A three-component, general and practical route for diastereoselective synthesis of aza-spirocyclic pyrazolonesviaa decarboxylative annulation process

Article abstract of DOI:10.1039/d0nj05915c

An efficient, general, and practical route for highly diastereoselective synthesis of aza-spirocyclic pyrazolones from easily available α-amino acids, aldehydes, and alkylidene pyrazolones by means of a decarboxylative annulation process is reported. This

Full text of DOI:10.1039/d0nj05915c

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A three-component, general and practical route
for diastereoselective synthesis of aza-spirocyclic
pyrazolones via a decarboxylative annulation
process†
Cite this: New J. Chem., 2021,
5, 2374
4
Received 4th December 2020,
Accepted 5th January 2021
ab
ab
a
Annapurna Awasthi, Pushpendra Yadav and Dharmendra Kumar Tiwari
*
DOI: 10.1039/d0nj05915c
rsc.li/njc
An efficient, general, and practical route for highly diastereoselec- regard, recently, we have demonstrated a highly diastereoselec-
tive synthesis of aza-spirocyclic pyrazolones from easily available tive synthesis of aza-spirocyclic pyrazolones from a-amino acids
1
2
a-amino acids, aldehydes, and alkylidene pyrazolones by means of a and alkylidene pyrazolones. This reaction proceeds through
decarboxylative annulation process is reported. This high-yielding an a-amino acid-mediated C–C double bond cleavage of unsaturated
reaction proceeds through a [3+2]-cycloaddition reaction between pyrazolones, which leads to in situ generation of azomethine
alkylidene pyrazolones and a nonstabilized azomethine ylide gener- ylides, which eventually undergo a [3+2]-cycloaddition reaction
ated in situ. This method provides easy and smooth access to a variety with another molecule of alkylidene pyrazolone to give the
of highly functionalized aza-spirocyclic pyrazolones in excellent yields aza-spirocyclic pyrazolones (Scheme 1).
(
up to 96%). The obtained spiro-pyrazolones comprise four contiguous
Although this methodology provides convenient access to
aza-spirocyclic pyrazolones, the major drawbacks associated
with this methodology are limited substrate scope, low yield,
stereogenic centers including a quaternary carbon center.
Pyrazolone and its derivatives are an important class of hetero- high reaction temperature (90 1C), prolonged reaction time
cycles present in various biologically important molecules and (24 h), the formation of pyrazolone as a side product, and most
drugs present in the market (Fig. 1A–C). In addition, they are importantly this reaction requires two equivalents of alkylidene
widely used in the fields of functional materials, coordination pyrazolones. To overcome all of these shortcomings, the develop-
1
–4
chemistry, dyes and pigments. In the recent past, spirocyclic ment of a mild, efficient and atom-economical methodology
pyrazolones have received great attention from synthetic and from readily available starting materials would be highly desirable.
medicinal chemists due to their frequent appearance in a Our current research focuses on the development of new methods
13
large number of bioactive natural alkaloids and pharmaceutical for the synthesis of biologically important heterocycles. In view
agents (Fig. 1D–F), associated with numerous biological of the pharmaceutical importance of spirocyclic pyrazolones, we
activities such as anti-bacterial, antidiabetic, analgesic, anti- herein report a mild and efficient three-component approach for
inflammatory, PPAR a-antagonists, antiviral, anticancer, and the synthesis of highly functionalized aza-spirocyclic pyrazolones
5
,6
type-4-phosphodiesterase inhibitor activities.
from readily available starting materials. This one-pot tandem
Given the widespread use of spirocyclic pyrazolones in reaction proceeds through a [3+2]-cycloaddition reaction between
medicinally relevant compounds, much attention has been
paid to the construction of these valuable scaffolds, and as a
result, a large number of elegant methods have been developed
7
–11
in the recent past.
However, a careful literature survey
reveals that only a few methods are reported for the synthesis
of aza-spiropyrazolones, despite it being an important core
structure of various biologically important molecules. In this
a
Molecular Synthesis and Drug Discovery Unit, Center of Biomedical Research
(
CBMR), SGPGIMS Campus, Raibareli Road, Lucknow, U.P. 226014, India.
E-mail: dkt80.org@gmail.com, dktiwari@cbmr.res.in
Department of Chemistry, Institute of Science, Banaras Hindu Universiy, 221005,
U.P., India
b
†
Electronic supplementary information (ESI) available. See DOI: 10.1039/
Fig. 1 Biologically active molecules containing spiro-pyrazolone
d0nj05915c
skeletons.
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(
3.0 mL) at room temperature for 6 h was found to be unsuccessful
and did not give any desired product (Table 1, entry 1). However,
when the reaction mixture was heated at 60 1C for 6 hrs, the
desired 4aaa was obtained in 45% yield (entry 2). To our delight,
the desired product 4aa was obtained in 74% yield when the
reaction temperature was increased to 75 1C (entry 3). At this stage,
the product was well characterized by various spectroscopic
1
13
techniques, including H and C NMR, and HRMS. The spectral
data of 3aaa were exactly matching with the previously reported
12
compound. It is also important to mention here that only one
14
diastereomer was obtained in this one-pot tandem reaction.
As water is expected as the by-product, the use of 4 Å
molecular sieves improved the yield to a greater extent (92%)
(
4
entry 4). Furthermore, almost a similar yield of the desired
aaa was obtained when the reaction time was reduced to 3 h
from 6 h (entry 5). To our delight, a slight increase in the yield
96%) of the desired 4aaa was noticed when the reaction time
Scheme 1 Previous work on the synthesis of aza-spiropyrazolones
(eqn (1a)) along with the present study (eqn (1b)).
(
was reduced to an hour (entry 6). Further decreasing the
reaction time to 30 mins provided an inferior yield (71%) of
the required product 4aaa (entry 7). No improvement in the
reaction yield was noticed by increasing the reaction tempera-
ture to 90 1C from 75 1C (entry 8). Afterwards, to improve the
reaction yield, a range of non-polar and polar solvents, including
alkylidene pyrazolones and azomethine ylides, generated in situ
from cyclic a-amino acids and aldehydes.
Results and discussion
To investigate this one-pot tandem reaction, we selected L-proline
3
ethylene dichloride (EDC), acetonitrile (CH CN), tetrahydrofuran
(1a), benzaldehyde (2a), and alkylidene pyrazolone (3a) as model
(THF), toluene, dioxane, DMSO, DMF, EtOH and MeOH, were
substrates for the optimization of the reaction conditions and the
details are summarized in Table 1. Our first attempt by treating
L-proline (1a, 1.0 mmol), benzaldehyde (2a, 1.0 mmol), and
screened; however, all of them provided the corresponding
desired product (4aaa) in diminished yields (entries 9–18). In
order to further improve the yield, the reaction was performed in
the presence of stoichiometric amounts of acid (p-TSA) and base
unsaturated pyrazolone (2a, 1.0 mmol) with anhydrous CHCl
3
(
K
2
CO
obtained in low yields (entries 19 and 20). Furthermore, employing
a catalytic amount of Lewis acids such as Sc(OTf) and In(OTf)
3
); however, in both cases, the desired product 4aaa was
a
Table 1 Optimization of the reaction conditions
3
3
was also found to be unsuccessful to increase the yield of the
desired product (entries 21 and 22).
After having the optimized reaction conditions in hand, the
substrate scope of this three-component tandem reaction was
Yields (%) evaluated with respect to various a-amino acids (1a–1f), aldehydes
b
En
Solvent
Additive
Temp [1C]
Time [h]
a
(
2a–2v), and alkylidene pyrazolones (3a–3i) (Schemes 2–4). Initially,
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
2
2
2
CHCl
CHCl
CHCl
CHCl
CHCl
CHCl
CHCl
CHCl
EDC
3
3
3
3
3
3
3
3
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
p-TSA
rt
6
6
6
6
3
1
1/2
1
1
1
1
1
1
1
1
1
1
1
1
1
1
n.o.
a
60
75
75
75
75
75
90C
75
75
75
75
75C
75
75C
75
75
75
75
75
75
55
various aldehydes (2a–2o) having both electron-donating (2b–2g)
and electron-withdrawing groups (2h–2q) on the aromatic rings
readily participated in this one-pot tandem reaction to furnish a
wide range of aza-spirocyclic pyrazolones (4aba–4aqa) in excellent
yields. Various functional groups, such as methoxy (2e), benzyloxy
a
74
c
92
c
93
c
96
c
71
95
93
91
85
78
93
73
72
79
80
89
c
c
(2f), trimethoxy (2g), fluoro (2h), trifluoromethyl (CF , 2i), chloro
3
c
0
1
2
4
5
6
7
8
9
0
1
2
CH
3
CN
(2j–2l), bromo (2m–2o), cyano (2p), and nitro (2q), were well
c
THF
c
tolerated in this reaction furnishing the desired products in very
good yields. To our delight, heterocyclic aldehydes such as
2-furaldehyde (2r) and thiophenecarboxaldehydes (2s & 2t) effec-
tively participated under the optimized reaction conditions to
furnish the desired products (4ara–4ata) in very good yields.
Furthermore, polycyclic aldehydes such as 2-naphthaldehyde (2u)
and pyran-carboxaldehyde (2v) smoothly underwent this reaction
to give the desired products (4aua & 4ava) in 86% and 85% yields,
respectively.
Toluene
Dioxane
DMSO
DMF
EtOH
MeOH
c
c
c
c
c
c
CHCl
CHCl
CHCl
CHCl
3
3
3
3
c
K
2
CO
Sc(OTf)
In(OTf)
3
74
d
3
85
d
3
85
a
Reaction was performed using 1a (1.0 mmol), 2a (1.0 mmol), 3a
atmosphere. Isolated yields.
When 4 Å MS was used. When 10 mole% of catalyst was used.
b
Afterwards, different unsaturated pyrazolones (3a–3h) con-
taining electron-neutral (–H), electron-donating (–OMe), and
(
1.0 mmol) solvent (3.0 mL), under N
2
c
d
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Scheme 5 Gram scale synthesis.
electron-withdrawing (Cl, –NO
2
) groups on the aromatic rings
smoothly participated under the optimized reaction conditions
to furnish the desired aza-spirocyclic pyrazolones (4aaa–4aah)
in very good to excellent yields (83–96%). Pleasingly, the
unsaturated pyrazolones containing thiophenyl (3i) and
naphthyl groups also participated in this reaction to form the
desired 4aai and 4aah products in 83% and 84% yields,
respectively.
Eventually, the substrate scope of the present methodology
was evaluated with different cyclic a-amino acids (1b–1f) and
the results are summarized in Scheme 4. Heteroatom substi-
Scheme 2 Substrate scope with respect to various aldehydes. Reaction tuted prolines such as thiazolidine-2-carboxylic acid (1b) and
conditions: 1a (1.0 mmol), 2a (1.0 mmol), 3a (1.0 mmol); anhy. CHCl
5 1C, 1 h, under nitrogen atmosphere.
3
(3.0 mL), thiazolidine-4-carboxylic acid (1c) easily reacted with unsatu-
rated pyrazolones (3a–3i) under the standard reaction condi-
tions to give the desired functionalized aza-spirocyclic
pyrazolones (4baa–4eaa, 4aai & 4aai) in very good yields.
Furthermore, pipecolic acid (1d) under the optimized reaction
conditions also furnished the corresponding product 4daa in
7
8
1
8% yield. Unfortunately, azetidine-2-carboxylic acid (1e) and
,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (1f) failed to
deliver the desired spirocyclic products.
Taking into consideration the potential importance of the
aza-spirocyclic pyrazolones in medicinal and material chemistry,
a gram scale synthesis for the present methodology was demon-
strated, wherein 4dad was prepared in 4.25 g, in 86% yield from
pipecolic acid (1d), benzaldehyde (1a) and alkylidene pyrazolone
(
3d) under the optimized reaction conditions (Scheme 5). This
Scheme 3 Different unsaturated alkylidenes. Reaction conditions: 1a result clearly indicates that there is not much loss of efficiency
1.0 mmol), 2a (1.0 mmol), 3a (1.0 mmol) CHCl
(3.0 mL), 75 1C, 1 h; under during the scale-up process.
atmosphere.
(
3
N
2
Based on the previous literature reports, a possible reaction
mechanism for this one-pot tandem reaction is given in
Scheme 6. The condensation reaction between L-proline (1a)
and benzaldehyde (2a) gave lactone intermediate A. The lactone
A undergoes decarboxylation to form the reactive azomethine
ylide B which subsequently undergoes a [3+2]-cycloaddition
1
5
Scheme 4 Substrate scope with different cyclic a-amino acids. Reaction
conditions: 1a (1.0 mmol), 2a (1.0 mmol), 3a (1.0 mmol) CHCl (3.0 mL),
5 1C, 1 h; under N atmosphere.
3
7
2
Scheme 6 Proposed reaction mechanism.
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reaction with alkylidene pyrazolone (3a) to form the desired The reaction mixture was stirred in a 75 1C preheated oil bath for
aza-spirocyclic product 4aaa.
1 h. The reaction mixture was then allowed to attain room
temperature and the solvent was allowed to evaporate under
reduced pressure to get the crude product (4aaa) which was
purified by column chromatography using silica gel 100–200
mesh to furnish the desired 4aaa in 96% yield as a white solid.
Conclusion
In summary, we have developed a three-component and highly
diastereoselective synthesis of aza-spiropyrazolone from readily
available a-amino acids, aromatic aldehydes and unsaturated
pyrazolones. This reaction proceeds through a [3+2]-cycloaddition
reaction between alkylidene pyrazolones and azomethine ylides
generated in situ from a-amino acids and aldehydes by means of
sequential condensation and decarboxylative annulation process
cascades in one pot. In this methodology, different a-amino acids
were reacted with variously substituted aldehydes and alkylidene
pyrazolones to prepare a wide variety of functionalized aza-
spiropyrazolones in excellent yields (up to 96%).
The compound 4aaa (404 mg, yield = 96%, R
: 3)) was isolated as a white solid; mp 209–211 1C; H NMR
800 MHz, CDCl ) d 7.62 (d, J = 8.2 Hz, 2H), 7.42 (d, J = 7.4 Hz,
f
= 0.50 (PE/EA =
1
7
(
3
2
7
5
1
2
H), 7.34 (dd, J = 8.2, 7.7 Hz, 2H), 7.25 (dd, J = 7.3, 6.0 Hz, 4H),
.20 (t, J = 7.3 Hz, 1H), 7.19–7.14 (m, 3H), 7.12 (t, J = 7.3 Hz, 1H),
.12 (d, J = 11.0 Hz, 1H), 4.43 (t, J = 7.0 Hz, 1H), 3.95 (d, J =
1.0 Hz, 1H), 3.06 (dd, J = 7.9, 4.9 Hz, 2H), 2.32 (s, 3H), 2.29–
.25 (m, 1H), 2.06–2.02 (m, 1H), 1.93–1.88 (m, 1H), 1.87–1.83
1
3
(
m, 1H); C NMR (200 MHz, CDCl
3
) d 172.28, 159.09, 137.42,
33.26, 128.79, 128.62, 128.48, 128.42, 128.30, 127.91, 127.51,
27.38, 125.14, 119.27, 70.27, 68.72, 68.20, 63.02, 53.07, 28.18,
7.18, 13.75; HRMS (ESI) m/z calcd for C28 O [M + H] exact
1
1
2
28 3
H N
Experimental
mass: 422.2227, found: 422.2219.
0
0
0
0
0
0
0
0
0
(
2 R,4S,7a S)-3-Methyl-1,2 -diphenyl-3 -(o-tolyl)-2 ,3 ,5 ,6 ,7 ,
All reagents were purchased from Sigma Aldrich, Alfa Aesar and local
venders and were used without further purification. All experiments
were carried out in a sealed tube. All the solvents used for the
reaction were distilled before use. Product purification by column
chromatography was accomplished using silica gel 100–200 mesh.
Analytical TLC was performed with Merck silica gel 60 F254 plates,
and the products were visualized by UV detection. H and C NMR
and HRMS spectra were recorded on Bruker Avance III spectro-
meters at 400 MHz, 100 MHz and 376 MHz, respectively, using
0
0
7
a -hexahydrospiro-[pyrazole-4,1 -pyrrolizin]-5(1H)-one (4aba).
The compound 4aba (409 mg, yield = 94%, R
f
= 0.48 (PE/EA =
1
8
: 2)) was isolated as a colourless oil; H NMR (400 MHz,
3
CDCl ) d 7.67 (d, J = 8.4 Hz, 3H), 7.34 (t, J = 7.9 Hz, 2H),
7
5
1
2
.22–7.11 (m, 4H), 7.11–7.03 (m, 4H), 6.97 (d, J = 7.5 Hz, 1H),
.39 (d, J = 11.0 Hz, 1H), 4.38 (t, J = 7.4 Hz, 1H), 4.00 (d, J =
1.0 Hz, 1H), 3.09–3.03 (m, 1H), 2.98–2.91 (m, 1H), 2.27 (s, 3H),
1
13
.26 (s, 3H), 2.24–2.17 (m, 1H), 2.01–1.94 (m, 1H), 1.89–1.78
13
(m, 2H); C NMR (100 MHz, CDCl ): d 172.78, 159.35, 139.54,
3
1
3
CDCl . In the Experimental section, the H NMR chemical shift is
1
1
6
37.52, 136.48, 133.49, 130.27, 128.68, 128.44, 128.24, 127.88,
27.14, 126.80, 126.21, 125.13, 119.24, 68.84, 68.73, 66.40,
3.81, 53.08, 28.23, 27.04, 19.57, 13.71; HRMS (ESI) m/z calcd
3
expressed in the form of ppm (d) relative to d = 7.26 for CDCl ,
13
whereas the C NMR chemical shift is expressed relative to d =
1
77.00. Multiplicities in the H NMR spectra are described as follows:
for C29
H
30
N
3
0
O [M + H] exact mass: 436.2383, found: 436.2381.
s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, bs =
broad singlet; coupling constants are reported in Hz. HRMS and
electrospray ionization (ESI) (m/z) spectra were recorded on an
Agilent Technologies 6530 Accurate-Mass Q-TOF LC/MS.
0
0
0
0
0
0
0
0
0
(2 R,4S,7a S)-3-Methyl-1,2 -diphenyl-3 -(p-tolyl) 2 ,3 ,5 ,6 ,7 ,7a -
0
hexahydrospiro[pyrazole-4,1 -pyrrolizin]-5(1H)-one (4aca). The com-
pound 4aca (404 mg, yield = 94%, R = 0.47 (PE/EA = 6:4)) was
f
1
isolated as a colourless oil; H NMR (400 MHz, CDCl ) d 7.65 (d, J =
3
7
2
1
.9 Hz, 2H), 7.38–7.27 (m, 5H), 7.19–7.12 (m, 5H), 7.08 (d, J = 7.7 Hz,
H), 5.10 (d, J = 11.1 Hz, 1H), 4.38 (t, J = 7.2 Hz, 1H), 3.94 (d, J =
1.1 Hz, 1H), 3.07–3.04 (m, 2H), 2.33 (s, 3H), 2.30 (s, 3H), 2.28–2.21
General procedure for the synthesis of unsaturated pyrazolones
(
3a–3h)
13
The starting materials (3a–3h) were prepared by the standard
(
m, 1H), 2.07–1.98 (m, 1H), 1.95–1.81 (m, 2H); C NMR (100 MHz,
CDCl ) d 172.31, 159.14, 138.47, 137.46, 136.75, 133.50, 128.93,
28.56, 128.48, 128.32, 128.20, 127.77, 127.16, 125.01, 119.20,
19.17, 69.96, 68.80, 68.09, 63.06, 53.07, 28.13, 27.23, 21.00, 13.68;
HRMS (ESI) m/z calcd for C H N O [M + H] exact mass: 436.2383,
1
2
method reported in the literature. To a solution of Edaravone
3
(
(
0.8 mmol, 1.1 equiv.) in acetic acid (2 mL) was added aldehydes
0.7 mmol, 1.0 equiv) and sodium acetate (0.07 g, 8.0 mmol, 1.1
1
1
equiv). The mixture was refluxed for 30 min and EtOAc (2 mL)
was added for dilution. The solution was extracted with EtOAc
29 30 3
found: 436.2385.
0
0
0
0
0
(
3 ꢀ 20 mL), dried over sodium sulfate, and concentrated under
(
2 R,3 S,4S,7a S)-3 -(4-Isopropylphenyl)-3-methyl-1,2 -diphenyl-
0
0
0
0
0
0
0
reduced pressure. The residue was subjected to column chro-
matography (silica gel) using petroleum ether/EtOAc (100 : 1) as
the eluent, which offered compounds 3a–3h in very good yields.
2
,3 ,5 ,6 ,7 ,7a -hexahydro-spiro[pyrazole-4,1 -pyrrolizin]-5(1H)-
one (4ada). The compound 4ada (425 mg, yield = 92%, R = 0.35
PE/EA = 8 : 2)) was isolated as a colourless oil. H NMR (400 MHz,
f
1
(
1
CDCl ) d H NMR (400 MHz, CDCl ) d 7.60 (d, J = 8.1 Hz, 1H), 7.31
3
3
General experimental procedure for the synthesis of
aza-spiropyrazolones (4aaa)
(
t, J = 7.8 Hz, 4H), 7.25 (d, J = 7.9 Hz, 2H), 7.17–7.07 (m, 7H), 5.08
d, J = 11.2 Hz, 1H), 4.35 (t, J = 7.5 Hz, 1H), 3.93 (d, J = 11.0 Hz, 1H),
3.06–3.02 (m, 2H), 2.87–2.79 (m, 1H), 2.30 (s, 3H), 2.25–2.20 (m,
3.0 mL) was added L-proline 1a (1.0 mmol) and benzaldehyde 2a 1H), 2.05–1.96 (m, 1H), 1.91–1.79 (m, 2H), 1.20 (d, J = 6.9 Hz, 6H);
(
To a solution of alkylidene pyrazolone 3a (1.0 mmol) in CHCl
3
(
(
13
1.0 mmol) at room temperature under nitrogen atmosphere.
3
C NMR (100 MHz, CDCl ) d 172.38, 159.14, 147.63, 138.87,
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1
1
5
37.50, 133.68, 128.58, 128.54, 128.21, 127.76, 127.21, 127.10, 133.26, 128.71, 128.63, 128.50, 128.36, 128.23, 127.98, 127.27,
26.30, 126.16, 125.04, 119.62, 119.26, 69.83, 68.99, 68.18, 62.89, 125.13, 119.25, 115.13, 114.92, 69.68, 68.72, 68.20, 63.54, 53.04,
3.27, 33.61, 28.19, 27.23, 23.86, 13.72; HRMS (ESI) m/z calcd for 28.28, 27.16, 13.71; HRMS (ESI) m/z calcd for C H FN O [M + H]
28
27
3
C H N O [M + H] exact mass: 464.2696, found: 464.2693.
exact mass: 440.2133, found: 440.2131.
31
34 3
0
0
0
0
0
0 0 0 0
(
2 R,3 S,4S,7a S)-3 -(3-Methoxyphenyl)-3-methyl-1,2 -diphenyl-
(2 R,4S,7a S)-3-Methyl-1,2 -diphenyl-3 -(4-(trifluoromethyl)-
0
0
0
0
0
0
0
0
0
0
0
0
0
0
2
,3 ,5 ,6 ,7 ,7a -hexahydro-spiro[pyrazole-4,1 -pyrrolizin]-5(1H)- phenyl)-2 ,3 ,5 ,6 ,7 ,7a -hexahydrospiro[pyrazole-4,1 -pyrrolizin]-
f
one (4aea). The compound 4aea (405 mg, yield = 90%, R = 0.35 5(1H)-one (4aia). The compound 4aia (435 mg, yield = 89%, R =
f
1
1
(PE/EA = 8 : 2)) was isolated as a colourless oil; H NMR (400 0.47 (PE/EA = 8 : 2)) was isolated as a brown oil; H NMR
3 3
MHz, CDCl ) d 7.53 (d, J = 8.2 Hz, 2H), 7.23 (t, J = 7.8 Hz, 2H), (400 MHz, CDCl ) d 7.71 (d, J = 8.2 Hz, 2H), 7.55 (s, 4H), 7.40
7
2
7
.15 (d, J = 7.5 Hz, 2H), 7.09–7.01 (m, 5H), 6.86 (d, J = 7.4 Hz, (t, J = 7.8 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 7.25–7.17 (m, 4H), 5.22
H), 6.65–6.60 (m, 1H), 4.97 (d, J = 10.9 Hz, 1H), 4.27 (t, J = (d, J = 10.9 Hz, 1H), 4.44 (t, J = 7.5 Hz, 1H), 3.89 (d, J = 10.9 Hz,
.5 Hz, 1H), 3.79 (d, J = 11.0 Hz, 1H), 3.62 (s, 3H), 2.98–2.92 1H), 3.12–3.05 (m, 2H), 2.34 (s, 3H), 2.32–2.24 (m, 1H), 2.13–2.03
1
3
(m, 2H), 2.19 (s, 3H), 2.17–2.10 (m, 1H), 1.97–1.87 (m, 1H), 1.80– (m, 1H), 1.97–1.87 (m, 2H); C NMR (100 MHz, CDCl ) d 172.31,
3
1
3
1
1
1
6
.70 (m, 2H); C NMR (100 MHz, CDCl
3
) d 172.39, 159.49, 158.80, 146.23, 137.45, 133.01, 128.64, 128.53, 128.46, 128.17,
59.13, 137.48, 133.55, 129.16, 128.62, 128.57, 128.30, 127.88, 127.48, 125.18, 125.15, 125.11, 119.25, 69.97, 68.83, 68.46, 63.74,
25.10, 119.63, 119.28, 112.90, 112.51, 70.22, 68.86, 68.28, 53.08, 28.39, 27.03, 13.66; HRMS (ESI) m/z calcd for C29
27 3 3
H F N O
3.22, 55.04, 53.16, 28.27, 27.15, 13.73; HRMS (ESI) m/z calcd [M + H] exact mass: 490.2101, found: 490.2097.
0 0 0 0
(2 R,4S,7a S)-3 -(2-Chlorophenyl)-3-methyl-1,2 -diphenyl-
2 R,4S,7a S)-3 -(4-(Benzyloxy)phenyl)-3-ethyl-,2 -diphenyl- 2 ,3 ,5 ,6 ,7 ,7a -hexahydrospiro-[pyrazole-4,1 -pyrrolizin]-5(1H)-
0 0 0 0 0 0
,3 ,5 ,6 ,7 ,7a -hexahydrospiro[pyrazole-4,1 -pyrrolizin]-5(1H)- one (4aja). The compound 4aja (395 mg, yield = 87%, R = 0.46
f
for C29
H
30
N
3
O [M + H] exact mass: 452.2333, found: 452.2327.
0
0
0
0
0
0
0
0
0
0
0
(
0
2
one (4afa). The compound 4afa (469 mg, yield = 89%, R = 0.45 (PE/EA = 7 : 3)) was isolated as a white solid; mp 172–174 1C;
f
1
1
(
PE/EA = 7 : 3)) was isolated as a colourless oil; H NMR (400
) d 7.60 (d, J = 8.1 Hz, 2H), 7.40–7.31 (m, 9H), 7.22 8.2 Hz, 2H), 7.35 (t, J = 8.0 Hz, 2H), 7.29 (dd, J = 10.1, 8.6 Hz,
d, J = 7.5 Hz, 2H), 7.23–7.13 (m, 4H), 6.87 (d, J = 8.5 Hz, 2H), 4H), 7.19–7.11 (m, 5H), 5.76 (d, J = 11.1 Hz, 1H), 4.40 (t, J =
3
H NMR (400 MHz, CDCl ) d 7.72 (d, J = 7.1 Hz, 1H), 7.65 (d, J =
MHz, CDCl
(
3
5
4
2
.09 (d, J = 11.1 Hz, 1H), 5.00 (s, 2H), 4.43 (t, J = 7.4 Hz, 1H), 7.3 Hz, 1H), 4.14 (d, J = 11.1 Hz, 1H), 3.20–3.14 (m, 1H), 3.00–
.03 (d, J = 11.1 Hz, 1H), 3.06–3.03 (m, 2H), 2.35 (s, 3H), 2.29– 2.93 (m, 1H), 2.37 (s, 3H), 2.29–2.26 (m, 1H), 2.02–1.93 (m, 2H),
1
3
13
.24 (m, 1H), 2.03–1.94 (m, 1H), 1.94–1.80 (m, 2H); C NMR 1.89–1.83 (m, 1H); C NMR (100 MHz, CDCl ) d 172.21, 158.93,
3
(
101 MHz, CDCl ) d 172.24, 159.25, 158.26, 137.41, 136.99, 138.61, 137.42, 134.30, 132.77, 129.65, 129.03, 128.62, 128.44,
3
1
1
5
33.27, 132.61, 128.62, 128.52, 128.44, 128.30, 127.90, 127.87, 128.17, 127.93, 127.11, 125.11, 119.26, 68.79, 68.31, 65.73,
27.49, 125.15, 119.32, 114.62, 69.91, 69.64, 68.55, 67.57, 62.21, 62.43, 52.94, 27.93, 27.35, 13.75; HRMS (ESI) m/z calcd for
2.96, 28.03, 27.29, 13.76; HRMS (ESI) m/z calcd for
[M + H] exact mass: 528.2646, found: 528.2649.
C
28
H
27ClN
3
O [M + H] exact mass: 456.1837, found: 456.1837.
0
0
0
0
C
35
H
34
N
3
O
2
(2 R,4S,7a S)-3 -(4-Chlorophenyl)-3-methyl-1,2 -diphenyl-
0 0 0 0 0 0 0 0 0 0 0
(
2 R,4S,7a S)-3-Methyl-1,2 -diphenyl-3 -(3,4,5-trimethoxy-phenyl)- 2 ,3 ,5 ,6 ,7 ,7a -hexahydrospiro-[pyrazole-4,1 -pyrrolizin]-5(1H)-
0
0
0
0
0
0
0
2
,3 ,5 ,6 ,7 ,7a -hexahydrospiro[pyrazole-4,1 -pyrrolizin]-5(1H)- one (4aka). The compound 4aka (386 mg, yield = 85%, R
f
= 0.46
one (4aga). The compound 4aga (444 mg, yield = 87%, R = 0.48 (PE/EA = 8 : 2)) was isolated as a white solid; mp 158–159 1C;
f
1
(
PE/EA = 7 : 3)) was isolated as a white solid; mp 165–167 1C;
H NMR (400 MHz, CDCl ) d 7.64 (d, J = 7.7 Hz, 2H), 7.34 (t, J =
3
1
H NMR (400 MHz, CDCl ) d 7.66 (d, J = 7.6 Hz, 2H), 7.34 (t, J = 7.9 Hz, 4H), 7.26–7.21 (m, 3H), 7.20–7.13 (m, 5H), 5.08 (d, J =
3
8.0 Hz, 2H), 7.28 (d, J = 6.6 Hz, 2H), 7.22–7.11 (m, 4H), 6.55 10.9 Hz, 1H), 4.37 (t, J = 7.5 Hz, 1H), 3.83 (d, J = 10.9 Hz, 1H),
(
(
s, 2H), 5.05 (d, J = 10.9 Hz, 1H), 4.35 (t, J = 7.5 Hz, 1H), 3.80 3.04–3.00 (m, 2H), 2.29 (s, 3H), 2.27–2.21 (m, 1H), 2.07–1.98 (m,
1
3
d, J = 10.9 Hz, 1H), 3.79 (s, 3H), 3.71 (s, 6H), 3.12–3.00 (m, 2H), 1H), 1.93–1.81 (m, 2H); C NMR (100 MHz, CDCl
3
) d 172.27,
2
.27 (s, 3H), 2.25–2.22 (m, 1H), 2.07–1.99 (m, 1H), 1.91–1.81 158.92, 140.20, 137.43, 133.10, 132.82, 128.62, 128.59, 128.49,
1
3
(m, 2H); C NMR (100 MHz, CDCl
3
) d 172.46, 159.18, 152.83, 128.39, 128.37, 128.05, 125.15, 119.25, 69.75, 68.69, 68.25,
1
1
5
37.46, 137.18, 136.66, 133.84, 128.79, 128.62, 128.30, 127.92, 63.49, 53.01, 28.28, 27.10, 13.68; HRMS (ESI) m/z calcd for
25.11, 119.19, 103.62, 70.45, 68.74, 68.17, 63.38, 60.66, 55.82, C H ClN O [M + H] exact mass: 456.1837, found: 456.1847.
2
8
27
3
0
0
0
0
3.23, 28.30, 27.07, 13.73; HRMS (ESI) m/z calcd for C H N O
34 3 4
(2 R,4S,7a S)-3 -(2,3-Dichlorophenyl)-3-methyl-1,2 -diphenyl-
3
1
0
0
0
0
0
0
0
[M + H] exact mass: 512.2544, found: 512.2542.
2 ,3 ,5 ,6 ,7 ,7a -hexahydro-spiro[pyrazole-4,1 -pyrrolizin]-5(1H)-
2 R,4S,7a S)-3 -(4-Fluorophenyl)-3-methyl-1,2 -diphenyl- one (4ala). The compound 4ala (420 mg, yield = 86%, R = 0.40
,3 ,5 ,6 ,7 ,7a -hexahydrospiro-[pyrazole-4,1 -pyrrolizin]-5(1H)-one (PE/EA = 8 : 2)) was isolated as a white solid; mp 195–197 1C;
0
0
0
0
0
(
0
f
0
0
0
0
0
2
1
(
4aha). The compound 4aha (387 mg, yield = 88%, R
EA = 7 : 3)) was isolated as a white solid; mp 204–206 1C; H NMR 8.2 Hz, 3H), 7.26–7.21 (m, 3H), 7.17–7.11 (m, 4H), 5.82 (d, J =
400 MHz, CDCl ) d 7.61 (d, J = 8.3 Hz, 2H), 7.35–7.27 (m, 4H), 11.0 Hz, 1H), 4.41 (t, J = 7.2 Hz, 1H), 4.08 (d, J = 11.0 Hz, 1H),
f
= 0.41 (PE/
3
H NMR (400 MHz, CDCl ) d 7.67–7.62 (m, 3H), 7.33 (t, J =
1
(
3
7
5
1
2
.21 (d, J = 7.4 Hz, 2H), 7.17–7.11 (m, 4H), 6.90 (t, J = 8.6 Hz, 2H), 3.17–3.10 (m, 1H), 2.99–2.91 (m, 1H), 2.34 (s, 3H), 2.30–2.22
1
3
.05 (d, J = 11.0 Hz, 1H), 4.34 (t, J = 7.5 Hz, 1H), 3.81 (d, J = (m, 1H), 2.00–1.82 (m, 3H); C NMR (100 MHz, CDCl ) d
3
1.0 Hz, 1H), 3.01–2.98 (m, 2H), 2.27 (s, 3H), 2.24–2.17 (m, 1H), 172.17, 158.67, 137.40, 133.04, 132.58, 132.43, 129.45, 128.83,
1
3
.05–1.95 (m, 1H), 1.90–1.85 (m, 1H), 1.85–1.77 (m, 1H);
C
128.66, 128.42, 128.30, 128.16, 127.42, 127.38, 127.03, 125.20,
3
NMR (100 MHz, CDCl ) d 172.32, 160.80, 159.03, 137.44, 137.33, 119.28, 118.97, 68.73, 68.44, 66.58, 62.80, 52.90, 28.02, 27.22,
2378 | New J. Chem., 2021, 45, 2374--2383
This journal is ©The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2021

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Communication
NJC
1
3.73; HRMS (ESI) m/z calcd for C28
H
26Cl
2
N
3
O [M + H] exact 13.68; HRMS (ESI) m/z calcd for C29
H
27
N
4
O [M + H] exact mass:
mass: 490.1447, found: 490.1445.
447.2179, found: 447.2180.
0
0
0
0
0
0
0
0
(
2 R,4S,7a S)-3 -(2-Bromophenyl)-3-methyl-1,2 -diphenyl-
(2 R,4S,7a S)-3-Methyl-3 -(4-nitrophenyl)-1,2 -diphenyl-
0
0
0
0
0
0
0
0
0
0
0
0
0
0
2
,3 ,5 ,6 ,7 ,7a -hexahydrospiro-[pyrazole-4,1 -pyrrolizin]-5(1H)-one 2 ,3 ,5 ,6 ,7 ,7a -hexahydrospiro-[pyrazole-4,1 -pyrrolizin]-
(
4ama). The compound 4ama (434 mg, yield = 87%, R = 0.40 (PE/ 5(1H)-one (4aqa). The compound 4aqa (400 mg, yield = 86%, R =
f
f
1
1
EA = 7:3)) was isolated as a brown oil. H NMR (400 MHz, CDCl
.58 (d, J = 7.8 Hz, 1H), 7.53 (d, J = 8.3 Hz, 2H), 7.35 (d, J = 8.0 Hz, (400 MHz, CDCl
H), 7.23 (t, J = 7.9 Hz, 2H), 7.18 (t, J = 7.0 Hz, 3H), 7.06–6.99 2H), 7.42 (d, J = 8.7 Hz, 2H), 7.25 (t, J = 7.9 Hz, 2H), 7.17–7.12
m, 4H), 6.98–6.92 (m, 1H), 5.64 (d, J = 11.1 Hz, 1H), 4.30 (t, J = (m, 2H), 7.11–7.03 (m, 4H), 5.10 (d, J = 10.9 Hz, 1H), 4.29 (t, J = 7.6
.2 Hz, 1H), 4.03 (d, J = 11.1 Hz, 1H), 3.11–3.05 (m, 1H), 2.88–2.80 Hz, 1H), 3.68 (d, J = 10.9 Hz, 1H), 2.96–2.89 (m, 2H), 2.19–2.11
3
) d 0.44 (PE/EA = 8 : 2)) was isolated as a brown oil. H NMR
7
1
(
7
3
) d 7.97 (d, J = 8.7 Hz, 2H), 7.56 (d, J = 7.9 Hz,
13
(m, 1H), 2.26 (s, 3H), 2.21–2.16 (m 1H), 1.87–1.79 (m, 2H) 1.76–1.71 (m, 4H), 1.99–1.89 (m, 1H), 1.83–1.72 (m, 2H); C NMR (100 MHz,
13
(m, 1H); C NMR (100 MHz, CDCl ) d 172.21, 158.91, 139.96, CDCl ) d 172.26, 158.63, 150.07, 147.28, 137.41, 132.70, 128.68,
3
3
137.45, 133.00, 132.71, 129.35, 128.87, 128.63, 128.57, 128.18, 128.62, 128.52, 128.40, 127.91, 125.27, 123.45, 119.26, 69.99, 68.72,
127.96, 127.74, 127.19, 125.13, 124.79, 119.30, 118.97, 68.26, 68.62, 64.05, 53.06, 28.50, 26.93, 13.68; HRMS (ESI) m/z calcd for
6
C
8.01, 62.53, 52.76, 27.88, 27.41, 13.76; HRMS (ESI) m/z calcd for
C
28
H
27
0
N
4
O
3
[M + H] exact mass: 467.2078, found: 467.2076.
0
0
0
28
H
27BrN
3
O [M + H] exact mass: 500.1332, found: 500.1342.
(2 R,4S,7a S)-3 -(Furan-2-yl)-3-methyl-1,2 -diphenyl-
0 0 0 0 0 0 0 0 0 0 0
(
2 R,4S,7a S)-3 -(3-Bromophenyl)-3-methyl-1,2 -diphenyl- 2 ,3 ,5 ,6 ,7 ,7a -hexahydrospiro-[pyrazole-4,1 -pyrrolizin]-5(1H)-
0
0
0
0
0
0
0
2
,3 ,5 ,6 ,7 ,7a -hexahydrospiro-[pyrazole-4,1 -pyrrolizin]-5(1H)- one (4ara). The compound 4ara (332 mg, yield = 81%, R
f
= 0.33
1
one (4ana). The compound 4ana (439 mg, yield = 88%, R = 0.43 (PE/EA = 6 : 4)) was isolated as a brown oil. H NMR (400 MHz,
f
(
PE/EA = 7 : 3)) was isolated as a white solid; mp 209–211 1C; CDCl ) d 7.47 (d, J = 8.1 Hz, 2H), 7.26–7.18 (m, 3H), 7.15–7.07
3
1
H NMR (400 MHz, CDCl ) d 7.69 (s, 1H), 7.63 (d, J = 8.1 Hz, 2H), (m, 4H), 7.06–7.01 (m, 2H), 6.14–6.07 (m, 2H), 5.10 (d, J =
3
7
7
1
2
.36–7.30 (m, 3H), 7.24 (d, J = 7.2 Hz, 2H), 7.21–7.12 (m, 5H), 11.3 Hz, 1H), 4.29–4.22 (m, 2H), 3.11–2.96 (m, 2H), 2.27 (s, 3H),
1
3
.04 (t, J = 7.8 Hz, 1H), 5.07 (d, J = 10.9 Hz, 1H), 4.37 (t, J = 7.5 Hz, 2.17–2.10 (m, 1H), 1.97–1.87 (m, 1H), 1.77–1.69 (m, 2H);
H), 3.83 (d, J = 10.9 Hz, 1H), 3.07–2.99 (m, 2H), 2.29 (s, 3H), NMR (100 MHz, CDCl ) d 172.09, 159.04, 153.15, 142.37, 137.32,
133.11, 128.62, 128.36, 127.95, 125.19, 119.30, 109.98, 107.81,
) d 172.28, 158.89, 144.28, 137.42, 133.01, 68.13, 67.56, 63.69, 58.27, 53.57, 27.96, 27.20, 13.79; HRMS (ESI)
30.39, 129.91, 129.66, 128.64, 128.51, 128.42, 128.10, 126.28, m/z calcd for C H N O [M + H] exact mass: 412.2020, found:
C
3
1
3
.26–2.19 (m, 1H), 2.08–1.97 (m, 1H), 1.91–1.82 (m, 2H);
C
NMR (100 MHz, CDCl
1
3
2
6
26 3 2
1
25.17, 122.60, 119.27, 69.86, 68.77, 68.34, 63.52, 53.04, 28.33, 412.2017.
0
0
0
0
27.06, 13.74; HRMS (ESI) m/z calcd for C H BrN O [M + H]
(2 R,4S,7a S)-3-Methyl-1,2 -diphenyl-3 -(thiophen-2-yl)-
2 ,3 ,5 ,6 ,7 ,7a -hexahydrospiro-[pyrazole-4,1 -pyrrolizin]-
2 R,4S,7a S)-3 -(4-Bromophenyl)-3-methyl-1,2 -diphenyl- 5(1H)-one (4asa)
2
8
27
3
0
0
0
0
0
0
0
exact mass: 500.1332, found: 500.1333.
0
0
0
0
(
0
0
0
0
0
0
0
2
,3 ,5 ,6 ,7 ,7a -hexahydrospiro-[pyrazole-4,1 -pyrrolizin]-5(1H)-
one (4aoa). The compound 4aoa (424 mg, yield = 85%, R = 0.40 8 : 2)) was isolated as a white solid; mp 197–198 1C; H NMR
PE/EA = 7 : 3)) was isolated as a white solid; mp 166–168 1C; (400 MHz, CDCl ) d 7.58 (d, J = 8.2 Hz, 2H), 7.30 (t, J = 7.8 Hz,
H NMR (400 MHz, CDCl ) d 7.62 (d, J = 7.8 Hz, 2H), 7.36–7.29 2H), 7.26 (d, J = 7.3 Hz, 2H), 7.20 (d, J = 6.9 Hz, 1H), 7.18–7.10
f
The compound 4asa (350 mg, yield = 82%, R = 0.32 (PE/EA =
1
f
(
3
1
3
(
(
(
m, 4H), 7.27–7.19 (m, 4H), 7.19–7.15 (m, 2H), 7.14–7.11 (m, 4H), 6.82–6.78 (m, 1H), 6.67 (d, J = 3.1 Hz, 1H), 5.38 (d, J =
m, 2H), 5.05 (d, J = 10.9 Hz, 1H), 4.34 (t, J = 7.5 Hz, 1H), 3.80 10.8 Hz, 1H), 4.34 (t, J = 7.5 Hz, 1H), 3.90 (d, J = 10.8 Hz, 1H),
d, J = 10.9 Hz, 1H), 3.03–2.95 (m, 2H), 2.27 (s, 3H), 2.25–2.18 3.22–3.15 (m, 1H), 3.10–3.04 (m, 1H), 2.28 (s, 3H), 2.25–2.21
13
13
(
m, 1H), 2.04–1.95 (m, 1H), 1.91–1.78 (m, 2H); C NMR (100 MHz, (m, 1H), 2.06–1.96 (m, 1H), 1.86–1.79 (m, 2H); C NMR (100 MHz,
CDCl ) d 172.26, 158.93, 140.86, 137.40, 133.08, 131.28, 128.94, CDCl ) d 172.16, 158.93, 137.41, 133.23, 128.64, 128.53, 128.41,
28.62, 128.48, 128.39, 128.05, 125.13, 120.93, 119.21, 69.76, 68.72, 128.09, 126.83, 125.19, 124.10, 123.74, 119.31, 68.81, 67.81, 66.10,
8.25, 63.50, 53.02, 28.31, 27.09, 13.70; HRMS (ESI) m/z calcd for 63.13, 53.39, 28.10, 27.27, 13.76; HRMS (ESI) m/z calcd for
3
3
1
6
C H BrN O [M + H] exact mass: 500.1332, found: 500.1330.
C H N OS [M + H] exact mass: 428.1791, found: 428.1789.
28
27
0
3
26 26 3
0
0
0
0
0
0
0
0
(
2 R,3 S,4S,7a S)-3 -(3-Isocyanophenyl)-3-methyl-1,2 -diphenyl-
(2 R,4S,7a S)-3-Methyl-1,2 -diphenyl-3 -(thiophen-3-yl)-
0
0
0
0
0
0
0
0
0
0
0
0
0
0
2
,3 ,5 ,6 ,7 ,7a -hexahydro-spiro[pyrazole-4,1 -pyrrolizin]-5(1H)- 2 ,3 ,5 ,6 ,7 ,7a -hexahydrospiro-[pyrazole-4,1 -pyrrolizin]-
one (4apa) 5(1H)-one (4ata). The compound 4ata (341 mg, yield = 80%, R = 0.33
The compound 4apa (379 mg, yield = 85%, R
f
1
f
= 0.40 (PE/EA = (PE/EA = 8 : 2)) was isolated as a white solid; mp 172–174 1C; H NMR
: 2)) was isolated as a colourless oil. H NMR (400 MHz, CDCl (400 MHz, CDCl ) d 7.65 (d, J = 8.2 Hz, 2H), 7.39–7.30 (m, 4H), 7.27–
1
8
3
)
3
d 7.83 (s, 1H), 7.67–7.61 (m, 2H), 7.45 (t, J = 8.8 Hz, 2H), 7.34 (t, 7.17 (m, 6H), 6.99–6.96 (m, 1H), 5.25 (d, J = 11.0 Hz, 1H), 4.37 (t, J =
J = 7.9 Hz, 2H), 7.28–7.22 (m, 3H), 7.21–7.13 (m, 4H), 5.12 (d, J = 7.5 Hz, 1H), 3.98 (d, J = 11.0 Hz, 1H), 3.23–3.16 (m, 1H), 3.16–3.08
1
3
0.9 Hz, 1H), 4.37 (t, J = 7.6 Hz, 1H), 3.76 (d, J = 10.9 Hz, 1H), (m, 1H), 2.34 (s, 3H), 2.29–2.24 (m, 1H), 2.11–2.01 (m, 1H), 1.93–1.84
13
.04–2.98 (m, 2H), 2.27 (s, 3H), 2.26–2.20 (m, 1H), 2.08–2.00 (m, 2H); C NMR (100 MHz, CDCl ) d 172.25, 159.05, 143.16, 137.43,
3
1
3
(m, 1H), 1.91–1.81 (m, 2H); C NMR (100 MHz, CDCl3) 133.68, 128.66, 128.59, 128.39, 128.37, 127.95, 126.24, 125.56, 125.50,
d 172.25, 158.68, 143.84, 137.39, 132.73, 131.90, 130.90, 125.08, 123.17, 121.43, 119.24, 119.18, 68.66, 68.03, 66.14, 61.99,
1
1
26 3
30.68, 128.79, 128.65, 128.56, 128.48, 128.31, 125.21, 119.24, 53.57, 28.22, 27.14, 13.71; HRMS (ESI) m/z calcd for C26H N OS
19.04, 112.35, 69.75, 68.74, 68.48, 63.96, 53.00, 28.44, 26.95, [M + H] exact mass: 428.1791, found: 428.1791.
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0 0 0 0
2 R,4S,7a S)-3-Methyl-3 -(naphthalen-1-yl)-1,2 -diphenyl- (s, 3H), 2.26–2.17 (m, 1H), 2.03–1.95 (m, 1H), 1.91–1.85 (m, 1H),
(
0
0
0
0
0
0
0
13
2
,3 ,5 ,6 ,7 ,7a -hexahydrospiro-[pyrazole-4,1 -pyrrolizin]-5(1H)- 1.84–1.77 (m, 1H); C NMR (100 MHz, CDCl
3
) d 172.73, 160.75,
one (4aua). The compound 4aua (405 mg, yield = 86%, R = 0.35 159.81, 158.35, 141.85, 137.67, 129.91, 128.55, 128.14, 127.47,
f
1
(PE/EA = 7 : 3)) was isolated as a colourless oil; H NMR 127.09, 124.86, 119.31, 114.34, 104.24, 98.11, 70.59, 68.35,
(
400 MHz, CDCl ) d 8.44 (d, J = 8.2 Hz, 1H), 7.69 (d, J = 68.19, 55.07, 55.05, 53.45, 53.35, 28.05, 27.33, 13.83; HRMS
3
7
.4 Hz, 2H), 7.61–7.53 (m, 3H), 7.36–7.28 (m, 3H), 7.24 (t, J = (ESI) m/z calcd for C30
H
32
N
3
O
3
[M + H] exact mass: 482.2436,
7
.8 Hz, 2H), 7.06 (d, J = 7.2 Hz, 3H), 6.92–6.87 (m, 3H), 5.80 (d, found: 482.2438.
0
0
0
0
J = 11.0 Hz, 1H), 4.41 (t, J = 7.2 Hz, 1H), 4.21 (d, J = 11.0 Hz, 1H),
3
(2 R,4S,7a S)-2 -(3,4-Dimethoxyphenyl)-3-methyl-1,3 -diphenyl-
0 0 0 0 0 0 0
.07–3.04 (m, 1H), 2.86–2.80 (m, 1H), 2.24 (s, 3H), 2.20–2.10 2 ,3 ,5 ,6 ,7 ,7a -hexahydro-spiro[pyrazole-4,1 -pyrrolizin]-5(1H)-
1
3
(m, 1H), 1.91–1.73 (m, 3H); C NMR (100 MHz, CDCl
3
) d one (4aad). The compound 4aad (437 mg, yield = 91%, R
f
= 0.45
1
1
1
1
72.72, 159.30, 137.54, 136.95, 133.92, 133.47, 132.18, 128.74, (PE/EA = 7 : 3)) was isolated as a brown oil; H NMR (400 MHz,
28.68, 128.25, 128.20, 127.96, 127.75, 125.50, 125.47, 125.17, CDCl ) d 7.71 (d, J = 8.3 Hz, 2H), 7.36–7.29 (m, 4H), 7.24–7.11
23.44, 119.36, 68.94, 68.34, 63.02, 53.28, 28.25, 27.24, 13.78; (m, 4H), 6.89 (s, 1H), 6.62–6.55 (m, 2H), 4.99 (d, J = 11.0 Hz, 1H),
3
HRMS (ESI) m/z calcd for C32
H N
30 3
O [M + H] exact mass: 4.34 (t, J = 7.5 Hz, 1H), 3.82 (d, J = 11.0 Hz, 1H), 3.73 (s, 3H), 3.72
4
72.2383, found: 472.2379.
(s, 3H), 3.04–2.99 (m, 2H), 2.25 (s, 3H), 2.23–2.17 (m, 1H), 2.06–
0
0
0
0
13
(
2 R,4S,7a S)-3-Methyl-1,2 -diphenyl-3 -(pyren-1-yl)- 1.97 (m, 1H), 1.89–1.78 (m, 2H); C NMR (100 MHz, CDCl
3
) d
0
0
0
0
0
0
0
2
,3 ,5 ,6 ,7 ,7a -hexahydrospiro[pyrazole-4,1 -pyrrolizin]-5(1H)- 172.75, 159.43, 148.48, 148.44, 141.57, 137.64, 128.67, 128.21,
= 0.50 127.25, 127.19, 126.03, 125.03, 121.34, 118.83, 111.04, 110.57,
one (4ava). The compound 4ava (463 mg, yield = 85%, R
f
(
PE/EA = 5 : 5)) was isolated as a white solid; mp 215–218 1C; 70.77, 68.87, 68.24, 63.26, 55.72, 55.54, 53.12, 28.27, 27.09,
1
H NMR (400 MHz, CDCl ) d 8.77 (d, J = 9.4 Hz, 1H), 8.45 (d, J = 13.68; HRMS (ESI) m/z calcd for C H N O [M + H] exact
3
30 32 3 3
8
.0 Hz, 1H), 8.21 (d, J = 8.0 Hz, 1H), 8.14 (t, J = 7.5 Hz, 2H), 8.07 mass: 482.2436, found: 482.2436.
0
0
0
0
(d, J = 9.3 Hz, 1H), 8.02 (s, 2H), 7.97 (t, J = 7.6 Hz, 1H), 7.76 (d, J =
(2 R,4S,7a S)-2 -(4-Chlorophenyl)-3-methyl-1,3 -diphenyl-
0
0
0
0
0
0
0
8
.1 Hz, 2H), 7.40 (t, J = 7.7 Hz, 2H), 7.26 (d, J = 7.3 Hz, 2H), 7.20 2 ,3 ,5 ,6 ,7 ,7a -hexahydrospiro-[pyrazole-4,1 -pyrrolizin]-5(1H)
= 0.34
.33 (d, J = 10.9 Hz, 1H), 4.61 (t, J = 7.1 Hz, 1H), 4.42 (d, J = (PE/EA = 8 : 2)) was isolated as a colourless oil. H NMR
0.9 Hz, 1H), 3.29–3.21 (m, 1H), 2.99–2.94 (m, 1H), 2.41 (s, 3H), (400 MHz, CDCl ) d 7.63 (d, J = 8.1 Hz, 2H), 7.34 (t, J =
8.1 Hz, 4H), 7.26–7.19 (m, 3H), 7.19–7.15 (m, 3H), 7.11 (d, J =
(t, J = 7.4 Hz, 1H), 7.00 (t, J = 7.3 Hz, 2H), 6.95 (d, J = 7.2 Hz, 1H), one (4aae). The compound 4aae (409 mg, yield = 90%, R
f
1
6
1
2
3
1
3
.39–2.33 (m, 1H), 2.10–2.01 (m, 2H), 1.98–190 (m, 1H);
C
NMR (100 MHz, CDCl ) d 172.76, 159.30, 137.56, 134.96, 133.25, 8.4 Hz, 2H), 5.02 (d, J = 11.0 Hz, 1H), 4.36 (t, J = 7.5 Hz, 1H), 3.88
3
1
1
1
1
5
31.27, 130.63, 130.47, 129.63, 128.69, 128.28, 128.20, 127.78, (d, J = 11.0 Hz, 1H), 3.03–2.98 (m, 2H), 2.27 (s, 3H), 2.23–2.17
1
3
27.34, 127.11, 127.05, 125.67, 125.25, 125.21, 124.90, 124.83, (m, 1H), 2.03–1.94 (m, 1H), 1.89–1.78 (m, 2H); C NMR (100
24.66, 122.69, 119.37, 68.98, 68.54, 63.90, 53.10, 28.15, 27.38, MHz, CDCl ) d 172.22, 158.97, 141.07, 137.42, 133.75, 132.12,
3
3.76; HRMS (ESI) m/z calcd for C38
H
32
N
3
O [M + H] exact mass: 129.92, 128.72, 128.56, 128.35, 127.50, 127.28, 125.27, 119.19,
46.2540, found: 546.2540.
70.55, 68.64, 68.33, 62.39, 53.09, 28.19, 27.23, 13.70; HRMS
0
0
0
0
(
2 R,4S,7a S)-2 -(4-Methoxyphenyl)-3-methyl-1,3 -diphenyl- (ESI) m/z calcd for C28
0 0 0 0 0 0
H
27ClN
3
O [M + H] exact mass: 456.1837,
0
2
,3 ,5 ,6 ,7 ,7a -hexahydrospiro[pyrazole-4,1 -pyrrolizin]-5(1H)- found: 456.1836.
0 0 0 0 0
(2 R,3 S,4S,7a S)-3-Methyl-2 -(4-nitrophenyl)-1,3 -diphenyl-
one (4aab). The compound 4aab (419 mg, yield = 93%, R = 0.48
f
1
0
0
0
0
0
0
0
(
PE/EA = 7 : 3)) was isolated as a brown oil. H NMR (400 MHz, 2 ,3 ,5 ,6 ,7 ,7a -hexahydrospiro-[pyrazole-4,1 -pyrrolizin]-5(1H)-
CDCl ) d 7.64 (d, J = 8.2 Hz, 2H), 7.39–7.29 (m, 4H), 7.25–7.16 one (4aaf). The compound 4aaf (424 mg, yield = 91%, R = 0.48
m, 3H), 7.14 (d, J = 8.2 Hz, 3H), 6.66 (d, J = 8.4 Hz, 2H), 5.02 (PE/EA = 6 : 4)) was isolated as a brown oil; H NMR (400 MHz,
d, J = 11.0 Hz, 1H), 4.36 (t, J = 7.5 Hz, 1H), 3.88 (d, J = 11.0 Hz, CDCl ) d 8.03 (d, J = 8.6 Hz, 2H), 7.64 (d, J = 8.2 Hz, 2H), 7.42
H), 3.66 (s, 3H), 3.05–3.00 (m, 2H), 2.28 (s, 3H), 2.24–2.17 (d, J = 8.6 Hz, 2H), 7.38–7.32 (m, 4H), 7.27–7.14 (m, 4H), 5.11
3
f
1
(
(
1
3
1
3
(m, 1H), 2.03–1.93 (m, 1H), 1.90–1.78 (m, 2H); C NMR (100 (d, J = 10.9 Hz, 1H), 4.40 (t, J = 7.4 Hz, 1H), 4.00 (d, J = 10.9 Hz,
MHz, CDCl ) d 172.50, 159.31, 158.99, 141.44, 137.55, 129.60, 1H), 3.03 (dd, J = 7.7, 4.9 Hz, 2H), 2.33 (s, 3H), 2.27–2.23
3
1
3
1
7
28.63, 128.23, 127.34, 127.28, 125.45, 125.07, 119.24, 113.67, (m, 1H), 2.08–1.98 (m, 1H), 1.92–1.82 (m, 2H); C NMR
0.54, 68.88, 68.07, 62.53, 55.00, 53.14, 28.20, 27.20, 13.72; (100 MHz, CDCl ) d 171.87, 158.62, 147.52, 141.26, 140.76,
3
HRMS (ESI) m/z calcd for C29
H
30
N
3
O [M + H] exact mass: 137.26, 129.64, 128.83, 128.55, 127.80, 127.19, 125.47, 123.56,
4
52.2333, found: 542.2331.
118.99, 70.67, 68.69, 68.59, 62.52, 53.11, 28.23, 27.33, 13.75;
0
0
0
0
(
2 R,4S,7a S)-2 -(2,4-Dimethoxyphenyl)-3-methyl-1,3 -diphenyl- HRMS (ESI) m/z calcd for C28
H
27
N
4
O
3
[M + H] exact mass:
0
0 0 0 0 0 0
2
,3 ,5 ,6 ,7 ,7a -hexahydro-spiro[pyrazole-4,1 -pyrrolizin]-5(1H)- 467.2078, found: 467.2084.
0
0
0
0
one (4aac). The compound 4aac (437 mg, yield = 91%, R
f
= 0.43
(2 R,4S,7a S)-3-Methyl-1,3 -diphenyl-2 -(thiophen-2-yl)-
0
0
0
0
0
0
0
(
PE/EA = 7 : 3)) was isolated as a white solid; mp 195–197 1C; 2 ,3 ,5 ,6 ,7 ,7a -hexahydrospiro-[pyrazole-4,1 -pyrrolizin]-
H NMR (400 MHz, CDCl ) d 7.65–7.60 (m, 3H), 7.41 (d, J = 5(1H)-one (4aag). The compound 4aag (354 mg, yield = 83%, R =
1
3
f
7
7
1
7
.5 Hz, 2H), 7.33 (t, J = 7.8 Hz, 2H), 7.25 (t, J = 7.4 Hz, 2H), 7.20– 0.37 (PE/EA = 8: 2)) was isolated as a white solid; mp 205–207 1C;
1
.10 (m, 2H), 6.36 (dd, J = 8.6, 2.0 Hz, 1H), 6.22 (d, J = 2.0 Hz,
3
H NMR (400 MHz, CDCl ) d 7.66 (d, J = 7.9 Hz, 2H), 7.31 (d, J =
H), 5.00 (d, J = 11.2 Hz, 1H), 4.59 (d, J = 11.2 Hz, 1H), 4.36 (t, J = 7.3 Hz, 2H), 7.26 (t, J = 7.9 Hz, 2H), 7.17 (t, J = 7.2 Hz, 2H), 7.14–
.5 Hz, 1H), 3.67 (s, 3H), 3.61 (s, 3H), 3.05–3.00 (m, 2H), 2.31 7.10 (m, 1H), 7.06 (t, J = 7.4 Hz, 1H), 6.92 (d, J = 5.0 Hz, 1H), 6.74
2380 | New J. Chem., 2021, 45, 2374--2383
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(d, J = 3.3 Hz, 1H), 6.69–6.65 (m, 1H), 4.87 (d, J = 10.8 Hz, 1H), 3.01 (dd, J = 11.5, 2.4 Hz, 1H), 2.94 (d, J = 11.0 Hz, 1H), 2.54
4
2
2
1
1
1
4
.23 (t, J = 7.5 Hz, 1H), 4.04 (d, J = 10.8 Hz, 1H), 2.93–2.88 (m, 2H), (s, 3H), 2.02 (td, J = 12.0, 2.3 Hz, 1H), 1.86 (d, J = 13.4 Hz, 1H),
.16 (s, 3H), 2.12–2.07 (m, 1H), 1.93–1.84 (m, 1H), 1.78–1.71 (m, 1.67 (d, J = 13.4 Hz, 1H), 1.61 (d, J = 11.3 Hz, 1H), 1.59–1.49 (m,
1
3
13
H); C NMR (101 MHz, CDCl ) d 172.33, 158.99, 141.41, 137.66, 2H), 1.38–1.30 (m, 1H); C NMR (200 MHz, CDCl ) d 172.31,
3
3
35.96, 128.67, 128.24, 127.45, 127.31, 126.62, 126.30, 125.07, 162.28, 139.73, 137.68, 134.96, 129.12, 128.57, 128.53, 127.98,
24.82, 119.09, 72.29, 68.76, 68.33, 58.34, 53.09, 28.14, 27.30, 127.65, 127.38, 124.75, 118.97, 73.42, 72.53, 71.95, 69.82, 66.56,
3.50; HRMS (ESI) m/z calcd for C26H N OS [M + H] exact mass: 59.22, 51.71, 51.62, 26.65, 24.96, 24.21, 15.98; HRMS (ESI) m/z calcd
26 3
28.1791, found: 428.1788.
for C29
H
30
0
N
3
O [M + H] exact mass: 436.2383, found: 436.2383.
0
0
0
0
0
0
0
0
(
2 R,4S,7a S)-3-Methyl-2 -(naphthalen-2-yl)-1,3 -diphenyl-
(2 R,3 S,4S,7a S)-3-Isopropyl-2 -(4-methoxyphenyl)-1,3 -diphenyl-
0
0
0
0
0
0
0
0 0 0 0 0 0 0
2
,3 ,5 ,6 ,7 ,7a -hexahydrospiro-[pyrazole-4,1 -pyrrolizin]-5(1H)-
2 ,3 ,5 ,6 ,7 ,7a hexahydrospiro[pyrazole-4,1 -pyrrolizin]-5(1H)-
one (4aah). The compound 4aah (395 mg, yield = 84%, R = 0.34 one (4aai). The compound 4aai (416 mg, yield = 87%, R = 0.34
f
f
1
(
PE/EA = 7 : 3)) was isolated as a white solid; mp 199–201 1C; (PE/EA = 9 : 1)) was isolated as a colourless oil H NMR
H NMR (400 MHz, CDCl ) d 7.74–7.59 (m, 7H), 7.50 (d, J = 7.5 (400 MHz, CDCl ) d 7.71 (d, J = 8.1 Hz, 2H), 7.35 (t, J = 7.5
1
3
3
Hz, 1H), 7.40 (d, J = 4.8 Hz, 3H), 7.29 (t, J = 7.8 Hz, 2H), 7.24–7.14 Hz, 4H), 7.25–7.20 (m, 3H), 7.18–7.16 (m, 3H), 6.66 (d, J = 8.6
m, 3H), 7.11 (t, J = 7.4 Hz, 1H), 5.24 (d, J = 10.9 Hz, 1H), 4.44 (t, Hz, 2H), 5.02 (d, J = 10.8 Hz, 1H), 4.50 (t, J = 7.4 Hz, 1H), 3.91
J = 7.5 Hz, 1H), 4.08 (d, J = 10.9 Hz, 1H), 3.14–3.04 (m, 2H), 2.34 (d, J = 11.0 Hz, 1H), 3.67 (s, 3H), 3.08 (dd, J = 8.2, 4.2 Hz, 2H),
s, 3H), 2.32–2.24 (m, 1H), 2.08–2.00 (m, 1H), 1.95–1.84 (m, 2H); 2.99–2.92 (m, 1H), 2.27–2.24 (m, 1H), 2.13–1.99 (m, 1H), 1.98–
(
(
1
3
13
3
C NMR (100 MHz, CDCl ) d 172.53, 159.16, 141.69, 133.06, 1.81 (m, 2H), 1.33 (d, J = 6.6 Hz, 6H); C NMR (100 MHz,
1
1
5
32.88, 131.28, 128.58, 128.25, 128.11, 128.05, 127.84, 127.45, CDCl ) d 172.54, 166.66, 159.00, 141.88, 137.78, 130.06, 129.93,
27.20, 126.14, 125.88, 125.05, 119.20, 70.64, 68.97, 68.61, 63.66, 129.55, 128.54, 128.13, 127.18, 127.11, 125.62, 124.92, 119.74,
3
3.21, 28.32, 27.15, 13.78; HRMS (ESI) m/z calcd for C H N O 119.27, 113.49, 70.57, 69.30, 67.85, 63.58, 54.93, 53.22, 28.50,
3
2
30 3
[
M + H] exact mass: 472.2383, found: 472.2377.
26.80, 26.77, 23.09, 20.46. HRMS (ESI) m/z calcd for
0
0
0
0
0
0
0
0
0
(
4S,5 S,6 R,7a S)-3-Methyl-1,5 ,6 -triphenyl-2 ,3 ,5 ,6 -tetrahydro-
C
31
H
34
N
3
O
2
0
[M + H] exact mass: 480.2646, found: 480.2650.
0
0
0
0
0
0
7
a H-spiro[pyrazole-4,7 -pyrrolo[2,1-b]thiazol]-5(1H)-one (4baa).
(4S,5 S,6 R,7a S)-3-Isopropyl-6 -(4-methoxyphenyl)-1,5 -diphenyl-
0 0 0 0 0 0
The compound 4baa (364 mg, yield = 83%, R
: 1)) was isolated as a white solid; mp 211–214 1C; H NMR zol]-5(1H)-one (4bai). The compound 4aai (422 mg, yield = 85%,
f
= 0.50 (PE/EA = 2 ,3 ,5 ,6 -tetrahydro-7a H-spiro[pyrazole-4,7 -pyrrolo[2,1-b]thia-
1
9
(
1
400 MHz, CDCl ): d 7.58 (d, J = 7.7 Hz, 2H), 7.45 (d, J = 7.0 Hz, R = 0.36 (PE/EA = 9 : 1)) was isolated as a colourless oil. H NMR
3 f
2
5
3
2
1
1
1
1
4
H), 7.34–7.27 (m, 4H), 7.25–7.20 (m, 3H), 7.17–7.10 (m, 4H), (400 MHz, CDCl ) d 7.44 (d, J = 8.1 Hz, 2H), 7.18 (d, J = 7.1 Hz,
3
.41 (s, 1H), 5.19 (d, J = 10.7 Hz, 1H), 3.78 (d, J = 10.7 Hz, 1H), 2H), 7.12 (t, J = 7.8 Hz, 2H), 7.08–6.97 (m, 3H), 6.92 (t, J = 8.0 Hz,
.52–3.44 (m, 1H), 3.36–3.29 (m, 1H), 3.05–2.95 (m, 1H), 2.91– 3H), 6.43 (d, J = 8.6 Hz, 2H), 5.30 (s, 1H), 4.91 (d, J = 10.4 Hz,
1
3
.83 (m, 1H), 2.37 (s, 3H); C NMR (100 MHz, CDCl
3
) d 170.98, 1H), 3.62–3.51 (m, 1H), 3.44 (s, 3H), 3.28–3.24 (m, 1H), 3.17–
57.66, 140.58, 137.44, 132.74, 128.90, 128.80, 128.74, 128.64, 3.13 (m, 1H), 2.90–2.87 (m, 1H), 2.72–2.69 (m, 1H), 1.18 (d, J =
1
3
3
28.59, 128.52, 128.45, 128.33, 127.99, 127.87, 127.78, 127.64, 7.6 Hz, 3H), 1.15 (d, J = 7.5 Hz, 3H); C NMR (101 MHz, CDCl )
25.22, 119.67, 119.02, 72.91, 70.19, 68.58, 59.97, 55.53, 32.37, d 171.03, 165.27, 159.13, 137.68, 130.21, 128.62, 128.41, 127.72,
3.80; HRMS (ESI) m/z calcd for C H N OS [M + H] exact mass: 125.11, 119.67, 113.61, 72.42, 70.52, 69.28, 55.57, 55.04, 32.61,
2
7
26 3
40.1791, found: 440.1791.
27.12, 23.24, 20.98; HRMS (ESI) m/z calcd for C H N O S [M +
30 32 3 2
0 0 0 0 0 0 0 0 0
(
4S,5 S,6 R,7a R)-3-Methyl-1,5 ,6 -triphenyl-1 ,5 ,6 ,7a -tetrahydro- H] exact mass: 498.2210, found: 498.2216.
0
0
0
Gram scale synthesis of (1S,2R,3S,8aS)-2-(3,4-dimethoxyphenyl)-3 -
3
H-spiro[pyrazole-4,7 -pyrrolo[1,2-c]thiazol]-5(1H)-one (4caa). The
= 0.6 (PE/EA = 8:2)) was methyl-1 ,3-diphenyl-2,3,6,7,8,8a-hexa-hydro-5H-spiro-[indolizine-1,4 -
0
0
compound 4caa (346 mg, yield = 79%, R
f
1
0 0
isolated as a colourless oil. H NMR (400 MHz, CDCl
.4 Hz, 4H), 7.38–7.30 (m, 5H), 7.26–7.21 (m, 4H), 7.20–7.13 (m, 2H),
.92 (d, J = 10.8 Hz, 1H), 4.20–4.10 (m, 3H), 3.90 (d, J = 10.8 Hz, 1H), (400 MHz, CDCl
.74 (dd, J = 11.5, 7.1 Hz, 1H), 2.97 (dd, J = 11.5, 7.8 Hz, 1H), 2.53 7.27 (m, 4H), 7.25 (d, J = 7.8 Hz, 1H), 7.11 (t, J = 7.7 Hz, 1H), 6.74 (d, J =
3
) d 7.53 (t, J = pyrazol]-5 (1 H)-one (4dad). The compound 4dad (1.16 g, yield = 86%,
1
8
4
3
R
f
= 0.48 (PE/EA = 7:3)) was isolated as a colourless oil H NMR
) d 7.60 (d, J = 8.1 Hz, 2H), 7.35 (d, J = 7.4 Hz, 2H), 7.33–
3
13
(s, 3H); C NMR (100 MHz, CDCl ) d 170.58, 160.44, 139.32, 137.25, 7.0 Hz, 2H), 6.68 (d, J = 8.6 Hz, 1H), 3.80 (s, 3H), 3.79 (s, 3H), 3.47 (d, J =
3
133.22, 128.79, 128.56, 128.55, 128.15, 128.04, 127.87, 127.82, 125.07, 9.9 Hz, 1H), 2.99 (d, J = 9.1 Hz, 1H), 2.93 (d, J = 9.4 Hz, 1H), 2.52 (s, 3H),
1
19.17, 70.12, 66.99, 65.10, 61.07, 55.92, 32.91, 13.72; HRMS (ESI) 2.00 (t, J = 10.4 Hz, 1H), 1.87–1.85 (m, 1H), 1.68–1.65 (m, 1H), 1.55–1.46
13
m/z calcd for C27
H
26
N
3
OS [M + H] exact mass: 440.1791, found: (m, 3H), 1.38–1.26 (m, 1H); C NMR (100 MHz, CDCl
148.33, 148.21, 139.83, 137.83, 128.68, 128.57, 127.70, 127.66, 127.57,
1S,2R,3S,8aS)-3 -Methyl-1 ,2,3-triphenyl-2,3,6,7,8,8a-hexahydro- 124.79, 121.48, 118.86, 112.46, 110.46, 74.06, 72.06, 66.63, 59.09, 55.89,
3
) d 172.49, 162.49,
440.1791.
0
0
(
0 0 0
5H-spiro[indolizine-1,4 -pyrazol]-5 (1 H)-one (4daa). The com- 55.65, 51.77, 26.70, 25.02, 24.28, 16.04; HRMS (ESI) m/z calcd for
pound 4daa (382 mg, yield = 88%, R = 0.5 (PE/EA = 9 : 1)) was C H N O [M + H] exact mass: 496.2595, found: 496.2624.
f
31 34 3 3
1
isolated as a white solid; mp 174–175 1C; H NMR (800 MHz,
CDCl ) d 7.54 (d, J = 7.9 Hz, 2H), 7.38 (d, J = 7.5 Hz, 2H), 7.31–7.28
3
(
1
1
m, 4H), 7.24 (t, J = 7.3 Hz, 1H), 7.23–7.20 (m, 4H), 7.17–7.15 (m,
H), 7.10 (t, J = 7.3 Hz, 1H), 4.01 (d, J = 10.0 Hz, 1H), 4.01 (d, J =
0.0 Hz, 1H), 3.54 (d, J = 10.0 Hz, 1H), 3.54 (d, J = 10.0 Hz, 1H), There are no conflicts to declare.
Conflicts of interest
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Acknowledgements
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The authors thank the Science and Engineering Research Board
(SERB), New Delhi, for the financial support in the form of a
Core Research Grant (File No. CRG/2020/000801). A.A. thanks
the Council of Scientific and Industrial Research (CSIR), New
Delhi (India), for the award of a research fellowship. P.Y. thanks
the University Grant Commission for the fellowship. A.A. and
P.Y. gratefully acknowledge the Banaras Hindu University
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