Intramolecular Huisgen [3+2] cycloaddition in water: Synthesis of fused pyrrolidine-triazoles

Article abstract of DOI:10.1016/j.tetasy.2012.02.011

The intramolecular alkyne-azide Huisgen [3+2] cycloaddition reaction as a 'click-chemistry' reaction without a metal catalyst has been studied under aerobic conditions. The synthesis of various pyrrolidine-triazole hybrid compounds has also been achieved

Full text of DOI:10.1016/j.tetasy.2012.02.011

Tetrahedron: Asymmetry 23 (2012) 225–229
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Tetrahedron: Asymmetry
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Intramolecular Huisgen [3+2] cycloaddition in water: synthesis of fused
pyrrolidine–triazoles
⇑
,
Indresh Kumar a, , Nisar A. Mir a, Chandrashaker V. Rode b, Basant P. Wakhloo c
a School of Biology & Chemistry, College of Sciences, Shri Mata Vaishno Devi University, Katra 182 320, J&K, India
b Chemical Engineering & Process Development Division, National Chemical Laboratory, Pune 411 008, India
c Instrumentation Division, Indian Institute of Integrative Medicine (IIIM-CSIR Lab.), Canal Road, Jammu 180 001, J&K, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 4 January 2012
Accepted 15 February 2012
The intramolecular alkyne–azide Huisgen [3+2] cycloaddition reaction as a ‘click-chemistry’ reaction
without a metal catalyst has been studied under aerobic conditions. The synthesis of various pyrroli-
dine–triazole hybrid compounds has also been achieved by using this intramolecular cycloaddition reac-
tion in water with complete 1,5-regioselectivity.
Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
also been widely applied to the construction of organic and bioor-
ganic molecular architectures.18
Subsequent to the isolation of potent glycosidase inhibitors,1
such as nojirimycin, 1-deoxynojirimycin, swanisonine, casuarine
from natural sources, there has been a growing interest in the
chemistry, biochemistry, and pharmacology of these compounds,
known as ‘imino-sugars’.2 Therefore, an attractive approach to po-
tent inhibitors is toward design molecules with a half-chair confor-
mation, which is known to be the transition state of the enzyme
catalyzed reactions.3 In this context, a new class of hybrid com-
pounds in which a piperidine or pyrrolidine nucleus is fused to a
triazole, tetrazole, pyrazole, or a pyrrole ring have been synthe-
sized and studied as inhibitors of various glycosidases.4 In particu-
lar, the synthesis of pyrrolidine-tetrazoles 1, piperidine–triazoles 2
and 3, and sugar-derived morpholine triazoles 4 has been accom-
plished starting from sugars in several steps (Fig. 1).2,5
Further attention has recently been focused on 1,2,3-triazole
derivatives6 since they are considered as biologically important
molecules with activities such as antibacterial,7 anti-HIV,8
herbicidal,9 antitumor,10 tuberculosis inhibition,11 tyrosinase
inhibition,12 antiallergic,13 and glycosidase inhibition.4,14 1,2,3-Tri-
azoles also offer an appealing structural motif in peptidomimetic
research because their structural and electronic characteristics
are similar to those of a peptide bond.15 The Huisgen dipolar cyclo-
addition reaction between organic azides and alkynes is an attrac-
tive route to 1,2,3-triazole heterocycles,16 which have also found a
number of important applications in the pharmaceutical and agro-
chemical industries.17 Stimulated by its high efficiency, and func-
tional group compatibility, the alkyne–azide cycloaddition has
The main problems associated with this traditional method are
long reaction times, high temperatures, and the formation of mix-
tures of 1,4- and 1,5-disubstituted triazoles with poor regioselec-
tivity. Sharpless et al. have developed a high yielding synthesis of
1,2,3-triazoles using a Cu(I)-catalyst with an excellent level of
1,4-regioselectivity under mild conditions using a set of reactions
defined as the ‘click-chemistry’ approach.19 Recently, regioselec-
tive 1,5-disubstituted triazoles have been prepared exclusively
from terminal alkynes and alkyl azide catalyzed by Cp⁄RuCl(PPh)3
in refluxing benzene.20 These catalytic reactions solve the prob-
lems associated with the traditional method. However, it is also
known that alkynes attached to electron-withdrawing groups en-
hance the rate of the cycloaddition reaction; high levels of regiose-
lectivity have been achieved, when the cycloaddition is carried out
between internal/terminal-activated alkynes with different azides
under mild conditions.21 In a continuation of our efforts toward
the synthesis of structural scaffolds of biological importance,22
and the study of intermolecular Huisgen [3+2] cycloadditions for
making hybrid triazolo-skeletons in water23 we were prompted
to develop a metal free intramolecular alkyne–azide cycloaddi-
tion24 approach for the synthesis of various triazolo-hybrid com-
pounds with different ring sizes (Scheme 1). Herein we report
the synthesis of pyrrolidine–triazole hybrid molecules using an
intramolecular Huisgen cycloaddition in water, which subse-
quently eliminate the use of organic solvents making this process
a green one.25
2. Results and discussion
⇑
Corresponding author. Tel.: +91 1991 285634x2533; fax: +91 1991 285691.
E-mail address: indresh.chemistry@gmail.com (I. Kumar).
The retrosynthetic analysis of our strategy to synthesize pyrrol-
idine–triazole hybrid molecules is shown in Scheme 2. Compound
Present address: Department of Chemistry, Birla Institute of Technology
Science, Pilani 333 031, India
&
0957-4166/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2012.02.011

226
I. Kumar et al. / Tetrahedron: Asymmetry 23 (2012) 225–229
OH
HO
HO
R
OH
HO
OH
X
R
HOOC
R1
OH
OH
OH
OMe
N
N
N
N
N
N
N
O
N
N
N
N
N
CH2OH
N
N
N
CH2OH
N
4, X = O, NCO2Me
5, R1 = H, EWG
2
3
1
Figure 1.
R'
4
R'
5
N
N
N
N
N
N
N
N
N
1
1
N
R
R
R1
N3
R1
intramolecular
Huisgen [3+2]
N
cycloaddition
N
N
R
R
Scheme 1. Complete 1,5-regioselectivity in intramolecular Huisgen [3+2] dipolar-cycloaddition reactions.
6 was visualized as a main synthetic intermediate from which
fused pyrrolidine–triazoles could be prepared using an intramolec-
ular Huisgen [3+2] cycloaddition with only 1,5-regioselectivity.
Compound 6 could in turn be derived from the protected 1,4-diol
7 through standard synthetic transformations. We initially started
with the simple 1,4-diol 9 prepared from commercially available
DL-aspartic acid by following the reported procedure.26 Selective
protection of the less hindered alcohol with TsCl followed by
nucleophilic substitution with NaN3 in DMSO/1,4-dioxane gave
azido-alcohol compound 10 in 74% yield. Our next aim was to
introduce an alkyne moiety in place of the hydroxyl group in com-
pound 10. For this purpose, we first proceeded with the oxidation
of the hydroxyl group of 10 to its corresponding aldehyde using
IBX in EtOAc at reflux for 4 h,27 followed by its conversion into
an azido-alkyne compound 11 using Ohira’s conditions28 with
68% yield over two steps. The intramolecular Huisgen cycloaddi-
tion of 11 was carried out in water by heating at 70 °C for 1 h to
give the corresponding pyrrolidine-triazolo hybrid compound 12
with 71% yield (Schemes 3 and 4).
NHBoc
OH
ref. 26
DL-aspartic Acid
HO
8
9
BocHN
(i)
BocHN
(ii)
OH
N3
N3
11
10
H
BocHN
(iii)
N
N
N
12
Scheme 3. Reagents and conditions: (i) (a) Et3N (1.5 equiv), TsCl (1.2 equiv), dry
DCM, 0 °C, 2 h, (b) NaN3, DMSO/1,4-dioxane (1:1), 65 °C, 6 h, 74% over two steps; (ii)
(a) IBX (3 equiv) EtOAc/Acetone (10:1), 80 °C, 4 h, (b) Ohira’s reagent (1.5 equiv),
K2CO3, MeOH, rt, overnight, 68% over two steps; (iii) H2O, 70 °C, 1 h, 71%.
R1
R1
intramolecular Huisgen cycloaddition of 16 was carried out in
water by heating at 70 °C for 1 h to give pyrrolidine–triazole com-
pound 17 in 60% yield (Scheme 4). Cycloadduct 17 was found to be
unstable when left for a long time, causing lower yields under ther-
mal cycloaddition conditions. Further deprotection of the aceto-
nide moiety from compound 17 under several different
conditions also leads to a complex reaction mixture from which
the desired product could not be isolated. Here, our efforts were fo-
cused on increasing the stability and yield of the cycloadduct by
making the alkyne moiety activated through the attachment of
an electron withdrawing group at the alkyne terminal position.
The attachment of a carboxylic ester moiety as the electron
withdrawing group on the terminal position of the alkyne was car-
ried out by treating compound 16 with sodamide (1.1 equiv) in dry
THF at ꢀ10 °C followed by trapping with methyl chloroformate
(1.2 equiv) to give 18 in 86% yield. The activated alkyne compound
18 quickly underwent [3+2] cycloaddition by heating in water at
70 °C for 30 min, to give the substituted fused pyrrolidine–triazole
R
OH
OH
R
R
N
N3
N
N
6
5
7
R1 = H, CO2Me
Scheme 2. Retrosynthetic analysis of pyrrolidine–triazole hybrids via intramolec-
ular Huisgen [3+2] cycloaddition reactions.
Next, L-(+)-tartaric acid 13 was converted into 1,4-diol 14
according to the reported procedure.29 Compound 14 was con-
verted into azido-alcohol 15 by using a two step one pot procedure.
For this purpose, compound 14 was subjected to mono-protection
with NaH/TsCl in dry THF at 0 °C for 2 h followed by nucleophilic
substitution with NaN3 in 1,4-dioxane/DMSO at 65 °C for 6 h to
provide azido-alcohol 15 in 87% yield. Azido-alcohol 15 was con-
verted into the corresponding azido-alkyne 16 using the sequence
of IBX-oxidation followed by Ohira’s conditions with 82% yield. The

I. Kumar et al. / Tetrahedron: Asymmetry 23 (2012) 225–229
227
OH
O
O
O
COOH
OH
OH
OH
N3
ref. 29
(i)
HOOC
OH
13
O
14
15
L-(+)-tartaric acid
O
H
O
O
(ii)
(iii)
N
O
N3
N
N
16
17
Scheme 4. Reagents and conditions: (i) (a) NaH, TsCl, dry THF, 0 °C, 2 h, (b) NaN3, DMSO/1,4-dioxane (1:1), 65 °C, 6 h, 87% over two steps; (ii) (a) IBX (3 equiv), EtOAc/Acetone
(10:1), 80 °C, 4 h, (b) Ohira’s reagent (1.2 equiv), K2CO3, MeOH, rt, overnight, 82% over two steps; (iii) H2O, 70 °C, 1 h, 60%.
compound 19 in 91% yield. Cycloadduct 19 was found to be stable
when left for a long time under freezing conditions. Next, the ace-
tonide deprotection of 19 was carried out in p-TSA/MeOH to give
the corresponding dihydroxy pyrrolidine–triazole 20 in 78% iso-
lated yield. Further functionalization can be carried out at the ester
moiety on the trizole-ring as shown in Scheme 5. All the new com-
pounds were fully characterized by spectroscopic means.
1H and 75 MHz for 13C). The chemical shifts are reported using the
d (delta) scale for 1H and 13C spectra. Choices of deuterated sol-
vents (CDCl3, D2O) are indicated below. LC–MS was recorded using
the electrospray ionization technique. All of the organic extracts
were dried over sodium sulfate and concentrated under an aspira-
tor vacuum at room temperature. Column chromatography was
performed using (100–200 and 230–400 mesh) silica gel obtained
from M/s Spectrochem India Ltd. Room temperature is referred as
rt.
CO2Me
O
4.2. tert-Butyl(4-azido-1-hydroxybutan-2-yl)carbamate 10
(i)
(ii)
16
N3
To a stirred solution of compound 9 (1.0 g, 4.87 mmol) and Et3N
(1.0 mL, 7.31 mmol) in dry DCM (10 mL) was added dropwise TsCl
(1.11 g, 5.85 mmol) solution in 5 mL dry DCM under an inert atmo-
sphere. The combined mixture was stirred for 4 h at the same tem-
perature and the solvent was evaporated under reduced pressure.
The resulting crude material was taken in DMSO/1,4-dioxane
(1:1, 10 mL) and heated with NaN3 (0.633 g, 9.74 mmol) at 65 °C
for 6 h. The reaction mixture was quenched with a dilute NaHCO3
solution (10 mL) and extracted with EtOAc (2 ꢁ 15 mL); the com-
bined organic layer was dried over Na2SO4 and concentrated under
reduced pressure. Purification over silica gel column chromatogra-
phy gave 10 (0.83 g, 74% in two steps) as a light yellow liquid. 1H
NMR (200 MHz, CDCl3) d: 1.55–1.87 (m, 11H), 2.91 (m, 2H),
3.69–3.85 (m, 3H), 13C NMR (75 MHz, CDCl3) d: 29.21 (3C), 31.04,
43.54, 54.01, 63.02, 80.64, 156.13. Anal. Calcd for C9H18N4O3
(230.26): C, 46.94; H, 7.88; N, 24.33; Found: C, 46.89; H, 7.84; N,
24.37.
O
18
CO2Me
O
HO
CO2Me
N
(iii)
N
O
HO
N
N
N
N
20
19
Scheme 5. Reagents and conditions: (i) NaNH2 (1.2 equiv), dry THF, ꢀ10 to 0 °C,
ClCO2Me (1.2 equiv), 2 h, 86%; (ii) H2O (8 mL), 70 °C, 30 min, 91%; (iii) p-TSA (cat.),
MeOH, rt, 2 h, 78%.
3. Conclusion
In conclusion, we have demonstrated the intramolecular Huis-
gen [3+2] dipolar cycloaddition as a ‘click-reaction’ in water for
the synthesis of various pyrrolidine–triazoles. Azido-alkynes de-
rived from amino acid/tartaric acid have been used and an alkyne
attached to an electron withdrawing group provides better yield
and stability to the product. The present approach can be used as
a general strategy for the rapid conversion of any 1,4-diol struc-
tural motifs to the corresponding fused pyrrolidine–triazoles.
4.3. tert-Butyl(5-azidopent-1-yn-3yl)carbamate 11
To a stirred solution of compound 10 (0.6 g, 2.60 mmol) in
EtOAc (26 mL) was added o-iodoxy-benzoic acid (IBX) (2.18 g,
7.82 mmol) and heated at reflux at 80 °C for 4 h. The reaction
was cooled at rt and filtered under suction to remove the solid res-
idue and washed twice with a sat. NaHCO3 solution followed by a
brine solution, dried over Na2SO4, and concentrated under reduced
pressure to give the corresponding aldehyde in almost quantitative
yield. The crude aldehyde was taken in MeOH (6 mL) and stirred
along with Ohira’s reagent (0.75 g, 3.91 mmol) followed by the
addition of solid anhydrous K2CO3 (1.08 g, 7.82 mmol) at 0 °C for
15 min and at rt for an additional 8 h to complete the reaction.
The progress of the reaction was monitored by TLC; when com-
plete, evaporation of the solvent and purification by column chro-
matography gave 11 (0.40 g, 68% in two steps). 1H NMR (200 MHz,
CDCl3) d: 1.49–1.83 (m, 11H), 2.37 (d, 1H Alkyne), 2.85 (m, 2H),
4.13 (m 1H); 13C NMR (75 MHz, CDCl3) d: 29.19 (3C), 31.23,
43.05, 47.23, 72.09, 80.64, 83.10, 156.19. Anal. Calcd for
4. Experimental
4.1. General methods
All reagents were used as supplied. The reactions involving
hygroscopic reagents were carried out under an argon atmosphere
using oven-dried glassware. THF was distilled from sodium-benzo-
phenone ketyl prior to use. Reactions were followed by TLC using
0.25 mm Merck silica gel plates (60F-254). Optical rotations were
measured using a JASCO P-1020 digital polarimeter using Na-light.
The NMR spectra were recorded on a Bruker system (200 MHz for

228
I. Kumar et al. / Tetrahedron: Asymmetry 23 (2012) 225–229
C10H16N4O2 (224.26): C, 53.56; H, 7.19; N, 24.98; Found: C, 53.51;
H, 7.14; N, 25.01.
chromatography gave 17 (0.219 g, 61%). ½a D25
¼ ꢀ64:5 (c 0.75,
ꢂ
MeOH); 1H NMR (200 MHz, CDCl3) d: 1.47 (s, 3H), 1.50 (s, 3H),
3.48 (dd, 1H), 3.74 (dd, 1H),, 4.48 (m, 1H), 5.12 (d, J = 11.6, 1H),
7.66 (s, 1H, alkene) 13C NMR (75 MHz, CDCl3) d: 26.34, 26.42,
51.84, 78.12, 81.05, 110.94, 126.21, 145.86; LC–MS (ESI-TOF): m/
z = [M+H]+; 182.06, [M+Na]+; 204.04, Anal. Calcd for C8H11N3O2
(181.19): C, 53.06; H, 6.12; N, 23.19; Found: C, 53.09; H, 6.18; N,
23.31.
4.4. tert-Butyl(5,6-dihydro-4H-pyrrolo[1,2-c][1,2,3]triazol-4-
yl)carbamate 12
Compound 11 (0.35 g, 1.56 mmol) was taken in water (6 mL)
and heated at 70 °C for 1 h with stirring. The reaction was then
cooled down and stirred with EtOAc (10 mL). The organic layer
was separated and dried over Na2SO4. Evaporation of the solvent
and purification of the crude product by column chromatography
gave 12 (0.25 g, 71%). 1H NMR (200 MHz, CDCl3) d: 1.43–1.67 (m,
9H), 2.45–2.61 (m, 2H), 3.49–3.56 (m, 2H), 4.82 (m, 1H), 7.57 (s,
1H); 13C NMR (75 MHz, CDCl3) d: 29.25 (3C), 37.31, 40.89, 55.68,
4.8. Methyl-3-((4S,5S)-5-(azidomethyl)-2,2-dimethyl-1,3-dioxo-
lan-4-yl)propiolate 18
To a stirred solution of compound 16 (0.45 g, 2.48 mmol) in dry
THF (10 mL) at ꢀ10 °C was added sodium amide (0.11 g,
2.98 mmol) and mixture was stirred for an additional 30 min at
the same temperature. Methyl chloroformate (0.28 g, 2.98 mmol)
in dry THF (2.0 mL) was added slowly to this stirred solution at
ꢀ10 °C and then allowed to return to room temperature. The reac-
tion was quenched with NH4Cl solution (6 mL) and stirred with
EtOAc (15 mL). The organic layer was separated and dried over
Na2SO4 and evaporated under reduced pressure. The crude mate-
rial was purified by column chromatography to give 18 (0.51 g,
86% yield) Rf = 0.45 (9:1 Hexane/EtOAc).
80.14, 131.79, 146.56, 156.68. Anal. Calcd for
C10H16N4O2
(224.26): C, 53.56; H, 7.19; N, 24.98; Found: C, 53.49; H, 7.17; N,
24.94.
4.5. ((4S,5S)-5-(Azidomethyl)-2,2-dimethyl-1,3-dioxolan-4-
yl)methanol 15
To a stirred solution of compound 14 (1.0 g, 6.17 mmol) in dry
THF (15 mL) was added sodium hydride (0.25 g, 6.17 mmol, 60%
in mineral oil) at 0 °C for 10 min and then stirred for a further
15 min. Next, a solution of TsCl (1.18 g, 6.17 mmol) in 10 mL dry
THF was added dropwise under an inert atmosphere. The com-
bined mixture was stirred for 30 min at the same temperature
and then quenched with a dilute NaHCO3 solution. The reaction
mixture was extracted with EtOAc (2 ꢁ 10 mL) and washed with
brine solution; the organic layer was dried over Na2SO4 and con-
centrated under reduced pressure to provide a crude mono-tosylat-
ed slightly yellowish solid compound, which was heated with
NaN3 (1.0 g, 12.35 mmol) in DMSO:1,4-dioxane (10 mL) at 65 °C
for 6 h, followed by evaporation of the solvent and the usual
work-up and purification by column chromatography to give 15
(1.01 g, 87% in two steps) Rf = 0.70 (8:2 Hexane/EtOAc).
[
a
]
D = ꢀ98.7 (c 0.75, CHCl3); 1H NMR (200 MHz, CDCl3) d: 1.46
(s, 3H), 1.51 (s, 3H), 3.31 (dd, 1H), 3.64 (dd, 1H), 4.02 (s, 3H),
4.42 (m, 1H), 5.25 (d, J = 7.4, 1H), 13C NMR (75 MHz, CDCl3) d:
25.96, 26.51, 50.49, 55.21, 72.32, 80.21, 82.85, 87.27, 111.51,
162.65; Anal. Calcd for C10H13N3O4 (239.23): C, 50.21; H, 5.48; N,
17.56; Found: C, 50.29; H, 5.57; N, 17.48.
4.9. (3bS,6aS)-Methyl 5,5-dimethyl-6a,7-dihydro-3bH-[1,3]-
dioxolo[40,50:3,4]pyrrolo[1,2-c][1,2,3]triazole-3-carboxylate 19
Compound 18 (0.50 g, 2.09 mmol) was taken in water (8 mL)
and stirred at 70 °C for 30 min after which the reaction was cooled
down and stirred with EtOAc (15 mL) for approximately 10 min.
The organic layer was separated and dried over Na2SO4. Evapora-
½
a 2D5
ꢂ
¼ ꢀ69:3 (c 1, CHCl3); 1H NMR (200 MHz, CDCl3) d: 1.40 (s,
3H), 1.43 (s, 3H), 2.86 (bs, 1H, OH), 3.31 (dd, J = 4.7, 13.2 Hz, 1H),
3.67 (dd, J = 3.8, 13.1 Hz, 1H), 3.71–3.85 (m, 2H), 3.90–4.11 (m,
2H), 13C NMR (75 MHz, CDCl3) d: 26.67, 26.87, 51.63, 61.62,
76.07, 78.31, 109.70; LC–MS (ESI-TOF): m/z = [M+ Na]+ 210.17;
Anal. Calcd for C7H13N3O3 (187.2): C, 44.91; H, 6.99; N, 22.45;
Found: C, 44.89; H, 6.86; N, 22.50.
tion of the solvent gave 19 (0.45 g, 91% yields). ½a D25
¼ ꢀ86:5 (c 1,
ꢂ
MeOH); 1H NMR (200 MHz, CDCl3) d: 1.45 (s, 3H), 1.52 (s, 3H),
3.73 (dd, 1H), 3.94 (dd, 1H), 4.10 (s, 3H), 4.51 (m, 1H), 5.41 (d,
J = 11.6, 1H), 13C NMR (75 MHz, CDCl3) d: 26.64, 26.94, 54.56,
58.72, 79.24, 83.16, 111.84, 136.26, 151.92, 172.32; Anal. Calcd
for C10H13N3O4 (239.23): C, 50.21; H, 5.48; N, 17.56; Found: C,
50.32; H, 5.52; N, 17.59.
4.6. (4S,5S)-4-(Azidomethyl)-5-ethynyl-2,2-dimethyl-1,3-dioxo-
lane 16
4.10. (4S,5S)-Methyl 4,5-dihydroxy-5,6-dihydro-4H-pyrrolo[1,2-
c][1,2,3]triazole-3-carboxylate 20
Similar to the previous two-step procedure using IBX oxidation
and Ohira’s condition; (82% from 15) For 16: Rf = 0.65 (9:1 Hexane/
EtOAc). ½a 2D5
ꢂ
¼ ꢀ109:6 (c 1, CHCl3); 1H NMR (200 MHz, CDCl3) d:
Compound 19 (0.36 g, 1.50 mmol) was taken in MeOH (6 mL)
and stirred with p-TSA (cat.) at rt for 2 h. Once the reaction was
seen to be over by TLC, MeOH was evaporated under reduced pres-
sure and passed through a small pad of silica to give 20 (0.23 g, 78%
1.45 (s, 3H), 1.49 (s, 3H), 2.54 (d, 1H, alkyne), 3.29 (dd, J = 4.4,
13.4 Hz, 1H), 3.61 (dd, J = 3.7, 13.4 Hz, 1H), 4.23 (m, 1H), 4.51
(dd, J = 2.1, 7.4, 1H), 13C NMR (75 MHz, CDCl3) d: 25.94, 26.48,
50.43, 67.03, 75.12, 79.95, 80.39, 111.13; Anal. Calcd for
C8H11N3O2 (181.19): C, 53.06; H, 6.12; N, 23.19; Found: C, 53.19;
H, 6.25; N, 23.24.
yields). ½a 2D5
ꢂ
¼ ꢀ38:5 (c 0.5, MeOH); 1H NMR (200 MHz, CDCl3/
D2O) d: 3.75 (dd, 1H), 3.88 (dd, 1H), 4.20–4.54 (m, 4H), 5.43 (d,
J = 11.6, 1H); 13C NMR (75 MHz, CDCl3) d: 53.96, 64.48, 78.12,
81.46, 132.28, 150.76, 171.94; LC–MS (ESI-TOF): m/z = [M+H]+;
200.76, [M+Na]+; 222.94, Anal. Calcd for C7H9N3O4 (199.16): C,
42.21; H, 4.55; N, 21.10; Found: C, 42.65; H, 5.83; N, 21.76.
4.7. (3bS,6aS)-5,5-Dimethyl-6a,7-dihydro-3bH-[1,3]dioxolo[40,50:
3,4]pyrrolo[1,2-c][1,2,3]triazole 17
Acknowledgments
Compound 16 (0.36 g, 2 mmol) was taken in 8 mL of water and
heated at 70 °C for 1 hr with stirring after which the reaction mix-
ture was cooled down and stirred with EtOAc (15 mL) for approx-
imately 10 min. The organic layer was separated and dried over
Na2SO4. Evaporation of the solvent and purification by column
The authors thank the UGC-New Delhi, for financial support.
The authors are also grateful to Ms. Deepika Singh (Scientist),
IIIM-Jammu, for instrumental analysis.

I. Kumar et al. / Tetrahedron: Asymmetry 23 (2012) 225–229
229
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