Reactions of vinyl sulfone with α-diazo-β-ketosulfone and Bestmann-Ohira reagent for the regioselective synthesis of highly functionalized pyrazoles

Article abstract of DOI:10.1016/j.tet.2014.01.022

The 1,3-dipolar cycloaddition of diazomethylsulfone anion, generated in situ from α-diazo-β-ketosulfone, with vinyl sulfone proceeds in a regioselective manner to provide sulfonylpyrazoles. Similar reaction of diazomethylphosphonate anion, derived from Bestmann-Ohira reagent, with vinyl sulfone leads to phosphonylpyrazoles. The sulfonyl group of vinyl sulfone undergoes chemoselective elimination in these reactions.

Full text of DOI:10.1016/j.tet.2014.01.022

Tetrahedron 70 (2014) 1794e1799
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Reactions of vinyl sulfone with a-diazo-b-ketosulfone and
BestmanneOhira reagent for the regioselective synthesis of highly
functionalized pyrazoles
*
Rahul Kumar, Deepa Nair, Irishi N.N. Namboothiri
Department of Chemistry, Indian Institute of Technology, Bombay, Mumbai 400 076, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The 1,3-dipolar cycloaddition of diazomethylsulfone anion, generated in situ from a-diazo-b-ketosulfone,
Received 17 December 2013
Received in revised form 10 January 2014
Accepted 13 January 2014
with vinyl sulfone proceeds in a regioselective manner to provide sulfonylpyrazoles. Similar reaction of
diazomethylphosphonate anion, derived from BestmanneOhira reagent, with vinyl sulfone leads to
phosphonylpyrazoles. The sulfonyl group of vinyl sulfone undergoes chemoselective elimination in these
reactions.
Available online 23 January 2014
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Pyrazoles
BestmanneOhira reagent
Diazosulfone
vinyl sulfone
1. Introduction
as well as alkyne 8,16 has been reported by us and Smietana et al.
recently (Scheme 1). The methodology has been successfully
The preeminence of pyrazoles among heterocycles as pharma-
ceutical and agrochemical agents has prompted various research
groups to develop regioselective methods for the synthesis of fused
and functionalized pyrazoles.1e3 The role of pyrazoles as ligands in
synthesis and as precursors to N-heterocyclic carbenes has attrac-
ted considerable attention.4 Extensive mechanistic studies on the
tautomerism exhibited by pyrazoles are also well-documented in
the literature.5
Among various functional groups, phosphonate,6 a transition
state analog of carboxylate, and sulfone,7 a versatile electron
withdrawing/stabilizing and easily removal group, are fabulous due
to their ability to enhance the synthetic and biological profiles of
pyrazoles. The classical methods such as the 1,3-dipolar cycload-
dition of diazoalkanes with alkenes or alkynes8 and the conden-
sation of 1,3-difunctional compounds with hydrazines9 have been
extended to the synthesis of phosphonyl- and sulfonylpyrazoles as
well.10,11
Highly regioselective synthesis of phosphonylpyrazoles 1, 4, 5,
and 9 (E¼PO(OEt)2) using the BestmanneOhira reagent BOR (
diazo-
-ketophosphonate) 7a12 and electron deficient alkenes such
as
-unsaturated nitro compounds 6,13 nitriles 3,14 and enones 215
a-
b
a,b
* Corresponding author. E-mail addresses: irishi@iitb.ac.in, inamboothiri@gmail.
com (I.N.N. Namboothiri).
Scheme 1.
0040-4020/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2014.01.022

R. Kumar et al. / Tetrahedron 70 (2014) 1794e1799
1795
extended by us to a-diazo-b
-ketosulfone 7b17 for the synthesis of
Table 2
corresponding sulfonylpyrazoles 53 and 916 (E¼SO2Ar), which led
to a highly efficient total synthesis of Withasomnine 10.3 Although
the above mentioned electron deficient alkenes proved to be good
cycloaddition partners with 7a,b, an excellent electron deficient
alkene such as a vinyl sulfone 1118 has not been employed in such
capacity.19,20 Therefore, we report here for the first time, a facile,
base mediated 1,3-dipolar cycloaddition of diazophosphonate 7a
and diazosulfone 7b with vinyl sulfone 11 for the high yielding and
regioselective synthesis of highly functionalized pyrazoles with
hitherto unreported substitution pattern.
Synthesis of sulfonylpyrazoles 13 via the 1,3-dipolar cycloaddition of vinyl sulfonyl
carboxylate 11 with diazosulfone 7b
Entry
Ar
E
Pyrazole
% Yielda
1
2
3
4
5
6
7
8
4-OMeC6H4
3,4-(OMe)2C6H3
Benzo[d][1,3]dioxole
4-MeC6H4
4-iPr-C6H4
C6H5
1-Naphthyl
4-ClC6H4
3-BrC6H4
4-CF3C6H4
2-Thienyl
Cyclohexyl
4-OMeC6H4
Ph
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CN
13a
13b
13c
13d
13e
13f
13g
13h
13i
13j
13k
13l
13m
13n
13o
95
85
87
87
82
90
78
84
77
87
79
75
93
90
86
2. Results and discussion
We initiated our studies by treating vinyl sulfonyl carboxylate
11a with diazosulfone 7b in the presence of different bases in EtOH
(Table 1). To our delight, the reaction proceeded smoothly with
NaOEt as base and furnished the highly substituted pyrazole 13a in
just 1 h in moderate yield (65%, entry 1). This positive result en-
couraged us to screen other hydroxide and carbonate bases to
improve the yield of this 1,3-dipolar cycloaddition (entries 2e8).
Although other hydroxide bases were also effective, we did not
observe any significant enhancement in the yield (70e78%) except
that the reaction time drastically improved to 10e20 min (entries
2e4). NaOtBu and K2CO3 were equally efficient in terms of the yield
9
10
11
12
13
14
15
CN
CN
4-ClC6H4
a
After purification by silica gel column chromatography.
other hand, the reaction of vinyl cyanosulfones 11meo afforded the
cyanopyrazoles 13meo in high yields (86e93%, entries 13e15). In
all the above cases, the sulfonyl group derived from vinyl sulfone 11
underwent elimination, which is particularly chemoselective in the
presence of a cyano group.
Table 1
Optimization of base for the 1,3-dipolar cycloaddition of vinyl sulfonyl carboxylate
11a with diazosulfone 7b
The above optimized conditions were suitable for parent vinyl
sulfone 14 as well, which reacted well with diazosulfone 7b and
provided the corresponding pyrazole 15 in 75% yield (Scheme 2).
Entry
Base
Time (min)
% Yielda
1
2
3
4
5
6
7
8
NaOEt
KOH
NaOH
LiOH
60
10
20
10
45
90
10
15
65
78
71
70
67
72
90
95b
NaOtBu
K2CO3
Cs2CO3
Cs2CO3
Scheme 2.
a
After purification by silica gel column chromatography.
At 0 ꢀC.
b
In view of the fact that a phosphonyl group is a synthetically and
biologically useful functionality, our methodology has been suc-
cessfully applied for the synthesis of highly substituted phospho-
nylpyrazoles 16 as well (Table 3). Thus, 1,3-dipolar cycloaddition of
selected vinyl sulfones 11 with the BestmanneOhira reagent (BOR)
(67e72%) but needed prolonged reaction time (entries 5 and 6).
However, spectacular improvement in the yield to 90% was ob-
served when Cs2CO3 was used as base, which was further enhanced
by performing the reaction at 0 ꢀC (entries 7 and 8).
Under the above optimized conditions, we examined the gen-
erality of our protocol for the synthesis of highly functionalized
pyrazoles 13 (Table 2). A variety of a,b-unsaturated sulfones 11 were
Table 3
Synthesis of phosphonylpyrazoles 16 via 1,3-dipolar cycloaddition of vinyl sulfonyl
carboxylate 11 with BOR 7a
treated with diazosulfone 7b in the presence of Cs2CO3 at 0 ꢀC. Vinyl
sulfonyl carboxylates 11aee bearing electron donating groups gave
the products 13aee in excellent yields (82e95%, entries 1e5). Vinyl
sulfonyl carboxylates 11f, 11h, and 11j, respectively, with phenyl
and weakly deactivating para-substituents such as Cl and CF3 on
the aromatic ring also gave the corresponding pyrazoles 13f, 13h,
and 13j in high yield (84e90%, entries 6, 8, and 10). The yields were
marginally lower with vinyl sulfonyl carboxylates 11g, 11i, and 11k,
respectively, possessing bulky and meta-substituted aromatic rings
as well as a heteroaromatic ring (77e79%, entries 7, 9, and 11).
Entry
R
Pyrazole
% Yielda
1
2
3
4
4-OMeC6H4
Benzo[d][1,3]dioxole
3-BrC6H4
16a
16c
16i
16l
72
74
70
67
Cyclohexyl
Lower yield was encountered with an alkyl substituent at the
b-
a
After purification by silica gel column chromatography.
position of the sulfonyl/carboxylate moiety (75%, entry 12). On the

1796
R. Kumar et al. / Tetrahedron 70 (2014) 1794e1799
7a provided phosphonylpyrazoles 16 in good yield. Vinyl sulfones
bearing relatively electron rich -aryl substituents 11a and 11c gave
better results (72e74% yield, entries 1 and 2) as compared to those
possessing electron-withdrawing as well as aliphatic substituents
11i and 11l (70% and 67%, respectively, entries 3 and 4).
The structure and regiochemistry of pyrazoles 13, 15 and 16
were determined by IR, 1H NMR, 13C NMR, and mass analysis
(see Experimental section and Supplementary data). In particular,
the regiochemistry was unambiguously established by 1He1H-2D-
NOESY analysis of a representative compound 13l. A positive NOE
between aromatic (tolyl) protons and cyclohexyl protons as well as
between ester methyl and cyclohexyl protons together with the
absence of any NOE between ester protons and aromatic (tolyl)
protons confirmed this assignment.
4. Experimental section
4.1. General
b
The melting points recorded are uncorrected. The 1H NMR
spectra were recorded at 400 MHz and the 1H decoupled 13C NMR
spectra were recorded at 100 MHz or 75 MHz with TMS as the
internal standard. The coupling constants (J values) are given in
hertz (Hz). The high resolution mass spectra were recorded under
ESI Q-TOF conditions.
4.2. General procedure for the synthesis of sulfonyl- and
phosphonylpyrazoles 13, 15, and 16
The proposed mechanism taking diazosulfone 7b as the repre-
sentative 1,3-dipole precursor involves alkoxide mediated deacy-
lation of 7b and the reaction of the resulting diazomethylsulfone
anion IIb with vinyl sulfone 11 in a 1,3-dipolar fashion (Scheme 3).
The initial cycloadduct pyrazoline III then undergoes elimination of
the sulfonyl group followed by tautomerization (path A) or pro-
tonation followed by base assisted elimination of the sulfonyl group
to generate trisubstituted pyrazole 13.
To a stirred solution of
a,b-unsaturated sulfones 11 (0.5 mmol)
and -diazo- -ketosulfone 7b (169 mg, 0.75 mmol) or BOR 7a
a
b
(165 mg, 0.75 mmol) in dry EtOH (5 mL) was added Cs2CO3 (1 mmol)
at 0 ꢀC and the resulting mixture was stirred until the reaction was
complete (monitored by TLC). Then the reaction mixture was con-
centrated in vacuo and the crude residue was directly subjected to
silica gel column chromatography (60e120 mesh, n-hexane/ethyl
acetate 3:2) to afford pure pyrazoles 13, 15, and 16.
Scheme 3.
Representative synthetic transformations of cyanosulfonylpyr-
azole 13n are reported in Scheme 4. Thus, desulfonation of 13n took
place smoothly in the presence of sodium amalgam in methanol to
afford cyanopyrazole 18 in 60% yield. A 1,3-dipolar cycloaddition of
cyanopyrazole 13n with sodium azide under microwave irradiation
conditions delivers tetrazole 17 in 75% yield.
4.2.1. Ethyl 4-(4-methoxyphenyl)-3-tosyl-1H-pyrazole-5-carboxylate
(13a). White solid; yield 190 mg, 95%; mp 159e161 ꢀC; Rf (40%
EtOAc/pet ether) 0.35; nmax (KBr) 3608 (br vs), 3002 (m), 2943 (m),
1733 (m), 1723 (m), 1633 (m), 1446 (m), 1375 (w), 1174 (m), 1152
(m), 1038 (s) cmꢁ1
; dH (400 MHz, CDCl3) 1.14 (t, J 7.1 Hz, 3H), 2.36 (s,
3H), 3.87 (s, 3H), 4.22 (q, J 7.1 Hz, 2H), 6.90 (dt, J 8.8, 2.5 Hz, 2H), 7.17
(d, J 8.2 Hz, 2H), 7.19 (dt, J 8.8, 2.5 Hz, 2H),7.51 (d, J 8.2 Hz, 2H), 11.98
(br s, 1H); dC (100 MHz, CDCl3) 13.8, 21.6, 55.3, 61.7, 112.9, 120.5,
125.5, 128.1, 129.4, 131.9, 133.6, 137.3, 144.6, 150.3, 158.9, 159.7;
HRMS (ESI) m/z found 401.1166 for C20H21N2O5S (MHþ), requires
401.1167.
Scheme 4.
4.2.2. Ethyl 4-(3,4-dimethoxyphenyl)-3-tosyl-1H-pyrazole-5-
carboxylate (13b). White solid; yield 183 mg, 85%; mp
160e162 ꢀC; Rf (40% EtOAc/pet ether) 0.22; nmax (KBr) 3545 (br w),
3231 (br w), 3021 (m), 2984 (w), 1733 (vs), 1596 (w), 1518 (w), 1374
(w), 1328 (w), 1249 (s), 1218 (m), 1150 (s), 1085 (w), 1046 (m), 1028
3. Conclusions
For the first time, vinyl sulfones have been subjected to 1,3-
dipolar cycloaddition with in situ generated diazosulfone and
diazophosphosphonate under mild reaction conditions to afford
highly functionalized pyrazoles as single regioisomers in good to
excellent yield. These pyrazoles are amenable for further synthetic
transformations to novel intermediates and products.
(m), 758 (vs) cmꢁ1
; dH (400 MHz, CDCl3) 1.16 (t, J 7.1 Hz, 3H), 2.36 (s,
3H), 3.81 (s, 3H), 3.94 (s, 3H), 4.23 (q, J 7.1 Hz, 2H), 6.77 (d, J 1.8 Hz,
1H), 6.83 and 6.87 (ABq, J 8.3 Hz, 2H, upper half further split into d, J
1.8 Hz), 7.15 (d, J 8.1 Hz, 2H), 7.49 (d, J 8.1 Hz, 2H), 11.47 (br s, 1H); dC
(100 MHz, CDCl3) 14.0, 21.7, 55.8, 56.0, 61.9, 110.2, 114.1, 120.7, 123.5,
125.5, 128.2, 129.0, 129.1, 129.5, 137.2, 144.7, 147.9, 149.1, 158.9;

R. Kumar et al. / Tetrahedron 70 (2014) 1794e1799
1797
HRMS (ESI) m/z found 453.1091 for C21H22N2O6SNa (MNaþ), re-
quires 453.1090.
133.9, 136.9, 144.3, 150.8, 157.8; HRMS (ESI) m/z found 443.1036 for
23H20N2O4SNa (MNaþ), requires 443.1036.
C
4.2.3. Ethyl 4-(benzo[d][1,3]dioxol-5-yl)-3-tosyl-1H-pyrazole-5-
carboxylate (13c). White solid; yield 180 mg, 87%; mp
163e165 ꢀC; Rf (40% EtOAc/pet ether) 0.50; nmax (KBr) 3249 (m),
2982 (w), 2905 (w), 1732 (vs), 1596 (w), 1506 (m), 1475 (s), 1404
(w), 1384 (w), 1328 (s), 1305 (m), 1232 (s), 1153 (s), 1039 (s), 934
4.2.8. Ethyl 4-(4-chlorophenyl)-3-tosyl-1H-pyrazole-5-carboxylate
(13h). White solid; yield 170 mg, 84%; mp 134e136 ꢀC; Rf (40%
EtOAc/pet ether) 0.22; nmax (KBr) 3582 (vs), 3002 (m), 2944 (m),
1739 (w), 1637 (s), 1448 (w), 1375 (w), 1154 (w), 1039 (m), 919 (w),
751 (w) cmꢁ1
; dH (400 MHz, CDCl3) 1.11 (t, J 7.1 Hz, 3H), 2.37 (s, 3H),
(m), 813 (m), 756 (m), 707 (m), 670 (m), 603 (s) cmꢁ1
;
dH (400 MHz,
4.20 (q, J 7.1 Hz, 2H), 7.15e7.17 (m, 4H), 7.32 (d, J 8.1 Hz, 2H), 7.51 (d, J
8.1 Hz, 2H); dC (100 MHz, acetone-d6) 14.1, 21.5, 62.1, 124.7, 128.3,
128.8, 129.3, 129.5, 130.5, 131.1, 131.4, 133.4, 134.5, 139.0, 145.7;
HRMS (ESI) m/z found 427.0490 for C19H17N2O4SClNa (MNaþ), re-
quires 427.0482.
CDCl3) 1.10 (t, J 7.1 Hz, 3H), 2.32 (s, 3H), 4.18 (q, J 7.1 Hz, 2H), 5.95 (s,
2H), 6.61 (d, J 1.5 Hz, 1H), 6.64 (dd, J 7.9, 1.5 Hz, 1H), 6.73 (d, J 7.9 Hz,
1H), 7.13 (d, J 8.2 Hz, 2H), 7.51 (d, J 8.2 Hz, 2H), 11.59 (br s, 1H); dC
(100 MHz, CDCl3) 13.9, 21.7, 61.9, 101.2, 107.6, 111.2, 121.8, 124.6,
125.3, 128.2, 129.5, 134.1, 137.2, 144.8, 146.9, 147.7, 150.0, 158.8;
HRMS (ESI) m/z found 437.0778 for C20H18N2O6SNa (MNaþ), re-
quires 437.077.
4.2.9. Ethyl 4-(3-bromophenyl)-3-tosyl-1H-pyrazole-5-carboxylate
(13i). White solid; yield 173 mg, 77%; mp 177e179 ꢀC; Rf (40%
EtOAc/pet ether) 0.45; nmax (KBr) 3551 (br m), 2984 (m), 2924 (s),
2851 (m), 1728 (vs), 1597 (w), 1563 (w), 1463 (m), 1383 (w), 1332
4.2.4. Ethyl 4-p-tolyl-3-tosyl-1H-pyrazole-5-carboxylate
(13d). White solid; yield 167 mg, 87%; mp 166e168 ꢀC; Rf (40%
EtOAc/pet ether) 0.40; nmax (KBr) 3433 (br w), 3021 (w), 2978 (w),
1732 (s), 1375 (w), 1266 (m), 1217 (w), 1151 (w), 1046 (w), 759
(w), 1242 (m), 1153 (s), 1027 (s), 757 (s) cmꢁ1
; dH (400 MHz, CDCl3)
1.11 (t, J 7.1 Hz, 3H), 2.40 (s, 3H), 4.20 (q, J 7.1 Hz, 2H), 7.16e7.18
(unresolved m, 1H), 7.20 (d, J 8.1 Hz, 2H), 7.25e7.27 (m, 2H),
7.50e7.54 (m, 3H), 11.85 (br s, 1H); dC (100 MHz, acetone-d6) 13.2,
20.7, 61.2, 120.7, 123.3, 127.9, 129.2, 129.6, 129.8, 130.9, 131.9, 133.4,
138.0, 144.8, 150.8, 158.0; HRMS (ESI) m/z found 470.9985 for
(vs) cmꢁ1
; dH (400 MHz, CDCl3) 1.13 (t, J 7.1 Hz, 3H), 1.85 (s, 3H), 2.37
(s, 3H), 4.21 (q, J 7.1 Hz, 2H), 7.12 (d, J 8.0 Hz, 2H), 7.16 and 7.18 (ABq,
J 7.9 Hz, 4H), 7.51 (d, J 8.0 Hz, 2H), 11.85 (br s, 1H); dC (100 MHz,
CDCl3) 13.9, 21.6, 21.8, 61.9, 125.5, 126.0, 128.3, 128.4, 129.6, 130.6,
134.2, 137.4, 138.4, 144.8, 150.3, 159.0; HRMS (ESI) m/z found
407.1036 for C20H20N2O4SNa (MNaþ), requires 407.1037.
C
19H17N2O4BrSNa (MNaþ), requires 470.9984.
4.2.10. Ethyl 3-tosyl-4-(4-(trifluoromethyl)phenyl)-1H-pyrazole-5-
carboxylate (13j). White solid; yield 191 mg, 87%; Rf (40% EtOAc/
pet ether) 0.48; mp 170e172 ꢀC; nmax (KBr) 3622 (vs), 3544 (s), 3165
(w), 3003 (m), 2944 (w), 1728 (w), 1632 (s), 1444 (s), 1376 (m), 1326
4.2.5. Ethyl 4-(4-isopropylphenyl)-3-tosyl-1H-pyrazole-5-
carboxylate (13e). White solid; yield 169 mg, 82%; mp
146e148 ꢀC; Rf (40% EtOAc/pet ether) 0.50; nmax (KBr) 3242 (br w),
2961 (w), 2925 (m), 2857 (w), 1725 (s), 1596 (w), 1463 (w), 1328
(w), 1168 (w), 1039 (vs), 919 (m), 750 (m) cmꢁ1
; dH (400 MHz,
CDCl3) 1.08 (t, J 7.1 Hz, 3H), 2.37 (s, 3H), 4.20 (q, J 7.1 Hz, 2H), 7.16 (d,
J 8.0 Hz, 2H), 7.35 (d, J 8.0 Hz, 2H), 7.51 (d, J 8.2 Hz, 2H), 7.60 (d, J
8.2 Hz, 2H), 12.32 (br s, 1H); dC (100 MHz, CDCl3) 13.8, 21.8, 62.3,
122.9, 124.1, 124.6 (q, JCeF¼36.0 Hz), 125.6, 128.3, 129.8, 130.6, 130.9,
131.2, 132.7, 137.0, 145.3, 158.6; HRMS (ESI) m/z found 461.0753 for
(m), 1300 (m), 1182 (m), 1152 (vs), 1086 (w) cmꢁ1
; dH (400 MHz,
CDCl3) 1.10 (t, J 7.1 Hz, 3H), 1.30 (d, J 6.9 Hz, 6H), 2.35 (s, 3H), 2.93
(septet, J 6.9 Hz, 1H), 4.19 (q, J 7.1 Hz, 2H), 7.11 (d, J 8.0 Hz, 2H), 7.14
(d, J 8.1 Hz, 2H), 7.20 (d, J 8.0 Hz, 2H), 7.44 (d, J 8.1 Hz, 2H), 11.5 (br s,
1H); dC (100 MHz, CDCl3) 13.8, 21.8, 24.2, 34.1, 61.9, 125.7, 125.8,
126.0, 128.3, 129.1, 129.5, 130.6, 137.1, 144.7, 149.4, 159.1; HRMS
(ESI) m/z found 435.1349 for C22H24N2O4SNa (MNaþ), requires
435.1354.
C
20H17N2O4SF3Na (MNaþ), requires 461.0748.
4.2.11. Ethyl 4-(thiophen-2-yl)-3-tosyl-1H-pyrazole-5-carboxylate
(13k). White solid; yield 149 mg, 79%; mp 169e171 ꢀC; Rf (40%
EtOAc/pet ether) 0.40; nmax (KBr) 3447 (m), 3253 (m), 2985 (w),
2925 (w), 1730 (s), 1638 (w), 1597 (w), 1375 (w), 1331 (w), 1265 (w),
4.2.6. Ethyl 4-phenyl-3-tosyl-1H-pyrazole-5-carboxylate
(13f). White solid; yield 167 mg, 90%; mp158e160 ꢀC; Rf (40%
EtOAc/pet ether) 0.50; nmax (KBr) 3264 (br w), 2924 (m), 2853 (m),
1725 (s), 1596 (w), 1552 (w), 1447 (w), 1332 (m), 1212 (w), 1152 (vs),
1217 (w), 1150 (m), 1086 (w), 1046 (w), 1019 (w), 759 (s) cmꢁ1
; dH
(400 MHz, CDCl3) 1.18 (t, J 7.1 Hz, 3H), 2.38 (s, 3H), 4.25 (q, J 7.1 Hz,
2H), 7.09 (dd, J 5.1, 3.6 Hz, 1H), 7.16 (dd, J 3.6,1.2 Hz, 1H), 7.18 (d, J
8.1 Hz, 2H), 7.43 (dd, J 5.1, 1.2 Hz, 1H), 7.54 (d, J 8.1 Hz, 2H), 11.63 (br
s, 1H); dC (100 MHz, CDCl3) 13.9, 21.8, 62.2, 118.2, 126.8, 127.4, 127.7,
128.3, 129.1, 129.7, 131.0, 136.9, 145.0, 151.2, 158.7; HRMS (ESI) m/z
found 399.0444 for C17H16N2O4S2Na (MNaþ), requires 399.0443.
1087 (m), 1020 (w), 764 (m) cmꢁ1
; dH (400 MHz, CDCl3) 1.06 (t, J
7.1 Hz, 3H), 2.34 (s, 3H), 4.18 (q, J 7.1 Hz, 2H), 7.12 (d, J 8.2 Hz, 2H),
7.18e7.20 (m, 2H), 7.30e7.39 (m, 3H), 7.48 (d, J 8.2 Hz, 2H), 12.51 (br
s, 1H); dC (100 MHz, CDCl3) 13.7, 21.7, 61.9, 125.7, 127.5, 128.2, 128.4,
128.7, 129.6, 130.7, 137.2, 144.8, 159.0; HRMS (ESI) m/z found
393.0879 for C19H18N2O4SNa (MNaþ), requires 393.0883.
4.2.12. Ethyl 4-cyclohexyl-3-tosyl-1H-pyrazole-5-carboxylate
(13l). White solid; yield 141 mg, 75%; mp 166e168 ꢀC; Rf (40%
EtOAc/pet ether) 0.55; nmax (KBr) 346 (br s), 2927 (m), 2851 (w),
1733 (m), 1639 (w), 1596 (w), 1546 (w), 1450 (w), 1376 (w), 1323
4.2.7. Ethyl 4-(naphthalen-1-yl)-3-tosyl-1H-pyrazole-5-carboxylate
(13g). White solid; yield 164 mg, 78%; mp 174e176 ꢀC; Rf (40%
EtOAc/pet ether) 0.40; nmax (KBr) 3585 (br vs), 3199 (w), 2984 (w),
1725 (m), 1643 (w), 1383 (w), 1331 (w), 1201 (m), 1152 (s), 1107 (w),
(m), 1213 (w), 1155 (s), 1084 (w), 1018 (w), 669 (m) cmꢁ1
; dH
(400 MHz, CDCl3) 1.24e1.34 (m, 2H), 1.39 (t, J 7.1 Hz, 3H), 1.45 (d, J
12.3 Hz, 2H), 1.67e1.81 (m, 4H), 1.93 (qd, J 12.3, 3.3 Hz, 2H), 2.42 (s,
3H), 3.37 (dddd collapsed to tt, J 8.9, 3.3 Hz, 1H), 4.39 (q, J 7.1 Hz,
2H), 7.32 (d, J 8.1 Hz, 2H), 7.87 (d, J 8.1 Hz, 2H), 11.26 (br s, 1H); dC
(100 MHz, CDCl3) 14.2, 21.7, 25.7, 26.8, 30.4, 34.1, 62.1, 128.0, 129.8,
131.2, 133.2, 138.1, 144.8, 150.1, 159.0; HRMS (ESI) m/z found
399.1349 for C19H24N2O4SNa (MNaþ), requires 399.1342. Regio-
chemistry was confirmed by 1He1H-2D-NOESY experiment.
1019 (w) cmꢁ1
; dH (400 MHz, DMSO-d6) 0.58 (t, J 7.0 Hz, 3H), 2.19 (s,
3H), 3.80e3.90 (m, 2H), 6.95e7.05 (unresolved m, 1H), 7.04 (d, J
7.9 Hz, 2H), 7.18e7.28 (m, 4H), 7.41 (t, J 7.5 Hz, 1H), 7.49 (t, J 7.5 Hz,
1H), 7.89 (d, J 8.2 Hz, 1H), 7.91 (d, J 8.2 Hz, 1H), 15.20 (br s, 1H); dH
(400 MHz, CDCl3) 0.63 (t, J 7.1 Hz, 3H), 2.17 (s, 3H), 3.87e4.02 (m,
2H), 6.79 (d, J 8.1 Hz, 2H), 6.89 (d, J 8.4 Hz, 1H), 7.11 (td, J 8.4, 0.9 Hz,
1H), 7.21 (d, J 8.1 Hz, 2H), 7.38 (td, J 7.0, 0.9 Hz, 2H), 7.51 (dd, J 8.0,
7.0 Hz, 1H), 7.81 (d, J 8.0 Hz, 1H), 7.90 (d, J 8.0 Hz, 1H), 12.06 (br s,
1H); dC (100 MHz, DMSO-d6) 13.1, 21.0, 60.8, 122.3, 124.7, 125.0,
125.4, 125.8, 127.2, 127.4, 127.9, 128.3, 128.4, 129.4, 132.1, 132.7,
4.2.13. 4-(4-Methoxyphenyl)-3-tosyl-1H-pyrazole-5-carbonitrile
(13m). White solid; yield 164 mg, 93%; mp 168e170 ꢀC; Rf (40%

1798
R. Kumar et al. / Tetrahedron 70 (2014) 1794e1799
EtOAc/pet ether) 0.55; nmax (KBr) 3598 (br vs), 3192 (w), 2933 (m),
2842 (m), 2294 (m),1613 (s), 1513 (m),1446 (w), 1374 (w), 1336 (m),
1251 (vs), 1181 (s), 1154 (vs), 1115 (w), 1086 (m), 1036 (vs), 920 (w),
(ESI) m/z found 397.1159 for C
17H22N2O7P (MHþ), requires
397.1161.
837 (vs), 817 (vs) cmꢁ1
;
dH (400 MHz, CDCl3) 2.36 (s, 3H), 3.87 (s,
4.2.19. Ethyl
4-(3-bromophenyl)-3-(diethoxyphosphoryl)-1H-pyr-
3H), 6.97 (dt, J 8.8, 2.5 Hz, 2H), 7.16 (dd, J 8.1, 1.4 Hz, 2H), 7.39 (dt, J
8.8, 2.5 Hz, 2H), 7.46 (dd, J 8.1, 1.4 Hz, 2H); dC (100 MHz, CDCl3) 21.8,
55.5, 111.9, 114.3, 118.4, 127.9, 129.2, 130.0, 131.3, 135.8, 146.1, 160.7;
HRMS (ESI) m/z found 376.0726 for C18H15N3O3SNa (MNaþ), re-
quires 376.0725.
azole-5-carboxylate (16i). White solid; yield 151 mg, 70%; mp
116e118 ꢀC; Rf (60% EtOAc/pet ether) 0.30; nmax (KBr) 3415 (br vs),
2930 (m), 1734 (m), 1648 (s), 1460 (w), 1269 (m), 1157 (m), 1113 (w),
1027 (s), 704 (m) cmꢁ1
; dH (400 MHz, CDCl3) 1.13 (t, J 7.1 Hz, 6H),
1.18 (td, J 7.1, 1.4 Hz, 3H), 3.93e3.99 (m, 2H), 4.01e4.09 (m, 2H), 4.24
(q, J 7.1 Hz, 2H), 7.23 (t, J 7.8 Hz, 1H), 7.30 (d, J 7.8 Hz, 1H), 7.48 (d, J
7.8 Hz, 1H), 7.52 (s, 1H), 13.84 (br s, 1H); dC (100 MHz, CDCl3) 14.0,
15.9 (d, JCeP 7.0 Hz), 61.3, 63.3 (d, JCeP 6.0 Hz), 121.4, 128.7 (d, JCeP
18.0 Hz), 129.0, 129.1, 130.9, 133.0, 133.2, 161.3; dP (162 MHz, CDCl3)
4.2.14. 4-Phenyl-3-tosyl-1H-pyrazole-5-carbonitrile
(13n). White
solid; yield 145 mg, 90%; mp 175e177 ꢀC; Rf (40% EtOAc/pet ether)
0.45; nmax (KBr) 3230 (br m), 3064 (w), 2927 (w), 2242 (m), 1596
(m), 1493 (w), 1448 (w), 1323 (vs), 1305 (s), 1147 (vs), 1086 (s), 1008
4.90; HRMS (ESI) m/z found 453.0185 for
C16H20N2O5PBrNa
(m), 815 (m), 703 (s), 595 (s), 538 (s) cmꢁ1
;
dH (400 MHz, CDCl3)
(MNaþ), requires 453.0188.
2.35 (s, 3H), 7.13 (d, J 8.1 Hz, 2H), 7.43e7.48 (m, 7H), 11.86 (br s, 1H);
dC (100 MHz, acetone-d6) 21.5, 112.6, 128.0, 128.6, 129.4, 129.5,
130.2, 130.8 (ꢂ 2), 137.8, 146.7; HRMS (ESI) m/z found 346.0621 for
4.2.20. Ethyl 4-cyclohexyl-3-(diethoxyphosphoryl)-1H-pyrazole-5-
carboxylate (16l). White solid; yield 120 mg, 67%; mp
125e127 ꢀC; Rf (60% EtOAc/pet ether) 0.50; nmax (KBr) 3473 (br m),
3138 (br m), 2985 (s), 2929 (vs), 2854 (s), 1727 (vs), 1634 (w), 1546
(w), 1450 (m), 1375 (m), 1248 (vs), 1232 (vs), 1145 (s), 1127 (s), 1024
C
17H13N3O2SNa (MNaþ), requires 346.0620.
4.2.15. 4-(4-Chlorophenyl)-3-tosyl-1H-pyrazole-5-carbonitrile
(13o). White solid; yield 154 mg, 86%; mp 219e221 ꢀC; Rf (40%
EtOAc/pet ether) 0.28; nmax (KBr) 3240 (br m), 2951 (w), 2929 (w),
2244 (w), 1596 (w), 1492 (w), 1469 (w), 1396 (w), 1330 (m), 1150
(vs), 977 (s), 757 (vs), 614 (s) cmꢁ1
; dH (400 MHz, CDCl3) 1.18 (t, J
7.1 Hz, 6H), 1.20e1.40 (m, 3H), 1.25 (t, J 7.1 Hz, 3H), 1.56 (d, J 12.3 Hz,
2H), 1.62e1.67 (m, 1H), 1.75 (d, J 12.3 Hz, 2H), 1.91, 1.98 (ABq, J
12.0 Hz, 2H), 3.11 (t, J 12.3 Hz, 1H), 4.00e4.10 (m, 2H), 4.11e4.19 (m,
2H), 4.34 (q, J 7.1 Hz, 2H), 13.15 (br s, 1H); dC (100 MHz, CDCl3) 14.3,
16.2 (d, JCeP 6.0 Hz), 25.8, 27.0, 31.3, 35.1, 61.1, 62.9 (d, JCeP 5.0 Hz),
136.0 (d, JCeP 21.0 Hz), 161.9; dP (162 MHz, CDCl3) 7.61; HRMS (ESI)
m/z found 381.1550 for C16H27N2O5PNa (MNaþ), requires 381.1546.
(vs), 1088 (m), 835 (m), 738 (m), 590 (s) cmꢁ1
; dH (400 MHz, CDCl3)
2.38 (s, 3H), 7.19 (d, J 8.2 Hz, 2H), 7.40, 7.44 (ABqd, J 6.5, 2.0 Hz, 4H),
7.47 (d, J 8.2 Hz, 2H), 11.80 (br s, 1H); dC (100 MHz, acetone-d6) 21.6,
112.4, 126.8, 128.2, 128.7, 129.5, 130.9, 132.5, 136.0, 137.7, 146.8;
HRMS (ESI) m/z found 380.0231 for C17H12N3O2SNaCl (MNaþ), re-
quires 380.0230.
4.3. 5-(4-Phenyl-3-tosyl-1H-pyrazol-5-yl)-2H-tetrazole (17)
4.2.16. 3-Tosyl-1H-pyrazole (15). White solid; yield 83 mg, 75%; mp
162e164 ꢀC (lit.21 162.5e164.5 ꢀC); Rf (40% EtOAc/pet ether) 0.28;
nmax (KBr) 3171 (br m), 2926 (s), 2857 (m), 1663 (w), 1596 (w), 1464
(w), 1325 (s), 1305 (m),1243 (w), 1197 (w), 1090 (m), 741 (s), 700 (s),
Pyrazole 13n (81 mg, 0.25 mmol) was dissolved in a 1:1 mixture
of H2O (2 mL) and THF (2 mL). NaN3 (65 mg, 1 mmol) and ZnBr2
(112 mg, 0.5 mmol) were added sequentially to the reaction mix-
ture and the solution was exposed to microwave irradiation at
140 ꢀC for 1 h. The reaction mixture was cooled to room temper-
ature, aqueous HCl (1 N solution, 10 mL) and EtOAc (10 mL) were
added and the mixture was vigorously stirred until no solid was
present. The organic layer was separated and the aqueous layer was
extracted with EtOAc (3ꢂ10 mL) and dried over Na2SO4. The filtrate
was concentrated in vacuo and the crude residue (white solid) was
purified by recrystallization from CHCl3/hexane to afford pure
compound 17. White solid; yield 69 mg, 75%; mp 214e216 ꢀC; Rf
(40% EtOAc/pet ether) 0.12; nmax (KBr) 3407 (br vs), 2925 (w), 1643
(m), 1416 (w), 1326 (w), 1261 (w), 1190 (w), 1151 (w), 1078
602 (s) cmꢁ1
; dH (400 MHz, CDCl3) 2.38 (s, 3H), 6.78 (d, J 2.2 Hz, 1H),
7.28 (d, J 7.9 Hz, 2H), 7.83 (d, J 7.9 Hz, 2H), 8.05 (d, J 2.2 Hz,1H), 14.23
(br s, 1H); dC (100 MHz, CDCl3) 21.7, 106.6, 127.7, 130.1, 132.8, 138.1,
144.8, 152.2; HRMS (ESI) m/z found 245.0355 for C10H10N2O2SNa
(MNaþ), requires 245.0358. 1H NMR data is consistent with the
literature.21
4.2.17. Ethyl 3-(diethoxyphosphoryl)-4-(4-methoxyphenyl)-1H-pyr-
azole-5-carboxylate (16a). White solid; yield 138 mg, 72%; mp
106e108 ꢀC; Rf (60% EtOAc/pet ether) 0.22; nmax (KBr) 3565 (br s),
3164 (w), 2996 (w), 2943 (w), 1736 (vs), 1634 (m), 1448 (w), 1375
(w), 1259 (vs), 1248 (vs), 1042 (s), 919 (m), 748 (s) cmꢁ1
;
dH
(w) cmꢁ1
; dH (400 MHz, CD3OD) 2.35 (s, 3H), 7.16 (d, J 7.5 Hz, 2H),
(400 MHz, CDCl3) 1.09 (t, J 7.1 Hz, 6H), 1.18 (t, J 7.1 Hz, 3H), 3.78 (s,
3H), 3.85e3.95 (m, 2H), 4.01e4.07 (m, 2H), 4.23 (q, J 7.1 Hz, 2H),
6.87 (d, J 8.6 Hz, 2H), 7.28 (d, J 8.6 Hz, 2H), 13.76 (br s, 1H); dC
(100 MHz, CDCl3) 14.2, 16.0 (d, JCeP 7.0 Hz), 55.3, 61.1, 63.1 (d, JCeP
5.0 Hz), 113.0, 122.8, 130.3 (d, JCeP 18.0 Hz), 131.5, 139.8, 159.5, 161.6;
dP (162 MHz, CDCl3) 5.73; HRMS (ESI) m/z found 405.1186 for
7.21 (d, J 7.3 Hz, 2H), 7.33 (t, J 7.3 Hz, 2H), 7.38e7.43 (m, 3H); dC
(100 MHz, CD3OD) 21.6, 124.5, 128.9, 129.0, 129.1, 129.6, 129.7, 130.8,
132.0, 138.5, 146.7, 151.7; HRMS (ESI) m/z found 389.0791 for
C
17H14N6O2SNa (MNaþ), requires 389.0794.
4.4. 4-Phenyl-1H-pyrazole-5-carbonitrile (18)
C
17H23N2O6NaP (MNaþ), requires 405.1183.
Na amalgam was freshly prepared from Na (231 mg, 10.04 g
atom) and Hg (3.874 g, 19.3 g atom). To a stirred suspension of this
and Na2HPO4 (1.28 g, 9.054 mmol) in MeOH (10 mL) under N2 was
added a solution of sulfonylpyrazole 13n (161 mg, 0.50 mmol) in
dry MeOH (4 mL). The reaction progress was monitored by TLC and
after 24 h, the reaction mixture was filtered and the filter cake was
washed with EtOAc (20 mL). The organic layer was concentrated in
vacuo and the crude residue was directly subjected to silica gel
column chromatography (60e120 mesh, 70:30 ethyl acetate/pet
ether) to afford pure compound 18. White solid; yield 51 mg, 60%;
mp 148e149 ꢀC (lit.22 154e156 ꢀC); Rf (40% EtOAc/pet ether) 0.58;
nmax (KBr) 3445 (br s), 3260 (br vs), 2924 (w), 2248 (m), 1645 (w),
4.2.18. Ethyl 4-(benzo[d][1,3]dioxol-5-yl)-3-(diethoxyphosphoryl)-
1H-pyrazole-5-carboxylate (16c). Yellow solid; yield 147 mg, 74%;
mp 124e126 ꢀC; Rf (60% EtOAc/pet ether) 0.25; nmax (KBr) 3124 (br
w), 2982 (w), 2930 (m), 2863 (w), 1729 (s), 1614 (w), 1517 (w),
1468 (w), 1388 (w), 1293 (w), 1247 (s), 1176 (s), 1026 (vs) cmꢁ1
; dH
(400 MHz, CDCl3) 1.13 (t, J 7.1 Hz, 6H), 1.19 (t, J 7.1 Hz, 3H),
3.89e3.99 (m, 2H), 4.01e4.09 (m, 2H), 4.23 (q, J 7.1 Hz, 2H),
5.92 (s, 2H), 6.77, 6.81 (ABqd, J 8.3, 1.6 Hz, 2H), 6.83 (d, J 1.6 Hz,
1H); dC (100 MHz, CDCl3) 14.0, 15.9 (d, JCeP 7.0 Hz), 61.0, 63.1
(d, JCeP 6.0 Hz), 101.1, 107.5, 110.8, 123.9, 124.1, 130.0 (d, JCeP
19.0 Hz), 146.8, 147.3, 161.3; dP (162 MHz, CDCl3) 5.53; HRMS

R. Kumar et al. / Tetrahedron 70 (2014) 1794e1799
1799
1445 (w), 1265 (w), 1166 (w), 1089 (w), 814 (s), 764 (s) cmꢁ1
; dH
6. Selected recent reviews: (a) Palacios, F.; Alonso, C.; de los Santos, J. M. Chem.
Rev. 2005, 105, 899; (b) Lejczak, B.; Kafarski, P. Top. Heterocycl. Chem. 2009, 20,
31; (c) Syamala, M. Org. Prep. Proced. Int. 2005, 37, 103; (d) Bera, K.; Nadkarni,
D.; Namboothiri, I. N. N. J. Chem. Sci. 2013, 125, 443.
7. Selected recent reviews: (a) Back, T. G.; Clary, K. N.; Gao, D. Chem. Rev. 2010, 110,
4498; (b) El-Awa, A.; Noshi, M. N.; Jourdin, X. M. D.; Fuchs, P. L. Chem. Rev. 2009,
109, 2315; (c) Alonso, D. A.; Najera, C. Org. React. 2008, 72, 367; (d) Prilezhaeva,
E. N. Russ. Chem. Rev. 2000, 69, 367.
(400 MHz, CDCl3) 7.39 (t, J 7.3 Hz, 1H), 7.46 (t, J 7.3 Hz, 2H), 7.65 (d, J
7.3 Hz, 2H), 7.95 (s, 1H), 12.12 (br s, 1H); dC (100 MHz, CDCl3) 114.3,
127.0, 127.8, 128.7, 129.2, 129.4; HRMS (ESI) m/z found 170.0713 for
C
10H8N3 (MHþ), requires 170.0716. IR and 1H NMR data are con-
sistent with the literature data.22
8. Selected books/reviews: (a) Molteni, G. ARKIVOC 2007, 224; (b) Regitz, M.;
Heydt, H. In 1,3-Dipolar Cycloaddition Chemistry; Padwa, A., Ed.; Wiley Inter-
science: New York, NY, 1984, Chapter 4; (c) Trivedi, G. K. J. Indian Chem. Soc.
2004, 81, 187; (d) Zollinger, H. Diazo Chemistry II-Aliphatic, Inorganic and Or-
ganometallic Compounds; VCH: Weinheim, Germany, 1995; p 11; (e) Diederrich,
F.; Isaacs, L.; Philip, D. Chem. Soc. Rev. 1994, 23, 243; (f) Mullins, R. J. In Name
Reactions in Heterocyclic Chemistry II; Li, J. J., Ed.; John Wiley & Sons: Hoboken,
New Jersey, 2011; p 327; (g) Harju, K.; Yli-Kauhaluoma, J. In Solid-phase Organic
Synthesis; Toy, P. H., Lam, Y., Eds.; John Wiley & Sons: Hoboken, New Jersey,
2012; p 355.
9. Selected reviews: (a) Kumar, V.; Aggarwal, R.; Singh, S. P. Heterocycles 2008, 75,
2893; (b) Kempson, J. In Name Reactions in Heterocyclic Chemistry II; Li, J. J., Ed.;
John Wiley & Sons: Hoboken, New Jersey, 2011; p 317.
10. Selected articles, phosphonylpyrazoles, diazoalkane approach: (a) Lu, R.; Yang,
H. Tetrahedron Lett. 1997, 38, 5201; (b) Shen, Y.; Zheng, J.; Xin, Y.; Lin, Y.; Qi, M. J.
Chem. Soc., Perkin Trans. 1 1995, 997; Hydrazine approach: (c) Budzisz, E.;
Malecka, M.; Nawrot, B. Tetrahedron 2004, 60, 1749.
Acknowledgements
I.N.N.N. thanks DAE/BRNS India for financial assistance. R.K.
thanks CSIR India and D.N. thanks UGC India for a senior research
fellowship.
Supplementary data
Copies of NMR spectra for all the new compounds. Supple-
mentary data associated with this article can be found in the online
version, at http://dx.doi.org/10.1016/j.tet.2014.01.022.
11. Selected articles, sulfonylpyrazoles, diazoalkane approach: (a) Padwa, A.;
Wannamaker, W. M. Tetrahedron 1990, 46, 1145; (b) Gao, D.; Zhai, H.; Parvez, M.;
Back, T. G. J. Org. Chem. 2008, 73, 8057; Hydrazine approach: (c) Savant, M. M.;
Pansuriya, M. A.; Bhuva, V. C.; Kapuriya, N.; Patel, N. A.; Audichya, B. V.; Pipaliya,
V. P.; Naliapara, T. Y. J. Comb. Chem. 2010, 12, 176; (d) Kanishchev, S. O.; Bandera,
P. Y.; Timoshenko, M. V.; Rusanov, B. E.; But, S. A.; Shermolovich, G. Y. Chem.
Heterocycl. Compd. 2007, 43, 887.
12. Meffre, P.; Hermann, S.; Durand, P.; Reginato, G.; Riu, A. Tetrahedron 2002, 58,
5159 and the references cited therein.
13. (a) Muruganantham, R.; Mobin, S. M.; Namboothiri, I. N. N. Org. Lett. 2007, 9,
1125; (b) Muruganantham, R.; Namboothiri, I. N. N. J. Org. Chem. 2010, 75,
2197.
14. In situ generated acrylo- and alkylidenemalononitrile: Mohanan, K.; Martin, A.
R.; Toupet, L.; Smietana, M.; Vasseur, J. Angew. Chem., Int. Ed. 2010, 49, 3196.
15. (a) Verma, D.; Mobin, S. M.; Namboothiri, I. N. N. J. Org. Chem. 2011, 76, 4764; (b)
In situ generated enone: Martin, A. R.; Mohanan, K.; Toupet, L.; Vasseur, J. J.;
Smietana, M. Eur. J. Org. Chem. 2011, 3184.
16. Kumar, R.; Verma, D.; Mobin, S. M.; Namboothiri, I. N. N. Org. Lett. 2012, 14,
4070.
17. Doyle, K.; Moody, C. Tetrahedron 1994, 50, 3761 and the references cited therein.
18. Tanikaga, R.; Tamura, T.; Nozaki, Y.; Kaji, A. J. Chem. Soc., Chem. Commun. 1984,
87.
19. Vinyl sulfones, recent reviews: (a) Nakata, T. Chem. Soc. Rev. 2010, 39, 1955; (b)
Zhu, Q.; Lu, Y. Aust. J. Chem. 2009, 62, 951; (c) Pathak, T. Tetrahedron 2008, 64,
3605; (d) Charette, A. B.; Cote, A.; Desrosiers, J.-N.; Bonnaventure, I.; Lindsay, V.
N. G.; Lauzon, C.; Tannous, J.; Boezio, A. A. Pure Appl. Chem. 2008, 80, 881; (e)
Ono, N. Heterocycles 2008, 75, 243; (f) Tsogoeva, S. B. Eur. J. Org. Chem. 2007,
1701; (g) Meadows, D. C.; Gervay-Hague, J. Med. Res. Rev. 2006, 26, 793.
20. 1,3-Dipolar cycloaddition of vinyl sulfones, recent articles: (a) Flores, M.; Gar-
cia-Garcia, P.; Garrido, N. M.; Marcos, I. S.; Sanz-Gonzalez, F.; Diez, D. J. Org.
Chem. 2013, 78, 7068; (b) Guideri, L.; De Sarlo, F.; Machetti, F. Chem.dEur. J.
2013, 19, 665; (c) Hernandez-Toribio, J.; Padilla, S.; Adrio, J.; Carretero, J. C.
Angew. Chem., Int. Ed. 2012, 51, 8854; (d) Dey, S.; Datta, D.; Pathak, T. Synlett
2011, 2521; (e) Shanahan, C. S.; Fuller, N. O.; Ludolph, B.; Martin, S. F. Tetra-
hedron Lett. 2011, 52, 4076; (f) Coldham, I.; Burrell, A. J. M.; Guerrand, H. D. S.;
Oram, N. Org. Lett. 2011, 13, 1267.
References and notes
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Org. Chem. 2013, 78, 3482; For other selected recent methods: (e) Ichikawa, H.;
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jumder, S.; Gipson, K. R.; Staples, R. J.; Odom, A. L. Adv. Synth. Catal. 2009, 351,
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K.; Bauer, R.; Bucar, F. Phytochemistry 2008, 69, 982; For fluorinated pyrazoles
with potential biological activity: (h) Fustero, S.; Roman, R.; Sanz-Cervera, J. F.;
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