3,5-Disubstituted 6H-pyrrolo[1,2-c][1,2,3]triazoles from Morita-Baylis-Hillman adducts of propargyl aldehydes

Article abstract of DOI:10.1016/j.tet.2010.03.017

A simple method for synthesizing several 6H-pyrrolo[1,2-c][1,2,3]triazole derivatives having a methoxycarbonyl or an acetyl group at C-5 position and 7,8-dihydro-4H-[1,2,3]triazolo[1,5-a]indol-5(6H)-ones via an intramolecular 1,3-dipolar cycloaddition reaction of azido enynes, which were readily obtained from the Morita-Baylis-Hillman acetates of propargyl aldehydes with sodium azide, has been developed.

Full text of DOI:10.1016/j.tet.2010.03.017

Tetrahedron 66 (2010) 3490–3498
Contents lists available at ScienceDirect
Tetrahedron
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3,5-Disubstituted 6H-pyrrolo[1,2-c][1,2,3]triazoles from Morita–Baylis–Hillman
adducts of propargyl aldehydes
*
Sun Pil Park, Sang-Hyun Ahn, Kee-Jung Lee
Organic Synthesis Laboratory, Department of Chemical Engineering, Hanyang University, Seoul 133-791, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple method for synthesizing several 6H-pyrrolo[1,2-c][1,2,3]triazole derivatives having a methoxy
carbonyl or an acetyl group at C-5 position and 7,8-dihydro-4H-[1,2,3]triazolo[1,5-a]indol-5(6H)-ones via
an intramolecular 1,3-dipolar cycloaddition reaction of azido enynes, which were readily obtained from
the Morita–Baylis–Hillman acetates of propargyl aldehydes with sodium azide, has been developed.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 7 December 2009
Received in revised form 3 March 2010
Accepted 3 March 2010
Available online 9 March 2010
Keywords:
1,3-Dipolar cycloaddition reaction
Morita–Baylis–Hillman
Propargyl aldehydes
Azido enynes
6H-Pyrrolo[1,2-c][1,2,3]triazoles
7,8-Dihydro-4H-[1,2,3]triazolo[1,5-a]-
indol-5(6H)-ones
1. Introduction
method has some drawbacks that the only simple alkyl substituted
azido enynes were prepared and their thermal cyclization was
1,2,3-Triazoles and 1,2,3-triazole-fused heterocycles are known to
exhibit a wide range of biological activities such as anti-HIV activity,1
antimicrobial activity against Gram positive bacteria,2 selective b3
adrenergic receptor agonism,3 and antianxiety activity.4 So it is im-
portant to develop new and more efficient synthetic methods to
a diverse array of 1,2,3-triazole pharmacophores. The most impor-
tant synthetic route involves a 1,3-dipolar cycloaddition reaction of
an azide with an alkyne5 or an alkyne equivalent, such as a vinyl
acetate, an enamine or an enol ether.6 Intramolecular applications of
this reaction in more flexible systems have proven to be especially
valuable for the synthesis of 1,2,3-triazole-fused heterocyles. For
examples, 3-(o-azidophenoxy)propynes, 3-(o-azidothiophenoxy)
propynes, and 1-(o-azidothiophenoxy)propynes cyclize upon heat-
ing to give triazolobenzoxazines,7 triazolobenzthiazines,8 and
triazolobenzthiazoles,8 respectively. The synthesis of 6H-pyrro-
lo[1,2-c][1,2,3]triazoles by the intramolecular 1,3-dipolar cyclo-
addtion reaction of 1-azido-2-penten-4-ynes has been reported by
Bertrand et al.9 and Dulcere et al.10 Azido enynes were obtained by
treatment of 1-chloro-2-penten-4-ynes11 with sodium azide, which
were prepared by the reaction of acrolein with ethynyl Grignard or
lithium reagent followed by treatment with hydrochloric acid. This
studied limitedly.
The Morita–Bayis–Hillman reaction is a versatile carbon–carbon
bond forming reaction which provides multi functionalized ad-
ducts,
a-methylene-b
-hydroxy carbonyl compounds.12a–j These
adducts and their derivatives have widely been explored for the
syntheses of a variety of useful heterocyclic compounds.13,14
Herein, we describe the synthesis of azido enynes from the
Morita–Baylis–Hillman adducts of several acetylenic aldehydes and
their conversion to the 6H-pyrrolo[1,2-c][1,2,3]triazoles and
7,8-dihydro-4H-[1,2,3]triazolo[1,5-a]indol-5(6H)-ones involving an
intramolecular 1,3-dipolar cycloaddition reaction of an azide to
carbon–carbon triple bond.15
2. Results and discussion
The readily available Morita–Baylis–Hillman adducts 2, whose
preparation has been previously described,16 provide a convenient
starting point for the synthesis of key intermediate azido enynes 4.
Treatment of several acetylenic aldehydes 1 with methyl acrylate in
the presence of 1,4-diazabicyclo[2,2,2]octane (DABCO) in dimethyl
sulfoxide at room temperature produced the adducts 2a–f in 47–64%
yields. For methyl vinyl ketone, the corresponding adducts 2g–l were
obtained in 56–64% yields. The Morita–Baylis–Hillman reactions of
phenylpropargyl aldehyde (1a) with cyclopent-2-enone and
* Corresponding author. Tel.: þ822 2220 0528; fax: þ822 2298 4101; e-mail
address: leekj@hanyang.ac.kr.
0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.03.017

S.P. Park et al. / Tetrahedron 66 (2010) 3490–3498
3491
cyclohex-2-enone were performed in aqueous tetrahydrofuran using
20 mol % 4-(dimethylamino)pyridine (DMAP) as a catalyst, such that,
2m and 2n were produced in 35% and 40% yields, respectively. Sim-
ilarly, the reaction of 2-octynal (1f) with cyclohex-2-enone the ad-
duct 2o was obtained in 30% yield. The reaction of adducts 2a–o with
acetic anhydride in the presence of catalytic amount of DMAP in
dichloromethane at 0–5 ꢀC gave the acetates of Morita–Baylis–Hill-
man adducts 3a–o (79–88%), as shown in Scheme 1 and Table 1. The
azidation reaction of the acetates 3a–o with sodium azide17 in
methanol/water (9:1) at room temperature for 1 h afforded the
Scheme 1. Reagents and conditions: (i) methyl acrylate or methyl vinyl ketone, DABCO, DMSO, rt, 20 min to 4 h; (ii) Ac2O, DMAP, CH2Cl2, 0–5 ꢀC, 5–60 min; (iii) NaN3, CH3OH/H2O
(9:1), rt, 1 h; (iv) toluene, reflux, 1 h; (v) cyclopent-2-enone or cyclohex-2-enone, DMAP, THF/H2O (1:1), rt, 1 h.

3492
S.P. Park et al. / Tetrahedron 66 (2010) 3490–3498
Table 1
5(6H)-ones via an intramolecular 1,3-dipolar cycloaddition reaction
of the corresponding azido enynes, which were readily obtained
from the Morita–Baylis–Hillman acetates of propargyl aldehydes
with sodium azide.
Preparation of adducts 2, acetates 3, azido enynes 4, and triazole derivatives 5
Entry 2 (Yield/time)
3 (Yield/time)
4 (Yield/time) 5 (Yield/time)
1
2
3
4
5
6
7
8
2a (61%/2 h)
2b (47%/4 h)
2c (55%/3 h)
2d (64%/2 h)
2e (53%/30 min)
2f (59%/1 h)
2g (64%/2 h)
2h (60%/2 h)
2i (58%/3 h)
2j (56%/2 h)
3a (87%/10 min)
3b (80%/5 min)
3c (79%/5 min)
4a (91%/1 h)
4b (91%/1 h)
4c (79%/1 h)
5a (81%/1 h)
5b (91%/1 h)
5c (88%/1 h)
5d (91%/1 h)
5e (86%/1 h)
5f (43%/1 h)
5g (62%/1 h)
5h (81%/1 h)
5i (75%/1 h)
5j (92%/1 h)
5k (80%/1 h)
5l (d)
4. Experimental
3d (87%/10 min) 4d (95%/1 h)
3e (82%/10 min)
3f (82%/15 min)
3g (80%/10 min)
3h (79%/10 min) 4h (74%/1 h)
3i (82%/5 min)
3j (83%/10 min)
4e (75%/1 h)
4f (87%/1 h)
4g (91%/1 h)
4.1. Synthesis general
The melting points were measured on an Electrothermal melt-
ing point apparatus and are uncorrected. TLC analyses were carried
out on Merck silica gel 60 F254 and spots were visualized under UV
light. Chromatography on silica gel was carried out on Merck silica
(70–230 mesh ASTM). IR spectra were determined on a Nicolet
Magna 550 FTIR spectrometer using KBr discs. 1H NMR spectra
were recorded on a Varian 300 spectrometer in CDCl3 or DMSO-d6
at 300 MHz. All chemical shifts are given in parts per million (ppm)
using dH Me4Si¼0 ppm as reference and J values are given in hertz.
The 13C NMR spectra were run in the same instrument at 75.4 MHz
using the solvent peak as internal reference. Low resolution mass
spectra were recorded on a ThermoQuest Polaris Q mass spec-
trometer operating at 70 eV. ESI-TOF mass spectra were recorded
on a Micromass spectrometer (Model No. LCT). Elemental analyses
were carried out on a Thermo Electron Corporation Flash EA 1112
instrument. Phenylpropargyl aldehyde (1a) and 2-octynal (1f) were
obtained from Aldrich and used without further purification. The
known propargyl aldehydes 1b–e were prepared by the procedure
for Sonogashira coupling of propargyl alcohol with the corre-
sponding aryl iodide20 followed by oxidation with manganese
dioxide21 according to the reported procedures.
9
4i (89%/1 h)
4j (68%/1 h)
10
11
12
13
14
15
2k (63%/20 min) 3k (81%/10 min) 4k (69%/1 h)
2l (58%/1 h)
2m (35%/1 h)
2n (40%/1 h)
2o (30%/1 h)
3l (80%/10 min)
3m (88%/1 h)
3n (80%/1 h)
4l (84%/1 h)
4m (90%/1 h)
4n (83%/1 h)
4o (90%/1 h)
5m (d)
5n (85%/1 h)
5o (47%/1 h)
3o (82%/15 min)
required key intermediate methyl 2-(azidomethyl)pent-2-en-4-
ynoates 4a–f (75–95%), 3-(azidomethyl)hex-3-en-5-yn-2-ones 4g–l
(68–91%),
4m (90%), 3-azido-2-(3-phenylprop-2-ynylidene)cyclohexanone 4n
(83%), and 3-azido-2-(oct-2-ynylidene)cyclohexanone 4o (90%), re-
spectively, solely with (E)-stereoselectivity. The stereochemistry of
the azido enynes 4 was established by comparing 1H NMR values of
olefinic and methylene protons with literature values of similar
3-azido-2-(3-phenylprop-2-ynylidene)cyclopentanone
compounds.17,18 The olefinic proton of 4a–l was observed at
7.11 and two methylene protons were resonated at 4.27–4.31 as
each singlet, except 4f and 4l.19 In the cases of 4m, 4n, and 4o the
vinyl proton was appeared at 6.89 as a doublet, 6.98 as a singlet
and 6.76 as a triplet and the methine protonwas observed at 5.04–
5.07, 5.24–5.28, and 5.13–5.17 as each multiplet, respectively.
d 6.94–
d
d
d
d
d
d
d
4.2. General procedure for the synthesis of the Morita–
Baylis–Hillman adducts 2a–l
Finally, the intramolecular 1,3-dipolar cycloaddition reaction of
4a–o between azide and alkyne groups in refluxing toluene for 1 h
produced the corresponding 6H-pyrrolo[1,2-c][1,2,3]triazole 5a–k
(43–92%), 3-phenyl-7,8-dihydro-4H-[1,2,3]triazolo[1,5-a]indol-
5(6H)-one 5n (85%), and 3-pentyl-7,8-dihydro-4H-[1,2,3]tri-
azolo[1,5-a]indol-5(6H)-one 5o (47%) after isomerization of the
expected 3-phenyl-6,7,8,8a-tetrahydro[1,2,3]triazolo[1,5-a]indol-
5-one 50n and 3-pentyl-6,7,8,8a-tetrahydro[1,2,3]triazolo[1,5-
a]indol-5-one 50o. In the cases of 4l and 4m very complex
un-isolable decomposition products were produced. Exploration of
different reaction conditions such as lower temperatures at 60, 80,
and 90 ꢀC in toluene and other solvent systems, such as tetrahy-
drofuran, acetonitrile at reflux temperature and dimethylforma-
mide at 60 ꢀC the desired triazoles 5l and 5n were not obtained. The
IR spectra of 5 showed the disappearance of absorption of carbon–
carbon triple bond and azide bands. In the 1H NMR spectra of 5a–k,
the characteristic chemical shift of the methine proton of C-4 was
A mixture of propargyl aldehyde 1 (20 mmol), methyl acrylate
(2.07 g, 24 mmol) or methyl vinyl ketone (1.68 g, 24 mmol), and
DABCO (1.12 g,10 mmol) in 20 mL of dimethyl sulfoxidewas stirred at
room temperature for 20 min to 4 h. The reaction mixture was di-
luted with water (100 mL) and extracted with ethyl acetate
(3ꢁ100 mL). The combined organic layers were dried over anhydrous
magnesium sulfate and the solvent was evaporated in vacuo. The
resulting mixture was chromatographed on silica gel eluting with
hexane and ethyl acetate (6:1 to 3:1) to produce 2 as an oil.
4.2.1. Methyl 3-hydroxy-2-methylene-5-phenylpent-4-ynoate
(2a). Reaction time: 2 h; yield: 61%; yellow oil; IR (neat) 3438,
2226, 1721 cmꢂ1; 1H NMR (CDCl3)
d
3.19 (d, J¼6.9 Hz, 1H, OH), 3.85
(s, 3H, CH3), 5.46 (d, J¼6.6 Hz, 1H, CH), 6.21 (s, 1H, CH), 6.38 (s, 1H,
CH), 7.29–7.34 (m, 3H, aromatic), 7.44–7.47 (m, 2H, aromatic); 13C
found at
were observed at
5n and 5o, two methylene protons of C-4 were appeared at
and
3.57 as a doublet of doublet and 1H–1H 2D COSY spectra of 5n
d
7.46–7.74 as a triplet, and two methylene protons of C-6
5.06–5.17 as a doublet. In the 1H NMR spectra of
3.82
NMR (CDCl3)
d 52.2, 62.6, 86.5, 86.7, 122.2, 127.1, 128.3, 128.7, 131.7,
d
139.0, 166.3. Anal. Calcd for C13H12O3: C, 72.21; H, 5.59. Found: C,
72.03; H, 5.41.
d
d
and 5o clearly showed long-range coupling of C-4 methylene pro-
tons and C-8 methylene protons. In DEPT 13C NMR experiments 5n
exhibited four CH2 absorption peaks (21.2, 22.2, 25.7, 37.3) and three
CH peaks (125.6, 128.3, 129.0). Compound 5o showed eight CH2
absorption peaks (21.2, 22.2, 22.4, 24.4, 25.3, 28.1, 31.4, 37.3) and one
CH3 peak (14.0). No CH absorption peak observed. The molecular ion
peaks of 5a–k were not observed in the EI mass spectra, but we
could observe [MþNa]þ peaks in ESI-TOF mass spectra.
4.2.2. Methyl 5-(4-chlorophenyl)-3-hydroxy-2-methylenepent-4-ynoate
(2b). Reaction time: 4 h; yield: 47%; yellow oil; IR (neat) 3426,
2228, 1721 cmꢂ1; 1H NMR (CDCl3)
d
3.21 (d, J¼5.5 Hz, 1H, OH), 3.84
(s, 3H, CH3), 5.43 (d, J¼5.5 Hz, 1H, CH), 6.18 (s, 1H, CH), 6.37 (s, 1H,
CH), 7.26–7.31 (m, 2H, aromatic), 7.36–7.39 (m, 2H, aromatic); 13C
NMR (CDCl3)
d 52.3, 62.7, 85.5, 87.6, 120.1, 127.1, 128.6, 133.0, 134.8,
138.9, 166.3. Anal. Calcd for C13H11ClO3: C, 62.29; H, 4.42. Found: C,
62.07; H, 4.26.
3. Conclusions
4.2.3. Methyl 5-(4-fluorophenyl)-3-hydroxy-2-methylenepent-
4-ynoate (2c). Reaction time: 3 h; yield: 55%; yellow oil; IR (neat)
In summary, we have prepared several 6H-pyrrolo[1,2-
c][1,2,3]triazoles and 7,8-dihydro-4H-[1,2,3]triazolo[1,5-a]indol-
3444, 2225, 1721 cmꢂ1
OH), 3.84 (s, 3H, CH3), 5.44 (d, J¼6.6 Hz, 1H, CH), 6.19 (s, 1H, CH),
;
1H NMR (CDCl3)
d
3.22 (d, J¼6.9 Hz, 1H,

S.P. Park et al. / Tetrahedron 66 (2010) 3490–3498
3493
6.37 (s, 1H, CH), 6.98–7.04 (m, 2H, aromatic), 7.41–7.47 (m, 2H, ar-
omatic); 13C NMR (CDCl3)
52.3, 62.6, 85.6, 86.3, 115.6
(d, J¼22.0 Hz), 118.3, 127.1, 133.7 (d, J¼8.6 Hz), 139.0, 162.7
(d, J¼249.8 Hz), 166.3. Anal. Calcd for C13H11FO3: C, 66.66; H, 4.73.
Found: C, 66.81; H, 4.90.
6.25 (s, 1H, CH), 6.43 (s, 1H, CH), 6.89–6.90 (m, 1H, aromatic), 6.98–
6.99 (m, 1H, aromatic), 7.03–7.06 (m, 1H, aromatic), 7.19–7.26
d
(m, 1H, aromatic); 13C NMR (CDCl3)
d 26.3, 55.3, 62.4, 86.6, 86.7,
115.3, 116.6, 123.3, 124.3, 127.6, 129.3, 146.6, 159.3, 199.7. Anal. Calcd
for C14H14O3: C, 73.03; H, 6.13. Found: C, 72.77; H, 5.89.
4.2.4. Methyl 3-hydroxy-5-(3-methoxyphenyl)-2-methylenepent-4-
4.2.11. 4-Hydroxy-3-methylene-6-(thiophen-2-yl)hex-5-yn-2-one
ynoate (2d). Reaction time: 2 h; yield: 64%; yellow oil; IR (neat)
(2k). Reaction time: 20 min; yield: 63%; red oil; IR (neat) 3414,
3440, 2235,1722 cmꢂ1; 1H NMR (CDCl3)
d
3.18 (d, J¼6.6 Hz,1H, OH),
2221, 1673 cmꢂ1 1H NMR (CDCl3)
; d 2.43 (s, 3H, CH3), 3.31
3.80 (s, 3H, CH3), 3.85 (s, 3H, CH3), 5.46 (d, J¼6.3 Hz, 1H, CH), 6.21
(s, 1H, CH), 6.38 (s, 1H, CH), 6.87–6.91 (m, 1H, aromatic), 6.98–6.99
(m, 1H, aromatic), 7.03–7.07 (m, 1H, aromatic), 7.19–7.26 (m, 1H,
(d, J¼6.1 Hz,1H, OH), 5.51 (d, J¼5.8 Hz,1H, CH), 6.26 (s,1H, CH), 6.40
(s, 1H, CH), 6.97 (dd, J¼5.2 and 3.6 Hz, 1H, aromatic), 7.24 (dd, J¼3.6
and 1.1 Hz, 1H, aromatic), 7.27 (dd, J¼5.2 and 1.1 Hz, 1H, aromatic);
aromatic); 13C NMR (CDCl3)
d
52.3, 55.3, 62.7, 86.3, 86.7, 115.3, 116.6,
13C NMR (CDCl3)
d 26.3, 62.5, 80.1, 90.6, 122.1, 126.9, 127.5, 127.8,
123.2, 124.3, 127.2, 129.4, 139.0 159.2, 166.3. Anal. Calcd for
C14H14O4: C, 68.28; H, 5.73. Found: C, 68.53; H, 6.01.
132.6, 146.3, 199.7. Anal. Calcd for C11H10O2S: C, 64.05; H, 4.89.
Found: C, 63.85; H, 4.72.
4.2.5. Methyl 3-hydroxy-2-methylene-5-(thiophen-2-yl)pent-
4-ynoate (2e). Reaction time: 30 min; yield: 52%; red oil; IR (neat)
4.2.12. 4-Hydroxy-3-methyleneundec-5-yn-2-one (2l). Reaction
time: 1 h; yield: 58%: yellow oil; IR (neat) 3414, 2226, 1677 cmꢂ1
;
3434, 2222,1717 cmꢂ1; 1H NMR (CDCl3)
d
3.20 (d, J¼6.9 Hz,1H, OH),
1H NMR (CDCl3)
d
0.90 (t, J¼7.2 Hz, 3H, CH3), 1.26–1.48 (m, 4H,
3.84 (s, 3H, CH3), 5.46 (d, J¼6.6 Hz, 1H, CH), 6.18(s, 1H, CH), 6.37
(s, 1H, CH), 6.97 (dd, J¼5.2 and 3.6 Hz, 1H, aromatic), 7.24 (dd, J¼3.6
and 1.1 Hz, 1H, aromatic), 7.27 (dd, J¼5.2 and 1.1 Hz, 1H, aromatic);
two CH2), 1.51–1.61 (m, 2H, CH2), 2.24 (dt, J¼7.2 and 2.2 Hz, 2H,
CH2), 2.40 (s, 3H, CH3), 3.12 (d, J¼5.8 Hz, 1H, OH), 5.27–5.28 (m,
1H, CH), 6.18 (s, 1H, CH), 6.36 (d, J¼1.1 Hz, 1H, CH); 13C NMR
13C NMR (CDCl3)
d
52.3, 62.8, 80.0, 90.4, 122.0, 126.9, 127.3, 127.6,
(CDCl3) d 13.9, 18.7, 22.1, 26.4, 28.2, 31.0, 62.0, 77.8, 88.1, 127.2,
132.6, 138.7, 166.2. Anal. Calcd for C11H10O3S: C, 59.44; H, 4.53.
Found: C, 59.16; H, 4.31.
147.1, 199.9. Anal. Calcd for C12H18O2: C, 74.19; H, 9.34. Found: C,
74.37; H, 9.50.
4.2.6. Methyl 3-hydroxy-2-methylenedec-4-ynoate (2f). Reaction
4.2.13. 2-(1-Hydroxy-3-phenylprop-2-yn-1-yl)cyclopent-2-enone
(2m). A mixture of phenylpropargyl aldehyde 1a (1.30 g, 10 mmol),
cyclopent-2-enone (0.82 g, 10 mmol), and DMAP (0.24 g, 2 mmol)
in 10 mL of aqueous tetrahydrofuran (1:1) was stirred at room
temperature for 1 h. The reaction mixture was diluted with water
(50 mL) and extracted with ethyl acetate (3ꢁ50 mL). The combined
organic layers were dried over anhydrous magnesium sulfate and
the solvent was evaporated in vacuo. The resulting mixture was
chromatographed on silica gel eluting with hexane and ethyl ace-
tate (3:1) to produce 2m (0.74 g, 35%) as a yellow oil; IR (neat) 3388,
time: 1 h; yield: 59%; yellow oil; IR (neat) 3425, 2227, 1726 cmꢂ1
;
1H NMR (CDCl3)
d
0.90 (t, J¼7.2 Hz, 3H, CH3), 1.26–1.42 (m, 4H,
two CH2), 1.48–1.58 (m, 2H, CH2), 2.24 (dt, J¼7.2 and 2.2 Hz, 2H,
CH2), 3.00 (d, J¼6.3 Hz, 1H, OH), 5.22 (dd, J¼6.6 and 0.8 Hz, 1H,
CH), 6.13 (s, 1H, CH), 6.30 (s, 1H, CH); 13C NMR (CDCl3)
d 13.9, 18.7,
22.1, 28.2, 31.0, 52.1, 62.3, 77.7, 88.0, 126.6, 139.6, 166.5. Anal.
Calcd for C12H18O3: C, 68.54; H, 8.63. Found: C, 68.32; H, 8.51.
4.2.7. 4-Hydroxy-3-methylene-6-phenylhex-5-yn-2-one
(2g)16a. Reaction time: 2 h; yield: 64%; yellow oil; IR (neat) 3413,
2229, 1701 cmꢂ1 1H NMR (CDCl3)
; d 2.53–2.56 (m, 2H, CH2), 2.67–
2219, 1674 cmꢂ1
;
1H NMR (CDCl3)
d
2.43 (s, 3H, CH3), 3.32
2.73 (m, 2H, CH2), 3.30 (d, J¼5.0 Hz, 1H, OH), 5.48 (br s, 1H, CH),
(d, J¼5.8 Hz, 1H, OH), 5.51 (d, J¼5.8 Hz, 1H, CH), 6.25 (s, 1H, CH),
7.31–7.34 (m, 3H, aromatic), 7.46–7.48 (m, 2H, aromatic), 7.78
6.44 (s, 1H, CH), 7.30–7.34 (m, 3H, aromatic), 7.44–7.47 (m, 2H,
(td, J¼2.8 and 1.1 Hz, 1H, CH); 13C NMR (CDCl3)
d 26.6, 35.3, 58.4,
86.0, 86.4, 122.1, 128.3, 128.7, 131.8, 144.3, 160.4, 208.7. Anal. Calcd
for C14H12O2: C, 79.22; H, 5.70. Found: C, 79.01; H, 5.58.
aromatic); 13C NMR (CDCl3)
d
26.4, 62.3, 86.7, 86.8, 122.2, 127.6,
128.3,128.6,131.7,146.6,199.8. Anal. Calcd for C13H12O2: C, 77.98; H,
6.04. Found: C, 77.73; H, 6.12.
4.2.14. 2-(1-Hydroxy-3-phenylprop-2-yn-1-yl)cyclohex-2-enone
(2n). A mixture of phenylpropargyl aldehyde 1a (1.30 g, 10 mmol),
cyclohex-2-enone (0.96 g, 10 mmol), and DMAP (0.24 g, 2 mmol) in
10 mL of aqueous tetrahydrofuran (1:1) was stirred at room tem-
perature for 1 h. The work-up procedure was the same as above to
produce 2n (0.90 g, 40%) as a yellow oil; IR (neat) 3414, 2232,
4.2.8. 6-(4-Chlorophenyl)-4-hydroxy-3-methylenehex-5-yn-2-one
(2h). Reaction time: 2 h; yield: 60%; yellow oil; IR (neat) 3414,
2232, 1674 cmꢂ1
; d 2.43 (s, 3H, CH3), 3.33
1H NMR (CDCl3)
(d, J¼6.3 Hz,1H, OH), 5.48 (d, J¼6.1 Hz,1H, CH), 6.25 (s,1H, CH), 6.41
(s, 1H, CH), 7.27–7.31 (m, 2H, aromatic), 7.36–7.39 (m, 2H, aro-
matic); 13C NMR (CDCl3)
d
26.3, 62.4, 85.6, 87.8, 120.7, 127.7, 128.6,
1669 cmꢂ1; 1H NMR (CDCl3)
d 2.01–2.10 (m, 2H, CH2), 2.46–2.54 (m,
133.0, 134.7, 146.4, 199.7. Anal. Calcd for C13H11ClO2: C, 66.53; H,
4.72. Found: C, 66.31; H, 4.52.
4H, two CH2), 3.50 (d, J¼4.9 Hz, 1H, OH), 5.49 (br s, 1H, CH), 7.31–
7.33 (m, 3H, aromatic), 7.37 (t, J¼4.1 Hz, 1H, CH), 7.46–7.49 (m, 2H,
aromatic); 13C NMR (CDCl3)
d 22.5, 25.7, 38.3, 61.9, 86.6, 87.0, 122.3,
4.2.9. 6-(4-Fluorophenyl)-4-hydroxy-3-methylenehex-5-yn-2-one
128.2, 128.6, 131.8, 137.7, 148.3, 199.9. Anal. Calcd for C15H14O2: C,
79.62; H, 6.24. Found: C, 79.43; H, 6.02.
(2i). Reaction time: 3 h; yield: 58%; yellow oil; IR (neat) 3408, 2238,
1673 cmꢂ1; 1H NMR (CDCl3)
d
2.43 (s, 3H, CH3), 3.33 (d, J¼6.1 Hz, 1H,
OH), 5.48 (d, J¼5.8 Hz,1H, CH), 6.25 (s,1H, CH), 6.42 (s,1H, CH), 6.98–
4.2.15. 2-(1-Hydroxyoct-2-yn-1-yl)cyclohex-2-enone (2o). A mix-
ture of 2-octynal 1f (1.24 g, 10 mmol), cyclohex-2-enone (0.96 g,
10 mmol), and DMAP (0.24 g, 2 mmol) in 10 mL of aqueous tetra-
hydrofuran (1:1) was stirred at room temperature for 1 h. The
work-up procedure was the same as above to produce 2o (0.66 g,
7.01 (m, 2H, aromatic), 7.41–7.46 (m, 2H, aromatic); 13C NMR (CDCl3)
d
26.3, 62.4, 85.7, 86.5, 115.6 (d, J¼22.0 Hz), 118.3, 127.6, 133.7
(d, J¼8.6 Hz), 146.5, 162.7 (d, J¼250.1 Hz), 199.7. Anal. Calcd for
C13H11FO2: C, 71.55; H, 5.08. Found: C, 71.76; H, 4.84.
30%) as a yellow oil; IR (neat) 3443, 2240, 1672 cmꢂ1
(DMSO-d6)
1.37–1.43 (m, 2H, CH2), 1.84–1.92 (m, 2H, CH2), 2.16 (td, J¼6.9 and
1.9 Hz, 2H, CH2), 2.32–2.42 (m, 4H, two CH2), 5.07 (d, J¼6.1 Hz, 1H,
OH), 5.45 (d, J¼6.1 Hz, 1H, CH), 7.18 (t, J¼4.1 Hz, 1H, CH); 13C NMR
;
1H NMR
4.2.10. 4-Hydroxy-6-(3-methoxyphenyl)-3-methylenehex-5-yn-2-
d
0.86 (t, J¼6.9 Hz, 3H, CH3), 1.26–1.30 (m, 4H, two CH2),
one (2j). Reaction time: 2 h; yield: 56%; yellow oil; IR (neat) 3426,
2225, 1674 cmꢂ1
;
1H NMR (CDCl3)
d
2.43 (s, 3H, CH3), 3.28
(d, J¼5.5 Hz, 1H, OH), 3.79 (s, 3H, CH3), 5.50 (d, 1H, J¼4.4 Hz, CH),

3494
S.P. Park et al. / Tetrahedron 66 (2010) 3490–3498
(DMSO-d6)
d
13.9, 18.0, 21.7, 22.4, 25.1, 27.9, 30.5, 37.9, 56.8, 81.2,
CH2),1.52–1.57 (m, 2H, CH2), 2.24 (dt, J¼7.4 and 2.2 Hz, 2H, CH2), 2.86
(s, 3H, CH3), 3.79 (s, 3H, CH3), 6.24 (s, 1H, CH), 6.29 (dt, J¼2.2 and
84.1, 139.4, 146.1, 196.7. Anal. Calcd for C14H20O2: C, 76.33; H, 9.15.
Found: C, 76.14; H, 9.02.
0.6 Hz, 1H, CH), 6.45 (s, 1H, CH); 13C NMR (CDCl3)
d 13.9, 18.7, 20.9,
22.1, 28.0, 31.0, 52.1, 74.9, 88.7, 128.8, 137.0, 165.1, 169.4. Anal. Calcd
for C14H20O4: C, 66.65; H, 7.99. Found: C, 66.43; H, 8.25.
4.3. General procedure for the synthesis of the Morita–
Baylis–Hillman acetates 3a–o
4.3.7. 4-Acetoxy-3-methylene-6-phenylhex-5-yn-2-one
To a stirred solution of the adduct 2 (10 mmol) in 20 mL of
dichloromethane added acetic anhydride (1.53 g, 15 mmol) and
DMAP (0.34 g, 3 mmol) at 0–5 ꢀC. After stirring at the same tem-
perature for 5 to 60 min the reaction mixture was diluted with water
(5 mL) and extracted with dichloromethane (3ꢁ20 mL). The com-
bined organic layers were dried over anhydrous magnesium sulfate
and the solvent was evaporated in vacuo. The mixture was chroma-
tographed on silica gel eluting with hexane and ethyl acetate (6:1) to
produce 3.
(3g). Reaction time: 10 min; yield: 80%; yellow oil; IR (neat) 2193,
1747, 1683 cmꢂ1 1H NMR (CDCl3)
; d 2.11 (s, 3H, CH3), 2.42 (s, 3H,
CH3), 6.35 (s, 1H, CH), 6.51 (s, 1H, CH), 6.58 (s, 1H, CH), 7.27–7.34
(m, 3H, aromatic), 7.36–7.50 (m, 2H, aromatic); 13C NMR (CDCl3)
d
20.9, 26.2, 61.4, 84.2, 87.1, 121.9, 128.2, 128.6, 128.8, 131.9, 144.5,
169.2, 196.3. Anal. Calcd for C15H14O3: C, 74.36; H, 5.82. Found: C,
74.19; H, 5.73.
4.3.8. 4-Acetoxy-6-(4-chlorophenyl)-3-methylenehex-5-yn-2-one
(3h). Reaction time: 10 min; yield: 79%; yellow solid; mp: 60–61 ꢀC
4.3.1. Methyl 3-acetoxy-2-methylene-5-phenylpent-4-ynoate
(hexane–EtOAc); IR (KBr) 2232, 1748, 1683 cmꢂ1 1H NMR (CDCl3)
;
(3a). Reaction time: 10 min; yield: 87%; yellow oil; IR (neat) 2232,
d
2.11 (s, 3H, CH3), 2.42 (s, 3H, CH3), 6.35 (s, 1H, CH), 6.47 (s, 1H, CH),
6.56 (s, 1H, CH), 7.28–7.30 (m, 2H, aromatic), 7.37–7.39 (m, 2H, ar-
omatic); 13C NMR (CDCl3)
20.8, 26.1, 61.3, 85.3, 85.8, 120.4, 128.5,
1748,1727 cmꢂ1; 1H NMR (CDCl3)
d
2.13 (s, 3H, CH3), 3.83 (s, 3H, CH3),
6.34 (s, 1H, CH), 6.53 (s, 1H, CH), 6.54 (s, 1H, CH), 7.29–7.39 (m, 3H,
aromatic), 7.45–7.48 (m, 2H, aromatic); 13C NMR (CDCl3)
20.9, 52.3,
d
d
128.6, 1331, 135.0, 144.4, 169.2, 196.2. Anal. Calcd for: C15H13ClO3: C,
65.11; H, 4.74. Found: C, 64.89; H, 4.61.
62.1, 83.7, 87.2, 121.8, 128.3, 128.9, 129.3, 131.9, 136.5, 164.9, 169.3.
Anal. Calcd for C15H14O4: C, 69.76; H, 5.46. Found: C, 69.56; H, 5.53.
4.3.9. 4-Acetoxy-6-(4-fluorophenyl)-3-methylenehex-5-yn-2-one
4.3.2. Methyl 3-acetoxy-5-(4-chlorophenyl)-2-methylenepent-
(3i). Reaction time: 5 min; yield: 82%; yellow oil; IR (neat) 2232,
4-ynoate (3b). Reaction time: 5 min; yield: 80%; yellow oil; IR
1747, 1678 cmꢂ1 1H NMR (CDCl3)
; d 2.11 (s, 3H, CH3), 2.42 (s, 3H,
(neat) 2234, 1749, 1731 cmꢂ1
;
1H NMR (CDCl3)
d
2.13 (s, 3H, CH3),
CH3), 6.35 (s, 1H, CH), 6.48 (s, 1H, CH), 6.56 (s, 1H, CH), 6.98–7.03
3.82 (s, 3H, CH3), 6.30 (s, 1H, CH), 6.51 (s, 1H, CH), 5.62 (s, 1H, CH),
(m, 2H, aromatic), 7.41–7.46 (m, 2H, aromatic); 13C NMR (CDCl3)
7.26–7.31 (m, 2H, aromatic), 7.37–7.41 (m, 2H, aromatic); 13C NMR
d
20.9, 26.1, 61.3, 84.0, 85.9, 115.6 (d, J¼22.2 Hz), 128.5, 133.9 (d,
(CDCl3)
d
20.8, 52.3, 62.0, 84.8, 86.0, 120.3, 128.7, 129.2, 133.2, 135.0,
J¼8.3 Hz), 144.4, 162.8, 162.8 (d, J¼250.4 Hz), 169.3, 196.3. Anal.
136.4, 164.8, 169.3. Anal. Calcd for C15H13ClO4: C, 61.55; H, 4.48.
Found: C, 61.36; H, 4.27.
Calcd for: C15H13FO3: C, 69.22; H, 5.03. Found: C, 68.97; H, 4.86.
4.3.10. 4-Acetoxy-6-(3-methoxyphenyl)-3-methylenhex-5-yn-2-one
4.3.3. Methyl 3-acetoxy-5-(4-fluorophenyl)-2-methylenepent-
(3j). Reaction time: 10 min; yield: 83%; yellow oil; IR (neat) 2235,
4-ynoate (3c). Reaction time: 5 min; yield: 79%; yellow oil; IR
1746, 1685 cmꢂ1 1H NMR (CDCl3)
; d 2.11 (s, 3H, CH3), 2.42 (s, 3H,
(neat) 2234, 1747, 1729 cmꢂ1
;
1H NMR (CDCl3)
d
2.13 (s, 3H, CH3),
CH3), 3.80 (s, 3H, CH3), 6.35 (s, 1H, CH), 6.51 (s, 1H, CH), 6.58 (s, 1H,
CH), 6.87–6.91 (m,1H, aromatic), 6.97–6.98 (m, 1H, aromatic), 7.04–
7.06 (m, 1H, aromatic), 7.19–7.26 (m, 1H, aromatic); 13C NMR
3.82 (s, 3H, CH3), 6.31 (s, 1H, CH), 6.51 (s, 1H, CH), 6.52 (s, 1H, CH),
6.97–7.05 (m, 2H, aromatic), 7.41–7.48 (m, 2H, aromatic); 13C NMR
(CDCl3)
d
20.9, 52.3, 62.1, 83.5, 86.1, 115.6 (d, J¼22.2 Hz), 118.0, 129.1,
(CDCl3) d 20.9, 26.2, 55.3, 61.4, 84.0, 87.0, 115.6, 116.6, 122.8, 124.4,
128.6, 129.3, 144.4, 159.2, 169.3, 196.3. Anal. Calcd for C16H16O4: C,
70.57; H, 5.92. Found: C, 70.42; H, 5.77.
133.9 (d, J¼8.6 Hz), 136.5, 162.9 (d, J¼250.1 Hz), 164.9, 169.3. Anal.
Calcd for C15H13FO4: C, 65.21; H, 4.74. Found: C, 64.92; H, 4.57.
4.3.4. Methyl 3-acetoxy-5-(3-methoxyphenyl)-2-methylenepent-4-
4.3.11. 4-Acetoxy-3-methylene-6-(thiophen-2-yl)hex-5-yn-2-one
ynoate (3d). Reaction time: 10 min; yield: 87%; yellow oil; IR (neat)
(3k). Reaction time: 10 min; yield: 81%; yellow oil; IR (neat) 2225,
2238,1748,1728 cmꢂ1; 1H NMR (CDCl3)
d
2.13 (s, 3H, CH3), 3.80 (s, 3H,
1747,1684 cmꢂ1; 1H NMR (CDCl3)
d 2.11 (s, 3H, CH3), 2.42 (s, 3H, CH3),
CH3), 3.82 (s, 3H, CH3), 6.33 (s, 1H, CH), 6.52 (s, 1H, CH), 6.53 (s, 1H,
CH), 6.88–6.92 (m, 1H, aromatic), 6.98–6.99 (m, 1H, aromatic), 7.04–
7.07 (m, 1H, aromatic), 7.19–7.26 (m, 1H, aromatic); 13C NMR (CDCl3)
6.36 (s, 1H, CH), 6.48 (s, 1H, CH), 6.59 (s, 1H, CH), 6.97 (dd, J¼5.2 and
3.6 Hz, 1H, aromatic), 7.26 (dd, J¼3.6 and 1.1 Hz, 1H, aromatic), 7.28
(dd, J¼5.2 and 1.1 Hz, 1H, aromatic); 13C NMR (CDCl3)
d 20.9, 26.1,
d
20.9, 52.3, 55.3, 62.1, 83.5, 87.1,115.6,116.7,122.8,124.5,129.2,129.4,
61.4, 80.4, 88.1, 121.7, 126.9, 127.9, 128.7, 133.1, 144.2, 169.2, 196.2.
Anal. Calcd for C13H12O3S: C, 62.88; H, 4.87. Found: C, 62.66; H, 4.59.
136.6, 159.3, 164.9, 169.3. Anal. Calcd for C16H16O5: C, 66.66; H, 5.59.
Found: C, 66.54; H, 5.31.
4.3.12. 4-Acetoxy-3-methyleneundec-5-yn-2-one
time: 10 min; yield: 80%; IR (neat) 2237, 1748, 1684 cmꢂ1
(CDCl3)
(3l). Reaction
4.3.5. Methyl 3-acetoxy-2-methylene-5-(thiophen-2-yl)pent-4-
;
1H NMR
ynoate (3e). Reaction time: 10 min; yield: 82%; yellow oil; IR (neat)
d
0.89 (t, J¼7.2 Hz,1H, CH3),1.30–1.39 (m, 4H, two CH2), 1.47–
2227, 1747, 1727 cmꢂ1
;
1H NMR (CDCl3)
d
2.13 (s, 3H, CH3), 3.82
1.54 (m, 2H, CH2), 2.05 (s, 3H, CH3), 2.23 (dt, J¼7.2 and 2.2 Hz, 2H,
(s, 3H, CH3), 6.30 (s, 1H, CH), 6.53 (s, 1H, CH), 6.54 (s, 1H, CH), 6.98
(dd, J¼5.2 and 3.6 Hz, 1H, aromatic), 7.26 (dd, J¼3.6 and 1.1 Hz, 1H,
aromatic), 7.29 (dd, J¼5.2 and 1.1 Hz, 1H, aromatic); 13C NMR
(CDCl3) 20.9, 52.3, 62.1, 80.5, 87.6, 121.6, 127.0, 128.0, 129.3, 133.2,
136.3, 164.8, 169.3. Anal. Calcd for C13H12O4S: C, 59.08; H, 4.58.
Found: C, 58.87; H, 4.39.
CH2), 2.38 (s, 3H, CH3), 6.27 (s, 1H, CH), 6.33 (dt, J¼2.2 and 1.1 Hz, 1H,
CH), 6.40 (d, J¼1.1 Hz, CH); 13C NMR (CDCl3)
d 13.9, 18.7, 20.9, 22.1,
26.2, 28.0, 31.0, 61.4, 75.3, 88.5, 128.1, 145.0, 169.3, 196.5. Anal. Calcd
for C14H20O3: C, 71.16; H, 8.53. Found: C, 69.94; H, 8.38.
4.3.13. 2-(1-Acetoxy-3-phenylprop-2-yn-1-yl)cyclopent-2-enone
(3m). Reaction time: 1 h; yield; 88%; yellow oil; IR (neat) 2231,
4.3.6. Methyl 3-acetoxy-2-methylenedec-4-ynoate (3f). Reaction
1745, 1707 cmꢂ1 1H NMR (CDCl3)
; d 2.13 (s, 3H, CH3), 2.51–2.54
time: 15 min; yield: 82%; yellow oil; IR (neat) 2237, 1747, 1731 cmꢂ1
;
(m, 2H, CH2), 2.69–2.72 (m, 2H, CH2), 6.38 (d, J¼1.3 Hz, 1H, CH),
1H NMR (CDCl3)
d
0.89 (t, J¼7.4 Hz, 1H, CH3), 1.26–1.37 (m, 4H, two
7.28–7.35 (m, 3H, aromatic), 7.45–7.49 (m, 2H, aromatic), 7.91

S.P. Park et al. / Tetrahedron 66 (2010) 3490–3498
3495
(td, J¼2.7 and 1.1 Hz, 1H, CH); 13C NMR (CDCl3)
d
20.9, 26.6, 35.1,
(s, 3H, CH3), 3.86 (s, 3H, CH3), 4.31 (s, 2H, CH2), 6.93–6.97 (m, 1H,
aromatic), 7.01–7.02 (m, 1H, aromatic), 7.08–7.12 (m, 1H, aromatic),
58.0, 83.9, 86.2, 121.8, 128.3, 128.9, 131.9, 142.0, 162.5, 169.5, 205.6.
Anal. Calcd for C16H14O3: C, 75.57; H, 5.55. Found: C, 75.35; H, 5.76.
7.10 (s, 1H, CH), 7.25–7.30 (m,1H, aromatic); 13C NMR (CDCl3)
d 48.2,
52.5, 55.3, 84.2, 104.1, 116.4, 116.6, 122.7, 124.5 (two), 129.6, 135.9,
159.4, 165.9; EIMS: m/z (%) 243 (63), 242 (100), 214 (23), 213 (35),
212 (22). Anal. Calcd for C14H13N3O3: C, 61.99; H, 4.83; N, 15.49.
Found: C, 62.21; H, 4.67; N, 15.24.
4.3.14. 2-(1-Acetoxy-3-phenylprop-2-yn-1-yl)cyclohex-2-enone
(3n). Reaction time: 1 h; yield: 80%; yellow solid; mp: 69–70 ꢀC
(hexane–EtOAc); IR (KBr) 2230, 1748, 1679 cmꢂ1 1H NMR (CDCl3)
;
d
2.02–2.06 (m, 2H, CH2), 2.09 (s, 3H, CH3), 2.48–2.53 (m, 4H, two
CH2), 6.56 (d, J¼0.8 Hz, 1H, CH), 7.29–7.34 (m, 3H, aromatic), 7.45–
4.4.5. (E)-Methyl 2-(azidomethyl)-5-(thiophen-2-yl)pent-2-en-4-
7.48 (m, 2H, aromatic), 7.50 (t, J¼4.1 Hz, 1H, CH); 13C NMR (CDCl3)
ynoate (4e). Yield: 75%; yellow solid; mp: 35–36 (hexane–
d
20.9, 22.4, 26.0, 38.1, 60.6, 84.3, 87.1, 122.0, 128.2, 128.8, 131.9,
EtOAc); IR (KBr) 2181, 2092, 1717 cmꢂ1 1H NMR (CDCl3)
; d 3.85
135.4, 150.0, 169.4, 196.2. Anal. Calcd for C17H16O3: C, 76.10; H, 6.01.
Found: C, 75.85; H, 6.29.
(s, 3H, CH3), 4.28 (s, 2H, CH2), 7.05 (dd, J¼4.9 and 3.1 Hz, 1H,
aromatic), 7.11 (s, 1H, CH), 7.35 (d, J¼3.1 Hz, 1H, aromatic), 7.42
(d, J¼4.9 Hz, 1H, aromatic); 13C NMR (CDCl3)
d 48.3, 52.5, 88.8,
4.3.15. 2-(1-Acetoxyoct-2-yn-1-yl)cyclohex-2-enone (3o). Reaction
97.5, 121.6, 124.1, 127.6, 129.8, 134.1, 135.2, 165.9; EIMS: m/z (%)
221 (100), 206 (14), 190 (22), 162 (88). Anal. Calcd for
C11H9N3O2S: C, 53.43; H, 3.67; N, 16.99. Found: C, 53.29; H, 3.45;
N, 17.15.
time: 15 min; yield: 82%; yellow oil; IR (neat) 2238,1745,1681 cmꢂ1
;
1H NMR (CDCl3)
d
0.89 (t, J¼7.2 Hz, 3H, CH3), 1.28–1.37 (m, 4H, two
CH2),1.48–1.55 (m, 2H, CH2), 2.02–2.09 (m, 2H, CH2), 2.05 (s, 3H, CH3),
2.23 (td, J¼7.2 and 1.9 Hz, 2H, CH2), 2.45–2.50 (m, 4H, two CH2), 6.31
(d, J¼0.8 Hz, 1H, CH), 7.40 (t, J¼4.1 Hz, 1H, CH); 13C NMR (CDCl3)
4.4.6. (E)-Methyl 2-(azidomethyl)dec-2-en-4-ynoate (4f). Yield:
d
13.9,18.7, 21.0, 22.1, 22.5, 25.9, 28.1, 31.0, 38.1, 60.6, 75.3, 88.5,135.8,
87%; yellow oil; IR (neat) 2213, 2097, 1720 cmꢂ1; 1H NMR (CDCl3)
149.6,169.5, 196.3. Anal. Calcd for C16H22O3: C, 73.25; H, 8.45. Found:
C, 72.98; H, 8.32.
d
0.92 (t, J¼7.2 Hz, CH3), 1.33–1.44 (m, 4H, two CH2), 1.57–1.64
(m, 2H, CH2), 2.44 (dt, J¼7.2 and 2.2 Hz, CH2), 3.82 (s, 3H, CH3),
4.20 (s, 2H, CH2), 6.89 (t, 1H, J¼2.2 Hz, CH); 13C NMR (CDCl3)
4.4. General procedure for the synthesis of azido enynes 4a–o
d 13.9, 20.0, 22.1, 27.9, 31.0, 47.9, 52.3, 76.3, 107.3, 125.8, 135.1,
166.2; EIMS: m/z (%) 235 (1) [Mþ], 207 (42), 176 (15), 164 (100),
132 (49). Anal. Calcd for C12H17N3O2: C, 61.26; H, 7.28; N, 17.86.
Found: C, 61.20; H, 7.10; N, 17.91.
To a stirred solution of the acetate 3 (4 mmol) in 10 mL of aqueous
methanol (MeOH/water: 9/1) was added sodium azide (0.39 g,
6 mmol) at room temperature. After stirring at the same temperature
for 1 h the reaction mixture was diluted with water (10 mL) and
extracted with dichloromethane (3ꢁ20 mL). The combined organic
layers were dried over anhydrous magnesium sulfate and the solvent
was evaporated invacuo. The mixturewas chromatographed on silica
gel eluting with hexane and ethyl acetate (6:1) to produce 4.
4.4.7. (E)-3-(Azidomethyl)-6-phenylhex-3-en-5-yn-2-one
(4g). Yield: 91%; yellow solid; mp: 32–34 ꢀC (hexane–EtOAc); IR
(KBr) 2193, 2099, 1668 cmꢂ1
;
1H NMR (CDCl3)
d
2.43 (s, 3H, CH3),
4.29 (s, 2H, CH2), 6.97 (s, 1H, CH), 7.36–7.43 (m, 3H, aromatic), 7.50–
7.53 (m, 2H, aromatic); 13C NMR (CDCl3)
25.5, 46.9, 84.6, 106.0,
d
121.7, 124.5, 128.6, 129.9, 132.0, 143.7, 196.9; EIMS: m/z (%) 197 (64),
182 (100), 154 (38), 127 (55). Anal. Calcd for C13H11N3O: C, 69.32; H,
4.92; N, 18.66. Found: C, 69.10; H, 4.70; N, 18.43.
4.4.1. (E)-Methyl 2-(azidomethyl)-5-phenylpent-2-en-4-ynoate
(4a). Yield: 91%; yellow solid; mp: 31–33 ꢀC (hexane–EtOAc); IR
(KBr) 2196, 2097, 1716 cmꢂ1
;
1H NMR (CDCl3)
d
3.86 (s, 3H, CH3),
4.31 (s, 2H, CH2), 7.11 (s, 1H, CH), 7.34–7.41 (m, 3H, aromatic), 7.48–
7.52 (m, 2H, aromatic); 13C NMR (CDCl3)
48.1, 52.5, 84.5, 104.2,
4.4.8. (E)-3-(Azidomethyl)-6-(4-chlorophenyl)hex-3-en-5-yn-2-one
d
(4h). Yield: 74%; white solid; mp: 64–65 ꢀC (hexane–EtOAc); IR
121.8, 124.6, 128.5, 129.7, 132.0, 135.8, 165.9; EIMS: m/z (%) 213 (97),
182 (100),154 (36),127 (61). Anal. Calcd for C13H11N3O2: C, 64.72; H,
4.60; N, 17.42. Found: C, 64.60; H, 4.39; N, 17.21.
(KBr) 2193, 2095, 1661 cmꢂ1
;
1H NMR (CDCl3)
d
2.43 (s, 3H, CH3),
4.27 (s, 2H, CH2), 6.94 (s, 1H, CH), 7.35–7.38 (m, 2H, aromatic), 7.42–
7.46 (m, 2H, aromatic); 13C NMR (CDCl3)
25.5, 47.0, 85.4, 104.5,
d
120.2, 124.0, 129.0, 133.2, 136.1, 144.1, 196.8; EIMS: m/z (%) 233 (20),
231 (61), 218 (32), 216 (100), 190 (9), 188 (26), 163 (11), 161 (57), 126
(20). Anal. Calcd for C13H10ClN3O: C, 60.12; H, 3.88; N, 16.18. Found:
C, 60.31; H, 3.72; N, 16.04.
4.4.2. (E)-Methyl 2-(azidomethyl)-5-(4-chlorophenyl)pent-2-en-4-
ynoate (4b). Yield: 91%; white solid; mp: 55–57 ꢀC (hexane–EtOAc);
IR (KBr) 2197, 2125,1720 cmꢂ1;1H NMR(CDCl3)
d
3.86 (s, 3H, CH3), 4.30
(s, 2H, CH2), 7.09 (s, 1H, CH), 7.33–7.37 (m, 2H, aromatic), 7.41–7.45 (m,
2H, aromatic); 13C NMR (CDCl3)
48.2, 52.6, 85.3, 102.7, 120.3, 124.2,
d
4.4.9. (E)-3-(Azidomethyl)-6-(4-fluorophenyl)hex-3-en-5-yn-2-one
129.0, 133.2, 136.0, 136.2, 165.8; EIMS: m/z (%) 249 (34), 247 (100), 218
(31), 216 (92),161 (34),153 (14). Anal. Calcd for C13H10ClN3O2: C, 56.64;
H, 3.66; N, 15.24. Found: C, 56.42; H, 3.46; N, 15.04.
(4i). Yield: 89%; white solid; mp: 40–42 ꢀC (hexane–EtOAc); IR
(KBr) 2196, 2095, 1669 cmꢂ1
;
1H NMR (CDCl3)
d
2.43 (s, 3H, CH3),
4.28 (s, 2H, CH2), 6.95 (s, 1H, CH), 7.05–7.12 (m, 2H, aromatic), 7.48–
7.54 (m, 2H, aromatic); 13C NMR (CDCl3)
25.5, 47.0, 84.4, 104.9,
d
4.4.3. (E)-Methyl 2-(azidomethyl)-5-(4-fluorophenyl)pent-2-en-4-
116.1 (d, J¼22.2 Hz), 117.9, 124.3, 134.1 (d, J¼8.8 Hz), 143.8, 163.4 (d,
J¼252.7 Hz), 196.8; EIMS: m/z (%) 215 (20), 200 (100), 172 (39), 145
(62), 125 (17). Anal. Calcd for C13H10FN3O: C, 64.19; H, 4.14; N, 17.28.
Found: C, 63.92; H, 3.97; N, 17.13.
ynoate (4c). Yield: 79%; white solid; mp: 42–44 ꢀC (hexane–
EtOAc); IR (KBr) 2197, 2099, 1716 cmꢂ1
;
1H NMR (CDCl3)
d
3.86
(s, 3H, CH3), 4.29 (s, 2H, CH2), 7.04–7.10 (m, 2H,aromatic), 7.09
(s, 1H, CH), 7.47–7.52 (m, 2H, aromatic); 13C NMR (CDCl3)
48.1,
d
52.5, 84.3, 103.0, 116.0 (d, J¼22.2 Hz), 118.0, 124.4, 134.1
(d, J¼8.6 Hz), 135.9, 163.3 (d, J¼252.1 Hz), 165.9; EIMS: m/z (%) 231
(94), 200 (100), 172 (32), 145 (57). Anal. Calcd for C13H10FN3O2: C,
60.23; H, 3.89; N, 16.21. Found: C, 60.08; H, 3.91; N, 16.04.
4.4.10. (E)-3-(Azidomethyl)-6-(3-methoxyphenyl)hex-3-en-5-yn-2-
one (4j). Yield: 68%; white solid; mp: 46–48 ꢀC (hexane–EtOAc); IR
(KBr) 2193, 2095, 1668 cmꢂ1 1H NMR (CDCl3)
; d 2.42 (s, 3H, CH3),
3.83 (s, 3H, CH3), 4.29 (s, 2H, CH2), 6.96 (s, 1H, CH), 6.98–7.03
(m, 2H, aromatic), 7.10–7.12 (m, 1H, aromatic), 7.26–7.32 (m, 1H,
4.4.4. (E)-Methyl 2-(azidomethyl)-5-(3-methoxyphenyl)pent-2-
aromatic); 13C NMR (CDCl3)
d 25.5, 47.0, 55.3, 84.3, 105.9, 116.4,
en-4-ynoate (4d). Yield: 95%; white solid; mp: 50–52 ꢀC (hexane–
116.6, 122.6, 124.4, 124.5, 129.7, 143.8, 159.4, 196.9; EIMS: m/z (%)
227 (90), 226 (100), 212 (30), 198 (22), 197 (34), 184 (20), 157 (25).
EtOAc); IR (KBr) 2196, 2098, 1716 cmꢂ1
;
1H NMR (CDCl3)
d
3.82

3496
S.P. Park et al. / Tetrahedron 66 (2010) 3490–3498
Anal. Calcd for: C14H13N3O2: C, 65.87; H, 5.13; N, 16.46. Found: C,
65.68; H, 4.82; N, 16.37.
1H, CH), 7.88–7.91 (m, 2H, aromatic); 13C NMR (CDCl3)
d 52.1, 52.5,
125.9, 127.4, 128.6, 129.1, 130.1, 137.7, 139.4, 139.9, 162.2; EIMS: m/z (%)
215 (100), 200 (13), 184 (52), 156 (83), 138 (29), 106 (33); HRMS
(FABþ): m/z C13H11N3O2Na [MþNa]þ calcd 264.0750, obsd 264.0747.
Anal. Calcd for C13H11N3O2: C, 64.72; H, 4.60; N,17.42. Found: C, 64.57;
H, 4.50; N, 17.28.
4.4.11. (E)-3-(Azidomethyl)-6-(thiophen-2-yl)hex-3-en-5-yn-2-one
(4k). Yield: 69%; yellow oil; IR (neat) 2181, 2094,1668 cmꢂ1; 1H NMR
(CDCl3) d 2.42 (s, 3H, CH3), 4.27 (s, 2H, CH2), 6.97 (s, 1H, CH), 7.07 (dd,
J¼5.2 and 3.9 Hz, 1H, aromatic), 7.37 (dd, J¼3.9 and 1.1 Hz, 1H, aro-
matic), 7.44 (dd, J¼5.2 and 1.1 Hz, 1H, aromatic); 13C NMR (CDCl3)
4.5.2. Methyl 3-(4-chlorophenyl)-6H-pyrrolo[1,2-c][1,2,3]triazole-
d
25.5, 47.1, 88.9, 99.4, 121.5, 124.0, 127.7, 130.1, 134.2, 143.1, 196.8;
5-carboxylate (5b). Yield: 91%; white solid; mp: 190–192 ꢀC (hex-
EIMS: m/z (%) 205 (98), 190 (59), 162 (41), 106 (100). Anal. Calcd for
ane–EtOAc); IR (KBr) 1720 cmꢂ1; 1H NMR (CDCl3)
d 3.91 (s, 3H, CH3),
C11H9N3OS: C, 57.13; H, 3.92; N,18.17. Found: C, 57.01;H, 4.06;N,17.89.
5.16 (d, J¼2.2 Hz, 2H, CH2), 7.41–7.46 (m, 2H, aromatic), 7.69 (t,
J¼2.2 Hz,1H, CH), 7.79–7.83 (m, 2H, aromatic); 13C NMR (CDCl3)
d 52.2,
4.4.12. (E)-3-(Azidomethyl)undec-3-en-5-yn-2-one (4l). Yield: 84%;
52.5,126.8,127.0,127.1,128.7,129.3,134.4,138.1,139.4,162.1; EIMS: m/
z (%) 251 (33), 249 (100), 220 (21), 218 (66),192 (25),190 (78),154 (28),
138 (36),106 (56); HRMS (FABþ): m/z C13H10ClN3O2Na [MþNa]þ calcd
298.0361, obsd 298.0360. Anal. Calcd for C13H10ClN3O2: C, 56.64; H,
3.66; N, 15.24. Found: C, 56.49; H, 3.78; N, 15.03.
yellow oil; IR (neat) 2211, 2095, 1671 cmꢂ1 1H NMR (CDCl3)
; d 0.92
(t, J¼7.2 Hz, 3H, CH3), 1.31–1.46 (m, 4H, two CH2), 1.56–1.65 (m, 2H,
CH2), 2.37 (s, 3H, CH3), 2.47 (dt, J¼7.2 and 2.2 Hz, 2H, CH2), 4.18 (s, 2H,
CH2), 6.75 (t, J¼2.2 Hz,1H, CH); 13C NMR (CDCl3)
d 13.9, 20.1, 22.1, 25.4,
27.9, 31.0, 46.7, 76.5, 109.3, 125.7, 143.4, 197.1; EIMS: m/z (%) 219 (1)
[Mþ],191 (71),176 (31),148 (87),106 (100). Anal. Calcd for C12H17N3O:
C, 65.73; H, 7.81; N, 19.16. Found: C, 65.59; H, 7.65; N, 19.01.
4.5.3. Methyl 3-(4-fluorophenyl)-6H-pyrrolo[1,2-c][1,2,3]triazole-5-
carboxylate (5c). Yield: 88%; white solid; mp: 196–197 ꢀC (hexane–
EtOAc); IR (KBr) 1722 cmꢂ1; 1H NMR (CDCl3)
d
3.91 (s, 3H, CH3), 5.16
(d, J¼1.9 Hz, 2H, CH2), 7.13–7.20 (m, 2H, aromatic), 7.69 (t, J¼1.9 Hz,
1H, CH), 7.85–7.89 (m, 2H, aromatic); 13C NMR (CDCl3)
52.1, 52.5,
4.4.13. (E)-3-Azido-2-(3-phenylprop-2-ynylidene)cyclopentanone
(4m). Yield: 90%; yellow oil; IR (neat) 2189, 2100, 1716, 1613 cmꢂ1
;
d
1H NMR (CDCl3)
d
2.08–2.17 (m, 2H, CH2), 2.34–2.44 (m, 1H, CH2),
116.1 (d, J¼21.7 Hz), 126.4, 127.1, 127.6 (d, J¼8.3 Hz),137.9,138.9,139.1,
162.1, 162.8 (d, J¼248.7 Hz); EIMS: m/z (%) 233 (100), 218 (13), 202
(53), 174 (76), 138 (24), 106 (42); HRMS (FABþ): m/z C13H10FN3O2Na
[MþNa]þ calcd 282.0656, obsd 282.0656. Calcd for: C13H10FN3O2: C,
60.23; H, 3.89; N, 16.21. Found: C, 60.02; H, 3.69; N, 16.03.
2.52–2.65 (m, 1H, CH2), 5.04–5.07 (m, 1H, CH), 6.89 (d, J¼1.7 Hz, 1H,
CH), 7.35–7.42 (m, 3H, aromatic), 7.53–7.56 (m, 2H, aromatic); 13C
NMR (CDCl3)
d 27.1, 35.7, 60.4, 86.0, 104.0, 117.8, 121.8, 128.6, 129.9,
132.3, 144.3, 202.8; EIMS: m/z (%) 209 (100), 181 (59), 180 (75), 155
(23). Anal. Calcd for C14H11N3O: C, 70.87; H, 4.67; N, 17.71. Found: C,
70.93; H, 4.86; N, 17.52.
4.5.4. Methyl 3-(3-methoxyphenyl)-6H-pyrrolo[1,2-c][1,2,3]triazole-
5-carboxylate (5d). Yield: 91%; white solid; mp: 150–152 ꢀC
4.4.14. (E)-3-Azido-2-(3-phenylprop-2-ynylidene)cyclohexanone
(hexane–EtOAc); IR (KBr) 1700 cmꢂ1; 1H NMR (CDCl3)
d 3.89 (s, 3H,
(4n). Yield: 83%; yellow oil; IR (neat) 2193, 2095, 1683 cmꢂ1
;
1H
CH3), 3.91 (s, 3H, CH3), 5.15 (d, J¼2.2 Hz, 2H, CH2), 6.90–6.94 (m, 1H,
NMR (CDCl3)
d
1.84–1.90 (m, 2H, CH2), 2.04–2.09 (m, 2H, CH2),
aromatic), 7.34–7.41 (m, 2H, aromatic), 7.49–7.50 (m, 1H, aromatic),
2.27–2.39 (m, 1H, CH2), 2.61–2.70 (m, 1H, CH2), 5.24–5.28 (m, 1H,
CH), 6.98 (s, 1H, CH), 7.35–7.41 (m, 3H, aromatic), 7.51–7.54 (m, 2H,
7.71 (t, J¼2.2 Hz, 1H, CH); 13C NMR (CDCl3)
d 52.1, 52.4, 55.4, 111.0,
114.7, 118.3, 127.3, 130.1, 131.5, 137.8, 139.5, 139.7, 160.2, 162.2; EIMS:
m/z (%) 245 (100), 230 (13), 214 (50), 186 (77), 138 (37), 106 (29);
HRMS (FABþ): m/z C14H13N3O3Na [MþNa]þ calcd 294.0856, obsd
294.0854. Anal. Calcd for C14H13N3O3: C, 61.99; H, 4.83; N, 15.49.
Found: C, 61.72; H, 4.76; N, 15.34.
aromatic); 13C NMR (CDCl3)
d 18.1, 28.9, 39.3, 58.7, 85.3, 104.6, 121.4,
121.9, 128.5, 129.7, 132.0, 142.0, 197.5; EIMS: m/z (%) 223 (90), 195
(100), 194 (27), 167 (38), 139 (10). Anal. Calcd for C15H13N3O: C,
71.70; H, 5.21; N, 16.72. Found: C, 71.57; H, 5.19; N, 16.48.
4.4.15. (E)-3-azido-2-(oct-2-ynylidene)cyclohexanone (4o). Yield:
4.5.5. Methyl 3-(thiophen-2-yl)-6H-pyrrolo[1,2-c][1,2,3]triazole-5-
90%; yellow oil; IR (neat) 2207, 2096, 1687 cmꢂ1
;
1H NMR (CDCl3)
carboxylate (5e). Yield: 86%; white solid; mp: 195–197 ꢀC (hexane–
d
0.92 (t, J¼7.2 Hz, 3H, CH3),1.33–1.43 (m, 4H, two CH2),1.55–1.62 (m,
EtOAc); IR (KBr) 1700 cmꢂ1; 1H NMR (CDCl3)
d 3.91 (s, 3H, CH3), 5.16
2H, CH2), 1.73–1.90 (m, 2H, CH2), 1.96–2.11 (m, 2H, CH2), 2.22–2.35
(m, 1H, CH2), 2.45 (td, J¼7.2 and 2.2 Hz, 2H, CH2), 2.57–2.66 (m, 1H,
CH2), 5.13–5.17 (m, 1H, CH), 6.76 (t, J¼2.2 Hz, 1H, CH); 13C NMR
(d, J¼1.9 Hz, 2H, CH2), 7.13 (dd, J¼5.2 and 3.0 Hz, 1H, aromatic), 7.38
(d, J¼5.2 Hz, 1H, aromatic), 7.46 (d, J¼3.0 Hz, 1H, aromatic), 7.67
(t, J¼1,9 Hz, 1H, CH); 13C NMR (CDCl3)
d 52.3, 52.5, 124.4, 124.7, 125.9,
(CDCl3)22
d
13.9,18.1, 20.1, 22.1, 27.9, 28.8, 31.0, 39.3, 58.5,107.9,122.7,
126.7,127.9,132.4,137.5,138.6,162.1;EIMS:m/z(%)221(100), 206(15),
190(23),162(88),138(10),106(42);HRMS(FABþ):m/zC11H9N3O2SNa
[MþNa]þ calcd 270.0315, obsd 270.0316. Anal. Calcd for C11H9N3O2S:
C, 53.43; H, 3.67; N, 16.99. Found: C, 53.21; H, 3.54; N, 17.24.
141.4, 197.8; 13C NMR (DMSO-d6)
d 13.9, 17.9, 19.3, 21.6, 27.4, 28.1,
30.5, 58.8, 77.0, 107.4, 121.2, 142.1, 197.4; EIMS: m/z (%) 217 (73), 174
(100), 161 (22),146 (22), 132 (11),118 (19). Anal. Calcd for C14H19N3O:
C, 68.54; H, 7.81; N, 17.13. Found: C, 68.26; H, 7.69; N, 17.01.
4.5.6. Methyl 3-pentyl-6H-pyrrolo[1,2-c][1,2,3]triazole-5-carboxylate
4.5. General procedure for the synthesis of 3,5-disubstituted
6H-pyrrolo[1,2-c][1,2,3]triazoles 5a–k and 7,8-dihydro-4H-
[1,2,3]triazolo[1,5-a]indol-5(6H)-ones 5n, 5o
(5f). Yield: 43%; white solid; mp: 70–72 ꢀC (hexane–EtOAc); IR
(KBr) 1722 cmꢂ1; 1H NMR (CDCl3)
d
0.91 (t, J¼7.2 Hz, 3H, CH3), 1.33–
1.39 (m, 4H, two CH2), 1.68–1.76 (m, 2H, CH2), 2.79 (t, J¼7.2 Hz, 2H,
CH2), 3.88 (s, 3H, CH3), 5.06 (d, J¼2.2 Hz, 2H, CH2), 7.46 (t, J¼2.2 Hz,
A stirred solution of the azido enyne 4 (2 mmol) in 6 mL of tol-
uene was heated at reflux temperature for 1 h and the solvent was
evaporated in vacuo. The mixture was chromatographed on silica gel
eluting with hexane and ethyl acetate (3:1) to produce 5 as a solid.
1H, CH); 13C NMR (CDCl3)
d 13.9, 22.4, 25.7, 28.8, 31.4, 51.9, 52.3,
127.2, 136.2, 140.1, 141.2, 162.5; EIMS: m/z (%) 207 (43), 176 (15), 164
(100), 138 (9), 132 (48); HRMS (FABþ): m/z C12H17N3O2Na [MþNa]þ
calcd 258.1220, obsd 258.1218. Anal. Calcd for C12H17N3O2: C, 61.26;
H, 7.28; N, 17.86. Found: C, 61.07; H, 7.04; N, 17.68.
4.5.1. Methyl 3-phenyl-6H-pyrrolo[1,2-c][1,2,3]triazole-5-carboxy-
late (5a). Yield: 81%; white solid; mp: 154–156 ꢀC (hexane–EtOAc);
4.5.7. 5-Acetyl-3-phenyl-6H-pyrrolo[1,2-c][1,2,3]triazole (5g). Yield:
IR (KBr) 1713 cmꢂ1
;
1H NMR (CDCl3)
d
3.92 (s, 3H, CH3), 5.17
62%; white solid; mp: 152–154 ꢀC (hexane–EtOAc); IR (KBr)
(d, J¼2.2 Hz, 2H, CH2), 7.36–7.50 (m, 3H, aromatic), 7.74 (t, J¼2.2 Hz,
1665 cmꢂ1; 1H NMR (CDCl3)
d
2.54 (s, 3H, CH3), 5.14 (d, J¼1.9 Hz, 2H,

S.P. Park et al. / Tetrahedron 66 (2010) 3490–3498
3497
CH2), 7.37–7.51 (m, 3H, aromatic), 7.57 (t, J¼1.9 Hz, 1H, CH), 7.87–
7.90 (m, 2H, aromatic); 13C NMR (CDCl3)
26.1, 51.9, 125.9, 126.3,
128.7, 129.1, 130.1, 139.5, 140.8, 146.5, 192.9; EIMS: m/z (%) 199 (75),
184 (100), 156 (16), 106 (54); HRMS (FABþ): m/z C13H11N3ONa
[MþNa]þ calcd 248.0801, obsd 248.0800. Anal. Calcd for C13H11N3O:
C, 69.32; H, 4.92; N, 18.66. Found: C, 69.13; H, 5.04; N, 18.49.
CH3), 1.32–1.37 (m, 4H, two CH2), 1.67–1.77 (m, 2H, CH2), 2.29–2.37
(m, 2H, CH2), 2.58–2.63 (m, 2H, CH2), 2.80 (t, J¼7.7 Hz, 2H, CH2),
3.12–3.18 (m, 2H, CH2), 3.57 (dd, J¼2.7 and 2.5 Hz, 2H, CH2); 13C
d
NMR (CDCl3) d 14.0, 21.2, 22.2, 22.4, 24.4, 25.3, 28.1, 31.4, 37.3, 129.0,
136.6, 141.9, 152.9, 195.2; EIMS: m/z (%) 245 (2) [Mþ], 217 (56), 174
(100), 146 (21), 132 (11), 118 (16); HRMS (FABþ): m/z C14H19N3ONa
[MþNa]þ calcd 268.1428, obsd 268.1425. Anal. Calcd for C14H19N3O:
C, 68.54; H, 7.81; N, 17.13. Found: C, 68.25; H, 7.92; N, 16.95.
4.5.8. 5-Acetyl-3-(4-chlorophenyl)-6H-pyrrolo[1,2-c][1,2,3]triazole
(5h). Yield: 81%; white solid; mp: 195–196 ꢀC; IR (KBr) 1661 cmꢂ1; 1H
NMR (CDCl3)
(m, 2H, aromatic), 7.56 (t, J¼1.9 Hz, 1H, CH), 7.81–7.85 (m, 2H, aro-
matic); 13C NMR (CDCl3)
26.2, 52.0, 125.9, 127.1, 128.7, 129.3, 134.6,
139.6,139.8,146.8,192.8; EIMS: m/z(%) 235 (21), 233 (64), 220 (51), 218
(100), 192 (4), 190 (12), 106 (68); HRMS (FABþ): m/z C13H10ClN3ONa
[MþNa]þ calcd 282.0412, obsd 282.0411. Anal. Calcd for C13H10ClN3O:
C, 60.12; H, 3.88; N, 16.18. Found: C, 59.92; H, 3.69; N, 15.89.
d
2.55 (s, 3H, CH3), 5.17 (d, J¼1.9 Hz, 2H, CH2), 7.44–7.48
Acknowledgements
d
This work was supported in part by Brain Korea 21 program,
Republic of Korea.
References and notes
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Dekker: New York, NY, 1969; pp 425–593; (b) Bastide, J.; Henri-Rousseau, O. In
The Chemistry of the Carbon-Carbon Triple Bond; Patai, S., Ed.; Interscience:
London, 1978; pp 447–522; (c) Padwa, A. In 1,3-Dipolar Cycloaddition Chemistry;
Taylor, E. C., Weissberger, A., Eds.; John Wiley: New York, NY, 1984; Vol. 2,
pp 277–386; (d) Fan, W.-Q.; Katritzky, A. R. In Comprehensive Heterocyclic
Chemistry II; Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds.; Elsevier Science:
Oxford, 1996; Vol. 4, pp 1–126; (e) Padwa, A. Angew. Chem., Int. Ed. Engl. 1976,
15, 123–136; (f) Oppolzer, W. Angew. Chem., Int. Ed. 1977, 16, 10–23; (g) Seebach,
D.; Enders, D.; Dach, R.; Pieter, R. Chem. Ber. 1977, 110, 1879–1886; (h) Pearson,
W. H.; Bergmeier, S. C.; Degan, S.; Lin, K.-C.; Poon, Y.-F.; Schkeryantz, J. M.;
Williams, J. P. J. Org. Chem. 1990, 55, 5719–5738; (i) Tezuka, K.; Compain, P.;
Martin, O. R. Synlett 2000, 1837–1839.
6. (a) Huisgen, R.; Mo¨bius, L.; Szeimies, G. Chem. Ber. 1965, 98, 1138–1152;
(b) Jones, H.; Fordice, M. W.; Greenwald, R. B.; Hannah, J.; Jacobs, A.;
Ruyle, W. V.; Walford, G. L.; Shen, T. Y. J. Med. Chem. 1978, 21, 1100–1104.
7. (a) Bastide, J.; Hamelin, J.; Txier, F.; VoQuang, Y. Bull. Soc. Chim. Fr. 1973, 2555–
2579; (b) Fusco, R.; Garanti, L.; Zecchi, G. J. Org. Chem. 1975, 40, 1906–1909;
(c) Tsuge, O.; Ueno, K.; Inabe, A. Heterocycles 1976, 4, 1–7.
8. Garanti, L.; Locatelli, A.; Zecchi, G. J. Heterocycl. Chem. 1976, 13, 657–679.
9. Bertrand, M.; Dulcere, J.-P.; Santelli, M. Tetrahedron Lett. 1977, 18,
1783–1784.
10. Dulcere, J.-P.; Tawil, M.; Santelli, M. J. Org. Chem. 1990, 55, 571–575.
11. (a) Heilbron, I. M.; Jones, E. R. H.; Lacey, R. N.; MeCombie, J. T.; Raphael, R.
J. Chem. Soc. 1945, 77–81; (b) Santelli, M,; Bertrand, M. Bull. Soc. Chim. Fr.
1973, 2331–2335.
12. For reviews of the Morita–Baylis-Hillman reaction, see: (a) Ciganek, E. In Or-
ganic Reactions; Paquette, L. A., Ed.; John Wiley: New York, NY, 1997; Vol. 51,
pp 201–350; (b) Drewes, S. E.; Roos, G. H. P. Tetrahedron 1988, 44, 4653–4670;
(c) Basavaiah, D.; Rao, P. D.; Hyma, R. S. Tetrahedron 1996, 52, 8001–8062; (d)
Langer, P. Angew. Chem., Int. Ed. 2000, 39, 3049–3052; (e) Masson, G.; Hous-
seman, C.; Zhu, J. Angew. Chem., Int. Ed. 2007, 46, 4614–4628; (f) Basavaiah, D.;
Rao, A. J.; Satyanarayana, T. Chem. Rev. 2003, 103, 811–891; (g) Basavaiah, D.;
Rao, K. V.; Reddy, R. J. Chem. Soc. Rev. 2007, 36, 1581–1588; (h) Shi, Y.-L.; Shi, M.
Eur. J. Org. Chem. 2007, 2905–2916; (i) Declerck, V.; Martinez, J.; Lamaty, F.
Chem. Rev. 2009, 109, 1–48; (j) Ma, G.-N.; Jiang, J.-J.; Wei, Y. Chem. Commun.
2009, 5496–5514.
4.5.9. 5-Acetyl-3-(4-fluorophenyl)-6H-pyrrolo[1,2-c][1,2,3]triazole
(5i). Yield: 75%; white solid; mp: 154–156 ꢀC; (hexane–EtOAc); IR
(KBr) 1665 cmꢂ1
;
1H NMR (CDCl3)
d
2.54 (s, 3H, CH3), 5.16
(d, J¼1.9 Hz, 2H, CH2), 7.15–7.21 (m, 2H, aromatic), 7.55 (t, J¼1.9 Hz,
1H, CH), 7.85–7.89 (m, 2H, aromatic); 13C NMR (CDCl3)
26.1, 52.0,
d
116.2 (d, J¼22.0 Hz), 126.0, 126.5, 127.7 (d, J¼8.6 Hz), 139.3, 140.0,
146.6, 162.9 (d, J¼249.0 Hz), 192.8; EIMS: m/z (%) 217 (73), 202
(100), 174 (17), 146 (9), 106 (77); HRMS (FABþ): m/z C13H10FN3ONa
[MþNa]þ calcd 266.0707, obsd 266.0705. Anal. Calcd for
C13H10FN3O: C, 64.19; H, 4.14; N, 17.28. Found: C, 64.26; H, 4.20; N,
17.01.
4.5.10. 5-Acetyl-3-(3-methoxyphenyl)-6H-pyrrolo[1,2-c][1,2,3]tri-
azole (5j). Yield: 92%; white solid; mp: 165–157 (hexane–EtOAc); IR
(KBr) 1672 cmꢂ1; 1H NMR (CDCl3)
d 2.54 (s, 3H, CH3), 3.90 (s, 3H, CH3),
5.16 (d, J¼1.9 Hz, 2H, CH2), 6.93–6.97 (m,1H, aromatic), 7.39–7.41 (m,
2H, aromatic), 7.50–7.51 (m, 1H, aromatic), 7.58 (t, J¼1.9 Hz, 1H, CH);
13C NMR (CDCl3)
d 26.2, 51.9, 55.4,111.2,114.5,118.2,126.3,130.1,131.4,
139.7, 140.7, 146.5, 160.1, 193.0; EIMS: m/z (%) 229 (70), 214 (100), 186
(20), 106 (42); HRMS (FABþ): m/z C14H13N3O2Na [MþNa]þ calcd
278.0907, obsd 278.0905. Anal. Calcd for C14H13N3O2: C, 65.87; H,
5.13; N, 16.46. Found: C, 65.63; H, 5.06; N, 16.21.
4.5.11. 5-Acetyl-3-(thiophen-2-yl)-6H-pyrrolo[1,2-c][1,2,3]triazole
(5k). Yield: 80%; white solid; mp: 157–158 ꢀC (hexane–EtOAc); IR
(KBr) 1673 cmꢂ1; 1H NMR (CDCl3)
d
2.54(s, 3H, CH3), 5.15 (d, J¼2.0 Hz,
2H, CH2), 7.14 (dd, J¼5.4 and 3.9 Hz,1H, aromatic), 7.39 (dd, J¼5.4 and
0.9 Hz, 1H, aromatic), 7.48 (dd, J¼3.9 and 0.9 Hz, 1H, aromatic), 7.51
(t, J¼2.0 Hz, 1H, CH); 13C NMR (CDCl3)
d 26.1, 52.1, 124.8, 125.6, 126.0,
128.0, 132.3, 136.2, 138.8, 146.3, 192.9; EIMS: m/z (%) 205 (98), 190
(58), 162 (40), 106 (100); HRMS (FABþ): m/z C11H9N3OSNa [MþNa]þ
calcd 254.0366, obsd 254.0365. Anal. Calcd for C11H9N3OS: C, 57.13; H,
3.92; N, 18.17. Found: C, 56.88; H, 3.81; N, 18.02.
4.5.12. 3-Phenyl-7,8-dihydro-4H-[1,2,3]triazolo[1,5-a]indol-5(6H)-
one (5n). Yield: 85%; light yellow solid; mp: 204–205 ꢀC (hexane–
EtOAc); IR (KBr) 1668, 1635 cmꢂ1 1H NMR (CDCl3)
; d 2.32–2.40
(m, 2H. CH2), 2.61–2.66 (m, 2H, CH2), 3.16–3.22 (m, 2H, CH2), 3.82
(dd, J¼2.7 and 2.5 Hz, 2H, CH2) 7.35–7.51 (m, 3H, aromatic), 7.85–
13. For
a review of heterocycle syntheses using the Morita–Baylis–Hillman
7.88 (m, 2H, aromatic); 13C NMR (CDCl3)
d 21.2, 22.2, 25.7, 37.3,
chemistry, see: Singh, V.; Batra, S. Tetrahedron 2008, 64, 4511–4574.
14. For our recent examples, see: (a) Song, Y. S.; Lee, C. H.; Lee, K.-J. J. Heterocycl.
Chem. 2003, 40, 939–941; (b) Park, J. B.; Ko, S. H.; Kim, B. G.; Hong, W. P.; Lee,
K.-J. Bull. Korean Chem. Soc. 2004, 25, 27–28; (c) Park, J. B.; Ko, S. H.; Hong, W. P.;
Lee, K.-J. Bull. Korean Chem. Soc. 2004, 25, 927–930; (d) Hong, W. P.; Lim, H. N.;
Park, H. W.; Lee, K.-J. Bull. Korean Chem. Soc. 2005, 26, 655–657; (e) Hong, W. P.;
Lee, K.-J. Synthesis 2005, 33–38; (f) Hong, W. P.; Lee, K.-J. Synthesis 2006, 963–
968; (g) Ji, S.-H.; Hong, W. P.; Ko, S. H.; Lee, K.-J. J. Heterocycl. Chem. 2006, 43,
799–801; (h) Yi, H.-W.; Park, H. W.; Song, Y. S.; Lee, K.-J. Synthesis 2006, 1953–
1960; (i) Lim, H.N.; Ji, S.-H.; Lee, K.-J. Synthesis 2007, 2454–2460; (j) Song, Y. S.;
Lee, K.-J. Synthesis 2007, 3037–3043; (k) Lim, H. N.; Song, Y. S.; Lee, K.-J. Syn-
thesis 2007, 3376–3384; (l) Jeon, K. J.; Lee, K.-J. J. Heterocycl. Chem. 2008, 45,
615–619; (m) Ahn, S.-H.; Lim, H. N.; Lee, K.-J. J. Heterocycl. Chem. 2008, 45,
125.6, 128.3, 129.0, 129.2, 129.9, 135.7, 140.6, 152.8, 195.0; EIMS: m/z
(%) 251 (2) [Mþ], 225 (89), 207 (31), 197 (34), 169 (100); HRMS
(FABþ): m/z C15H13N3ONa [MþNa]þ calcd 274.0958, obsd 274.0953.
Anal. Calcd for C15H13N3O: C, 71.70; H, 5.21; N, 16.72. Found: C,
71.56; H, 5.47; N, 16.50.
4.5.13. 3-Pentyl-7,8-dihydro-4H-[1,2,3]triazolo[1,5-a]indol-5(6H)-
one (5o). Yield: 47%; yellow solid; mp: 49–50 ꢀC (hexane–EtOAc);
IR (KBr) 1670, 1634 cmꢂ1
;
1H NMR (CDCl3)
d
0.90 (t, J¼6.1 Hz, 3H,

3498
S.P. Park et al. / Tetrahedron 66 (2010) 3490–3498
1701–1706; (n) Park, S. P.; Song, Y. S.; Lee, K.-J. Tetrahedron 2009, 65, 4703–
Roy, A. K.; Batra, S.; Bhaduri, A. P. Synlett 2002, 1819–1822; (c) Ko, S. H.; Lee, K.-J.
J. Heterocycl. Chem. 2004, 41, 613–616.
18. The (E)-1-azido-3-methylpent-2-en-4-yne do not undergo intramolecular cy-
cloaddition, see: Ref. 10.
4708; (o) Han, E.-G.; Kim, H. J.; Lee, K.-J. Tetrahedron 2009, 65, 9619–9625.
15. For our recent examples, see: (a) Lee, C. H.; Song, Y. S.; Cho, H. I.; Yang, J. W.;
Lee, K.-J. J. Heterocycl. Chem. 2003, 40, 1103–1106; (b) Ko, S. H.; Lee, K.-J. J.
Heterocycl. Chem. 2006, 43, 799–801.
16. (a) Krishna, P. R.; Swkhar, E. R.; Kannan, V. Tetrahedron Lett. 2003, 44, 4973–
4975; (b) Krishna, P. R.; Manjuvani, A.; Kannan, V.; Sharma, G. V. M. Tetrahedron
Lett. 2004, 45, 1183–1185.
19. The olefinic proton of 4f and 4l was observed at
and two methylene protons were appeared at
d
6.89 and 6.75 as each triplet,
d
d
4.20 and d 4.18 as each singlet.
20. Kwong, F. Y.; Lee, H. W.; Lam, H. W.; Qiu, L.; Chan, A. S. C. Tetrahedron: Asym-
metry 2006, 17, 1238–1252.
17. For early reports of azidation of the Morita–Baylis–Hillman acetates, see: (a)
Foucaud, A.; El Guemmout, F. Bull. Soc. Chim. Fr. 1989, 403–408; (b) Patra, A.;
21. Auffrant, A.; Diederich, F. Helv. Chim. Acta 2004, 87, 3085–3105.
22. One missing carbon signal was observed at
d 77.0 in DMSO-d6 solvent system.