Rapid and selective synthesis of spiropyrazolines and pyrazolylphthalides employing Seyferth-Gilbert reagent

Article abstract of DOI:10.1039/c7ob01417a

An unexpected product-selectivity in the reaction of 2-arylideneindane-1,3-dione with dimethyl diazomethylphosphonate leading to the formation of two different types of products is reported. The reaction carried out in acetone in the presence of catalytic amount of cesium fluoride afforded spiropyrazoline phosphonates via 1,3-dipolar cycloaddition reaction, whereas the reaction in methanol yielded an interesting class of pyrazolylphthalides. This strategy provides an efficient alternative method for the construction of pyrazolylphthalides, and moreover, the process is general, works under mild conditions, and exhibits high functional group compatibility.

Full text of DOI:10.1039/c7ob01417a

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Rapid and selective synthesis of spiropyrazolines and
pyrazolylphthalides employing Seyferth-Gilbert reagent†
Ashis Kumar Gupta,a,b Narendra Kumar Vaishanv,a Ruchir Kantc and Kishor Mohanan*,a,b
Received 00th January 20xx,
Accepted 00th January 20xx
An unexpected product-selectivity in the reaction of 2-arylideneindane-1,3-dione with dimethyl
diazomethylphosphonate leading to the formation of two different types of products is reported. The reaction
carried out in acetone in the presence of catalytic amount of cesium fluoride afforded spiropyrazoline
phosphonates via 1,3-dipolar cycloaddition reaction, whereas the reaction in methanol yielded an interesting
class of pyrazolylphthalides. This strategy provides an efficient alternative method for the construction of
pyrazolylphthalides, and moreover, the process is general, works under mild conditions, and exhibits high
functional group compatibility.
DOI: 10.1039/x0xx00000x
www.rsc.org/
synthesis of spiropyrazolines. We envisioned that the use of a
highly reactive 1,1-diactivated alkene such as 2-
arylideneindane-1,3-dione7 as dipolarophile would provide the
spirocyclic skeleton via a formal 1,3-dipolar cycloaddition
reaction. The only report on the synthesis of
INTRODUCTION
Dimethyl (diazomethyl)phosphonate (Seyferth-Gilbert reagent,
SGR) and its Bestmann-Ohira modification (dimethyl 1-diazo-2-
oxopropylphosphonate, BOR) have been extensively employed
for the convenient generation of homologated terminal and
internal carbon-carbon triple bonds from aldehydes and
ketones under ambient reaction conditions.1,2 Subsequently,
spiropyrazolineindane-1,3-dione relies on the cycloaddition
reaction of diazoindane-1,3-dione with vinylphosphonate (Fig.
1a).8 Herein, we report a highly effective and mild protocol for
the synthesis of phosphonylspiropyrazoline derivatives and
quite interestingly, further investigations revealed an
attractive product selectivity switch on changing the reaction
the
1,3-dipolar
cycloaddition
reaction
involving
conditions, introducing
a new and efficient route to
diazomethylphosphonate (DAMP) anion, the key intermediate
generated from these reagents, and various activated olefins
has emerged as an important methodology for the synthesis of
phosphonylated pyrazoles.3 In fact, a variety of activated
olefins have been reported to undergo cycloaddition reaction
with the Seyferth-Gilbert reagent, and these transformations
generally proceed through a pyrazoline intermediate which
subsequently undergoes air-oxidation or elimination reaction
to afford pyrazole derivatives. Although great progress has
been achieved in the synthesis of phosphonylpyrazoles using
pyrazolylphthalides (Fig. 1b)
.
a) Previous work
O
P
O
P
O
O
O
O
OEt
OEt
OEt
OEt
O
EtBr
OEt
OEt
LiOH
H2O/CHCl3
+
N2
P
N
N
N
N
Et
H
O
O
O
b) This work
O
OMe
OMe
H
P
N
O
P
O
O
1
R
R
N
OMe
OMe
Seyferth-Gilbert reagent, relatively
a few protocols are
O
R
NaOH (2.5 equiv)
MeOH, 25 °C
CsF (0.1 equiv)
acetone, 25 °C
+
reported for the synthesis of spiropyrazolines.4 On the basis of
the fact that this reagent has found only limited applications in
the synthesis of spiropyrazolines, and inspired by the attractive
features of spiropyrazolines,5,6 we sought to explore further
the possibility of employing diazophosphonate for the
O
N
N
OMe
OMe
O
H
P
H
O
N2
SGR
Fig.
Selective synthesis of spiropyrazolineindane-1,3-diones and
pyrazolylphthalides.
Results and Discussion
We initiated our experiments by subjecting 2-benzylideneindane-
1,3-dione 1a to a stoichiometric amount of Seyferth-Gilbert reagent
2 under reaction conditions similar to those previously reported for
the synthesis of pyrazoles. Thus, the reaction carried out by treating
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1a with Seyferth-Gilbert reagent 2 in acetonitrile using DBU as a
base afforded the spiropyrazolineindane-1,3-dione 3a in 75% yield
(See the SI for details). The reaction was further evaluated under
different conditions to improve the efficiency. For instance, the
reaction conducted with Et3N afforded the product in 82% yield.
However, the reactions tried using alkoxide bases such as NaOEt
and t-BuOK were unsuccessful. Upon further reaction optimizations,
we found that the spiropyrazoline 3a could be rendered catalytic by
treatment of 1a with 0.1 equivalent of CsF in acetone in 87% yield
(Scheme 1). Our subsequent attempts to use other bases in
catalytic amounts gave the product in lower yields.
Table 1 Scope of the spiropyrazoline synthesis: Variation of 2-arylideneindane-1,3-
dionesa
O
P
O
R
O
O
OMe
OMe
O
P
OMe
OMe
CsF (0.1 equiv)
H
+
N
acetone, 25 °C
1.5 h
R
N
H
N2
2
1
3
O
R1
1 = OMe, 75%
3b,
R
3c, R1 =i-Pr, 92%
O
P
O
OMe
OMe
3d, R1 = Et, 88%
O
O
O
OMe
P
1
3e,
R
= Me, 88%
OMe
N
3f, R1 = Ph, 90%
N
H
N
N
R
1 = Br, 85%
O
3g,
H
3h, R1 = Cl, 77%
3a, 87%
Cl
OMe
O
O
P
O
P
CH3
O
O
O
P
O
OMe
OMe
O
OMe
OMe
O
OMe
OMe
CsF (0.1 equiv)
O
OMe
P
H
O
OMe
+
P
OMe
acetone, 25 °C
1.5 h
OMe
N2
N
N
O
N
N
N
N
N
N
H
H
O
H
2
O
H
O
3a
, 87%
1a
Scheme 1 Synthesis of spiropyrazolineindane-1,3-diones.
3j,
3i,
86%
93%
3k, 88 %
OMe
OMe
OMe
MeO
OMe
O
Under the optimized conditions, we next evaluated the scope and
limitations of the spiropyrazoline synthesis. It is evident from the
data shown in Table 1 that the electronic nature of arylidene moiety
has little influence on the efficiency of this reaction. Products from
the reactions of substrates bearing electron-withdrawing and
electron-donating substituents at 4-position with S-G reagent were
obtained in consistently high yields (3b_3h). Arylideneindane-1,3-
diones with chloro and methoxy substituents at m-position also
participated well in this reaction to deliver the spiropyrazolines in
excellent yield (3i, 3j). A methyl substituent at o-position was also
compatible for the reaction (3k) and the structure of the compound
3k was unequivocally confirmed by X-ray analysis (Fig. 2).9 Besides,
the reactions of di- and trisubstituted substrates also occurred to
yield the corresponding spiropyrazoline derivatives (3l, 3m). The
reactions attempted using heteroarylideneindane-1,3-diones of
pyrrole and thiophene were also successful, and the products were
obtained in good yields (3n, 3o). Notably, the reaction tolerated
substrates containing naphthyl and ferrocenyl moiety (3p, 3q). The
selective formation of spiropyrazoline in this case may be attributed
to the lack of nucleophiles in the reaction media.
HN
O
P
O
OMe
OMe
O
P
O
O
O
O
OMe
OMe
OMe
P
N
OMe
N
N
N
H
N
N
O
H
H
3n,
80%
3l,
65 %
3m, 80 %
O
H
N
N
S
O
O
P
O
OMe
OMe
OMe
OMe
O
O
O
P
P
OMe
OMe
O
N
N
N
N
Fe
3q,
H
O
H
3o,
87 %
87%
3p, 89 %
aGeneral conditions: 1 (0.30 mmol), 2 (0.33 mmol), CsF (0.03 mmol), acetone
(5.0 mL), 1.5 h. Isolated yield after silica gel column chromatography.
Fig. 2 ORTEP diagram of 3k drawn with 30% ellipsoid probability.
During the course of reaction optimization for the synthesis of
spiropyrazolineindane-1,3-diones, we observed an unusual product
selectivity switch when the reaction of 1a with SGR was carried out
in methanol under basic conditions. The reaction proceeded
2 | J. Name., 2012, 00, 1-3
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smoothly to afford structurally and biologically relevant phthalide in
72% yield (Scheme 2). Phthalides, an interesting class of compound
frequently found in nature, exhibit an exceptionally broad spectrum
of biological activities.10 n-Butylphthalide,11 a marketed antiplatelet
drug and Mycophenolic acid12 are some of the examples of
pharmaceutically important phthalide-containing natural products.
They also serve as versatile building blocks for the synthesis of
polyaryl natural products.13 As a consequence, the development of
novel strategies for the synthesis of C3 substituted phthalides
remains an attractive area for chemists.
Table 2 Scope of 3-pyrazolylphthalide synthesis: Variation of 2-arylideneindane-1,3-
dionesa
O
OMe
H
P
N
OMe
O
O
N
O
P
OMe
OMe
R
NaOH (2.5 equiv)
H
+
R
MeOH, 25 °C
1.5 h
O
N2
O
1
2
4
, R1 = OAllyl, 73%
, R1 = OMe, 58%
4b
O
O
OMe
OMe
OMe
OMe
4c
H
N
H
P
P
O
4d, R1 = OPh, 79%
N
OMe
OMe
H
N
P
N
N
, R1 = t-Bu, 77%
4e
O
O
N
4f, R1 = i-Pr, 80%
O
P
OMe
OMe
K2CO3 (2.5 equiv)
, R1 = Et, 96%
H
+
4g
O
O
R1
MeOH, 25 °C
1.5 h
, R1 = Me, 86%
O
4h
N2
4a
, 86%
4i, R1 = Ph, 95%
O
O
O
, R1 = Br, 74%
O
P
4j
1a
2
4a
, 72%
OMe
OMe
O
OMe
OMe
H
N
4k, R1 = Cl, 60%
P
N
, R1 = F, 62%
4l
HN
N
Scheme 2 Synthesis of 3-Pyrazolylphthalides.
O
OMe
OMe
H
N
P
O
The selective formation of pyrazolylphthalides was particularly
interesting, and a brief optimization study carried out using various
bases showed that NaOH provided the product in 86% yield (See
the SI for details). Subsequently, a range of arylideneindane-1,3-
diones was used to evaluate the scope of pyrazolylphthalides
synthesis as shown in Table 2. A series of substrates bearing
electron-donating and electron-withdrawing substituents at p-
position of the aryl group was employed for the reaction and the
phthalide derivatives were obtained in reasonable to excellent
yields (4b_4l). The reaction was feasible with alkoxy, alkyl, bromo,
chloro and fluoro substituted aryilideneindane-1,3-diones. Similar
results were observed with m-substituted arylidenes affording the
products in good yields (4m-4o). The reactions of ortho-, di- and
trisubstituted aryilideneindane-1,3-diones also occurred to form the
products 4p_4r in reasonable yields. The structure of 4q was further
confirmed by X-ray analysis (Fig. 3).9 The reaction was compatible
with substrates bearing heteroaryl groups such as thiophene, furan,
and pyrrole (4s_4u) and comparably high yields were obtained in all
cases. Furthermore, when ferrocene-substituted olefin was
subjected to the reaction conditions the desired product was
generated, albeit in a lower yield (4v). The reaction is not limited to
arylidenes, and our attempt using alkylideneindane-1,3-dione,
though less efficient, afforded the product 4w in 50% yield.
OMe
N
O
R1
O
O
4m, R1 = OMe, 78%
O
OMe
, R1 = Cl, 69%
4p, 75%
4n
MeO
4o, R1 = Br, 69%
O
4q
, 67%
O
P
O
OMe
OMe
H
N
OMe
H
O
P
OMe
OMe
N
OMe
H
P
N
N
N
N
OMe
OMe
S
O
O
O
O
O
MeO
O
4s
, 58%
4t,
O
83%
O
4r
, 67%
O
P
O
P
OMe
OMe
OMe
OMe
OMe
H
H
H
N
P
N
N
OMe
N
N
N
HN
Fe
O
O
O
O
O
O
4u
, 89%
4v
4w
, 50%
, 50%
aGeneral conditions: 1 (0.30 mmol), 2 (0.45 mmol), NaOH (0.75 mmol), MeOH
(5.0 mL), 1.5 h. Isolated yield after silica gel column chromatography.
Fig. 3 ORTEP diagram of 4q drawn with 30% ellipsoid probability.
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In analogy to the related reactions involving S-G and BOR reagents, electron-rich, electron-deficient and heterocyclic moieties.
the following mechanistic pathway is proposed (Scheme 3). The Furthermore,
the
mechanistic
studies
proved
that
1,3-dipolar cycloaddition reaction of dimethyl pyrazolyphthalide is formed by
a
methanol-mediated
(diazomethyl)phosphonate (DAMP) anion generated in situ with 2- rearrangement of spiropyrazoline phosphonates. The mild reaction
arylideneindane-1,3-dione would take place first to afford the conditions allowed the incorporation of wide range of
a
spiropyrazoline derivative 3. The formation of phthalide 4 would synthetically useful functional groups in the substrates. Further
involve the generation of spiropyrazoline 3. Subsequently, the studies on the applications of diazomethylphosphonate in the
nucleophilic attack of methoxide ion at one of the carbonyl moieties synthesis of heterocycles are currently underway in our laboratory.
would result in the ring opening of the spirocyclic 1,3-dione to
afford the enolate intermediate I. Intermediate I cyclizes to afford
the arylidenephthalide derivative II which spontaneously generates
the pyrazolylphthalides derivative 4 through a 1,3-H shift.
Experimental Section
Unless otherwise specified, all reactions were carried out under air
atmosphere in oven dried round-bottom flasks. Dimethyl 2-
oxopropylphosphonate and 1,3-Indanedione were purchased from
commercial sources and were used without further purification.
The reactions were monitored by TLC visualized by UV (254 nm)
and/or with iodine. Flash chromatography was performed on 100-
200 mesh silica gel using the gradient system ethyl acetate-hexane
(0-50%)/Acetone-Dichloromethane (0-30%). NMR data were
recorded at Bruker AV 400 MHz in DMSO-d6/CDCl3 using as internal
standards the residual DMSO signal for 1H NMR (δ = 2.50 ppm),
CHCl3 (δ = 7.26 ppm) respectively. The corresponding deuterated
solvent signal for 13C NMR were assigned as DMSO (δ = 39.51 ppm),
CDCl3 (77.16). Coupling constants are given in Hertz (Hz) and the
classical abbreviations are used to describe the signal multiplicities.
Melting points were measured with a Büchi B-540 apparatus and
are uncorrected. High resolution mass spectra were obtained using
Q-TOF mass spectrometer. All commercially available reagents were
used as received.
Scheme 3 Reaction mechanism.
General procedure for the synthesis of spiropyrazolines 3
To an oven-dried round bottom flask was added 2-(benzylidene)-
1H-indene-1,3(2H)-dione 1a (50 mg, 0.21 mmol) and dissolved in 3
mL of acetone. Subsequently, a solution of Seyferth Gilbert reagent
(33 mg, 0.24 mmol) in 2 mL of acetone was added to the reaction
To get more insight into the mechanism of the phthalide formation,
we carried out an experiment subjecting spiropyrazoline 3a to the
reaction conditions used for phthalide synthesis (NaOH, MeOH) and
pleasingly, the reaction proceeded smoothly to afford the phthalide
mixture and kept stirring. After addition of cesium fluoride (3.0 mg,
derivative 4a in 83% yield (Scheme 4). This experiment confirms
0.021 mmol), the reaction mixture was stirred at 25 °C for 1.5 h.
that the formation of phthalides
4 proceeds through the
After the completion of reaction, as indicated by TLC, solvent was
evaporated off and extracted using ethyl acetate. The organic layer
was dried over Na2SO4 and evaporated under reduced pressure. The
residue was purified using column chromatography (100-200 mesh
silica gel) using acetone/dichloromethane as the eluent to afford
the corresponding spiropyrazoline 3a as a white solid (70 mg) in
87% yield. Rf (Acetone/Dichloromethane: 1/9) = 0.29. Mp 178-180
°C. 13C NMR (100 MHz, ppm/CDCl3): 197.1 (C), 195.4 (C), 142.6 (d, JC-
intermediacy of spiropyrazoline 3a via methanol-induced
rearrangement.
= 227.0 Hz, C), 141.6 (C), 140.1 (C), 136.6 (CH), 136.4 (CH), 131.8
P
(C), 129.5 (CH), 129.5 (CH), 128.7 (CH), 128.5 (CH), 128.5 (CH), 124.1
(CH), 123.5 (CH), 79.1 (d, JC-P = 23.8 Hz, C), 65.3 (d, JC-P = 23.8 Hz,
1
CH), 53.6 (d, JC-P = 5.5 Hz, CH3), 53.4 (d, JC-P = 5.9 Hz, CH3). H NMR
Scheme 4 Mechanistic studies.
(400 MHz, ppm/CDCl3): 7.98 (d, J = 7.6 Hz, 1H), 7.82 (t, J = 7.6 Hz, 1H
), 7.73 (t, J = 7.4 Hz, 1H), 7.54 (d, J = 7.6 Hz, 1H), 7.16-7.15 (m, 3H),
6.93-6.91 (m, 3H), 4.72 (s, 1H), 3.62 (d, J = 11.6 Hz, 3H), 3.58 (d, J =
11.2 Hz, 3H). 31P NMR (161.9 MHz, CDCl3): 8.95. HRMS for
C19H18N2O5P+: calcd. [M+H]+: 385.0948, found: 385.0949.
General procedure for the synthesis of pyrazolylphthalides 4
To an oven-dried round bottom flask was added 2-(benzylidene)-
1H-indene-1,3(2H)-dione 1a (50 mg, 0.21 mmol) and dissolved in 3
mL of MeOH. Subsequently, Seyferth Gilbert reagent (48 mg, 0.33
mmol) in 2 mL of MeOH was added to the reaction mixture and
kept stirring. After addition of Sodium hydroxide (21.0 mg, 0.53
mmol), the reaction mixture was stirred at 25 °C for 1.5 h. After the
completion of reaction, as indicated by TLC, solvent was evaporated
off and extracted using ethyl acetate. The organic layer was dried
Conclusions
In summary, we have uncovered an efficient protocol for the
synthesis of spiropyrazoline phosphonates and pyrazolylphthalides
employing the Seyferth-Gilbert reagent. The reaction of 2-
arylideneindane-1,3-dione
conducted
with
dimethyl
diazomethylphosphonate in acetone gave spiropyrazolineindane-
1,3-dione, while the use of basic methanol provided hitherto
unknown pyrazolylphthalide derivatives. The strategy was explored
for the synthesis of various functionalized spiropyrazolines and
pyrazolylphthalides and was found to be tolerant to a wide range of
4 | J. Name., 2012, 00, 1-3
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5
(a) Â. Monteiro, L. M. Gonçalves and M. M. M. Santos, Eur. J.
Med. Chem., 2014, 79, 266; (b) S. Dadiboyena, Eur. J. Med.
Chem., 2013, 63, 347; (c) W. M. Abdou, M. D. Khidre and R.
E. Khidre, J. Heterocyclic Chem., 2008, 45, 1571.
(a) A. P. Molchanov, V. S. Korotkov and R. R. Kostikov, Russ. J.
Org. Chem., 2004, 40, 470; (b) H. M. Hassaneen, N. M. Elwan
and H. M Hassaneen, Synth. Commun., 2002, 32, 3047.
(a) J. Duan, Y. Cheng, R. Li and P. Li, Org. Chem. Front., 2016,
over Na2SO4 and evaporated under reduced pressure. The residue
was purified using column chromatography (100-200 mesh silica
gel) using acetone/dichloromethane as the eluent to afford
pyrazolylphthalides 4a as a white solid (69 mg) in 86 % yield. Rf
(Acetone/Dichloromethane: 2/8) = 0.42. Mp 162-164 °C. 13C NMR
(100 MHz, ppm/CDCl3): 170.3 (C), 148.1 (C), 146.0 (C), 134.1 (CH),
130.0 (CH), 130.0 (CH), 129.9 (C), 129.3 (CH), 128.5 (C), 128.3 (C),
128.2 (CH), 128.2 (CH), 128.2 (CH), 126.3 (C), 125.4 (CH), 123.1 (CH),
6
7
3, 1614; (b) J. Duan, J. Cheng and P. Li, Org. Chem. Front.,
2015, 2, 1048; (c) Y.-Y. Zhang, R. Gurubrahamam and K.
1
76.0 (CH), 53.4 (CH3), 53.4 (CH3). H NMR (400 MHz, ppm/CDCl3):
12.70 (s, 1H), 7.76 (d, J = 7.6 Hz, 1H), 7.61 (t, J = 7.6 Hz, 1H), 7.47 (t,
J = 7.6 Hz, 1H), 7.33-7.27 (m, 6H), 6.53 (s, 1H), 3.67 (d, J = 11.6 Hz,
3H), 3.58 (d, J = 11.6 Hz, 3H). 31P NMR (161.9 MHz, CDCl3): 8.52.
HRMS for C19H18N2O5P+: calcd. [M+H]+: 385.0948, found: 385.0944.
Chen, Adv. Synth. Catal., 2015, 357, 2457; (d) M. Amireddy
and K. Chen, Tetrahedron, 2015, 71, 8003; (e) S. Anwar, S. M.
Li and K. Chen, Org. Lett., 2014, 16, 2993; (f) H.-H. Kuan, C.-H.
Chien and K. Chen, Org. Lett., 2013, 15, 2880; (g) E. Li, Y.
Huang, L. Liang and P. Xie, Org. Lett., 2013, 15, 3138.
W. M. Abdou, M. D. Khidre and R. E. Khidre, Eur. J. Med.
Chem., 2009, 44, 526.
Crystallographic data for 3k and 4q: CCDC 1547228 and
1547535 contain the supplementary crystallographic data for
this manuscript. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
8
9
Acknowledgements
Financial support from CSIR-CDRI and UGC-New Delhi (Junior
Research Fellowship to A. K. G. and N. K. V.) is gratefully
acknowledged. We thank Dr. Tejender S. Thakur, MSB division,
CSIR-CDRI for supervising the X-ray data collection and structure
determination. We thank SAIF division for analytical support.
10 (a) R. Karmakar, P. Pahari and D. Mal, Chem. Rev., 2014, 114
,
6213; (b) G. Lin, S. S.-K. Chan, H.-S. Chung and S.-L. Li, Stud.
Nat. Prod. Chem., 2005, 32, 611.
11 H. Mitsuhashi, T. Muramatsu, U. Nagai, T. Nakano and K.
Ueno, Chem. Pharm. Bull., 1963, 11, 1317.
12 (a) D. Floryk and E. Huberman, Cancer Lett., 2006, 231, 20;
(b) A. Chapuis, P. Rizzardi, C. D’Agostino, A. Attinger, C.
Knabenhans, S. Fleury, H. Acha-Orbea and G. Pantaleo, Nat.
Notes and references
1
(a) J. C. Gilbert and U. Weerasooriya, J. Org. Chem., 1982, 47,
1837; (b) D. Seyferth, R. S. Marmor and P. Hilbert, J. Org.
Chem., 1971, 36, 1379.
Med., 2000, 6, 762.
2
(a) T. H. Jepsen and J. L. Kristensen, J. Org. Chem., 2014, 79
,
13 (a) C. D. Donner, Tetrahedron, 2013, 69, 3747; (b) D. Mal and
P. Pahari, Chem. Rev., 2007, 107, 1892; (c) K. Rathwell and
M. A. Brimble, Synthesis, 2007, 643; (d) V. Snieckus, Chem.
Rev., 1990, 90, 879.
9423; (b) D. Habrant, V. Rauhala and A. M. P. Koskinen,
Chem. Soc. Rev., 2010, 39, 2007; (c) I. R. Baxendale, S. V. Ley,
A. C. Mansfield and C. D. Smith, Angew. Chem., Int. Ed.,
2009, 48, 4017; (d) D. Luvino, C. Amalric, M. Smietana and J.-
J. Vasseur, Synlett, 2007, 3037; (e) E. Quesada, S. A. Raw, M.
Reid, E. Roman and R. J. K. Taylor, Tetrahedron, 2006, 62
,
6673; (f) G. J. Roth, B. Liepold, S. G. Müller and H. J.
Bestmann, Synthesis, 2004, 59; (g) D. G. Brown, E. J.
Velthuisen, J. R. Commerford, R. G. Brisbois and T. R. Hoye, J.
Org. Chem., 1996, 61, 2540; (h) S. Müller, B. Liepold, G. J.
Roth, and H. J. Bestmann, Synlett, 1996, 521; (i) S. Ohira,
Synth. Commun., 1989, 19, 561.
3
(a) M. Marinozzi, F. Pertusati and M. Serpi, Chem. Rev., 2016,
116, 13991; (b) S. Ahamad, R. Kant and K. Mohanan,
ChemistrySelect, 2016, 1, 5276; (c) M. Marinozzi, S. Tondi, G.
Marcelli and G. Giorgi, Tetrahedron, 2014, 70, 9485; (d) M.
M. D. Pramanik, R. Kant and N. Rastogi, Tetrahedron, 2014,
70, 5214; (e) R. Kumar, D. Nair and I. N. N. Namboothiri,
Tetrahedron, 2014, 70, 1794; (f) S. Mohapatra, C. Bhanja, S.
Jena, S. Chakroborty and S. Nayak, Synth. Commun., 2013,
43, 1993; (g) R. Kumar, D. Verma, S. M. Mobin and I. N. N.
Namboothiri, Org. Lett., 2012, 14, 4070; (h) A. R. Martin, K.
Mohanan, L. Toupet, J.-J. Vasseur and M. Smietana, Eur. J.
Org. Chem., 2011, 3184; (i) R. Muruganantham and I. N. N.
Namboothiri, J. Org. Chem., 2010, 75, 2197; (j) K. Mohanan,
A. R. Martin, L. Toupet, M. Smietana and J.-J. Vasseur,
Angew. Chem., Int. Ed., 2010, 49
Muruganantham, S. M. Mobin and I. N. N. Namboothiri, Org.
Lett., 2007, , 1125.
,
3196; (k) R.
9
4
Synthesis of spiropyrazoline phosphonates: (a) A. K. Gupta, S.
Ahamad, E. Gupta, R. Kant and K. Mohanan, Org. Biomol.
Chem., 2015, 13, 9783; (b) A. M. Shelke and G. Suryavanshi,
Org. Biomol. Chem., 2015, 13, 8669; (c) D. Verma, S. M.
Mobin and I. N. N. Namboothiri, J. Org. Chem., 2011, 76
,
4764; (d) For enantioselective spiropyrazoline phosphonate
synthesis, see: T. Du, F. Du, Y. Ning and Y. Peng, Org. Lett.,
2015, 17, 1308.
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Organic & Biomolecular Chemistry
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DOI: 10.1039/C7OB01417A
Rapid and selective synthesis of spiropyrazolines and
pyrazolylphthalides employing Seyferth-Gilbert reagent
Ashis Kumar Gupta, Narendra Kumar Vaishanv, Ruchir Kant and Kishor Mohanan
An efficient protocol for the selective synthesis of spiropyrazoline phosphonates and
pyrazolylphthalides employing Seyferth-Gilbert reagent is reported.