Construction of highly substituted pyrazole derivatives with P-C bond: Access to racemic and enantioselective forms by conjugate addition of diarylphosphane oxides to α,β-unsaturated pyrazolones

Article abstract of DOI:10.1016/j.tet.2013.11.038

The synthesis of organophosphorus compounds is of great importance to industrial, agricultural, and pharmaceutical chemistry. In this paper, we have reported the synthesis of highly substituted pyrazole derivatives through P-C bond formation under catalys

Full text of DOI:10.1016/j.tet.2013.11.038

Tetrahedron 70 (2014) 417e426
Contents lists available at ScienceDirect
Tetrahedron
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Construction of highly substituted pyrazole derivatives with PeC
bond: access to racemic and enantioselective forms by conjugate
addition of diarylphosphane oxides to a,b-unsaturated pyrazolones
Zhi-Cong Geng a, Jin-Xin Zhang a, Ning Li a, Jian Chen a, Xiao-Fei Huang a,
,
a,
*
Shao-Yun Zhang a, Hai-Yan Li a, Jing-Chao Tao b , Xing-Wang Wang
*
a Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University,
Suzhou 215123, PR China
b Department of Chemistry, Zhengzhou University, Zhengzhou 450001, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 17 August 2013
Received in revised form 6 November 2013
Accepted 14 November 2013
Available online 20 November 2013
The synthesis of organophosphorus compounds is of great importance to industrial, agricultural, and
pharmaceutical chemistry. In this paper, we have reported the synthesis of highly substituted pyrazole
derivatives through PeC bond formation under catalyst-free conditions. On the other hand, the first
catalytic asymmetric version of this reaction has also been developed under catalysis by an isosteviol
derived thiourea organocatalyst. The optically active phosphorus-containing compounds have been
obtained in good chemical yields with moderate enantioselectivities.
Keywords:
Diarylphosphane oxide
Ó 2013 Elsevier Ltd. All rights reserved.
a,b-Unsaturated pyrazolone
Catalyst-free
Organo-catalysis
Isosteviol derived thiourea
1. Introduction
Michael addition has also been well achieved by metal-catalysis6 or
organo-catalysis.7
In recent years, organophosphorus compounds have been
widely studied, because they not only serve as a valuable class of
building blocks, but also play an important role in industrial, agri-
cultural, and pharmaceutical chemistry because of their wide
spectrum biological activities (Fig. 1).1 PeC bond formations can be
constructed in various methods. Among them, Michael addition
reaction of trivalent and pentavalent phosphorus species to
electron-poor alkenes was a straightforward and efficient strategy.2
It was usually promoted by bases, Lewis acids and also microwave
condition.3 The direct addition of diaryl or dialkylphosphine oxides
(R2P(O)H) to activated alkenes was a convenient and efficient
method to the synthesis of stable precursors of phosphine com-
pounds.4 Because of the importance of phosphines used as ligands
in metal-catalysis or organocatalyst,5 so, the development of new
and efficient reaction to access this transformation is necessary.
Besides, asymmetric synthesis of organophosphorus compound via
Pyrazole, a five-membered heterocycle compound containing
two adjacent nitrogen atoms, is a motif found in a number of small
molecules that possess a wide range of agricultural and pharma-
ceutical activities (Fig.1).8 They could be achieved by Knorr reaction
of hydrazine derivatives with 1,3-dicarbonyl compounds,9 1,3-
dipolar cycloaddition,10 and other methods.11 Among them, the
addition of nucleophile to a,b-unsaturated pyrazolones was a direct
and efficient method to synthesize pyrazol-5-ol. However, there
were only a few reports on this kind of transformations. In 1999,
Menget al. reported the solid-state Michael addition of indole to a,b-
unsaturated pyrazolones.12 Two years later, Khidre and co-workers
reported the Michael addition of alkyl phosphites or hexamethyl-
phosphorus triamides to
noted that the products were obtained with 75e85% yield at 100 ꢀC.
So, we are interested in the search of new nucleophile with a,b-
a,b
-unsaturated pyrazolones.13 It should be
unsaturated pyrazolones as acceptor under mild reaction condi-
tions. Based on our previous work on constructing carbon-hetero-
atom bond and the importance of molecules containing phosphines
atoms, herein, we wish to report our preliminary work about the
* Corresponding author. Fax: þ86 512 6588 0378 (X.-W.W.); fax: þ86 371 6776
7200 (J.-C.T); e-mail addresses: jctao@zzu.edu.cn (J.-C. Tao), wangxw@suda.edu.cn
(X.-W. Wang).
addition of diarylphosphane oxides to a,b-unsaturated pyrazolones
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.11.038

418
Z.-C. Geng et al. / Tetrahedron 70 (2014) 417e426
Fig. 1. Some phosphorus and pyrazole-substituted important compounds.
in racemic form under catalyst-free conditions and chiral form cat-
alyzed by isosteviol derived thiourea organocatalyst developed by
Tao’s and our group.14
as solvent, the reaction was proceeded completely for about 15 min
and the product was obtained in 96% yield (Table 1, entry 8). The
molar ratio of 1a to 2a and diarylphosphane oxide substrates 1b
and 1c with methyl substituents on the phenyl rings were further
investigated for this transformation (Table 1, entries 9e14). Finally,
the optimal reaction conditions were finally established as the re-
action being performed for diphenyl oxide 1a as nucleophile with
2:1 molar ratio of 1a to 2a in diethyl ether for further substrate
scope.
2. Results and discussion
Initially, we found that the Michael reaction between 1a and 2a
was smoothly proceeded in CHCl3 in the absence of catalyst to
furnish the desired product 3a in 88% yield (Table 1, entry 1). With
this result in hand, the screening of solvents for Michael addition of
With the optimized reaction conditions in hand, the substrate
scope of this reaction was then investigated and the results were
diphenyl oxide 1a to a,b-unsaturated pyrazolone 2a was further
summarized in Table 2. All the reactions between 1a and
a,b-
carried out. As we could see from Table 1, the solvents showed great
influence on the reactivity (Table 1, entries 1e8). With diethyl ether
Table 2
Substrate scope
Table 1
Optimization of the reaction conditions and diarylphosphane oxides
Entrya
R1/R2/R3
Time (min)
Product
Yieldb (%)
1
2
3
4
5
6
7
8
Ph/Me/Ph/2a
20
20
20
30
7
120
150
90
40
140
40
180
60
5
10
30
35
15
30
35
3a
3b
3c
3d
3e
3f
3g
3h
3i
96
97
95
98
97
99
97
94
96
98
95
93
93
96
94
93
95
93
94
94
4-ClC6H4/Me/Ph/2b
4-BrC6H4/Me/Ph/2c
3-ClC6H4/Me/Ph/2d
2,4-Cl2C6H3/Me/Ph/2e
4-MeC6H4/Me/Ph/2f
4-MeOC6H4/Me/Ph/2g
4-MeSC6H4/Me/Ph/2h
3,5-(MeO)2C6H3/Me/Ph/2i
3,4-(OCH2O)C6H3/Me/Ph/2j
2-Naphthyl/Me/Ph/2k
2-Furyl/Me/Ph/2l
Ph/Me/4-BrC6H4/2m
Ph/CF3/Ph/2n
Ph/CF3/4-BrC6H4/2o
4-ClC6H4/Me/4-BrC6H4/2p
4-BrC6H4/Me/4-BrC6H4/2q
Ph/Me/4-ClC6H4/2r
Entrya
1 (mmol)
2a (mmol)
Solvent
Time (min)
Yieldb (%)
1
2
3
4
5
6
7
8
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.25
0.2
0.15
0.11
0.2
0.2
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
CHCl3
CH2Cl2
MeOH
MeCN
Toluene
THF
EtOAc
Et2O
Et2O
Et2O
Et2O
Et2O
Et2O
420
270
100
60
45
45
30
15
20
20
3a/88
3a/91
3a/89
3a/91
3a/95
3a/93
3a/92
3a/96
3a/95
3a/96
3a/95
3a/96
4a/96
5a/95
9
10
11
12
13
14
15
16
17
18
19
20
3j
3k
3l
9
3m
3n
3o
3p
3q
3r
3s
3t
10
11
12
13c
14d
50
90
60
60
Et2O
4-ClC6H4/Me/4-ClC6H4/2s
4-BrC6H4/Me/4-ClC6H4/2t
a
Unless noted, the reactions were carried out with 1, 2a in Et2O (1.0 mL) at room
temperature.
b
c
a
Isolated yield.
Unless noted, the reactions were carried out with 1a (0.60 mmol), 2 (0.3 mmol)
With 1b as substrate.
With 1c as substrate.
in Et2O (3.0 mL) at room temperature.
d
b
Isolated yield.

Z.-C. Geng et al. / Tetrahedron 70 (2014) 417e426
419
Scheme 1. The addition of diphenylphosphine oxide 1a to
2a on gram-scale.
a
,
b-unsaturated pyrazolone
unsaturated pyrazolones 2aet were proceeded smoothly and the
products were obtained in high yields (93e99%) within 5e150 min
(Table 2, entries 1e20). Generally, the reactions for a,b-unsaturated
Scheme 2. Proposed transition state and mechanism.
pyrazolones 2bee with electron-withdrawing groups on the aro-
matic rings were proceeded more fast (7e30mins) (Table 2, entries
Then, we turned our attention to the development of the
asymmetric version of this reaction.16 Because the background re-
action could take place readily at room temperature, the model
reaction of 1a and 2a was carried out at 0 ꢀC with toluene as solvent
in the presence of 20 mol % of chiral organocatalyst and the results
were summarized in Table 3. A series of chiral organocatalysts 6aeo
were screened (Table 3, entries 1e15). Quinine and its derivatives
6aed were firstly tested and very low enantioselectivities were
observed. (Table 3, entries 1e4). The tertiary amino-thiourea
organocatalysts 6e and 6f also showed disappointing catalytic re-
sults (Table 3, entries 5 and 6).17 Chiral squaramides organo-
catalysts 6gej could not improve the enantioselectivity of the
desired products (Table 3, entries 7e10).18 Subsequently, chiral
organocatalysts 6keo were further investigated (Table 3, entries
11e15). To our delight, chiral organocatalyst 6l gave the promising
result and the product was obtained in 95% yield and 40% enan-
tioselectivity (Table 3, entry 12).
2e5), whereas the reactions for a,b-unsaturated pyrazolones 2fej
bearing electron-donating groups on the aromatic rings were car-
ried out longer reaction time (40e150mins) to complete (Table 2,
entries 6e10). The 2-naphthyl substituted
a,b-unsaturated pyr-
azolone 2k showed quite good performance to give the desired
product 3k in 95% yield with 40 min (Table 2, entry 11). When the
substrate 2l with 2-furyl group was used for the reaction, 93% yield
was obtained, although with longest reaction time (Table 2, entry
12). In addition, more
a,b-unsaturated pyrazolones 2met with
different R2 and R3 groups were also investigated. To our delight, all
these substrates 2met were also well tolerated for this trans-
formation, and the corresponding products 3met were, re-
spectively, obtained in 93e96% yield within 35 min (Table 2, entries
13e20). To further evaluate the synthetic potential of this reaction
system, gram-scale synthesis of the product 3a was performed. As
shown in Scheme 1, the product 3a could be obtained in 94% yield
in 30 min. Fortunately, the single crystals of racemic compounds 3c
and 3g were obtained by recrystallization from CDCl3, and the
relative configurations of the desired compounds were un-
ambiguously determined by X-ray analyses (Fig. 2).15
With 6l as the optimal chiral organocatalyst, the reaction
conditions were further optimized by adjusting several reaction
parameters, including reaction temperature, reaction medium,
Fig. 2. X-ray crystal structures of racemic 3c and 3g.
Although the mechanistic detail remains ambiguous, it is pre-
sumed that the diphenylphosphine oxides firstly equilibrate with
the tautomer phosphinous acids, which is the nucleophilic form.
substrate concentration, catalyst loading, additives, and diary-
lphosphane oxide substrates, and the results were summarized in
Table 4. Firstly, some common solvents were screened for this
transformation, and toluene was proved to be the best solvent (Table
4, entry 1 vs entries 2e7). When the temperature was dropped
to ꢁ40 ꢀC, the enantioselectivity of product 3a was increased from
40% to 48% (Table 4, entry 8 vs 1). To our delight, the enantiose-
The phosphinous acids activate the
a,b-unsaturated pyrazolones
through the hydrogen bonding and the intramolecular Michael
addition is smoothly proceeded, which provides the intermediate I
of Michael addition. Subsequently, aromatization of intermediate I
generates the desired products (Scheme 2).
ꢀ
lectivity could be further improved to 61% by adding activated 4 A

420
Z.-C. Geng et al. / Tetrahedron 70 (2014) 417e426
Table 3
Optimization of chiral organocatalysts
Entrya
Cat
Time (h)
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
6l
6m
6n
6o
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
95
93
91
95
81
93
86
92
94
80
87
95
92
90
88
17
2
1
12
2
15
7
24
14
1
14
40
30
20
26
9
10
11
12
13
14
15
a
Unless noted, the reactions were carried out with 1a (0.15 mmol), 2a (0.1 mmol), and 6 (20 mol %) in toluene (2.0 mL) at 0 ꢀC.
Isolated yield.
Determined by chiral HPLC analysis.
b
c

Z.-C. Geng et al. / Tetrahedron 70 (2014) 417e426
421
Table 4
3. Conclusion
Optimization of the reaction conditions
In conclusion, we have developed the conjugate addition re-
action of diarylphosphane oxides to -unsaturated pyrazolones in
a,b
high yields under catalyst-free conditions. The asymmetric version
of this conjugate addition has also been realized with the isosteviol
derived thiourea 6l as an organocatalyst. A series of enantiomeri-
cally enriched phosphorus-containing compounds have been ob-
tained in moderate to good chemical yields with moderate
enantioselectivities. The development of new chiral organocatalyst
to improve both the reactivity and enantioselectivity of this re-
action is now in progress in our lab.
Entrya
Solvent
T (ꢀC)
Concn (M)
Time (h)
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
Toluene
o-Xylene
Mesitylene
PhCl
CH2Cl2
(ClCH2)2
Et2O
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
0
0
0
0
0
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.025
0.020
0.025
0.025
12
12
12
20
40
40
2
60
60
60
60
60
84
84
96
96
3a/95
3a/95
3a/97
3a/92
3a/72
3a/78
3a/95
3a/85
3a/78
3a/77
3a/78
3a/89
3a/85
3a/76
4a/46
5a/50
40
39
39
34
30
28
25
48
56
60
61
70
73
74
48
44
4. Experimental section
4.1. General
0
0
8
ꢁ40
ꢁ40
ꢁ40
ꢁ40
ꢁ40
ꢁ40
ꢁ40
ꢁ40
ꢁ40
Unless otherwise stated, all reagents were purchased from
commercial suppliers and used without further purification. All
reactions were carried out in air and using undistilled solvent,
without any precautions to exclude moisture unless otherwise
noted. Organic solutions were concentrated under reduced pressure
on an EYELA N-1001 rotary evaporator. Reactions were monitored
by thin-layer chromatography (TLC) on silica gel precoated glass
plates (0.2ꢂ0.03 mm thickness, GF-254, particle size 0.01e0.04 mm)
from Yantai Chemical Industry Research Institute, P.R. China. Chro-
matograms were visualized by fluorescence quenching with UV
light at 254 nm. Flash column chromatography was performed using
silica gel (particle size 0.04e0.05 mm) from Yantai Chemical In-
dustry Research Institute, P.R. China. 1H and 13C NMR spectra were
recorded in CDCl3 on Varian Inova (400 MHz or 300 MHz and
100 MHz or 75 MHz, respectively) spectrometer. Chemical shifts
9d
10e
11f
12g,f
13g,h
14g,i
15g,h,j
16g,h,k
a
Unless noted, the reactions were carried out with 1 (0.15 mmol), 2a (0.1 mmol),
and 6l (20 mol %) in solvent (2.0 mL) at 0 ꢀC.
b
Isolated yield.
Determined by chiral HPLC analysis.
With additive Na2SO4 200 mg.
With additive MgSO4 200 mg.
With additive 4 A MS 200 mg.
With 30 mol % of catalyst.
With additive 4 A MS 400 mg, in 4.0 mL toluene.
With additive 4 A MS 500 mg, in 5.0 mL toluene.
c
d
e
f
ꢀ
g
h
ꢀ
i
ꢀ
(d
ppm) are relative to the resonance of the deuterated solvent as the
internal standard (CDCl3, 7.27 ppm for proton NMR, 77.23 ppm for
carbon NMR).1H NMR data are reported as follows: chemical shift (
j
With lb as substrate, in 4.0 mL toluene.
With lc as substrate, in 4.0 mL toluene.
d
d
k
d
,
ppm), multiplicity (s¼singlet, d¼doublet, q¼quartet, m¼multiplet),
coupling constants (J), and assignment. Data for 13C NMR are re-
ported in terms of chemical shift (d, ppm). High-resolution mass
molecular sieves at ꢁ40 ꢀC in toluene (Table 4, entry 11). After in-
vestigating the effects of substrate concentration, catalyst loading,
and diarylphosphane oxides (Table 4, entries 13e16), the best cat-
alytic results (85% yield, 73% ee) were obtained by using diphenyl
oxide 1a as nucleophile with the concentration of 0.025 M to 2a and
30 mol % catalyst loading (Table 4, entry 13).
spectra (HRMS) for all the compounds were determined on Micro-
mass GCT-TOF mass spectrometer with ESI resource. High perfor-
mance liquid chromatography (HPLC) was performed on an Agilent
1200 Series chromatographs using a Daicel Chiralpak AD-H, OD-H
column (0.46 cmꢃ25 cm). X-ray data were recorded on a Rigaku
Mercury CCD/AFC diffractometer. Optical rotations are reported as
Having established the optimized reaction conditions, the scope
of the substrate was then explored wꢀith thiourea 6l (30 mol %) as
follows: [
a]
rt (c in g per 100 mL, solvent).
D
ꢀ
the organocatalyst in toluene at ꢁ40 C with 4 A molecular sieves
as additive and the results were summarized in Table 5. A variety of
4.2. General experimental procedure for conjugate addition
a
,
b
-unsaturated pyrazolone derivatives 2 were examined to study
the effects of electronic property and steric hindrance on enan-
tioselectivities and reactivities. The -unsaturated pyrazolone
of diarylphosphane oxides to
racemic form
a,b-unsaturated pyrazolones in
a,b
derivatives 2bed with electron-deficient or 2feh with electron-
rich substituents in m-, or p-position of aromatic ring gave the
desired products 3bed, 3feh in 61e91% yield and 67e75% enan-
tioselectivity, respectively (Table 5). The substrate 2k with mod-
erately electron-rich 2-naphthyl system was also well tolerated,
and the reaction provided the desired product 3k in 75% yield with
76% enantioselectivity (Table 5). In addition, 92% yield and 58% ee
In an ordinary tube equipped with a magnetic stirring bar, the
solution of diarylphosphane oxides 1 (0.6 mmol) in Et2O (3.0 mL)
was added
a,b-unsaturated pyrazolone 2 (0.30 mmol) at room
temperature. After the reaction mixture was stirred for 5e180 min
at room temperature. The reaction mixture was directly loaded
onto a silica gel and purified by flash chromatography (eluant:
petroleum ether/dichloromethane or petroleum ether/ethyl ace-
tate) to give desired products 3e5.
were obtained with aromatic heterocyclic
a
,b
-unsaturated pyr-
azolone 2l (Table 5). Besides, R3 group of
a,b-unsaturated pyr-
azolones were also examined. With 2m and 2r as substrates, the
products 3m and 3r were obtained in good yields with moderate
enantioselectivities (Table 5). However, when 2p, 2q, 2s, and 2t
were employed as the substrates, the products were obtained in
only moderate yields and enantioselectivities. We thought that low
solubility of these substrates in the toluene leaded to the relatively
poor results.
4.2.1. 4-((Diphenylphosphoryl)(phenyl)methyl)-3-methyl-1-phenyl-
1H-pyrazol-5-ol (3a). Yield 96%, 1H NMR (400 MHz, CDCl3):
d 12.86
(s, 1H), 7.86 (dd, J¼11.0, 7.2 Hz, 2H), 7.77 (d, J¼7.6 Hz, 2H), 7.60e7.55
(m,1H), 7.54e7.45 (m, 2H), 7.44e7.34 (m, 5H), 7.29 (dd, J¼7.6, 2.8 Hz,
2H), 7.24e7.18 (m, 3H), 7.16e7.10 (m, 3H), 4.59 (d, J¼11.6 Hz,1H), 2.15
(s,1H); 13C NMR (75 MHz, CDCl3)
JC,P¼9.75 Hz),139.12,136.14 (d, JC,P¼3.75 Hz),132.73 (d, JC,P¼1.50 Hz),
d
151.93 (d, JC,P¼4.50 Hz),147.35 (d,

422
Z.-C. Geng et al. / Tetrahedron 70 (2014) 417e426
Table 5
Substrate scope of asymmetric additiona
132.35(d, JC,P¼2.25 Hz),131.32(d, JC,P¼9.0Hz),130.99(d, JC,P¼9.0Hz),
129.34 (d, JC,P¼5.25 Hz), 129.16 (d, JC,P¼11.25 Hz), 128.75, 128.52,
128.37 (d, JC,P¼12.00 Hz), 127.29 (d, JC,P¼1.50 Hz), 125.61, 121.62,
95.26 (d, JC,P¼4.50 Hz), 44.25 (d, JC,P¼64.50 Hz), 12.98; 31P NMR
d
12.80 (s, 1H), 7.90e7.80 (m, 2H), 7.75 (d, J¼7.6 Hz, 2H), 7.58 (t,
J¼7.2 Hz,1H), 7.55e7.28 (m, 9H), 7.20 (t, J¼7.2 Hz,1H), 7.16e7.08 (m,
4H), 4.57 (d, J¼11.6 Hz, 1H), 2.14 (s, 1H); 13C NMR (75 MHz, CDCl3)
d
151.81 (d, JC,P¼5.25 Hz), 147.16 (d, JC,P¼9.00 Hz), 138.99, 134.74 (d,
(121 MHz, CDCl3)
d
42.24; IR (KBr) nmax: 3447.6, 3058.2, 3029.7,
JC,P¼3.75 Hz), 133.21 (d, JC,P¼2.25 Hz), 132.82 (d, JC,P¼1.50 Hz),
132.56 (d, JC,P¼¼2.25 Hz), 131.22 (d, JC,P¼9.00 Hz), 130.86 (d,
JC,P¼9.00 Hz), 130.56 (d, JC,P¼4.50 Hz), 129.17 (d, JC,P¼12.00 Hz),
128.75, 128.62, 128.45, 125.68, 121.58, 94.88 (d, JC,P¼4.50 Hz), 43.58
1595.5,1523.4,1498.1,1451.1,1436.9,1137.6, 752.7, 724.8, 699.7 cmꢁ1
;
HRMS (ESI): m/z¼487.1528 (calcd for C29H25N2O2PþNaþ¼487.1546).
4.2.2. 4-((4-Chlorophenyl)(diphenylphosphoryl)methyl)-3-methyl-1-
(d, JC,P¼64.50 Hz),12.92; 31P NMR (121 MHz, CDCl3)
d 41.87; IR (KBr)
phenyl-1H-pyrazol-5-ol (3b). Yield 97%, 1H NMR (400 MHz, CDCl3):
nmax: 3471.3, 3058.6, 1591.5, 1574.0, 1521.6, 1488.7, 1455.9, 1140.1,

Z.-C. Geng et al. / Tetrahedron 70 (2014) 417e426
423
879.6, 849.3, 756.1 cmꢁ1; HRMS (ESI): m/z¼521.1144 (calcd for
CDCl3):
d
12.84 (s, 1H), 7.95e7.77 (m, 2H), 7.76 (d, J¼8.0 Hz, 2H),
C
29H24ClN2O2PþNaþ¼521.1156).
7.63e7.45 (m, 3H), 7.45e7.26 (m, 7H), 7.25e7.15 (m, 1H), 7.11 (d,
J¼7.6 Hz, 2H), 6.68 (d, J¼8.0 Hz, 2H), 4.55 (d, J¼11.2 Hz, 1H), 3.73 (s,
4.2.3. 4-((4-Bromophenyl)(diphenylphosphoryl)methyl)-3-methyl-1-
3H), 2.15 (s, 3H); 13C NMR (101 MHz, CDCl3)
d 158.83, 151.89 (d,
phenyl-1H-pyrazol-5-ol (3c). Yield 95%, 1H NMR (400 MHz, CDCl3):
JC,P¼3.75 Hz), 147.29 (d, JC,P¼6.00 Hz), 139.20, 132.75 (d,
JC,P¼1.50 Hz), 132.40, 131.45 (d, JC,P¼6.75 Hz), 131.08 (d,
JC,P¼6.75 Hz), 130.45 (d, JC,P¼3.00 Hz), 129.21 (d, JC,P¼8.25 Hz),
128.83, 128.48 (d, JC,P¼9.00 Hz), 128.09 (d, JC,P¼2.25 Hz), 125.67,
121.70, 114.00, 95.59 (d, JC,P¼3.00 Hz), 55.38, 43.33 (d,
d
12.78 (s, 1H), 7.90e7.80 (m, 2H), 7.75 (d, J¼8.0 Hz, 2H), 7.57 (t,
J¼7.2 Hz, 1H), 7.55e7.30 (m, 10H), 7.30e7.25 (m, 1H), 7.20 (t,
J¼7.2 Hz, 1H), 7.06 (d, J¼7.6 Hz, 2H), 4.55 (d, J¼11.2 Hz, 1H), 2.13 (s,
1H); 13C NMR (75 MHz, CDCl3)
d
151.86 (d, JC,P¼5.25 Hz), 147.18 (d,
JC,P¼9.00 Hz), 139.04, 135.32 (d, JC,P¼3.75 Hz), 132.91 (d,
JC,P¼2.25 Hz), 132.65 (d, JC,P¼2.25 Hz), 131.64, 131.32 (d,
JC,P¼9.60 Hz), 131.00, 130.92, 129.26 (d, JC,P¼12.00 Hz), 128.82,
128.63 (d, JC,P¼12.00 Hz), 125.78, 121.69, 94.83 (d, JC,P¼4.50 Hz),
JC,P¼48.75 Hz), 13.04; 31P NMR (121 MHz, CDCl3)
d 42.08; IR (KBr)
nmax: 3477.0, 3415.2, 3057.5, 2903,6, 1591.2, 1519.9, 1498.1, 1455.5,
1248.8, 1138.1, 840.1, 761.6 cmꢁ1; HRMS (ESI): m/z¼495.1813 (calcd
for C30H27N2O3PþHþ¼495.1832).
43.77 (d, JC,P¼63.75 Hz), 13.00; 31P NMR (121 MHz, CDCl3)
d 41.66;
IR (KBr) nmax: 3479.6, 3056.3, 2955.2, 1594.3, 1522.2, 1485.2, 1455.2,
1436.2, 1143.6, 868.9, 840.6 cmꢁ1; HRMS (ESI): m/z¼565.0627
(calcd for C29H24BrN2O2PþNaþ¼565.0651).
4.2.8. 4-((Diphenylphosphoryl)(4-(methylthio)phenyl)methyl)-3-
methyl-1-phenyl-1H-pyrazol-5-ol (3h). Yield 94%, 1H NMR
(400 MHz, CDCl3):
d 12.81 (s, 1H), 7.90e7.80 (m, 2H), 7.75 (d,
J¼8.0 Hz, 2H), 7.60e7.55 (m, 1H), 7.55e7.46 (m, 2H), 7.46e7.30 (m,
7H), 7.20 (t, J¼7.6 Hz, 1H), 7.11 (d, J¼7.2 Hz, 2H), 7.03 (d, J¼8.0 Hz,
2H), 4.55 (d, J¼11.6 Hz, 1H), 2.41 (s, 3H), 2.14 (s, 3H); 13C NMR
4.2.4. 4-((3-Chlorophenyl)(diphenylphosphoryl)methyl)-3-methyl-1-
phenyl-1H-pyrazol-5-ol (3d). Yield 98%, 1H NMR (400 MHz, CDCl3):
d
12.79 (s,1H), 7.90e7.80 (m, 2H), 7.77 (d, J¼7.6 Hz, 2H), 7.65e7.55 (m,
(75 MHz, CDCl3)
d
151.92 (d, JC,P¼5.25 Hz), 147.27 (d, JC,P¼9.00 Hz),
1H), 7.55e7.45 (m, 3H), 7.43e7.30 (m, 6H), 7.20 (t, J¼7.2 Hz, 1H),
139.15, 137.65 (d, JC,P¼3.00 Hz), 132.90 (d, JC,P¼4.50 Hz), 132.82 (d,
JC,P¼2.25 Hz), 132.51 (d, JC,P¼3.00 Hz), 131.43 (d, JC,P¼9.75 Hz),
131.04 (d, JC,P¼8.25 Hz), 129.77 (d, JC,P¼4.50 Hz), 129.24 (d,
JC,P¼11.25 Hz), 128.84, 128.55 (d, JC,P¼12.00 Hz), 126.65 (d,
JC,P¼0.75 Hz), 125.73, 121.72, 95.21 (d, JC,P¼4.50 Hz), 43.74 (d,
7.15e7.07 (m, 3H), 7.07 (s,1H), 4.55 (d, J¼11.6 Hz,1H), 2.15 (s, 3H); 13
C
NMR (75 MHz, CDCl3)
d
151.99 (d, JC,P¼5.25 Hz), 147.27 (d,
JC,P¼9.00 Hz),139.07,138.14 (d, JC,P¼4.50 Hz),134.22 (d, JC,P¼2.25 Hz),
132.96 (d, JC,P¼2.25 Hz), 132.71 (d, JC,P¼2.25 Hz), 131.35 (d,
JC,P¼9.75 Hz), 131.03 (d, JC,P¼9.00 Hz), 129.80, 129.44, 129.37, 129.21,
128.83, 128.59 (d, JC,P¼9.00 Hz), 127.54, 125.79, 121.72, 94.61 (d,
JC,P¼4.50 Hz), 44.13 (d, JC,P¼64.50 Hz), 13.02; 31P NMR (121 MHz,
JC,P¼65.25 Hz), 15.90, 13.03; 31P NMR (121 MHz, CDCl3)
d 41.88; IR
(KBr) nmax: 3478.3, 3053.7, 2923.4, 1591.1, 1521.4, 1496.6, 1437.2,
1139.9, 758.2, 691.3 cmꢁ1; HRMS (ESI): m/z¼533.1404 (calcd for
CDCl3)
d
42.00; IR (KBr) nmax: 3472.0, 3416.1, 3053.3, 2916.9, 1593.6,
C
30H27N2O2PSþNaþ¼533.1423).
1589.4,1525.0,1481.9,1438.9,1142.0, 892.8, 763.8, 689.4cmꢁ1; HRMS
(ESI): m/z¼499.1320 (calcd for C29H24ClN2O2PþHþ¼499.1337).
4.2.9. 4-((3,5-Dimethoxyphenyl)(diphenylphosphoryl)methyl)-3-
methyl-1-phenyl-1H-pyrazol-5-ol (3i). Yield 96%,1H NMR (400 MHz,
4.2.5. 4-((2,4-Dichlorophenyl)(diphenylphosphoryl)methyl)-3-
CDCl3):
d
12.80 (s, 1H), 7.90e7.80 (m, 2H), 7.75 (d, J¼8.0 Hz, 2H),
methyl-1-phenyl-1H-pyrazol-5-ol (3e). Yield 97%, 1H NMR
7.62e7.28 (m, 10H), 7.25e7.15 (m, 1H), 6.37 (s, 2H), 6.25 (s, 1H), 4.52
(400 MHz, CDCl3):
d
12.93 (s,1H), 7.95e7.85 (m, 3H), 7.74 (d, J¼8.0 Hz,
(d, J¼11.6 Hz,1H), 3.64 (s, 6H), 2.16 (s, 3H); 13C NMR (75 MHz, CDCl3)
2H), 7.65e7.50 (m, 3H), 7.46 (t, J¼7.2 Hz, 1H), 7.38 (t, J¼7.2 Hz, 4H),
d
160.65, 152.03 (d, JC,P¼4.50 Hz), 147.34 (d, JC,P¼9.00 Hz), 139.15,
7.33e7.28 (m, 3H), 7.20 (t, J¼7.2 Hz, 1H), 7.10 (s, 1H), 5.39 (d,
138.22 (d, JC,P¼3.00 Hz), 132.59 (d, JC,P¼4.50 Hz), 132.78, 132.40,
131.45 (d, JC,P¼9.75 Hz), 131.03 (d, JC,P¼9.00 Hz), 129.19 (d,
JC,P¼12.00 Hz), 128.79, 128.45 (d, JC,P¼12.00 Hz), 125.68, 121.73,
107.45 (d, JC,P¼4.50 Hz), 99.68, 95.04 (d, JC,P¼5.25 Hz), 55.38, 44.52
J¼12.0 Hz, 1H), 2.16 (s, 1H); 13C NMR (75 MHz, CDCl3)
d 152.13 (d,
JC,P¼4.50Hz),147.68(d, JC,P¼9.00Hz),139.03,133.98(d, JC,P¼3.00Hz),
133.63 (d, JC,P¼3.00 Hz), 133.45 (d, JC,P¼6.75 Hz), 133.13 (d,
JC,P¼2.25 Hz),132.83 (d, JC,P¼2.25 Hz),132.61 (d, JC,P¼3.00 Hz),131.48
(d, JC,P¼9.75 Hz), 131.17 (d, JC,P¼9.00 Hz), 129.37 (d, JC,P¼12.00 Hz),
128.85,128.75,128.45,128.28,125.86,121.75, 94.89 (d, JC,P¼5.25 Hz),
(d, JC,P¼65.25 Hz),13.04; 31P NMR (121 MHz, CDCl3)
d 42.14; IR (KBr)
nmax: 3477.6, 3414.9, 3067.6, 2993.3, 2955.7, 1595.4, 1455.7, 1420.1,
1204.4, 1140.1, 838.4, 764.3, 706.5 cmꢁ1; HRMS (ESI): m/z¼547.1743
(calcd for C31H29N2O4PþNaþ¼547.1757).
39.19 (d, JC,P¼65.25 Hz),13.24; 31P NMR (121 MHz, CDCl3)
d 42.01; IR
(KBr) nmax: 3476.0, 3415.1, 3058.6, 1592.6, 1573.5, 1522.7, 1476.9,
1438.0,1138.6, 752.6, 693.6 cmꢁ1; HRMS (ESI): m/z¼533.0927 (calcd
for C29H24Cl2N2O2PþHþ¼533.0947).
4.2.10. 4-(Benzo[d][1,3]dioxol-5-yl(diphenylphosphoryl)methyl)-3-
methyl-1-phenyl-1H-pyrazol-5-ol (3j). Yield 98%,1H NMR (400 MHz,
CDCl3):
d
12.80 (s, 1H), 7.92e7.78 (m, 2H), 7.76 (d, J¼7.6 Hz, 2H),
4.2.6. 4-((Diphenylphosphoryl)(p-tolyl)methyl)-3-methyl-1-phenyl-
7.60e7.40 (m, 6H), 7.40e7.30 (m, 4H), 7.19 (d, J¼7.6 Hz, 1H), 6.84 (s,
1H), 6.55 (s, 2H), 5.88 (d, J¼14.4 Hz, 2H), 4.51 (d, J¼11.6 Hz, 1H), 2.15
1H-pyrazol-5-ol (3f). Yield 99%, 1H NMR (400 MHz, CDCl3):
d 12.82
(s, 1H), 7.90e7.80 (m, 2H), 7.76 (d, J¼8.0 Hz, 2H), 7.60e7.45 (m, 3H),
7.45e7.33 (m, 5H), 7.32e7.27 (m, 2H), 7.18 (t, J¼7.2 Hz, 1H), 7.09 (d,
J¼7.2 Hz, 2H), 6.95 (d, J¼7.6 Hz, 2H), 6.06 (d, J¼11.6 Hz, 1H), 2.24 (s,
(s, 3H); 13C NMR (75 MHz, CDCl3)
d
151.78 (d, JC,P¼4.50 Hz), 147.88,
147.26 (d, JC,P¼9.00 Hz), 146.87 (d, JC,P¼2.25 Hz), 139.10, 132.74,
132.45 (d, JC,P¼1.50 Hz), 131.38 (d, JC,P¼9.00 Hz), 130.97 (d,
JC,P¼9.00 Hz), 129.84 (d, JC,P¼3.75 Hz), 129.18 (d, JC,P¼11.25 Hz),
128.79, 128.49 (d, JC,P¼12.00 Hz), 128.68, 122.67 (d, JC,P¼6.00 Hz),
121.69,109.80 (d, JC,P¼3.75 Hz),108.07,101.18, 95.42 (d, JC,P¼4.50 Hz),
65.99, 43.83 (d, JC,P¼65.25 Hz), 12.98; 31P NMR (121 MHz, CDCl3)
3H), 2.14 (s, 3H); 13C NMR (75 MHz, CDCl3)
d
151.89 (d, JC,P¼5.25 Hz),
147.28 (d, JC,P¼9.75 Hz), 139.16, 136.94 (d, JC,P¼3.00 Hz), 133.03 (d,
JC,P¼3.75 Hz),132.65 (d, JC,P¼2.25 Hz),132.30 (d, JC,P¼2.25 Hz),131.36
(d, JC,P¼9.00 Hz), 131.00, 130.89, 129.22, 129.04, 128.74, 128.37 (d,
JC,P¼12.00 Hz), 125.57, 121.62, 95.46 (d, JC,P¼4.50 Hz), 43.73 (d,
d
42.11; IR (KBr) nmax: 3475.0, 3415.1, 3058.1, 2892.5, 1595.4, 1575.5,
JC,P¼65.25 Hz), 21.11, 12.97; 31P NMR (121 MHz, CDCl3)
d
42.08; IR
1523.0,1487.5,1437.7,1248.4,1139.1, 753.6, 691.2 cmꢁ1; HRMS (ESI):
(KBr) nmax: 3475.8, 3415.5, 3054.3, 2917.1, 1591.8, 1521.5, 1500.2,
1455.6,1438.6,1141.1, 752.9, 692.1 cmꢁ1; HRMS (ESI): m/z¼501.1685
(calcd for C30H27N2O2PþNaþ¼501.1702).
m/z¼531.1421 (calcd for C30H25N2O4PþNaþ¼531.1444).
4.2.11. 4-((Diphenylphosphoryl)(naphthalen-2-yl)methyl)-3-methyl-
1-phenyl-1H-pyrazol-5-ol (3k). Yield 95%, 1H NMR (400 MHz,
4.2.7. 4-((Diphenylphosphoryl)(4-methoxyphenyl)methyl)-3-methyl-
CDCl3):
d
12.94 (s, 1H), 7.95e7.85 (m, 2H), 7.79 (d, J¼7.6 Hz, 2H),
1-phenyl-1H-pyrazol-5-ol (3g). Yield 97%, 1H NMR (400 MHz,
7.75e7.68 (m, 1H), 7.65e7.48 (m, 6H), 7.45e7.28 (m, 8H), 7.23e7.13

424
Z.-C. Geng et al. / Tetrahedron 70 (2014) 417e426
(m, 3H), 4.77 (d, J¼11.6 Hz, 1H), 2.16 (s, 3H); 13C NMR (75 MHz,
1166.3, 888.6, 690.5 cmꢁ1; HRMS (ESI): m/z¼597.0538 (calcd for
CDCl3)
d
152.04 (d, JC,P¼4.50 Hz), 147.42 (d, JC,P¼9.00 Hz), 139.20,
C
29H21BrF3N2O2PþHþ¼597.0549).
133.63 (d, JC,P¼4.50 Hz), 133.28 (d, JC,P¼4.50 Hz), 132.81 (d,
JC,P¼1.50 Hz), 132.45, 131.40 (d, JC,P¼9.75 Hz), 131.07 (d,
JC,P¼8.25 Hz), 129.24 (d, JC,P¼11.25 Hz), 128.84, 128.53, 128.47,
128.37, 128.30, 127.97, 127.64, 127.22 (d, JC,P¼4.50 Hz), 126.17 (d,
JC,P¼12.00 Hz), 125.71, 121.73, 95.22 (d, JC,P¼4.50 Hz), 44.43 (d,
4.2.16. 1-(4-Bromophenyl)-4-((4-chlorophenyl)(diphenylphosphoryl)
methyl)-3-methyl-1H-pyrazol-5-ol (3p). Yield 93%, 1H NMR
(400 MHz, CDCl3):
Hz, 2H), 7.58e7.34 (m, 8H), 7.33e7.27 (m, 2H), 7.14e7.06 (m, 4H),
4.57 (d, J¼11.6 Hz, 1H), 2.13 (s, 3H); 13C NMR (100 MHz, CDCl3)
d
13.03 (s, 1H), 7.90e7.80 (m, 2H), 7.70 (d, J¼8.8
JC,P¼64.50 Hz), 13.06; 31P NMR (121 MHz, CDCl3)
d 42.10; IR (KBr)
nmax: 3475.8, 3414.8, 3057.6, 1595.1, 1522.7, 1500.9, 1436.3, 1138.5,
d
152.06 (d, JC,P¼5.00 Hz), 147.65 (d, JC,P¼9.00 Hz), 138.19, 134.63 (d,
861.4, 748.6, 691.4 cmꢁ1; HRMS (ESI): m/z¼515.1858 (calcd for
JC,P¼4.00 Hz), 133.39 (d, JC,P¼3.00 Hz), 132.96 (d, JC,P¼2.00 Hz),
132.69 (d, JC,P¼3.00 Hz), 131.78, 131.30 (d, JC,P¼10.00 Hz), 130.93 (d,
JC,P¼8.00 Hz),130.56 (d, JC,P¼4.00 Hz),130.27,129.53,129.34,129.29,
129.22, 128.74, 128.72, 128.69, 128.57, 128.52, 122.88, 118.80, 95.24
(d, JC,P¼4.00 Hz), 43.60 (d, JC,P¼65.00 Hz),12.93; 31P NMR (162 MHz,
C
33H27N2O2PþHþ¼515.1883).
4.2.12. 4-((Diphenylphosphoryl)(furan-2-yl)methyl)-3-methyl-1-
phenyl-1H-pyrazol-5-ol (3l). Yield 93%, 1H NMR (400 MHz, CDCl3):
d
12.37 (s, 1H), 7.90e7.70 (m, 4H), 7.68e7.46 (m, 6H), 7.45e7.30 (m,
CDCl3) d 42.14; IR (KBr) nmax: 3445.8, 3061.3, 1590.9, 1520.3, 1487.3,
4H), 7.25e7.15 (m, 1H), 7.12 (s, 1H), 6.40 (s, 1H), 6.23 (s, 1H), 4.82 (d,
1453.3, 1437.1, 1182.8, 1140.3, 878.9, 795.1 cmꢁ1; HRMS (ESI): m/
z¼577.0430 (calcd for C29H23BrClN2O2PþHþ¼577.0442).
J¼11.2 Hz, 1H), 2.13 (s, 3H); 13C NMR (75 MHz, CDCl3)
d 152.37 (d,
JC,P¼3.75 Hz), 148.77 (d, JC,P¼3.00 Hz), 147.00 (d, JC,P¼0.75 Hz),
141.90, 139.07, 132.88, 132.62 (d, JC,P¼1.50 Hz), 131.27 (d,
JC,P¼9.75 Hz), 130.94 (d, JC,P¼9.00 Hz), 129.16 (d, JC,P¼12.00 Hz),
128.85, 128.66 (d, JC,P¼12.00 Hz), 125.79, 121.67, 111.20, 109.33 (d,
JC,P¼4.50 Hz), 93.40 (d, JC,P¼4.50 Hz), 38.16 (d, JC,P¼66.75 Hz),12.85;
4.2.17. 1-(4-Bromophenyl)-4-((4-bromophenyl)(diphenylphosphoryl)
methyl)-3-methyl-1H-pyrazol-5-ol (3q). Yield 95%, 1H NMR
(400 MHz, CDCl3):
d 13.04 (s, 1H), 7.86e7.76 (m, 2H), 7.70 (d,
J¼8.8 Hz, 2H), 7.55e7.35 (m, 8H), 7.34e7.20 (m, 4H), 7.10e7.00 (m,
31P NMR (121 MHz, CDCl3)
d 40.08; IR (KBr) nmax: 3477.5, 3414.7,
2H), 4.56 (d, J¼11.6 Hz, 1H), 2.13 (s, 3H); 13C NMR (100 MHz, CDCl3)
3058.6, 1594.1, 1525.1, 1500.5, 1456.7, 1436.6, 1140.2, 739.9 cmꢁ1
;
d
152.10 (d, JC,P¼5.00 Hz), 147.68 (d, JC,P¼9.00 Hz), 138.22, 135.20 (d,
HRMS (ESI): m/z¼477.1317 (calcd for C27H23N2O3PþNaþ¼477.1339).
JC,P¼4.00 Hz), 133.02 (d, JC,P¼2.00 Hz), 132.76 (d, JC,P¼3.00 Hz),
131.84, 131.75 (d, JC,P¼2.00 Hz), 131.36 (d, JC,P¼10.00 Hz), 131.04,
130.95, 130.31, 129.57, 129.35 (d, JC,P¼11.00 Hz), 129.33, 128.70 (d,
JC,P¼12.00 Hz), 128.57, 122.95, 121.60 (d, JC,P¼3.00 Hz), 118.88, 95.20
(d, JC,P¼5.00 Hz), 44.25 (d, JC,P¼65.00 Hz),13.01; 31P NMR (162 MHz,
4.2.13. 1-(4-Bromophenyl)-4-((diphenylphosphoryl)(phenyl)methyl)-
3-methyl-1H-pyrazol-5-ol (3m). Yield 93%, 1H NMR (400 MHz,
CDCl3):
d
13.04 (s, 1H), 7.86 (t, J¼8.8 Hz, 2H), 7.70 (d, J¼8.0 Hz, 2H),
7.60e7.55 (m, 1H), 7.55e7.45 (m, 4H), 7.45e7.40 (m, 1H), 7.40e7.32
(m, 2H), 7.32e7.26 (m, 1H), 7.20e7.10 (m, 5H), 4.57 (d, J¼11.2 Hz,
CDCl3) d 42.01; IR (KBr) nmax: 3442.0, 3036.5, 1636.4, 1590.7, 1570.8,
1520.9, 1486.4, 1437.0, 1182.3, 1140.3, 878.8, 792.4 cmꢁ1; HRMS
1H), 2.14 (s, 3H); 13C NMR (75 MHz, CDCl3)
d
152.11 (d, JC,P¼5.25
(ESI): m/z¼620.9920 (calcd for C29H23Br2N2O2PþHþ¼620.9937).
Hz), 147.81 (d, JC,P¼9.00 Hz), 138.31, 135.98 (d, JC,P¼3.75 Hz),
132.82 (d, JC,P¼2.25 Hz), 132.43 (d, JC,P¼2.25 Hz), 131.72, 131.31
(d, JC,P¼9.00 Hz), 130.97 (d, JC,P¼9.00 Hz), 129.31, 129.28, 129.13,
128.57, 128.41 (d, JC,P¼12.75 Hz), 127.37 (d, JC,P¼2.25 Hz),
122.81, 118.59, 95.56 (d, JC,P¼4.50 Hz), 44.17 (d, JC,P¼64.50 Hz),
4.2.18. 1-(4-Chlorophenyl)-4-((diphenylphosphoryl)(phenyl)methyl)-
3-methyl-1H-pyrazol-5-ol (3r). Yield93%,1H NMR(400 MHz, CDCl3):
d
13.05 (s,1H), 7.90e7.80 (m, 2H), 7.76 (d, J¼8.8 Hz, 2H), 7.60e7.45 (m,
3H), 7.44e7.29(m, 5H), 7.28e7.22 (m, 2H), 7.21e7.16(m, 2H), 7.15e7.08
(m, 3H), 4.58 (d, J¼11.6 Hz,1H), 2.14 (s, 3H); 13C NMR (100 MHz, CDCl3)
12.99; 31P NMR (121 MHz, CDCl3)
d 42.49; IR (KBr) nmax:
3474.6, 3415.3, 3063.0, 1590.2, 1520.1, 1483.4, 1421.3, 1136.5, 832.4,
d
152.21 (d, JC,P¼5.00 Hz), 147.79 (d, JC,P¼9.00 Hz), 137.75, 136.07 (d,
707.6, 692.8 cmꢁ1
C
;
HRMS (ESI): m/z¼565.0655 (calcd for
JC,P¼4.00 Hz), 132.93 (d, JC,P¼3.00 Hz), 132.51 (d, JC,P¼2.00 Hz), 131.46
(d, JC,P¼9.00 Hz),131.12 (d, JC,P¼8.00 Hz),131.02,129.42,129.37,129.26,
128.91,128.69 (d, JC,P¼2.00Hz),128.56,128.44,127.49(d,JC,P¼3.00Hz),
122.73, 95.66 (d, JC,P¼5.00Hz),44.32(d,JC,P¼65.00Hz),12.99;31PNMR
29H24BrN2O2PþNaþ¼565.0651).
4.2.14. 4-((Diphenylphosphoryl)(phenyl)methyl)-1-phenyl-3-(tri-
fluoromethyl)-1H-pyrazol-5-ol (3n). Yield 96%, 1H NMR (400 MHz,
(162 MHz, CDCl3) d 42.48; IR (KBr) nmax: 3440.2, 3045.8,1593.5,1518.6,
CDCl3):
d
13.59 (s, 1H), 7.95e7.85 (m, 2H), 7.85e7.65 (m, 2H),
1492.2, 1452.5, 1436.9, 1139.2, 873.9, 748.7, 693.1 cmꢁ1; HRMS (ESI):
7.65e7.45 (m, 3H), 7.45e7.17 (m, 10H), 7.16e7.05 (m, 3H), 4.85 (d,
m/z¼499.1347 (calcd for C29H24ClN2O2PþHþ¼499.1337).
J¼11.6 Hz, 1H); 13C NMR (75 MHz, CDCl3)
153.05 (d, JC,P¼5.25 Hz),
d
138.25, 135.62 (d, JC,P¼3.75 Hz), 133.10 (d, JC,P¼2.25 Hz), 132.68 (d,
JC,P¼2.25 Hz), 131.40, 131.27, 131.15, 129.38, 129.31, 129.23, 128.99,
128.68, 128.63, 128.47, 127.67 (d, JC,P¼1.50 Hz), 127.29, 122.69, 95.17
(d, JC,P¼4.50 Hz), 43.33 (d, JC,P¼64.50 Hz); 31P NMR (121 MHz,
4.2.19. 1-(4-Chlorophenyl)-4-((4-chlorophenyl)(diphenylphosphoryl)
methyl)-3-methyl-1H-pyrazol-5-ol (3s). Yield 94%, 1H NMR
(400 MHz, CDCl3):
d
13.00 (s,1H), 7.86e7.80(m, 2H), 7.75(d, J¼8.8Hz,
2H), 7.60e7.35 (m, 6H), 7.35e7.25 (m, 4H), 7.15e7.05 (m, 4H), 4.57 (d,
CDCl3)
d
42.66; IR (KBr) nmax: 3476.9, 3032.5, 2924.6, 1597.3, 1567.1,
J¼11.2 Hz, 1H), 2.13 (s, 3H); 13C NMR (100 MHz, CDCl3)
d 152.07 (d,
1522.9, 1457.7, 1436.9, 1139.6, 755.1, 694.4 cmꢁ1; HRMS (ESI): m/
JC,P¼5.00 Hz),147.61 (d, JC,P¼9.00 Hz),137.70,134.67(d, JC,P¼4.00 Hz),
133.45 (d, JC,P¼3.00 Hz), 133.01 (d, JC,P¼3.00 Hz), 132.73 (d,
JC,P¼3.00 Hz), 131.35 (d, JC,P¼10.00 Hz), 130.99 (d, JC,P¼8.00 Hz),
130.61 (d, JC,P¼5.00 Hz), 130.34, 129.61, 129.33 (d, JC,P¼12.00 Hz),
128.88, 128.78 (d, JC,P¼12.00 Hz), 128.67 (d, JC,P¼12.00 Hz), 122.66,
95.22 (d, JC,P¼4.00 Hz), 43.66 (d, JC,P¼64.00 Hz), 12.95; 31P NMR
z¼511.1439 (calcd for C29H22F3N2O2PþHþ¼519.1444).
4.2.15. 1-(4-Bromophenyl)-4-((diphenylphosphoryl)(phenyl)methyl)-
3-(trifluoromethyl)-1H-pyrazol-5-ol (3o). Yield 94%, 1H NMR
(400 MHz, CDCl3): d 13.79 (s, 1H), 7.99e7.85 (m, 2H), 7.75e7.65 (m,
2H), 7.65e7.45 (m, 5H), 7.45e7.40 (m, 1H), 7.39e7.25 (m, 4H),
(162 MHz, CDCl3) d 42.12; IR (KBr) nmax: 3443.2, 3038.6, 1590.2,
7.24e7.10 (m, 5H), 4.84 (d, J¼11.6 Hz, 1H); 13C NMR (75 MHz, CDCl3)
1519.3,1488.9,1451.3,1436.9,1183.9, 879.4, 794.3 cmꢁ1; HRMS (ESI):
d
153.27 (d, JC,P¼5.25 Hz), 137.40, 135.49 (d, JC,P¼4.50 Hz), 133.16 (d,
m/z¼533.0929 (calcd for C29H23Cl2N2O2PþHþ¼533.0947).
JC,P¼2.25 Hz), 132.73 (d, JC,P¼3.00 Hz), 132.02, 131.39, 131.25, 131.12,
129.42, 129.32, 129.26, 128.72, 128.71, 128.66, 128.49, 127.73 (d,
JC,P¼2.25 Hz), 123.89, 120.63, 95.38 (d, JC,P¼3.75 Hz), 43.25 (d,
4.2.20. 4-((4-Bromophenyl)(diphenylphosphoryl)methyl)-1-(4-
chlorophenyl)-3-methyl-1H-pyrazol-5-ol (3t). Yield, 1H NMR
JC,P¼63.75 Hz); 31P NMR (121 MHz, CDCl3)
d
42.88; IR (KBr) nmax
:
(400 MHz, CDCl3):
2H), 7.62e7.36 (m, 6H), 7.35e7.20 (m, 6H), 7.10e7.00 (m, 2H), 4.56 (d,
d
13.00 (s,1H), 7.87e7.81(m, 2H), 7.75(d, J¼8.8Hz,
3475.6, 3415.4, 3058.8, 2849.6, 1588.7, 1567.6, 1524.0, 1436.9,

Z.-C. Geng et al. / Tetrahedron 70 (2014) 417e426
425
J¼11.6 Hz, 1H), 2.13 (s, 3H); 13C NMR (101 MHz, CDCl3)
d
152.06 (d,
H, hexane/i-PrOH (80:20), flow rate: 1.0 mL minꢁ1
,
l
¼254 nm,
JC,P¼5.00 Hz),147.59 (d, JC,P¼9.00 Hz),137.69,135.21 (d, JC,P¼4.00 Hz),
133.00 (d, JC,P¼2.00 Hz), 132.74 (d, JC,P¼3.00 Hz), 131.73 (d,
JC,P¼2.00 Hz), 131.35 (d, JC,P¼9.00 Hz), 131.02, 130.95, 130.93, 130.91,
130.32, 129.58, 129.33 (d, JC,P¼11.00 Hz), 128.88, 128.68 (d,
JC,P¼12.00 Hz), 122.65, 121.58 (d, JC,P¼3.00 Hz), 95.14 (d,
JC,P¼4.00 Hz), 43.73 (d, JC,P¼64.00 Hz), 12.95; 31P NMR (162 MHz,
tR(major)¼9.817, tR(minor)¼14.057]; [
a
]
26 ꢁ215.7 (c 0.35, CHCl3).
D
4.3.4. (ꢁ)-4-((3-Chlorophenyl)(diphenylphosphoryl)methyl)-3-methyl-
1-phenyl-1H-pyrazol-5-ol (3d). Yield 83%, 67% ee [Daicel Chiralcel
OD-H, hexane/i-PrOH (90:10), flow rate: 1.0 mL minꢁ1
,
l
¼254 nm,
tR(major)¼7.685, tR(minor)¼11.083]; [
a
]
26 ꢁ140.8 (c 0.99, CHCl3).
D
CDCl3)
d 41.98; IR (KBr) nmax: 3421.8, 3062.7, 1636.3, 1590.5, 1519.4,
1488.3,1437.1,1140.8, 879.4, 793.4 cmꢁ1; HRMS (ESI): m/z¼577.0449
4.3.5. (ꢁ)-4-((Diphenylphosphoryl)(p-tolyl)methyl)-3-methyl-1-
phenyl-1H-pyrazol-5-ol(3f). Yield 80%, 75% ee [Daicel Chiralcel AD-H,
(calcd for C29H23BrClN2O2PþHþ¼577.0442).
hexane/i-PrOH (80:20), flow rate: 1.0 mL minꢁ1
,
l¼254 nm,
4.2.21. 4-((Di-p-tolylphosphoryl)(phenyl)methyl)-3-methyl-1-
tR(major)¼10.259, tR(minor)¼14.061]; [
a
]
26 ꢁ135.4 (c 1.12, CHCl3).
D
phenyl-1H-pyrazol-5-ol (4a). Yield 96%, 1H NMR (400 MHz, CDCl3):
d
12.98 (s,1H), 7.80e7.70 (m, 4H), 7.37 (t, J¼7.6 Hz, 2H), 7.32e7.12 (m,
10H), 7.10e7.02 (m, 2H), 4.53 (d, J¼11.2 Hz, 1H), 2.40 (s, 3H), 2.31 (s,
3H), 2.14 (s, 3H); 13C NMR (75 MHz, CDCl3)
4.3.6. (ꢁ)-4-((Diphenylphosphoryl)(4-methoxyphenyl)methyl)-3-
methyl-1-phenyl-1H-pyrazol-5-ol (3g). Yield 61%, 70% ee [Daicel Chir-
d
152.03 (d, JC,P¼5.25 Hz),
alcel AD-H, hexane/i-PrOH (80:20), flow rate: 1.0 mL minꢁ1
,
l
¼254 nm,
147.42 (d, JC,P¼10.50 Hz), 143.30 (d, JC,P¼3.00 Hz), 142.91 (d,
JC,P¼3.00 Hz), 139.25, 136.49 (d, JC,P¼4.50 Hz), 131.44 (d,
JC,P¼9.75 Hz), 131.03 (d, JC,P¼9.00 Hz), 129.94 (d, JC,P¼12.00 Hz),
129.45 (d, JC,P¼4.50 Hz), 129.15 (d, JC,P¼12.75 Hz), 128.80, 128.56,
127.25 (d, JC,P¼2.25 Hz),125.59,121.66, 95.55 (d, JC,P¼4.50 Hz), 44.47
tR(major)¼12.335, tR(minor)¼15.128]; [
a
]
D
26 ꢁ171.2 (c 0.73, CHCl3).
4.3.7. (ꢁ)-4-((Diphenylphosphoryl)(4-(methylthio)phenyl)methyl)-3-
methyl-1-phenyl-1H-pyrazol-5-ol (3h). Yield 70%, 71% ee [Daicel Chir-
alcel AD-H, hexane/i-PrOH (80:20), flow rate: 1.0 mL minꢁ1
,
l
¼254 nm,
(d, JC,P¼64.50 Hz), 21.75,13.04; 31P NMR (121 MHz, CDCl3)
d
42.61; IR
tR(major)¼12.195, tR(minor)¼16.386]; [
a
]
26 ꢁ212.6 (c 0.87, CHCl3).
D
(KBr) nmax: 3476.7, 3414.6, 3056.4, 3027.5, 2918.5, 1595.3, 1522.7,
1497.9, 1452.3, 1419.2, 1118.6, 805.5, 754.0, 693.8 cmꢁ1; HRMS (ESI):
m/z¼515.1865 (calcd for C31H29N2O2PþNaþ¼515.1859).
4.3.8. (ꢁ)-4-((Diphenylphosphoryl)(naphthalen-2-yl)methyl)-3-methyl-
1-phenyl-1H-pyrazol-5-ol (3k). Yield 75%, 76% ee [Daicel Chiralcel AD-
H, hexane/i-PrOH (80:20), flow rate: 1.0 mL minꢁ1
,
l
¼254 nm,
4.2.22. 4-((Bis(3,5-dimethylphenyl)phosphoryl)(phenyl)methyl)-3-
tR(major)¼11.677, tR(minor)¼21.821]; [
a
]
26 ꢁ127.9 (c 0.61, CHCl3).
D
methyl-1-phenyl-1H-pyrazol-5-ol (5a). Yield95%,1HNMR(400MHz,
CDCl3):
d
12.98 (s, 1H), 7.77 (d, J¼7.6 Hz, 2H), 7.45 (d, J¼11.2 Hz, 2H),
4.3.9. (ꢁ)-4-((Diphenylphosphoryl)(furan-2-yl)methyl)-3-methyl-1-
phenyl-1H-pyrazol-5-ol(3l). Yield 92%, 58% ee [Daicel Chiralcel AD-H,
7.38 (t, J¼7.6 Hz, 2H), 7.25e7.10 (m, 7H), 7.02 (s,1H), 6.87 (d, J¼11.2 Hz,
2H), 4.53 (d, J¼11.2 Hz, 1H), 2.36 (s, 6H), 2.17 (m, 9H); 13C NMR
hexane/i-PrOH (80:20), flow rate: 1.0 mL minꢁ1
,
l
¼254 nm,
(75 MHz, CDCl3)
d
152.05 (d, JC,P¼5.25 Hz), 147.27 (d, JC,P¼9.00 Hz),
tR(major)¼12.417, tR(minor)¼17.206]; [
a]
26 ꢁ33.2 (c 1.32, CHCl3).
D
139.18, 138.71 (d, JC,P¼12.00 Hz), 137.95 (d, JC,P¼12.75 Hz), 136.40 (d,
JC,P¼4.50 Hz),134.45 (d, JC,P¼1.50 Hz),133.94 (d, JC,P¼2.25 Hz),129.42
(d, JC,P¼4.50 Hz), 128.91 (d, JC,P¼9.75 Hz), 128.68, 128.56 (d,
JC,P¼9.00 Hz),128.32,127.10 (d, JC,P¼1.50 Hz),125.45,121.52, 95.53 (d,
JC,P¼4.50 Hz), 44.12 (d, JC,P¼64.50 Hz), 21.45, 21.14, 12.94; 31P NMR
4.3.10. (ꢁ)-1-(4-Bromophenyl)-4-((diphenylphosphoryl)(phenyl)methyl)-
3-methyl-1H-pyrazol-5-ol (3m). Yield 82%, 68% ee [Daicel Chiralcel OD-
H, hexane/i-PrOH (90:10), flow rate: 1.0 mL minꢁ1
,
l
¼254 nm,
tR(major)¼9.817, tR(minor)¼14.057]; [a D26
]
ꢁ200.3 (c 0.63, CHCl3).
(121 MHz, CDCl3) d 43.13; IR (KBr) nmax: 3477.1, 3414.8, 3029.3, 2913.5,
1594.1, 1575.7, 1524.5, 1497.2, 1144.2, 903.2, 765.7, 691.4 cmꢁ1; HRMS
4.3.11. (ꢁ)-1-(4-Bromophenyl)-4-((4-chlorophenyl)(diphenylphosphoryl)
methyl)-3-methyl-1H-pyrazol-5-ol (3p). Yield 45%, 44% ee [Daicel Chir-
(ESI): m/z¼521.2350 (calcd for C33H33N2O2PþHþ¼521.2352).
alcel OD-H, hexane/i-PrOH (90:10), flow rate: 1.0 mL minꢁ1
,
l¼254 nm,
4.3. General experimental procedure for the enantioselective
conjugate addition of diarylphosphane oxides to
saturated pyrazolones
tR(major)¼8.453, tR(minor)¼9.362]; [a D26
]
ꢁ109.3 (c 0.55, CHCl3).
a,b-un-
4.3.12. (ꢁ)-1-(4-Bromophenyl)-4-((4-bromophenyl)(diphenylphosphoryl)
methyl)-3-methyl-1H-pyrazol-5-ol (3q). Yield 55%, 50% ee [Daicel Chir-
In an ordinary tube equipped with a magnetic stirring bar, the
alcel OD-H, hexane/i-PrOH (90:10), flow rate: 1.0 mL minꢁ1
,
l¼254 nm,
solution of diarylphosphane oxides 1 (0.15 mmol), 4 A MS (400 mg),
tR(major)¼8.833, tR(minor)¼9.756]; [a D26
]
ꢁ113.8 (c 0.94, CHCl3).
ꢀ
catalyst 6l (30 mol %) in toluene (4.0 mL) was stirred at ꢁ40 ꢀC for
30 min, and then
a
,
b-unsaturated pyrazolone 2 (0.10 mmol) was
4.3.13. (ꢁ)-1-(4-Chlorophenyl)-4-((diphenylphosphoryl)(phenyl)
methyl)-3-methyl-1H-pyrazol-5-ol (3r). Yield 71%, 64% ee [Daicel Chir-
added. After the reaction mixture was stirred for 84e144 h at
ꢁ40 ꢀC. The reaction mixture was directly loaded onto a silica gel
and purified by flash chromatography (eluant: petroleum ether/
dichloromethane) to give desired products 3e5.
alcel OD-H, hexane/i-PrOH (90:10), flow rate: 1.0 mL minꢁ1
,
l¼254 nm,
tR(major)¼7.551, tR(minor)¼8.761]; [a D26
]
ꢁ112.5 (c 0.12, CHCl3).
4.3.14. (ꢁ)-1-(4-Chlorophenyl)-4-((4-chlorophenyl)(diphenylphosphoryl)
methyl)-3-methyl-1H-pyrazol-5-ol (3s). Yield 41%, 49% ee [Daicel Chir-
4.3.1. (ꢁ)-4-((Diphenylphosphoryl)(phenyl)methyl)-3-methyl-1-
phenyl-1H-pyrazol-5-ol (3a). Yield 85%, 73% ee [Daicel Chiralcel
alcel OD-H, hexane/i-PrOH (90:10), flow rate: 1.0 mL minꢁ1
,
l
¼254 nm,
AD-H, hexane/i-PrOH (80:20), flow rate: 1.0 mL minꢁ1
,
l
¼254 nm,
tR(major)¼8.089, tR(minor)¼9.135]; [a D26
]
ꢁ93.4 (c 0.35, CHCl3).
26
tR (major)¼8.974, tR(minor)¼12.425]; [
a]
ꢁ254.6 (c 0.26, CHCl3).
D
4.3.15. (ꢁ)-4-((4-Bromophenyl)(diphenylphosphoryl)methyl)-1-(4-
chlorophenyl)-3-methyl-1H-pyrazol-5-ol (3t). Yield 43%, 50% ee
4.3.2. (ꢁ)-4-((4-Chlorophenyl)(diphenylphosphoryl)methyl)-3-methyl-
1-phenyl-1H-pyrazol-5-ol (3b). Yield 91%, 70% ee [Daicel Chiralcel
[Daicel Chiralcel OD-H, hexane/i-PrOH (90:10), flow rate:
26
AD-H, hexane/i-PrOH (80:20), flow rate: 1.0 mL minꢁ1
,
l
¼254 nm,
1.0 mL minꢁ1
ꢁ105.5 (c 0.40, CHCl3).
,
l
¼254 nm, tR(major)¼8.396, tR(minor)¼9.480]; [
a]
D
tR(major)¼9.690, tR(minor)¼14.287]; [
a
]
26 ꢁ219.8 (c 0.48, CHCl3).
D
4.3.3. (ꢁ)-4-((4-Bromophenyl)(diphenylphosphoryl)methyl)-3-methyl-
1-phenyl-1H-pyrazol-5-ol(3c). Yield 88%, 70% ee [Daicel Chiralcel AD-
4.3.16. (ꢁ)-4-((Di-p-tolylphosphoryl)(phenyl)methyl)-3-methyl-1-
phenyl-1H-pyrazol-5-ol (4a). Yield 46%, 48% ee [Daicel Chiralcel AD-

426
Z.-C. Geng et al. / Tetrahedron 70 (2014) 417e426
H, hexane/i-PrOH (80:20), flow rate: 1.0 mL minꢁ1
,
l
¼254 nm,
Zhou, Z. Q.; Li, X.; Liang, X. M.; Ye, J. X. RSC Adv. 2011, 1, 698e705; (c) Wen, S. G.;
Li, P. F.; Wu, H. B.; Yu, F.; Liang, X. M.; Ye, J. X. Chem. Commun. 2010, 4806e4808;
(d) Russo, A.; Lattanzi, A. Eur. J. Org. Chem. 2010, 6736e6739; (e) Fu, X.; Jiang, Z.
Y.; Tan, C. H. Chem. Commun. 2007, 5058e5060; (f) Maerten, E.; Cabrera, S.;
Kjærsgaard, A.; Jørgensen, K. A. J. Org. Chem. 2007, 72, 8893e8903; (g) Carlone,
A.; Bartoli, G.; Bosco, M.; Sambri, L.; Melchiorre, P. Angew. Chem., Int. Ed. 2007,
46, 4504e4506; (h) Ibrahem, I.; Rios, R.; Vesely, J.; Hammar, P.; Eriksson, L.;
tR(major)¼32.263, tR(minor)¼20.327]; [
a
]
26 ꢁ127.2 (c 0.57, CHCl3).
D
4.3.17. (ꢁ)-4-((Bis(3,5-dimethylphenyl)phosphoryl)(phenyl)methyl)-3-
methyl-1-phenyl-1H-pyrazol-5-ol (5a). Yield 50%, 44% ee [Daicel
Chiralcel AD-H, hexane/i-PrOH (70:30), flow rate: 1.0 mL minꢁ1
,
ꢁ
Himo, F.; Cordova, A. Angew. Chem., Int. Ed. 2007, 46, 4507e4510; (i) Ibrahem, I.;
26
ꢁ
Hammar, P.; Vesely, J.; Rios, R.; Eriksson, L.; Cordova, A. Adv. Synth. Catal. 2008,
l
¼254 nm, tR(major)¼5.014, tR(minor)¼4.304]; [
a
]
ꢁ92.9 (c 0.70,
D
350, 1875e1884.
CHCl3).
8. (a) Dadiboyena, S.; Nefzi, A. Eur. J. Med. Chem. 2011, 46, 5258e5275; (b)
Shiohara, H.; Fujikura, H.; Fushimi, N.; Ito, F.; Isaji, M. PCT Int. Appl. WO
ꢁ
Acknowledgements
2002098893, 2002; Chem. Abstr. 2003, 138, 24917; (c) Szabo, G.; Varga, B.;
ꢁ
Lengyel, D. P.; Szemzo, A.; Erdelyi, P.; Vukics, K.; Szikra, J.; Hegyi, E.; Vastag, M.;
ꢁ
Kiss, B.; Laszy, J.; Gyertyan, I.; Fischer, J. J. Med. Chem. 2009, 52, 4329e4337; (d)
We are grateful for financial support of the National Natural
Science Foundation of China (21072145, 21272166), the Program for
New Century Excellent Talents in University (NCET-12-0743), the
Major Basic Research Project of the Natural Science Foundation of
the Jiangsu Higher Education Institutions (13KJA150004), and the
Priority Academic Program Development of Jiangsu Higher Edu-
cation Institutions (PAPD).
Cox, S. R.; Lesman, S. P.; Boucher, J. F.; Krautmann, M. J.; Hummel, B. D.; Savides,
M.; Marsh, S.; Fielder, A.; Stegemann, M. R. J. Vet. Pharmacol. Ther. 2010, 33,
461e470; (e) Lee, E.; Choi, M. K.; Youk, H. J.; Kim, C. H.; Han, I. O.; Yoo, B. C.; Lee,
M. K.; Lim, S. J. J. Cancer Res. Clin. Oncol. 2006, 132, 223e233.
9. (a) Patel, M. V.; Bell, R.; Majest, S.; Henry, R.; Kolasa, T. J. Org. Chem. 2004, 69,
7058e7065; (b) Knorr, L. Ber. 1883, 16, 2587e2599.
10. (a) Li, F.; Nie, J.; Sun, L.; Zheng, Y.; Ma, J. A. Angew. Chem., Int. Ed. 2013, 52,
6255e6258, http://dx.doi.org/10.1002/anie.201301870; (b) Synthetic Applica-
tions of 1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural
Products; Padwa, A., Pearson, W. H., Eds.; John Wiley & Sons: New York, NY,
2002; (c) Mohanan, K.; Martin, A. R.; Toupet, L.; Smietana, M.; Vasseur, J. Angew.
Chem., Int. Ed. 2010, 49, 3196e3199.
Supplementary data
11. For review, see: (a) Fustero, S.; Sanchez-Rosello, M.; Barrio, P.; Simon-Fuentes,
A. Chem. Rev. 2011, 111, 6984e7034; For selected examples, see: (b) Neumann, J.
J.; Suri, M.; Glorius, F. Angew. Chem., Int. Ed. 2010, 49, 7790e7794; (c) Zora, M.;
Kivrak, A. J. Org. Chem. 2011, 76, 9379e9390; (d) Suri, M.; Jousseaume, T.;
Neumann, J. J.; Glorius, F. Green Chem. 2012, 14, 2193e2196; (e) Martin, R.;
Rivero, M. R.; Buchwald, S. L. Angew. Chem., Int. Ed. 2006, 45, 7079e7082.
12. Li, X. L.; Wang, Y. M.; Matsuura, T.; Meng, J. B. J. Heterocycl. Chem. 1999, 67,
697e701.
13. Khidre, M. D.; Abou-Yousef, H. M.; Refat, M.; Mahran, H. Phosphorus, Sulfur, and
silicon 2002, 177, 647e658.
14. (a) Ma, Z. W.; Liu, Y. X.; Huo, L. J.; Gao, X.; Tao, J. C. Tetrahedron: Asymmetry 2012,
23, 443e448; (b) Ma, Z. W.; Wu, Y.; Sun, B.; Du, H. L.; Shi, W. M.; Tao, J. C.
Tetrahedron: Asymmetry 2013, 24, 7e13.
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2013.11.038
References and notes
1. (a) Seto, H.; Kuzuyama, T. Nat. Prod. Rep. 1999, 16, 589e596; (b) Fields, S. C.
Tetrahedron 1999, 55, 12237e12273; (c) Smith, J. D. In The Role of Phosphonates
in Living Systems; Hilderbrand, R. L., Ed.; CRC: Boca Raton, FL, 1983; pp 31e53;
(d) Shie, J. J.; Fang, J. M.; Wang, S. Y.; Tsai, K. C.; Cheng, Y. S. E.; Yang, A. S.; Hsiao,
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synthesis of 3-hydroxyl pyrazole by organocatalysis using pyrazolones as
substrates, see: (f) Li, F.; Sun, L.; Teng, Y. O.; Yu, P.; Zhao, C. G.; Ma, J. A. Chem.
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€
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Org. Biomol. Chem. 2013, doi:10.1039/c1ob000000x; For only one example
about synthesis of 3-hydroxyl pyrazole by organocatalysis using
a,b-un-
saturated pyrazolones as substrates, see: (i) Geng, Z. C.; Chen, X.; Zhang, J. X.; Li,
N.; Chen, J.; Huang, X. F.; Zhang, S. Y.; Tao, J. C.; Wang, X. W. Eur. J. Org. Chem.
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2095e2108; (b) Glueck, D. S. Chem.dEur. J. 2008, 14, 7108e7117; For selected
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17. For selected reviews on bifunctional amino-thiourea catalysts, see: (a) Taylor,
M. S.; Jacobsen, E. N. Angew. Chem., Int. Ed. 2006, 45, 1520e1543; (b) Connon, S.
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ꢁ
18. Aleman, J.; Parra, A.; Jiang, H.; Jørgensen, K. A. Chem.dEur. J. 2011, 17,
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