmol), K2CO3 (1.0 mmol), THF (2.0 mL) at 1008C, sealed
tube, air, 12 h.
Isolated yield.
[b]
the corresponding products 3v–x in 82–90% yields acted with 2a smoothly to give the corresponding
(Table 2, entries 22–24). products 4r–u in 70–77% yields (Table 3, entries 18–
Next, we investigated Ag2O-catalyzed 1,2-addition 21).
reaction of 1-aryl-1H-tetrazoles with alkyl propiolates
The reactions of 1a with methyl propiolate (2b), 4-
in the presence of K2CO3 (2 equiv.), leading to (E)-N- methylbenzyl propiolate (2c), and 4-chlorobenzyl pro-
cyano enamines in good yields and high stereoselec- piolate (2d) afforded the desired products 4v–x in 72–
tivity. As can be seen from Table 3, a similar electron 77% yields (Table 3, entries 22–24). It should be
effect was also observed as compared with Table 2. noted that a only trace amount of (Z)-N-cyano enam-
The reactivity of the 1-aryl-1H-tetrazoles with an ines (<5%) was observed in the presence of Ag2O
electron-donating substitute, such as Me, Et, i-Pr, and K2CO3.
MeO or EtO at the para-position of benzene ring,
On the basis of our experiment results, a plausible
was more than that of the tetrazoles with an electron- mechanism for the stereocontrolled 1,2-addition reac-
withdrawing substitutes, including F, Cl, Br, I, NO2, tion was proposed, as shown in Scheme 2. Firstly, 1-
CF3 or MeCO at the para-position (Table 3, entries 2– phenyl-1H-tetrazole (1a) was transformed into N-phe-
ꢀ
6, 12 and 13 vs. 7–11). The substituent groups occupy- nylcyanamide (5a) with loss of N2, and the C C bond
ing the meta-position of the substrates 1n–p gave the of ethyl propiolate (2a) was activated by Ag(I) to
desired products 4n–p in 80–83% yields, and the form intermediate I.[15] In the case of Ag2O as the
ortho-position effect was also observed when 1q was only catalyst in the reaction system, 5a underwent
used as substrate (Table 3, entries 14–17). As expect- a 1,2-trans addition of N and Ag+ to I, affording inter-
ed, the multi-substituted 1-aryl-1H-tetrazoles 1r–u re- mediate II through a coordination effect, then fol-
770
asc.wiley-vch.de
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 765 – 780

A Stereocontrolled 1,2-Addition Reaction of Tetrazoles with Alkyl Propiolates
Conclusions
In conclusion, a stereocontrolled 1,2-addition reaction
of tetrazoles with alkyl propiolates for the prepara-
tion of highly functionalized enamines has been de-
veloped. Depending on the presence or absence of
K2CO3 in the Ag2O-catalyzed reaction, synthesis of
either (Z)- or (E)-N-cyano enamines could be
achieved in good to excellent yields with high selec-
tivity. (Z)-N-Cyano enamines were obtained exclu-
sively when Ag2O was used as catalyst, whereas the
use of Ag2O catalyst in the presence of K2CO3 gave
predominantly (E)-N-cyano enamines. It is important
to note that 1-aryl-1H-tetrazoles could represent the
synthetic equivalents of cyanamides for the synthesis
of the N-cyano enamines, which are the potiential
pharmaceuticals with biological activity.
Scheme 2. Proposed reaction mechanism.
Experimental Section
General Remarks
Scheme 3. Conversion of 3a to 4a in the presence of K2CO3.
All the stereocontrolled 1,2-addition reaction of tetrazoles
with alkyl propiolates were carried out under an air atmos-
1
phere. H and 13C NMR spectra were measured on a Bruker
Avance NMR spectrometer (400 MHz or 100 MHz, respec-
tively) with CDCl3 as solvent and recorded in ppm relative
to internal tetramethylsilane standard. The peak patterns
are indicated as follows: s, singlet; d, doublet; t, triplet; m,
multiplet; q, quartet. The coupling constants, J, are reported
in Hertz (Hz). High resolution mass spectroscopic data of
the products were collected on a Waters Micromass GCT in-
strument using EI (70 eV) or an Agilent Technologies 6540
UHD Accurate-Mass Q-TOF LC/MS using ESI.
The starting materials tetrazoles were prepared in our lab-
oratory according to the literature method.[16] The identity
and purity of known products, 1a,[17] 1b,[17] 1d,[18] 1e,[19] 1f,[17]
1g,[17] 1h,[20] 1i,[17] 1j,[19] 1k,[17] 1l,[17] 1m,[21] 1n,[17] 1p,[22] 1q,[17]
Scheme 4. The reactions of cyanamide with ethyl propiolate.
1
1r,[23] and 1t[17] were confirmed by H and 13C NMR spectro-
lowed by a proton transfer process and regeneration
of Ag(I) to produce (Z)-enamine (3a) exclusively. On
the other hand, in the case of Ag2O and K2CO3
(2 equiv.) in the reaction system, the obtained (Z)-en-
amine (3a) could be transformed into the more stable
(E)-enamine (4a) via an allenoate isomerization pro-
cess. To verify this process, when the prepared (Z)-en-
amine (3a) was performed in THF at 1008C in
a sealed tube in the presence of K2CO3 for 12 h, 95%
conversion of 3a to 4a was obtained (Scheme 3).
In order to further understand the reaction process,
5a was synthesized from the reaction of 1-phenyl-1H-
tetrazole (1a) with NaOH (aq.) at the room tempera-
ture. Upon treatment of 5a and 2a under the above
reaction conditions, expected products 3a and 4a were
isolated in 86% and 82% yields, respectively, as
shown in Scheme 4.
scopic analysis, and new products, 1c, 1o, 1s, and 1u were
fully characterized.
Silver oxide (Ag2O, AR) was commercially available from
Aladdin Chem. Co. Ltd. (Shanghai, batch number: 30284;
item number: 1125429) and used in the reactions directly.
General chemicals and solvents were purchased from com-
mercial suppliers and used without further purification.
Representative Procedure for the Synthesis of 1-
Phenyl-1H-tetrazole
A 100-mL reaction flask equipped with a magnetic stirrer
bar was charged with aniline (10.0 mmol, 930 mg), NaN3
(11.0 mmol, 715 mg), triethyl orthoformate (30.0 mmol,
3018 mg) and AcOH (80.0 mmol, 4800 mg). The mixture
was stirred at 808C for 4 h, cooled to room temperature, di-
luted with brine water (100 mL), and finally an appropriate
amount of sodium carbonate was added until the gas evolu-
tion ceased. The precipitate was separated by filtration,
washed with water and dried under vacuum at 508C to give
1-phenyl-1H-tetrazole (1a).
Adv. Synth. Catal. 2013, 355, 765 – 780
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
771

Kai Luo et al.
FULL PAPERS
1.29 (d, J=6.8 Hz, 6H); 13C NMR (100 MHz, CDCl3): d=
151.6, 140.6, 133.7, 130.0, 128.2, 119.4, 118.5, 34.0, 23.7; HR-
MS (ESI): m/z=189.1144 [M+H]+, calcd. for C10H12N4:
189.1140.
General Procedure for Ag2O-Catalyzed 1,2-Addition
Reaction of Tetrazole with Alkyl Propiolate
A sealable reaction tube equipped with a magnetic stirrer
bar was charged with tetrazole (0.50 mmol), alkyl propiolate
(0.60 mmol), Ag2O (0.10 mmol) and THF (2.0 mL). The
rubber septum was then replaced by a Teflon-coated screw
cap, and the reaction vessel was placed in an oil bath at
1008C [An Ace pressure tube is highly recommended to be
employed for safety considerations]. After stirring of the
mixture at this temperature for 12 h, it was cooled to room
temperature and diluted with ethyl acetate, washed with
water and brine, dried over MgSO4. After the solvent had
been removed under reduced pressure, the residue was puri-
fied by column chromatography on silica gel (petroleum
ether/EtOAc=20:1) to afford the desired product (Z)-N-
cyano enamine.
1-(3,4-Dimethylphenyl)-1H-tetrazole (1s): Yellow solid,
1
mp 61–628C. H NMR (400 MHz, CDCl3): d=9.04 (s, 1H),
7.45 (s, 1H), 7.38 (d, J=8.0 Hz, 1H), 7.26 (d, J=8.2 Hz,
1H), 2.31 (s, 3H), 2.29 (s, 3H); 13C NMR (100 MHz,
CDCl3): d=140.4, 138.8, 138.7, 131.4, 130.8, 121.9, 118.2,
19.7, 19.3; HR-MS (ESI): m/z=175.0981 [M+H]+, calcd.
for C9H10N4: 175.0984.
General Procedure for Ag2O-Catalyzed 1,2-Addition
Reaction of Tetrazole with Alkyl Propiolate in the
Presence of K2CO3
A sealable reaction tube equipped with a magnetic stirrer
bar was charged with tetrazole (0.50 mmol), alkyl propiolate
(0.60 mmol), Ag2O (0.10 mmol), K2CO3 (1.0 mmol) and
THF (2.0 mL). The rubber septum was then replaced by
a Teflon-coated screw cap, and the reaction vessel was
placed in an oil bath at 1008C [An Ace pressure tube is
highly recommended to be employed for safety considera-
tions]. After stirring of the mixture at this temperature for
12 h, it was cooled to room temperature and diluted with
ethyl acetate, washed with water and brine, dried over
MgSO4. After the solvent had been removed under reduced
pressure, the residue was purified by column chromatogra-
phy on silica gel (petroleum ether/EtOAc=20:1) to afford
the desired product (E)-N-cyano enamine.
1-(2,5-Dimethylphenyl)-1H-tetrazole (1u): Yellow liquid.
1H NMR (400 MHz, CDCl3): d=8.78 (s, 1H), 7.28–7.27 (m,
2H), 7.12 (s, 1H), 2.38 (s, 3H), 2.14 (s, 3H); 13C NMR
(100 MHz, CDCl3): d=143.0, 137.3, 132.6, 131.6, 131.5,
130.3, 126.2, 20.6, 17.2; HR-MS (ESI): m/z=175.0984 [M+
H]+, calcd. for C9H10N4: 175.0984.
Characterization Data for New Starting Material
Tetrazoles and All Products
(Z)-Ethyl 3-(N-phenylcyanamido)acrylate (3a): Yellow
1
liquid. H NMR (400 MHz, CDCl3): d=7.44–7.41 (m, 2H),
7.28–7.23 (m, 3H), 6.44 (d, J=8.9 Hz, 1H), 5.67 (d, J=
8.8 Hz, 1H), 4.26 (q, J=7.1 Hz, 2H), 1.31 (t, J=7.1 Hz,
3H); 13C NMR (100 MHz, CDCl3): d=163.3, 139.3, 135.6,
129.8, 126.3, 118.4, 109.6, 108.4, 60.7, 14.1; IR (KBr): n=
1-(4-Ethylphenyl)-1H-tetrazole (1c): Yellow solid, mp 75–
768C. H NMR (400 MHz, CDCl3): d=9.06 (s, 1H), 7.59 (d,
1
2234 (C N), 1716 cmÀ1 (C=O); HR-MS (ESI): m/z=
ꢀ
217.0972, [M+H]+, calcd. for C12H13N2O2: 217.0977.
J=8.3 Hz, 2H), 7.35 (d, J=8.2 Hz, 2H), 2.68 (q, J=7.6 Hz,
2H), 1.23 (t, J=7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d=146.4, 140.5, 131.4, 129.3, 121.0, 28.3, 15.1; HR-MS
(ESI): m/z=175.0979 [M+H]+, calcd. for C9H10N4:
175.0984.
(Z)-Ethyl 3-(N-p-tolylcyanamido)acrylate (3b): Yellow
1
liquid. H NMR (400 MHz, CDCl3): d=7.24 (d, J=8.3 Hz,
2H), 7.15 (d, J=8.4 Hz, 2H), 6.40 (d, J=8.9 Hz, 1H), 5.63
(d, J=9.0 Hz, 1H), 4.28 (q, J=7.1 Hz, 2H), 2.37 (s, 3H),
1.33 (t, J=7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=
1-(3-Isopropylphenyl)-1H-tetrazole (1o): Yellow liquid.
1H NMR (400 MHz, CDCl3): d=9.06 (s, 1H), 7.57 (s, 1H),
7.49–7.46 (m, 2H), 7.39–7.38 (m, 1H), 3.05–2.98 (m, 1H),
163.5, 137.1, 136.5, 136.1, 130.3, 118.7, 108.8, 108.7, 60.8,
À1
ꢀ
20.7, 14.2; IR (KBr): n=2232 (C N), 1711 cm ) (C=O);
772
asc.wiley-vch.de
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 765 – 780

A Stereocontrolled 1,2-Addition Reaction of Tetrazoles with Alkyl Propiolates
HR-MS (ESI): m/z=231.1130 [M+H]+, calcd. for
C13H15N2O2: 231.1134.
d=163.2, 137.9, 135.1, 131.9, 129.9, 119.6, 110.4, 108.1, 60.9,
À1
ꢀ
14.1; IR (KBr): n=2236 (C N), 1713 cm (C=O); HR-MS
(ESI): m/z=251.0587 [M+H]+, calcd. for C12H12N2O2Cl:
251.0587.
(Z)-Ethyl 3-[N-(4-ethylphenyl)cyanamido]acrylate (3c):
1
Yellow liquid. H NMR (400 MHz, CDCl3): d=7.24 (d, J=
8.3 Hz, 2H), 7.15 (d, J=8.4 Hz, 2H), 6.40 (d, J=8.9 Hz,
1H), 5.61 (d, J=8.9 Hz, 1H), 4.25 (q, J=7.1 Hz, 2H), 2.64
(q, J=7.6 Hz, 2H), 1.30 (t, J=7.1 Hz, 3H), 1.21 (t, J=
7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=163.4, 142.7,
137.1, 136.0, 129.1, 118.7, 108.7, 108.6, 60.6, 28.0, 15.3, 14.1;
À1
ꢀ
IR (KBr): n=2233 (C N), 1715 cm (C=O); HR-MS (ESI):
m/z=245.1288, [M+H]+, calcd. for C14H17N2O2: 245.1290.
(Z)-Ethyl 3-[N-(4-bromophenyl)cyanamido]acrylate (3g):
1
White solid, mp 82–848C. H NMR (400 MHz, CDCl3): d=
7.55 (d, J=8.9 Hz, 2H), 7.13 (d, J=8.8 Hz, 2H), 6.40 (d, J=
8.8 Hz, 1H), 5.71 (d, J=8.8 Hz, 1H), 4.27 (q, J=7.2 Hz,
2H), 1.31 (t, J=7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d=163.2, 138.4, 135.0, 132.8, 119.9, 119.5, 110.6, 108.0, 60.9,
À1
ꢀ
14.1; IR (KBr): n=2235 (C N), 1715 cm (C=O); HR-MS
(ESI): m/z=295.0081 [M+H]+, calcd. for C12H12N2O2Br:
295.0082.
(Z)-Ethyl
3-[N-(4-isopropylphenyl)cyanamido]acrylate
1
(3d): Yellow liquid. H NMR (400 MHz, CDCl3): d=7.27 (d,
J=8.4 Hz, 2H), 7.17 (d, J=8.9 Hz, 2H), 6.40 (d, J=8.9 Hz,
1H), 5.61 (d, J=8.9 Hz, 1H), 4.26 (q, J=7.0 Hz, 2H), 2.95–
2.88 (m, 1H), 1.30 (t, J=7.1 Hz, 3H), 1.23 (d, J=6.9 Hz,
6H); 13C NMR (100 MHz, CDCl3): d=163.4, 147.4, 137.2,
135.9, 127.7, 118.7, 108.8, 108.7,À61 0.6, 33.4, 23.8, 14.1; IR
ꢀ
(KBr): n=2233 (C N), 1717 cm (C=O); HR-MS (ESI):
(Z)-Ethyl 3-[N-(4-iodophenyl)cyanamido]acrylate (3h):
White solid, mp 93–958C. H NMR (400 MHz, CDCl3): d=
m/z=259.1449 [M+H]+, calcd. for C15H19N2O2: 259.1447.
1
7.73 (d, J=8.6 Hz, 2H), 7.00 (d, J=8.6 Hz, 2H), 6.40 (d, J=
8.8 Hz, 1H), 5.71 (d, J=8.8 Hz, 1H), 4.27 (q, J=7.1 Hz,
2H), 1.32 (t, J=7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d=163.2, 139.2, 138.8, 134.8, 120.1, 110.8, 108.0, 90.2, 60.9,
À1
ꢀ
14.1; IR (KBr): n=2234 (C N), 1711 cm (C=O); HR-MS
(ESI): m/z=342.9942 [M+H]+, calcd. for C12H12N2O2I:
342.9943.
(Z)-Ethyl 3-[N-(4-fluorophenyl)cyanamido]acrylate (3e):
White solid, mp 52–548C. H NMR (400 MHz, CDCl3): d=
1
7.25–7.22 (m, 2H), 7.15–7.10 (m, 2H), 6.37 (d, J=8.9 Hz,
1H), 5.65 (d, J=8.9 Hz, 1H), 4.26 (q, J=7.1 Hz, 2H), 1.31
(t, J=7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=163.3,
160.8 (d, JC,F =245.8 Hz), 135.7, 135.6 (d, JC,F =2.7 Hz), 120.7
(d, JC,F =8.5 Hz), 116.7 (d, JC,F =23.3 Hz),À1109.5, 108.6, 60.8,
ꢀ
14.1; IR (KBr): n=2234 (C N), 1715 cm (C=O); HR-MS
(ESI): m/z=235.0878 [M+H]+, calcd. for C12H12N2O2F:
235.0883.
(Z)-Ethyl 3-[N-(4-nitrophenyl)cyanamido]acrylate (3i):
Yellow solid, mp 94–958C. H NMR (400 MHz, CDCl3): d=
1
8.29 (d, J=9.0 Hz, 2H), 7.35 (d, J=9.0 Hz, 2H), 6.57 (d, J=
8.6 Hz, 1H), 5.90 (d, J=8.6 Hz, 1H), 4.25 (q, J=7.1 Hz,
2H), 1.29 (t, J=7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3):
(Z)-Ethyl 3-[N-(4-chlorophenyl)cyanamido]acrylate (3f):
Yellow solid, mp 61–628C. H NMR (400 MHz, CDCl3): d=
7.39 (d, J=7.2 Hz, 2H), 7.18 (d, J=7.4 Hz, 2H), 6.40 (d, J=
8.8 Hz, 1H), 5.70 (d, J=8.8 Hz, 1H), 4.26 (q, J=7.0 Hz,
2H), 1.31 (t, J=7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3):
1
d=162.7, 145.0, 144.1, 133.5, 125.5, 117.4, 113.9, 107.1, 61.2,
À1
ꢀ
14.0; IR (KBr): n=2236 (C N), 1719 cm (C=O); HR-MS
Adv. Synth. Catal. 2013, 355, 765 – 780
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
773

Kai Luo et al.
FULL PAPERS
(ESI): m/z=262.0823 [M+H]+, calcd. for C12H12N3O4:
262.0828.
7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=163.5, 157.6,
136.6, 132.5, 120.9, 115.4, 109.1, 107.7, 63.8, 60.6, 14.6, 14.1;
À1
ꢀ
IR (KBr): n=2232 (C N), 1711 cm (C=O); HR-MS (ESI):
(Z)-Ethyl
3-{N-[4-(trifluoromethyl)phenyl]cyanamido}-
m/z=261.1240 [M+H]+, calcd. for C14H17N2O3: 261.1239.
1
acrylate (3j): White solid, mp 89–918C. H NMR (400 MHz,
CDCl3): d=7.69 (d, J=8.2 Hz, 2H), 7.34 (d, J=8.4 Hz, 2H),
6.50 (d, J=8.7 Hz, 1H), 5.81 (d, J=8.7 Hz, 1H), 4.26 (q, J=
7.0 Hz, 2H), 1.30 (t, J=7.0 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d=163.0, 142.0, 134.2, 128.1 (q, JC,F =33.0 Hz),
127.1 (q, JC,F =3.7 Hz), 123.5 (q, JC,F =270.3 Hz), 117.8,
À1
ꢀ
112.2, 107.7, 61.0, 14.0; IR (KB): n=2238 (C N), 1712 cm
(C=O); HR-MS (ESI) ([M+H]+): calcd. for C13H12N2O2F3:
285.0851. Found 285.0849.
(Z)-Ethyl 3-(N-m-tolylcyanamido)acrylate (3n): Yellow
liquid. H NMR (400 MHz, CDCl3): d=7.31–7.27 (m, 1H),
1
7.06–7.01 (m, 3H), 6.42 (d, J=8.9 Hz, 1H), 5.64 (d, J=
8.9 Hz, 1H), 4.25 (q, J=7.1 Hz, 2H), 2.36 (s, 3H), 1.30 (t,
J=7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=163.3,
140.0, 139.2, 135.7, 129.5, 127.0, 118.9, 115.4, 109.2,À11 08.5,
ꢀ
60.6, 21.2, 14.1; IR (KBr): n=2234 (C N), 1716 cm (C=
O); HR-MS (ESI): m/z=231.1131 [M+H]+, calcd. for
C13H15N2O2: 231.1134.
(Z)-Ethyl 3-(N-(4-acetylphenyl)cyanamido)acrylate (3k):
White liquid. H NMR (400 MHz, CDCl3): d=8.03 (d, J=
1
8.6 Hz, 2H), 7.31 (d, J=8.6 Hz, 2H), 6.52 (d, J=8.7 Hz,
1H), 5.82 (d, J=8.7 Hz, 1H), 4.28 (q, J=7.1 Hz, 2H), 2.60
(s, 3H), 1.32 (t, J=7.1 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d=196.2, 163.1, 142.8, 134.6, 134.3, 130.2, 117.3,
ꢀ
112.2, 107.6, 61.1, 26.5, 14.1; IR (KBr): n=2236 (C N), 1716
(C=O), 1707 cmÀ1 (C=O); HR-MS (ESI): m/z=259.1079
[M+H]+, calcd. for C14H15N2O3: 259.1083.
(Z)-Ethyl
3-[N-(3-isopropylphenyl)cyanamido]acrylate
1
(3o): Yellow liquid. H NMR (400 MHz, CDCl3): d=7.35–
7.31 (m, 1H), 7.14–7.12 (m, 1H), 7.10 (s, 1H), 7.05–7.03 (m,
1H), 6.44 (d, J=8.9 Hz, 1H), 5.65 (d, J=8.9 Hz, 1H), 4.26
(q, J=7.0 Hz, 2H), 2.96–2.89 (m, 1H), 1.31 (t, J=7.1 Hz,
3H), 1.24 (d, J=6.8 Hz, 6H); 13C NMR (100 MHz, CDCl3):
d=163.4, 151.1, 139.3, 135.8, 129.7, 124.5, 116.6, 116.0, 109.2,
ꢀ
108.6, 60.7, 34.0, 23.6, 14.1; IR (KBr): n=2234 (C N),
1717 cmÀ1 (C=O); HR-MS (ESI): m/z=259.1449 [M+H]+,
(Z)-Ethyl
3-(N-(4-methoxyphenyl)cyanamido)acrylate
1
(3l): Yellow liquid. H NMR (400 MHz, CDCl3): d=7.20 (d,
J=8.9 Hz, 2H), 6.94 (d, J=9.0 Hz, 2H), 6.33 (d, J=9.0 Hz,
1H), 5.57 (d, J=9.0 Hz, 1H), 4.27 (q, J=7.1 Hz, 2H), 3.82
(s, 3H), 1.32 (t, J=7.1 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d=163.6, 158.4, 136.6, 132.8, 121.0, 115.0, 109.À11,
calcd. for C15H19N2O2: 259.1447.
ꢀ
107.9, 60.7, 55.6, 14.2; IR (KBr): n=2231 (C N), 1715 cm
(C=O); HR-MS (ESI): m/z=247.1078 [M+H]+, calcd. for
C13H15N2O3: 247.1083.
(Z)-Ethyl 3-[N-(4-ethoxyphenyl)cyanamido]acrylate (3m):
Yellow liquid. H NMR (400 MHz, CDCl3): d=7.16 (d, J=
8.9 Hz, 2H), 6.90 (d, J=8.9 Hz, 2H), 6.32 (d, J=9.0 Hz,
1H), 5.55 (d, J=9.0 Hz, 1H), 4.24 (q, J=7.2 Hz, 2H), 4.01
(q, J=7.0 Hz, 2H), 1.39 (t, J=7.0 Hz, 3H), 1.30 (t, J=
1
(Z)-Ethyl 3-[N-(3-chlorophenyl)cyanamido]acrylate (3p):
Yellow liquid. 1H NMR (400 MHz, CDCl3): d=7.35–7.30
(m, 1H), 7.19–7.18 (m, 2H), 7.11–7.09 (m, 1H), 6.42 (d, J=
8.8 Hz, 1H), 5.70 (d, J=8.8 Hz, 1H), 4.22 (q, J=7.0 Hz,
774
asc.wiley-vch.de
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 765 – 780

A Stereocontrolled 1,2-Addition Reaction of Tetrazoles with Alkyl Propiolates
2H), 1.27 (t, J=7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d=163.0, 140.2, 135.5, 134.7, 130.7, 126.1, 118.2, 116.1, 110.9,
À1
ꢀ
107.7, 60.7, 14.0; IR (KBr): n=2237 (C N), 1717 cm (C=
O); HR-MS (ESI): m/z=251.0584 [M+H]+, calcd. for
C12H12N2O2Cl: 251.0587.
9.2 Hz, 1H), 5.36 (d, J=9.2 Hz, 1H), 4.20 (q, J=7.1 Hz,
2H), 2.33 (d, J=11.2 Hz, 6H), 1.29 (t, J=7.1 Hz, 3H);
13C NMR (100 MHz, CDCl3): d=163.7, 139.3, 138.5, 136.0,
134.2, 132.3, 128.0, 125.3, 110.1, 104.5, 60.4, 20.8, 17.2, 14.1;
À1
ꢀ
IR (KBr): n=2228 (C N), 1715 cm (C=O); HR-MS (ESI):
m/z=245.1287 [M+H]+, calcd. for C14H17N2O2: 245.1290.
(Z)-Ethyl 3-(N-o-tolylcyanamido)acrylate (3q): Yellow
1
liquid. H NMR (400 MHz, CDCl3): d=7.33–7.26 (m, 4H),
6.14 (d, J=9.2 Hz, 1H), 5.40 (d, J=9.2 Hz, 1H), 4.19 (q, J=
7.1 Hz, 2H), 2.39 (s, 3H), 1.28 (t, J=7.1 Hz, 3H); 13C NMR
(100 MHz, CDCl3): d=163.6, 138.4, 138.2, 134.6, 131.9,
129.2, 127.5, 125.4, 110.0,À1105.0, 60.5, 17.4, 14.1; IR (KBr):
ꢀ
(Z)-Ethyl 3-[N-(2,5-dimethylphenyl)cyanamido]acrylate
(3u): Yellow liquid. H NMR (400 MHz, CDCl3): d=7.18–
n=2229 (C N), 1714 cm (C=O); HR-MS (ESI): m/z=
231.1134 [M+H]+, calcd. for C13H15N2O2: 231.1134.
1
7.16 (m, 2H), 7.13–7.11 (m, 1H), 6.13 (d, J=9.2 Hz, 1H),
5.40 (d, J=9.2 Hz, 1H), 4.23 (q, J=7.2 Hz, 2H), 2.35 (d, J=
6.5 Hz, 6H), 1.32 (t, J=7.1 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d=163.8, 138.4, 138.3, 137.7, 131.7, 131.3, 130.1,
ꢀ
126.0, 104.9, 60.6, 20.7, 17.0, 14.2; IR (KBr): n=2228 (C N),
1713 cmÀ1 (C=O); HR-MS (ESI): m/z=245.1288 [M+H]+,
calcd. for C14H17N2O2: 245.1290.
(Z)-Ethyl 3-[N-(2,3-dimethylphenyl)cyanamido]acrylate
(3r): Yellow solid, mp 66–688C. 1H NMR (400 MHz,
CDCl3): d=7.15–7.09 (m, 3H), 6.09 (d, J=9.2 Hz, 1H), 5.34
(d, J=9.2 Hz, 1H), 4.17 (q, J=7.0 Hz, 2H), 2.26 (d, J=
10.1 Hz, 6H), 1.26 (t, J=7.0 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d=163.5, 139.1, 138.5, 133.2, 130.5, 126.6, 123.0,
ꢀ
110.0, 104.3, 60.2, 20.0, 13.9, 13.6; IR (KBr): n=2229 (C N),
(Z)-Methyl 3-(N-phenylcyanamido)acrylate (3v): Yellow
liquid. H NMR (400 MHz, CDCl3): d=7.44–7.40 (m, 2H),
1
1714 cmÀ1 (C=O); HR-MS (ESI): m/z=245.1285 [M+H]+,
7.28–7.22 (m, 3H), 6.45 (d, J=8.9 Hz, 1H), 5.68 (d, J=
8.9 Hz, 1H), 3.79 (s, 3H); 13C NMR (100 MHz, CDCl3): d=
calcd. for C14H17N2O2: 245.1290.
163.7, 139.2, 135.9, 129.8, 126.4, 118.4, 115.2, 108.9, 51.5; IR
À1
ꢀ
(KBr): n=2231 (C N), 1716 cm (C=O); HR-MS (ESI):
m/z=203.0826 [M+H]+, calcd. for C17H11N2O2: 203.0821.
(Z)-Ethyl 3-[N-(3,4-dimethylphenyl)cyanamido]acrylate
(3s): Yellow liquid. 1H NMR (400 MHz, CDCl3): d=7.13–
7.11 (m, 1H), 6.99 (s, 1H), 6.93–6.91 (m, 1H), 6.37 (d, J=
8.9 Hz, 1H), 5.58 (d, J=8.9 Hz, 1H), 4.22 (q, J=7.0 Hz,
2H), 2.22 (d, J=10.8 Hz, 6H), 1.28 (t, J=7.0 Hz, 3H);
13C NMR (100 MHz, CDCl3): d=163.3, 138.2, 137.0, 136.0,
(Z)-4-Methylbenzyl 3-(N-phenylcyanamido)acrylate (3w):
Yellow solid, mp 98–998C. H NMR (400 MHz, CDCl3): d=
134.8, 130.5, 119.6, 115.8, 108.6, 108.3, 60.4, 19.6, 18.8, 14.0;
1
À1
ꢀ
IR (KBr): n=2234 (C N), 1716 cm (C=O); HR-MS (ESI):
7.47–7.43 (m, 2H), 7.32 (d, J=7.8 Hz, 2H), 7.29–7.26 (m,
3H), 7.19 (d, J=7.8 Hz, 2H), 6.46 (d, J=8.9 Hz, 1H), 5.71
(d, J=8.9 Hz, 1H), 5.23 (s, 2H), 2.36 (s, 3H); 13C NMR
(100 MHz, CDCl3): d=163.2, 139.5, 138.2, 136.2, 132.6,
129.9, 129.2, 128.8, 126.5, 118.6, 109.2, 108.4, 66.5, 21.2; IR
m/z=245.1295 [M+H]+, calcd. for C14H17N2O2: 245.1290.
(Z)-Ethyl 3-[N-(2,4-dimethylphenyl)cyanamido]acrylate
(3t): Yellow liquid. 1H NMR (400 MHz, CDCl3): d=7.21–
7.19 (m, 1H), 7.09 (s, 1H), 7.06–7.04 (m, 1H), 6.10 (d, J=
Adv. Synth. Catal. 2013, 355, 765 – 780
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
775

Kai Luo et al.
FULL PAPERS
À1
ꢀ
(KBr): n=2229 (C N), 1718 cm (C=O): HR-MS (EI):
m/z=292.1209 [M+], calcd. for C18H16N2O2: 292.1212.
À1
ꢀ
IR (KBr): n=2231 (C N), 1714 cm (C=O); HR-MS (ESI):
m/z=245.1288 [M+H]+, calcd. for C14H17N2O2: 245.1290.
(Z)-4-Chlorobenzyl 3-(N-phenylcyanamido)acrylate (3x):
White solid, mp 103–1048C. 1H NMR (400 MHz, CDCl3):
d=7.47–7.43 (m, 2H), 7.37–7.30 (m, 5H), 7.27–7.25 (m,
2H), 6.48 (d, J=8.9 Hz, 1H), 5.71 (d, J=8.9 Hz, 1H), 5.23
(s, 2H); 13C NMR (100 MHz, CDCl3): d=163.1, 139.3, 136.5,
134.2, 134.0, 129.9, 129.9, 128.7, 126.6, 1À118.6, 115.3, 108.6,
(E)-Ethyl
3-[N-(4-isopropylphenyl)cyanamido]acrylate
1
ꢀ
65.7; IR (KBr): n=2230 (C N), 1712 cm (C=O); HRMS
(4d): Yellow liquid. H NMR (400 MHz, CDCl3): d=7.51 (d,
J=13.6 Hz, 1H), 7.29 (d, J=7.8 Hz, 2H), 7.21 (d, J=8.3 Hz,
2H), 5.82 (d, J=13.6 Hz, 1H), 4.20 (q, J=7.0 Hz, 2H),
2.95–2.88 (m, 1H), 1.27 (t, J=7.1 Hz, 3H), 1.23 (d, J=
6.8 Hz, 6H); 13C NMR (100 MHz, CDCl3): d=165.8, 148.4,
(EI): m/z=312.0665 [M+], calcd. for C17H13N2O2Cl:
312.0666.
141.2, 135.3, 128.0, 120.1, 108.7, 104.3, 60.4, 33.5, 23.7, 14.1;
À1
ꢀ
IR (KBr): n=2230 (C N), 1719 cm (C=O); HR-MS (ESI):
m/z=259.1449 [M+H]+, calcd. for C15H19N2O2: 259.1447.
(E)-Ethyl 3-(N-phenylcyanamido)acrylate (4a): Yellow
1
liquid. H NMR (400 MHz, CDCl3): d=7.56 (d, J=13.6 Hz,
1H), 7.50–7.46 (m, 2H), 7.36–7.31 (m, 3H), 5.91 (d, J=
13.5 Hz, 1H), 4.24 (q, J=7.1 Hz, 2H), 1.31 (t, J=7.1 Hz,
3H); 13C NMR (100 MHz, CDCl3): d=166.0, 140.7, 137.8,
130.2, 127.4, 119.9, 108.6, 105.1, 60.7, 14.2; IR (KBr): n=
(E)-Ethyl 3-[N-(4-fluorophenyl)cyanamido]acrylate (4e):
White solid, mp 59–618C. H NMR (400 MHz, CDCl3): d=
7.44 (d, J=13.6 Hz, 1H), 7.30–7.27 (m, 2H), 7.16–7.12 (m,
2H), 5.79 (d, J=13.6 Hz, 1H), 4.19 (q, J=7.1 Hz, 2H), 1.27
(t, J=7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=165.7,
161.3 (d, JC,F =247.3 Hz), 141.1, 133.7 (d, JC,F =3.0 Hz), 122.5
2232 (C N), 1715 cmÀ1 (C=O); HR-MS (ESI): m/z=
1
ꢀ
217.0972 [M+H]+, calcd. for C12H13N2O2: 217.0977.
(d, JC,F =8.6 Hz), 117.1 (d, JC,F =23.3 Hz), 108.6, 104.8, 60.5,
À1
ꢀ
14.1; IR (KBr): n=2231 (C N), 1715 cm (C=O); HR-MS
(ESI): m/z=235.0878 [M+H]+, calcd. for C12H12N2O2F:
235.0883.
(E)-Ethyl 3-(N-p-tolylcyanamido)acrylate (4b): Yellow
1
liquid. H NMR (400 MHz, CDCl3): d=7.49 (d, J=13.6 Hz,
1H), 7.24 (d, J=8.2 Hz, 2H), 7.17 (d, J=8.2 Hz, 2H), 5.82
(d, J=13.5 Hz, 1H), 4.20 (q, J=7.1 Hz, 2H), 2.35 (s, 3H),
1.28 (t, J=7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=
165.9, 141.2, 137.5, 135.2, 130.6, 120.0, 108.8, 1À014.3, 60.5,
ꢀ
20.7, 14.1; IR (KBr): n=2230 (C N), 1715 cm (C=O);
(E)-Ethyl 3-[N-(4-chlorophenyl)cyanamido]acrylate (4f):
Yellow solid, mp 65–668C. H NMR (400 MHz, CDCl3): d=
7.49 (d, J=13.6 Hz, 1H), 7.44 (d, J=8.8 Hz, 2H), 7.26 (d,
J=8.8 Hz, 2H), 5.90 (d, J=13.6 Hz, 1H), 4.23 (q, J=7.1 Hz,
2H), 1.31 (t, J=7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3):
HR-MS (ESI): m/z=231.1130 [M+H]+, calcd. for
1
C13H15N2O2: 231.1134.
(E)-Ethyl 3-[N-(4-ethylphenyl)cyanamido]acrylate (4c):
Yellow liquid. H NMR (400 MHz, CDCl3): d=7.52 (d, J=
1
d=165.6, 140.0, 136.2, 132.9, 130.2, 121.0, 108.0, 105.4, 60.6,
13.6 Hz, 1H), 7.29 (d, J=8.5 Hz, 2H), 7.22 (d, J=8.5 Hz,
2H), 5.84 (d, J=13.6 Hz, 1H), 4.23 (q, J=7.1 Hz, 2H), 2.67
(q, J=7.6 Hz, 2H), 1.30 (t, J=7.1 Hz, 3H), 1.24 (t, J=
7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=166.0, 144.0,
141.3, 135.4, 129.5, 120.3, 108.9, 104.5, 60.5, 28.2, 15.3, 14.2;
À1
ꢀ
14.1; IR (KBr): n=2233 (C N), 1716 cm (C=O); HR-MS
(ESI): m/z=251.0587 [M+H]+, calcd. for C12H12N2O2Cl:
251.0587.
776
asc.wiley-vch.de
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 765 – 780

A Stereocontrolled 1,2-Addition Reaction of Tetrazoles with Alkyl Propiolates
1H), 4.25 (q, J=7.1 Hz, 2H), 1.31 (t, J=7.1 Hz, 3H);
13C NMR (100 MHz, CDCl3): d=165.5, 140.6, 138.9, 129.1
(q, JC,F =33.2 Hz), 127.5 (q, JC,F =3.8 Hz), 123.4 (q, JC,F
=
270.5 Hz), 119.0, 107.5, 106.7, 60.8, 14.1; IR (KBr): n=2238
À1
ꢀ
(C N), 1714 cm (C=O); HR-MS (ESI): m/z=285.0849
[M+H]+, calcd. for C13H12N2O2F3: 285.0851.
(E)-Ethyl 3-[N-(4-bromophenyl)cyanamido]acrylate (4g):
1
White solid, mp 86–888C. H NMR (400 MHz, CDCl3): d=
7.57 (d, J=8.7 Hz, 2H), 7.48 (d, J=13.6 Hz, 1H), 7.18 (d,
J=8.7 Hz, 2H), 5.89 (d, J=13.5 Hz, 1H), 4.21 (q, J=7.1 Hz,
2H), 1.29 (t, J=7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d=165.6, 139.9, 136.8, 133.2, 121.2, 120.6, 108.0, 105.6, 60.7,
À1
ꢀ
14.1; IR (KBr): n=2231 (C N), 1714 cm (C=O); HR-MS
(ESI): m/z=295.0081 [M+H]+, calcd. for C12H12N2O2Br:
295.0082.
(E)-Ethyl 3-[N-(4-acetylphenyl)cyanamido]acrylate (4k):
White solid, mp 82–848C. H NMR (400 MHz, CDCl3): d=
1
8.05 (d, J=8.5 Hz, 2H), 7.62 (d, J=13.6 Hz, 1H), 7.38 (d,
J=8.6 Hz, 2H), 6.00 (d, J=13.5 Hz, 1H), 4.23 (q, J=7.1 Hz,
2H), 2.60 (s, 3H), 1.30 (t, J=7.1 Hz, 3H); 13C NMR
(100 MHz, CDCl3): d=196.0, 165.5, 141.2, 138.7, 135.3,
130.4, 118.3, 107.4, 106.6, 60.8, 26.4, 14.2; IR (KBr): n=2242
À1
ꢀ
(C N), 1714 (C=O), 1701 cm
(C=O); HR-MS (ESI):
m/z=259.1079 [M+H]+, calcd. for C14H15N2O3: 259.1083.
(E)-Ethyl 3-[N-(4-iodophenyl)cyanamido]acrylate (4h):
1
White solid, mp 95–978C. H NMR (400 MHz, CDCl3): d=
7.79 (d, J=8.4 Hz, 2H), 7.50 (d, J=13.6 Hz, 1H), 7.08 (d,
J=8.6 Hz, 2H), 5.93 (d, J=13.6 Hz, 1H), 4.24 (q, J=7.2 Hz,
2H), 1.32 (t, J=7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d=165.7, 139.8, 139.2, 137.6, 121.3, 108.0, 105.8, 91.4, 60.7,
À1
ꢀ
14.2; IR (KBr): n=2232 (C N), 1715 cm (C=O); HR-MS
(ESI): m/z=342.9942 [M+H]+, calcd. for C12H12N2O2I:
342.9943.
(E)-Ethyl
3-[N-(4-methoxyphenyl)cyanamido]acrylate
1
(4l): Yellow liquid. H NMR (400 MHz, CDCl3): d=7.40 (d,
J=13.6 Hz, 1H), 7.19 (d, J=8.4 Hz, 2H), 6.92 (d, J=8.5 Hz,
2H), 5.69 (d, J=13.4 Hz, 1H), 4.17 (q, J=7.0 Hz, 2H), 3.78
(s, 3H), 1.25 (t, J=7.0 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d=165.8, 159.0, 142.1, 130.3, 122.7, 115.1, 109.2,
À1
ꢀ
103.7, 60.3, 55.4, 14.1; IR (KBr): n=2229 (C N), 1715 cm
(C=O); HR-MS (ESI): m/z=247.1078 [M+H]+, calcd. for
C13H15N2O3: 247.1083.
(E)-Ethyl 3-[N-(4-nitrophenyl)cyanamido]acrylate (4i):
Yellow solid, mp 129–1318C. H NMR (400 MHz, CDCl3):
1
d=8.37 (d, J=9.1 Hz, 2H), 7.65 (d, J=13.5 Hz, 1H), 7.49
(d, J=9.1 Hz, 2H), 6.10 (d, J=13.5 Hz, 1H), 4.27 (q, J=
7.1 Hz, 2H), 1.33 (t, J=7.2 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d=165.3, 145.7, 142.6, 137.8, 125.9, 118.5, À11 08.0,
ꢀ
106.9, 61.1, 14.2; IR (KBr): n=2241 (C N), 1723 cm (C=
O); HR-MS (ESI): m/z=262.0823 [M+H]+, calcd. for
C12H12N3O4: 262.0828.
(E)-Ethyl 3-[N-(4-ethoxyphenyl)cyanamido]acrylate (4m):
1
Yellow liquid. H NMR (400 MHz, CDCl3): d=7.42 (d, J=
13.6 Hz, 1H), 7.20 (d, J=8.8 Hz, 2H), 6.93 (d, J=8.8 Hz,
2H), 5.71 (d, J=13.6 Hz, 1H), 4.19 (q, J=7.0 Hz, 2H), 4.02
(q, J=6.9 Hz, 2H), 1.40 (t, J=6.9 Hz, 3H), 1.27 (t, J=
7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=165.9, 158.4,
(E)-Ethyl
3-{N-[4-(trifluoromethyl)phenyl]cyanamido}-
142.2, 130.2, 122.8, 115.7, 109.3, 103.7, 63.8, 60.4, 14.5, 14.1;
acrylate (4j): White solid, mp 98–1008C. 1H NMR
(400 MHz, CDCl3): d=7.74 (d, J=8.5 Hz, 2H), 7.60 (d, J=
13.5 Hz, 1H), 7.44 (d, J=8.5 Hz, 2H), 6.01 (d, J=13.5 Hz,
À1
ꢀ
IR (KBr): n=2229 (C N), 1715 cm (C=O); HR-MS (ESI):
m/z=261.1240 [M+H]+, calcd. for C14H17N2O3: 261.1239.
Adv. Synth. Catal. 2013, 355, 765 – 780
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
777

Kai Luo et al.
FULL PAPERS
O); HR-MS (ESI): m/z=231.1134 [M+H]+, calcd. for
(E)-Ethyl 3-(N-m-tolylcyanamido)acrylate (4n): Yellow
liquid. H NMR (400 MHz, CDCl3): d=7.54 (d, J=13.6 Hz,
1
C13H15N2O2: 231.1134.
1H), 7.36–7.32 (m, 1H), 7.14–7.09 (m, 3H), 5.88 (d, J=
13.6 Hz, 1H), 4.23 (q, J=7.1 Hz, 2H), 2.40 (s, 3H), 1.31 (t,
J=7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=166.0,
140.8, 140.6, 137.7, 129.9, 128.1, 120.4, 116.8, 108.6,À11 04.8,
ꢀ
60.6, 21.3, 14.2; IR (KBr): n=2234 (C N), 1716 cm (C=
O); HR-MS (ESI): m/z=231.1131 [M+H]+, calcd. for
C13H15N2O2: 231.1134..
(E)-Ethyl 3-[N-(2,3-dimethylphenyl)cyanamido]acrylate
1
(4r): Yellow liquid. H NMR (400 MHz, CDCl3): d=7.35 (d,
J=13.6 Hz, 1H), 7.22–7.21 (m, 1H), 7.18–7.14 (m, 1H),
7.10–7.08 (m, 1H), 5.34 (d, J=13.6 Hz, 1H), 4.14 (q, J=
7.1 Hz, 2H), 2.29 (s, 3H), 2.20 (s, 3H), 1.23 (t, J=7.1 Hz,
3H); 13C NMR (100 MHz, CDCl3): d=165.7, 144.0, 139.4,
135.3, 133.3, 131.3, 127.0, 123.9, 110.1, 102.4, 60.2, 20.0, 14.0,
(E)-Ethyl
3-[N-(3-isopropylphenyl)cyanamido]acrylate
À1
ꢀ
13.6; IR (KBr): n=2230 (C N), 1715 cm ) (C=O); HR-MS
1
(4o): Yellow liquid. H NMR (400 MHz, CDCl3): d=7.55 (d,
J=13.6 Hz, 1H), 7.38–7.34 (m, 1H), 7.19–7.17 (m, 1H), 7.14
(s, 1H), 7.11–7.09 (m, 1H), 5.88 (d, J=13.6 Hz, 1H), 4.22
(q, J=7.0 Hz, 2H), 2.97–2.90 (m, 1H), 1.29 (t, J=7.7 Hz,
3H), 1.25 (d, J=6.9 Hz, 6H); 13C NMR (100 MHz, CDCl3):
d=165.9, 151.5, 140.9, 137.7, 130.0, 125.5, 118.0, 117.2, 108.6,
(ESI): m/z=245.1285 [M+H]+, calcd. for C14H17N2O2:
245.1290.
ꢀ
104.6, 60.5, 34.0, 23.6, 14.1; IR (KBr): n=2233 (C N),
1715 cmÀ1 (C=O); HR-MS (ESI): m/z=259.1449 [M+H]+,
calcd. for C15H19N2O2: 259.1447.
(E)-Ethyl 3-[N-(3,4-dimethylphenyl)cyanamido]acrylate
(4s): Yellow solid, mp 62–638C. 1H NMR (400 MHz,
CDCl3): d=7.51 (d, J=13.6 Hz, 1H), 7.21–7.19 (m, 1H),
7.08 (s, 1H), 7.04–7.01 (m, 1H), 5.83 (d, J=13.6 Hz, 1H),
4.23 (q, J=7.2 Hz, 2H), 2.29 (d, J=10.3 Hz, 6H), 1.30 (t,
J=7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=166.0,
141.3, 138.9, 136.2, 135.4, 131.0, 121.3, 117.5, 108.9, 104.2,
(E)-Ethyl 3-[N-(3-chlorophenyl)cyanamido]acrylate (4p):
Yellow liquid. H NMR (400 MHz, CDCl3): d=7.51 (d, J=
À1
ꢀ
60.5, 19.8, 19.1, 14.2; IR (KBr): n=2233 (C N), 1715 cm
1
(C=O); HR-MS (ESI): m/z=245.1295 [M+H]+, calcd. for
13.5 Hz, 1H), 7.42–7.38 (m, 1H), 7.32–7.29 (m, 2H), 7.23–
7.21 (m, 1H), 5.93 (d, J=13.6 Hz, 1H), 4.24 (q, J=7.2 Hz,
2H), 1.31 (t, J=7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d=165.6, 139.6, 138.8, 136.0, 131.1, 127.4, 119.8, 117.5,À11 07.8,
C14H17N2O2: 245.1290.
ꢀ
105.9, 60.8, 14.2; IR (KBr): n=2235 (C N), 1715 cm (C=
O); HR-MS (ESI): m/z=251.0584 [M+H]+, calcd. for
C12H12N2O2Cl: 251.0587.
(E)-Ethyl 3-(N-o-tolylcyanamido)acrylate (4q): Yellow
1
liquid. H NMR (400 MHz, CDCl3): d=7.37 (d, J=13.6 Hz,
(E)-Ethyl 3-[N-(2,4-dimethylphenyl)cyanamido]acrylate
1H),7.35–7.32 (m, 2H), 7.30–7.25 (m, 2H), 5.41 (d, J=
13.6 Hz, 1H), 4.18 (q, J=7.1 Hz, 2H), 2.36 (s, 3H), 1.26 (t,
J=7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=165.8,
143.8, 135.4, 134.7, 132.0, 130.0, 127.9, 126.4, 109.9,À11 02.8,
ꢀ
1
(4t): Yellow liquid. H NMR (400 MHz, CDCl3): d=7.36 (d,
J=13.6 Hz, 1H), 7.14–7.08 (m, 3H), 5.37 (d, J=13.6 Hz,
1H), 4.17 (q, J=7.1 Hz, 2H), 2.33 (d, J=16.1 Hz, 6H), 1.26
60.4, 17.2, 14.1; IR (KBr): n=2229 (C N), 1714 cm (C= (t, J=7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=165.9,
778
asc.wiley-vch.de
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 765 – 780

A Stereocontrolled 1,2-Addition Reaction of Tetrazoles with Alkyl Propiolates
144.1, 140.3, 134.4, 132.8, 132.6, 128.5, 126.2, 110.2, 102.5,
À1
ꢀ
60.4, 21.0, 17.1, 14.1; IR (KBr): n=2228 (C N), 1715 cm
(C=O); HR-MS (ESI): m/z=245.1287 [M+H]+, calcd. for
C14H17N2O2: 245.1290.
(EI): m/z=312.0665 [M]+, calcd. for C17H13N2O2Cl:
312.0666.
(E)-Ethyl 3-[N-(2,5-dimethylphenyl)cyanamido]acrylate
1
(4u): Yellow liquid. H NMR (400 MHz, CDCl3): d=7.36 (d,
N-Phenylcyanamide (5a):[13b] 1H NMR (400 MHz, CDCl3):
J=13.6 Hz, 1H), 7.21–7.15 (m, 2H), 7.07 (s, 1H), 5.41 (d,
J=13.6 Hz, 1H), 4.19 (q, J=7.1 Hz, 2H), 2.32 (d, J=
15.4 Hz, 6H), 1.27 (t, J=7.1 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d=165.9, 143.9, 138.0, 135.2, 131.8, 131.4, 130.8,
d=7.75 (s, 1H), 7.38–7.34 (m, 2H), 7.12–7.09 (m, 3H);
13C NMR (100 MHz, CDCl3): d=137.2, 129.6, 123.4, 115.4,
111.9; IR (KBr): n=2233 cmÀ1 (C N).
ꢀ
126.7, 110.1, 102.7, 60.4, 20.6, 16.7, 14.2; IR (KBr): n=2231
À1
ꢀ
(C N), 1715 cm (C=O); HR-MS (ESI): m/z=245.1288
[M+H]+, calcd. for C14H17N2O2: 245.1290.
Acknowledgements
This work was financially supported by the National Science
Foundation of China (Nos. 21172092 and 20102039).
References
(E)-Methyl 3-(N-phenylcyanamido)acrylate (4v): Yellow
liquid. H NMR (400 MHz, CDCl3): d=7.55 (d, J=13.6 Hz,
[1] a) R. V. Joshi, Z.-Q. Xu, M. Ksebati, D. Kessel, T. H.
Corbett, J. C. Drach, J. Zemlicka, J. Chem. Soc. Perkin
Trans. 1 1994, 1089–1098; b) M. F. Oliveira, T. L. G.
Lemos, M. C. D. Mattos, T. A. Segundo, G. M. P. San-
tiago, R. Braz-Filho, An. Acad. Bras. Cienc. 2002, 74,
211–221; c) Enamines: Synthesis Structure and Reac-
tions, (Ed.: A. G. Cook), Marcel Dekker Inc., New
York, 1988, p 717; d) T. D. Beeson, A. Mastracchio, J.-
B. Hong, K. Ashton, K. W. C. Macmillan, Science 2007,
316, 582–585; e) D. Enders, M. R. M. Hꢂttl, C. Gron-
dal, G. Raabe, Nature 2006, 441, 861–863; f) S. Mukher-
jee, J. W. Yang, S. Hoffmann, B. List, Chem. Rev. 2007,
107, 5471–5569.
1
1H), 7.47–7.44 (m, 2H), 7.33–7.29 (m, 3H), 5.88 (d, J=
13.6 Hz, 1H), 3.75 (s, 3H); 13C NMR (100 MHz, CDCl3):
d=166.2, 140.8, 137.7, 130.1, 127.3, 119.7, 108.4, 104.4, 51.6;
À1
ꢀ
IR (KBr): n=2234 (C N), 1715 cm (C=O); HR-MS (ESI):
m/z=203.0826 [M+H]+, calcd. for C17H11N2O2: 203.0821.
[2] a) B. List, Acc. Chem. Res. 2004, 37, 548–557; b) S. Mu-
kherjee, J. W. Yang, S. Hoffmann, B. List, Chem. Rev.
2007, 107, 5471–5569; c) D. A. Evans, J. Am. Chem.
Soc. 1970, 92, 7593–7595.
(E)-4-Methylbenzyl 3-(N-phenylcyanamido)acrylate (4w):
Yellow solid, mp 105–1068C. H NMR (400 MHz, CDCl3):
1
[3] A. Leyva-Pꢃrez, J. R. Cabrero-Antonino, ꢄ. Cantin, A.
d=7.59 (d, J=13.6 Hz, 1H), 7.50–7.46 (m, 2H), 7.36–7.28
(m, 5H), 7.21–7.19 (m, 2H), 5.94 (d, J=13.6 Hz, 1H), 5.19
(s, 2H), 2.37 (s, 3H); 13C NMR (100 MHz, CDCl3): d=
165.9, 141.1, 138.2, 137.8, 132.8, 130.2, 129.3, 128.4, 127.5,
Corma, J. Org. Chem. 2010, 75, 7769–7780.
[4] a) M.-J. Fan, G.-Q. Li, Y.-M. Liang, Tetrahedron 2006,
62, 6782–6791; b) B. M. Trost, G. R. Dake, J. Am.
Chem. Soc. 1997, 119, 7595–7596; c) J. S. Yadav, B. V. S.
Reddy, N. N. Yadav, M. K. Gupta, Tetrahedron Lett.
2008, 49, 2815–2819.
[5] For selected reviews, see: a) M. Naodovic, H. Yamamo-
to, Chem. Rev. 2008, 108, 3132–3148; b) J.-M. Weibel,
A. Blanc, P. Pale, Chem. Rev. 2008, 108, 3149–3173;
c) M. ꢄlvarez-Corral, M. MuÇoz-Dorado, I. Rodrꢅguez-
Garcꢅa, Chem. Rev. 2008, 108, 3174–3198.
[6] a) S. Su, J. A. Porco Jr, J. Am. Chem. Soc. 2007, 129,
7744–7745; b) P. A. Wender, D. Strand, J. Am. Chem.
Soc. 2009, 131, 7528–7529; c) G.-Y. Lin, C.-W. Li, S.-H.
Hung, R.-S. Liu, Org. Lett. 2008, 10, 5059–5062.
ꢀ
120.0, 108.5, 104.8, 66.4, 21.2; IR (KBr): n=2232 (C N),
1712 cmÀ1 (C=O); HR-MS (EI): m/z=292.1209 [M+, calcd.
for C18H16N2O2: 292.1212.
(E)-4-Chlorobenzyl 3-(N-phenylcyanamido)acrylate (4x):
1
Yellow solid, mp 115–1168C. H NMR (400 MHz, CDCl3):
d=7.59 (d, J=13.6 Hz, 1H), 7.50–7.46 (m, 2H), 7.37–7.35
(m, 3H), 7.33–7.31 (m, 4H), 5.94 (d, J=13.6 Hz, 1H), 5.19
(s, 2H); 13C NMR (100 MHz, CDCl3): d=165.7, 141.5, 137.7,
134.3, 134.3, 130.2, 129.6, 128.8, 127.6, 120.0, 108.5, 104.4,
À1
ꢀ
65.6; IR (KBr): n=2233 (C N), 1716 cm (C=O); HRMS
Adv. Synth. Catal. 2013, 355, 765 – 780
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
779

Kai Luo et al.
FULL PAPERS
[7] X. Zhang, B. Liu, X. Shu, Y. Gao, H. Lv, J. Zhu, J. Org.
Chem. 2012, 77, 501–510.
[8] a) Y. Luo, Z. Li, C.-J. Li, Org. Lett. 2005, 7, 2675–2678;
b) W. Liu, H. Jiang, L. Huang, Org. Lett. 2010, 12, 312–
315.
[9] a) C. Wei, Z. Li, C.-J. Li, Org. Lett. 2003, 5, 4473–4475;
b) J.-X. Ji, T. T.-L. Au-Yeung, J. Wu, C. W. Yip, A. S. C.
Chan, Adv. Synth. Catal. 2004, 346, 42–46.
[10] a) B. M. Trost, F. D. Toste, K. Greenman, J. Am. Chem.
Soc. 2003, 125, 4518–4526; b) C. H. Oh, S. Karmakar,
H. Park, Y. Ahn, J. W. Kim, J. Am. Chem. Soc. 2010,
132, 1792–1793; c) M. Yu, R. Skouta, L. Zhou, H.-F.
Jiang, X. Yao, C.-J. Li, J. Org. Chem. 2009, 74, 3378–
3383; d) A. Blanc, K. Tenbrink, J.-M. Weibel, P. Pale, J.
Org. Chem. 2009, 74, 4360–4363; e) M. Bera, S. Roy, J.
Org. Chem. 2009, 74, 8814–8817; f) Z. Guo, M. Cai, J.
Jiang, L. Yang, W. Hu, Org. Lett. 2010, 12, 652–655.
[11] a) N. Kambe, Y. Moriwaki, Y. Fujii, T. Iwasaki, J.
Terao, Org. Lett. 2011, 13, 4656–4659; b) Z. Shi, C. He,
J. Org. Chem. 2004, 69, 3669–3671.
[14] a) D. Bꢃguꢃ, G. G. Qiao, C. Wentrup, J. Am. Chem.
Soc. 2012, 134, 5339–5350; b) X. Liu, X. Wang, Q. Li,
M. P. Kozar, V. Melendez, M. T. OꢀNeil, A. J. Lin, J.
Med. Chem. 2011, 54, 4523–4525; c) R. M. Stolley, W.
Guo, J. Louie, Org. Lett. 2012, 14, 322–325; d) A. Tana-
tani, K. Yamaguchi, I. Azumaya, R. Fukutomi, K.
Shudo, H. Kagechika, J. Am. Chem. Soc. 1998, 120,
6433–6442; e) M.-H. Larraufie, G. Maestri, M. Malac-
ria, C. Ollivier, L. Fensterbank, E. Lacꢇte, Synthesis
2012, 44, 1279–1292.
[15] a) W. Liu, H. Jiang, L. Huang, Org. Lett. 2010, 12, 312–
315; b) Y. Sugawara, W. Yamada, S. Yoshida, T. Ikeno,
T. Yamada, J. Am. Chem. Soc. 2007, 129, 12902–12903;
c) U. Lꢃtinois-Halbes, P. Pale, S. Berger, J. Org. Chem.
2005, 70, 9185–9190.
[16] A. N. Vorobiov, P. N. Gaponik, P. T. Petrov, O. A.
Ivashkevich, Synthesis 2006, 1307–1312.
[17] D. Habibi, M. Nasrollahzadeh, T. A. Kamali, Green
Chem. 2011, 13, 3499–3504.
[18] T. M. Potewar, S. A. Siddiqui, R. J. Lahoti, K. V. Srini-
vasan, Tetrahedron Lett. 2007, 48, 1721–1724.
[19] G. Aridoss, K. K. Laali, Eur. J. Org. Chem. 2011, 15,
2827–2835.
[20] V. Balsanek, L. Tichotova, J. Kunes, M. Spulak, M.
Pour, I. Votruba, V. Buchta, Collect. Czech. Chem.
Commun. 2009, 74, 1161–1178.
[12] a) M. Brown, U.S. Patent 3,338,915, 1967; Chem. Abstr.
1968, 87299; b) V. A. Ostrovskii, M. S. Pevzner, T. P.
Kofmna, M. B. Shcherbinin, I. V. Tselinskii, Targets
Heterocycl. Syst. 1999, 3, 467–526; c) M. Hiskey, D. E.
Chavez, D. L. Naud, S. F. Son, H. L. Berghout, C. A.
Bome, Proc. Int. Pyrotech. Semin. 2000, 27, 3–14; d) M.
ˇ
ˇ
´
ˇ
Spulꢆk, R. Lubojacky, P. Senel, J. Kunes, M. Pour, J.
[21] A. N. Vorobiov, P. N. Gaponik, P. T. Petrov, O. A.
Org. Chem. 2010, 75, 241–244.
Ivashkevich, Synthesis 2006, 1307–1312.
[22] S. N. Dighe, K. S. Jain, K. V. Srinivasan, Tetrahedron
Lett. 2009, 50, 6139–6142.
[23] D. Kundu, A. Majee, A. Hajra, Tetrahedron Lett. 2009,
50, 2668–2670.
[13] For the first reports on the degradation reactions of 1-
substituted tetrazoles, see: a) R. Stolle, F. Henke-Stark,
J. Prakt. Chem. 1929, 124, 261–300; for selected exam-
ple, see: b) A. N. Vorobiov, P. N. Gaponik, P. T. Petrov,
O. A. Ivashkevich, Synthesis 2006, 1307–1312.
780
asc.wiley-vch.de
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 765 – 780