Oxa-Michael–Michael Reaction of MBH Alcohol and 2-Arylidene-1,3-indanedione: Regioselective Formal [4+2] Cycloaddition towards Tetrahydrospiropyran Scaffolds

Article abstract of DOI:10.1002/ejoc.201801709

A regioselective formal [4+2] cycloaddition reaction of nitrostyrene derived MBH alcohol and 2-arylidene-1,3-indanedione resulted in functionalized tetrahydrospiropyran derivatives with excellent chemical yields (up to 93 %). The reaction tolerated variou

Full text of DOI:10.1002/ejoc.201801709

A Journal of
Accepted Article
Title: Oxa-Michael-Michael Reaction of MBH Alcohol and 2-
Arylidene-1,3-indanedione: Regioselective Formal [4+2]
Cycloaddition Towards Tetrahydrospiropyran Scaffolds
Authors: Veera Babu Gudise, Poorna Chandrasekhar Settipalli, Eeda
Koti Reddy, and Anwar Shaik
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10.1002/ejoc.201801709
European Journal of Organic Chemistry
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Oxa-Michael-Michael Reaction of MBH Alcohol and 2-Arylidene-
1,3-indanedione: Regioselective Formal [4+2] Cycloaddition
Towards Tetrahydrospiropyran Scaffolds
Veera Babu Gudise,[a] Poorna Chandrasekhar Settipalli,[a] Eeda Koti Reddy[a] and Shaik Anwar*[a]
Dedicated to my teachers: Prof. M. Periasamy and Prof. D. Basavaiah
Abstract: A regioselective formal [4+2] cycloaddition reaction of
nitrostyrene derived MBH alcohol and 2-arylidene-1,3-indanedione
resulted in functionalized tetrahydrospiropyran derivatives with
excellent chemical yields (up to 93 %). The reaction tolerated
various electron rich and electron deficient substituents on the aryl
group of 2-arylidene-1,3-indanedione as well as MBH alcohol. The
utility of MBH alcohol as an ambident substrate i.e., performing the
dual role of nucleophile
& electrophile with 2-arylidene-1,3-
indanediones was successfully demonstrated for 20 derivatives. A
single isomer was obtained exclusively in all the products via
cascade process which followed an oxa-Michael-Michael addition
sequence using cesium carbonate as base. Control experiments
were carried out to understand the mechanistic details of the
reaction. These experiments prove that the reaction undergoes a
stepwise pathway rather than a concerted mechanism.
Scheme 1. Synthesis of tetrahydrospiropyran derivatives utilising MBH alcohol
1 and 2-arylidene-1,3-indanedione 2
The feasibility of this reaction is mainly due to the ambident
nature of nitroolefin
1 which undergoes a formal [4+2]
cycloaddition with 2-arylidene-1.3-indanedione via oxa-Michael-
Michael pathway resulting in spirocyclic adduct 3 as a single
isomer. Till date, though most of the literature studies report
MBH alcohol i.e., (E)-2-nitro-3-phenylprop-2-en-1-ol 1 as an
electrophile or nucleophile, there are hardly any reports utilising
1 for the synthesis of spiropyran derivatives 3. Tetrahydropyran
moiety occupies the core structure of various bioactive natural
products and drugs19 like FR901464,20 Ophiocerins21 and
Houttuynoids.22
Due to the interesting molecular structure and biological
activity23 of the spirocycles, various strategies have been
reported.24 Tetrahydrospiropyrans are essential moieties in
medicinal chemistry since they are the main core in many
bioactive molecules, which show pharmacological activity.
Besides of all above, they can be utilized for the construction of
various chiral ligands.25 These spiropyran derivatives are known
for their biological activity and medicinal value in several API
and pharmaceutical ingredients (Figure 1).
Introduction
Morita-Baylis-Hillman (MBH) reaction1 is a distinguished C-C
bond formation, which involves activated alkene and an
aldehyde. MBH reaction leads to the formation of various MBH
adducts with different functionalities that have been used as
building blocks for various synthetic transformations.2 Morita-
Baylis-Hillman adducts possessing three chemospecific groups
i.e., an olefinic bond, hydroxyl group and an electron
withdrawing group, which can be appropriately utilized towards a
variety of cyclic compounds. Previously, nitrostyrene derived
MBH alcohol has been explored towards the synthesis of
tetrahydropyrans,3
dihydropyrans,4
phosphonylpyrazoles,5
sulfonylpyrazoles,6 functionalized cyclobutanes,7 isoxazoline N-
oxides,8 benzoxepine,9 3-nitrothietans,10 triazoles,11 bicyclics,12
hydroisochromenes,13 chromenes14 as well as organocatalytic
desymmetrization of cyclic meso-anhydrides.15 In continuation
with our research interest on cascade reactions of nitrostyrene
derived MBH adducts,16 we envisioned that synthesis of
tetrahydrospiropyran derivatives could be made feasible using
nitrostyrene derived MBH alcohol
1 and 2-arylidene-1.3-
indanedione17,18 2 (Scheme 1).
[a]
V. B. Gudise, P.C. Settipalli, Dr. E. K. Reddy, Dr. Shaik Anwar
Division of Chemistry, Department of Sciences and Humanities,
Vignan’s Foundation for Science, Technology and Research
(Deemed to be University),Vadlamudi, Guntur – 522 213,
Andhra Pradesh, India
E-mail: shaikanwarcu@gmail.com; ska_sh@vignanuniversity.org
http://www.vignanuniversity.org/bshanwar.php
Figure 1. Selected bioactive and natural products having tetrahydrospiropyran
skeleton.
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10.1002/ejoc.201801709
European Journal of Organic Chemistry
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withdrawing and -rich substituents on aryl ring of substrate 2.
Alkyl substituents at para- position such as methyl and isopropyl
gave moderate yield for product formation 3b and 3c in 71 &
60 % yield. Electron-rich substituents such as methoxy and
benzyloxy group gave products 3d and 3e in 67 & 56 %. Among
the electron withdrawing substituents like CN product 3g
displayed outstanding yield of 93 % in comparison to the
nitrogroup 3f. Use of halogen substituent retained an excellent
yield of 92 % in 3h. Further addition of o,p-dichloro substituents
slightly decreased the yield for product 3i. Substituents at ortho-
and meta- gave reasonable to good yield for products 3j and 3k.
Heterocyclic entities such as 3l and 3m gave a low yield of 45 &
21 %. Use of aliphatic derivatives of 2 gave poor yields probably
due to decreased electrophilicity of the starting material i.e. 2-
alkylidene-1,3-indanediones.
Results and Discussion
In continuation with our strategy, we herein report a unique
protocol for synthesis of novel spiropyrans utilising MBH alcohol
1 and 2-arylidene-1,3-indanediones. In order to validate our
hypothesis, we carried out initial optimisation studies by
screening various solvents for the reaction of nitroallylic alcohol
1a with 2-benzylidene-1,3-indanedione 2a using cesium
carbonate as base. Polar aprotic solvents like DMF and DMSO
resulted in trace quantities of product formation (Table 1, entry 1
& 2). Use of polar solvents such as THF resulted in formation of
product 3a in 73 % (Table 1, entry 3). No improvement in yield
i.e. 71 % was found on use of 1,4-dioxane as solvent (Table 1,
entry 4). Shifting to organic bases in non-polar solvents also
could not lead to the completion of the reaction (Table 1, entries
5 & 6) resulting in poor yields. It was found to be cesium
carbonate was the ideal base for our studies with the formation
of single isomer. Use of polar solvent such as acetonitrile
provided an improved yield of 79 % (entry 8). Use of chlorinated
solvents gave promising results, with CHCl3 as suitable solvent
with maximum yield of 87 % (table 1, entries 9-13). The structure
3a was further confirmed by single crystal XRD.31
Table 2. Substrate scope for the synthesis of tetrahydrospiropyrans using
substituted 2-arylidene-1,3-indanedione.
Table 1. Solvent screening studies towards the synthesis of
tetrahydrospiropyran 3a[a]
S. No
Solvent
Base
Yield(%)[b]
dr[c]
1
2
3
4
5
6
7
8
DMF
DMSO
THF
1,4-dioxane
Toluene
Benzene
Diethyl ether
Acetonitrile
CHCl3
CH2Cl2
CCl4
1,2-DCE
Chlorobenzene
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Pyrrolidine
Piperidine
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
5
-
-
trace
73
71
<5
<5
63
79
87
82
84
48
75
99:1
99:1
-
-
-
99:1
99:1
99:1
99:1
-
9
10
11
12
13
99:1
[a] The reaction was carried out by using 1a (0.2 mmol), 2a (0.1 mmol), base
(0.3 mmol).
[b] Purified by flash column chromatography.
[c] Determined by crude 1H NMR
With the best optimised conditions, the substrate scope of
various 2-arylidene-1,3-indanediones were investigated using
alcohol 1a (Table 2). The reaction tolerated various electron-
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10.1002/ejoc.201801709
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We further explored the substituent effect on the phenyl ring of
MBH alcohol 1a using the previous optimized conditions. (Table
3). Among the halogen substituents, p-Fluoro substituted MBH
alcohol gave the high yield of 77 % towards the formation of 3n.
On the other hand, p-bromo substituted yielded 3o in 60 %. The
o,p-disubstituted halo compound 3p resulted in very less yield of
47 %. The presence of electron donating groups on MBH
alcohol gave good to excellent yields of 77 % and 90 % for the
formation of products 3q and 3r respectively. Presence of
electron-rich substituents in meta-position reduced the yield to
63 % for product 3s. The yield was dropped with the use of
electron withdrawing group i.e -CN for the formation of
compound 3t in 53 % yield. Reaction of 2a with allylic alcohols
derived from aliphatic nitroolefins resulted in complex mixture as
aliphatic allylic alcohols of 1 were unstable in presence of base
under the present reaction conditions.
Table 3. Substrate scope for the synthesis of tetrahydrospiropyrans using
Scheme 2. Attempted three component and one pot preparation of 3a.
substituted MBH alcohol
To further demonstrate the practical and scalable utility of our
protocol we have carried out gram scale preparation of
tetrahydrospiropyran 3a. As per our expectation, we observed
the retention of diastereoselectivity even at gram scale (Scheme
3a). To explore the synthetic utility of the final cyclized
spiropyran 3a, we intended to convert nitrogroup to the
corresponding amine derivative. Treatment of 3a with Pd/C in
MeOH led to the cleavage of the spiropyran skeleton
presumably at the benzylic carbon atoms (Scheme 3b).
Scheme 3. Gram scale preparation of product 3a.
In order to gain comprehensive information regarding the
mechanistic details of stepwise regioselective formal [4+2]
cycloaddition, a set of control experiments were carried out at
low temperature.34
2-benzylidene 1,3-indanedione 2a on treatment with nitroallylic
alcohol 1a under the optimized reaction conditions led to
intermediate B which on reaction with nitrostyrene resulted in
formation of C (Scheme 4a). Similarly under the identical
reaction conditions, intermediate B on reaction with electrophiles
such as benzyl bromide and methyl iodide led to formation of D
and E eventually detected by HRMS (Scheme 4b, 4c).
We further explored the possibility of three component cascade
reaction of 1,3-indanedione, benzaldehyde and nitroallylic
alcohol 1a (Scheme 2a). Contrary to our expectation, product 3a
was not formed with recovery of starting material.32 Parallely,
one pot preparation of 3a was carried out by stepwise synthesis
of 2-benzylidene-1,3-indanedione 2a, followed by addition of
nitroalcohol 1a to the reaction mixture. The corresponding
product 3a was isolated in 65 % yield. The decreased yield is
presumably due to decomposition of nitroallylic alcohol 1a under
prolonged reaction time (Scheme 2b).33
These detected intermediate products clearly paves way for
stepwise mechanism rather than a concerted one (Figure 2).
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10.1002/ejoc.201801709
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Conclusions
We have demonstrated the utility of MBH alcohol as an
ambident substrate i.e. performing the dual role of nucleophile &
electrophile for synthesis of tetrahydrospiropyran derivatives.
These tetrahydrospiropyran derivatives were obtained as a
single isomer via cascade oxa-Michael-Michael addition
sequence using cesium carbonate as base. The scope of this
reaction was studied at room temperature with a variety of
substituents to yield in a total of 20 tetrahydrospiropyran
derivatives.
Experimental Section
General Procedure for the synthesis of (2'R,4'R,5'R)-5'-nitro-2',4'-
diphenyl-2',4',5',6'-tetrahydrospiro[indene-2,3'-pyran]-1,3-dione: To a
solution of benzylidene-1,3-indanedione
2 (0.1 mmol) and cesium
carbonate (0.3 mmol) in chloroform (3 mL), MBH alcohol 1 (0.2 mmol)
was added at room temperature. The reaction mixture was allowed to stir
at room temperature, monitored by TLC until the completion of the
reaction. The crude mixture was extracted with dichloromethane (20 mL),
later washed with brine solution, dried over Na2SO4 and concentrated
under reduced pressure. The crude compound was purified by flash
column chromatography on silica gel (5-7 %, ethyl acetate in hexane) to
afford the final products.
Scheme 4. Control Experiments
Analytical data for final Compounds
(2'R,4'R,5'R)-5'-nitro-2',4'-diphenyl-2',4',5',6'-tetrahydrospiro[indene-2,3'-
pyran]-1,3-dione (3a):To a solution of 2a (0.1 mmol, 23.4 mg) and
cesium carbonate (0.3 mmol, 97.7 mg) in chloroform (3 mL), nitroallylic
alcohol 1a (0.2 mmol, 35.8 mg) was added at room temperature. The
reaction mixture was stirred at room temperature for 4 h. Yield: 87 % (36
1
mg). White solid; m.p. 148-149 0C. H NMR (400 MHz, CDCl3): = 7.53-
7.41 (m, 4 H), 7.13-7.11 (m, 3 H), 7.08-7.04 (m, 3 H), 7.02-6.96 (m, 4 H),
6.33-6.26 (m, 1 H), 5.06 (s, 1 H), 4.86 (dd, J = 10.8, 4.8 Hz, 1 H), 4.36 (d,
J = 12 Hz, 1 H), 4.19 (t, J = 10.8 Hz, 1 H) ppm. 13C NMR (100 MHz,
CDCl3)  = 199.5, 198.6, 142.7, 141.7, 135.5, 135.3, 135.2, 133.1, 128.7,
128.6,128.6, 128.3, 128.1, 126.6, 122.6, 122.3, 84.0, 81.1, 70.3, 63.9,
49.0. IR (neat): cm-1= 2923, 1735, 1699, 1591, 1559, 1452, 1353, 1245,
1097, 753, 698. HRMS (ESI): m/z calcd. for C25H20NO5 [M + H]+:
414.1341; found: 414.1341.
Figure 2. ESI Mass spectras of control experiments
It is expected that in the presence of inorganic base i.e., cesium
carbonate, nitroallaylic alcohol 1a generates nucleophile A. The
nucleophilic oxygen atom attacks the benzylic carbon of
electrophile 2 to generate B. Rearrangement of enol to ketone
and subsequent attack on the electrophilic olefinic site via formal
[4+2] cycloaddition results in formation of 3 in a regioselective
manner (Scheme 5).
(2'R,4'R,5'R)-5'-nitro-4'-phenyl-2'-(p-tolyl)-2',4',5',6'-
tetrahydrospiro[indene-2,3'-pyran]-1,3-dione (3b): To a solution of 2b
(0.1 mmol, 24.8 mg) and cesium carbonate (0.3 mmol, 97.7 mg) in
chloroform (3 mL), nitroallylic alcohol 1a (0.2 mmol, 35.8 mg) was added
at room temperature. The reaction mixture was stirred at room
temperature for 6 h. Yield: 71 % (23 mg). Pale yellow solid; m.p. 158-160
0C. 1H NMR (400 MHz, CDCl3): = 7.54-7.43 (m, 4 H), 7.12-7.10 (m, 2
H), 7.06-6.98 (m, 3 H), 6.95 (d, J = 8 Hz, 2 H), 6.8 (d, J = 8 Hz, 2 H),
6.31-6.24 (m, 1 H), 5.02 (s, 1 H), 4.85 (dd, J = 10.4, 4.8, Hz, 1 H), 4.33
(d, J = 12 Hz, 1 H), 4.17 (t, J = 10.4 Hz, 1 H), 2.06 (s, 3 H) ppm. 13C
NMR (100 MHz, CDCl3)  = 199.6, 198.7, 142.7, 141.7, 138.3, 135.4,
135.2, 133.1, 132.2, 128.7, 128.6, 128.2, 126.5, 122.6, 122.3, 83.9, 81.1,
70.3, 63.9, 49.1, 20.8. IR (neat): cm-1= 2922, 2851, 1734, 1695, 1592,
1550, 1456, 1351, 1249, 1099, 761, 698. HRMS (ESI): m/z calcd. for
C26H22NO5 [M + H]+: 428.1498; found: 428.1498.
(2'R,4'R,5'R)-2'-(4-isopropylphenyl)-5'-nitro-4'-phenyl-2',4',5',6'-
tetrahydrospiro [indene-2,3'-pyran]-1,3-dione (3c):To a solution of 2c (0.1
mmol, 27.6 mg) and cesium carbonate (0.3 mmol, 97.7 mg) in chloroform
(3 mL), nitroallylic alcohol 1a (0.2 mmol, 35.8 mg) was added at room
temperature. The reaction mixture was stirred at room temperature for 6
h. Yield: 60 % (18 mg). Pale yellow solid; m.p. 162-163 0C. 1H NMR (400
MHz, CDCl3): = 7.51-7.41 (m, 4 H), 7.14-7.12 (m, 2 H), 7.07-6.95 (m, 3
H), 6.96 (d, J = 8.4 Hz, 2 H), 6.82 (d, J = 8 Hz, 2 H), 6.34-6.27 (m, 1 H),
5.02 (s, 1 H), 4.85 (dd, J = 10.8, 4.8, Hz, 1 H), 4.35 (d, J = 12 Hz, 1 H),
Scheme 5. Plausible mechanism for the formation of product 3.
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10.1002/ejoc.201801709
European Journal of Organic Chemistry
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4.18 (t, J = 10.4 Hz, 1 H), 2.60 (sept, J = 7.2 Hz, 1 H), 0.96 (d, J = 7.2
Hz, 6 H) ppm. 13C NMR (100 MHz, CDCl3)  = 199.6, 198.6, 149.5,
142.8, 141.8, 135.2, 135.0, 133.3, 132.5, 128.8, 128.6, 128.2, 126.6,
126.0, 122.6, 122.4, 84.2, 81.2, 70.3, 64.2, 48.9, 33.6, 23.6. IR (neat):
cm-1= 2922, 2960, 2874, 1739, 1703, 1593, 1545, 1456, 1352, 1244,
1104, 810, 769, 699. HRMS (ESI): m/z calcd. for C28H26NO5 [M + H]+:
456.1811; found: 456.1815.
(2'R,4'R,5'R)-2'-(4-bromophenyl)-5'-nitro-4'-phenyl-2',4',5',6'-
tetrahydrospiro[indene-2,3'-pyran]-1,3-dione (3h):To a solution of 2h (0.1
mmol, 31.3 mg) and cesium carbonate (0.3 mmol, 97.7 mg) in chloroform
(3 mL), nitroallylic alcohol 1a (0.2 mmol, 35.8 mg) was added at room
temperature. The reaction mixture was stirred at room temperature for 6
h. Yield: 92 % (45 mg). Pale yellow solid; m.p. 168-169 0C. 1H NMR (400
MHz, CDCl3): = 7.55-7.48 (m, 4 H), 7.16-7.14 (m, 2 H), 7.10-6.96 (m,
7H), 6.27-6.20 (m, 1 H), 5.02 (s, 1 H), 4.85 (dd, J = 10.4, 4.8, Hz, 1 H),
4.32 (d, J = 12 Hz, 1 H), 4.17 (t, J = 10.8 Hz, 1 H) ppm. 13C NMR (100
MHz, CDCl3)  = 199.3, 198.6, 141.6, 135.8, 135.6, 134.4, 131.3, 128.7,
128.6, 128.4, 122.7, 122.5, 83.1, 80.9, 70.2, 63.5, 49.2. IR (neat): cm-1=
2955, 2919, 2850, 1735, 1696, 1591, 1545, 1456, 1351, 1249, 1097,
805, 767, 699, 584. HRMS (ESI): m/z calcd. for C25H19NO5Br [M + H]+:
492.0447; found: 492.0446.
(2'R,4'R,5'R)-2'-(4-methoxyphenyl)-5'-nitro-4'-phenyl-2',4',5',6'-
tetrahydrospiro[indene-2,3'-pyran]-1,3-dione (3d):To a solution of 2d (0.1
mmol, 26.4 mg) and cesium carbonate (0.3 mmol, 97.7 mg) in chloroform
(3 mL), nitroallylic alcohol 1a (0.2 mmol, 35.8 mg) was added at room
temperature. The reaction mixture was stirred at room temperature for 8
h. Yield: 67 % (18 mg). Pale yellow solid; m.p. 148-150 0C. 1H NMR (400
MHz, CDCl3): = 7.55-7.44 (m, 4 H), 7.11-7.09 (m, 2 H), 7.05-6.99 (m, 5
H), 6.54-6.51 (m, 2 H), 6.30-6.23 (m, 1 H), 5.01 (s, 1 H), 4.84 (dd, J =
10.4, 4.8, Hz, 1 H), 4.32 (d, J = 12 Hz, 1 H), 4.17 (t, J = 10.8 Hz, 1 H),
3.59 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3)  = 199.8, 198.8, 159.6,
142.8, 141.8, 135.5, 135.2, 133.2, 128.7, 128.6, 128.3, 128.0, 127.5,
122.6, 122.4, 113.5, 83.7, 81.1, 70.4, 64.0, 55.0, 49.2. IR (neat): cm-1=
2955, 2922, 2852, 1732, 1699, 1582, 1547, 1455, 1347, 1244, 1174,
1104, 809, 736, 699. HRMS (ESI): m/z calcd. for C26H21NO6Na [M +
Na]+: 466.1267; found: 466.1265.
(2'S,4'R,5'R)-2'-(2,4-dichlorophenyl)-5'-nitro-4'-phenyl-2',4',5',6'-
tetrahydrospiro[indene-2,3'-pyran]-1,3-dione (3i):To a solution of 2i (0.1
mmol, 30.3 mg) and cesium carbonate (0.3 mmol, 97.7 mg) in chloroform
(3 mL), nitroallylic alcohol 1a (0.2 mmol, 35.8 mg) was added at room
temperature. The reaction mixture was stirred at room temperature for 8
h. Yield: 87 % (42 mg). White solid; m.p. 162-164 0C. 1H NMR (400 MHz,
CDCl3): = 7.61-7.58 (m, 2 H), 7.54-7.51 (m, 2 H), 7.27 (d, J = 8.8 Hz, 1
H), 7.15-7.13 (m, 2 H), 7.08-6.96 (m, 5 H), 6.32-6.25 (m, 1 H), 5.5 (s, 1
H), 4.81 (dd, J = 10.8, 4.8, Hz, 1 H), 4.41 (d, J = 11.6 Hz, 1 H), 4.2 (t, J =
10.8 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3)  = 199.9, 198.6, 135.8,
135.2, 132.9, 132.8, 132.2, 130.4, 130.3, 129.3, 129.2, 128.6, 128.4,
127.1, 123.0, 122.4, 81.1, 78.8, 70.4, 63.4, 49.1. IR (neat): cm-1 = 2921,
2852, 1740, 1701, 1251, 1590, 1545, 1467, 1350, 1096, 849, 819, 763,
740. HRMS (ESI): m/z calcd. for C25H17Cl2NO5Na [M + Na]+: 504.0381;
found: 504.0383.
(2'R,4'R,5'R)-2'-(4-(benzyloxy)phenyl)-5'-nitro-4'-phenyl-2',4',5',6'-
tetrahydrospiro [indene-2,3'-pyran]-1,3-dione (3e):To a solution of 2e (0.1
mmol, 34.0 mg) and cesium carbonate (0.3 mmol, 97.7 mg) in chloroform
(3 mL), nitroallylic alcohol 1a (0.2 mmol, 35.8 mg) was added at room
temperature. The reaction mixture was stirred at room temperature for 10
h. Yield: 56 % (23 mg). Off white solid; m.p. 152-154 0C. 1H NMR (400
MHz, CDCl3): = 7.54-7.43 (m, 4 H), 7.30-7.25 (m, 3 H), 7.23 (d, J= 2
Hz, 2 H), 7.11-7.09 (m, 2 H), 7.05- 6.98 (m, 5 H), 6.61-6.58 (m, 2 H),
6.30-6.23 (m, 1 H), 5.00 (s, 1 H), 4.86-4.82 (m, 3 H), 4.32 (d, J = 12 Hz,
1 H), 4.17 (t, J = 10.8 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3)  =
198.9, 198.3, 158.7, 142.8, 136.6, 135.5, 135.3, 133.2, 128.7, 128.6,
128.5, 128.3, 128.0, 127.9, 127.2, 122.6, 122.4, 114.6, 83.7, 81.2, 70.4,
69.8, 64.0, 49.1. IR (neat): cm-1= 2917, 2849, 1734, 1696, 1590, 1543,
1455, 1250, 1102, 812, 766, 741, 696. HRMS (ESI): m/z calcd. for
C32H25NO6Na [M +Na]+: 542.1580; found: 542.1581.
(2'R,4'R,5'R)-2'-(3-methoxyphenyl)-5'-nitro-4'-phenyl-2',4',5',6'-
tetrahydrospiro[indene-2,3'-pyran]-1,3-dione (3j):To a solution of 2j (0.1
mmol, 26.4 mg) and cesium carbonate (0.3 mmol, 97.7 mg) in chloroform
(3 mL), nitroallylic alcohol 1a (0.2 mmol, 35.8 mg) was added at room
temperature. The reaction mixture was stirred at room temperature for 10
h. Yield: 68 % (30 mg). Off white solid; m.p. 144-146 0C. 1H NMR (400
MHz, CDCl3): = 7.54-7.51 (m, 2 H), 7.47-7.44 (m, 2 H), 7.12-7.10 (m, 2
H), 7.06-6.99 (m, 3 H), 6.89 (t, J = 7.6 Hz, 1 H), 6.62 (d, J = 7.6 Hz, 2 H),
6.50-6.48 (m, 1 H), 6.32-6.25 (m, 1 H), 5.03 (s, 1 H), 4.86 (dd, J = 10.4,
4.8,Hz, 1 H), 4.34 (d, J = 11.6 Hz, 1 H), 4.18 (t, J = 10.8 Hz, 1 H), 3.64
(s, 3 H) ppm. 13C NMR (100 MHz, CDCl3)  = 199.5, 198.5, 159.2, 142.8,
141.8, 136.7, 135.5, 135.2, 133.1, 129.2, 128.8, 128.6, 128.3, 122.6,
122.3, 119.1, 114.9, 111.7, 84.0, 81.1, 70.2, 63.9, 55.2, 49.0. IR (neat):
cm-1= 2970, 2920, 1740, 1701, 1583, 1542, 1452, 1357, 1249, 1163,
1107, 869, 761, 753, 695. HRMS (ESI): m/z calcd. for C26H22NO6 [M +
H]+: 444.1447; found: 444.1447.
(2'R,4'R,5'R)-5'-nitro-2'-(4-nitrophenyl)-4'-phenyl-
2',4',5',6'tetrahydrospiro[indene-2,3'-pyran]-1,3-dione (3f):To a solution of
2f (0.1 mmol, 247.9 mg) and cesium carbonate (0.3 mmol, 97.7 mg) in
chloroform (3 mL), nitroallylic alcohol 1a (0.2 mmol, 35.8 mg) was added
at room temperature. The reaction mixture was stirred at room
temperature for 12 h. Yield: 74 % (33 mg). Off white solid; m.p. 148-150
0C. 1H NMR (400 MHz, CDCl3): = 7.89 (d, J = 8.8 Hz, 2 H), 7.56-7.48
(m, 4 H), 7.30 (d, J = 8.8 Hz, 2 H), 7.10-7.00 (m, 5 H), 6.27-6.20 (m, 1
H), 5.18 (s, 1 H), 4.89 (dd, J = 10.8, 4.8, Hz, 1 H), 4.34 (d, J = 11.6 Hz, 1
H), 4.20 (t, J = 10.4 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3)  = 198.8,
198.3, 147.8, 142.4, 142.3, 141.5, 136.1, 135.9, 132.5, 128.8, 128.6,
127.8, 123.2, 122.8, 122.6, 82.5, 80.7, 70.1, 63.3, 49.3. IR (neat): cm-1=
2954, 2919, 2851, 1697, 1590, 1549, 1457, 1346, 1245, 1101, 856, 696,
741. HRMS (ESI): m/z calcd. for C25H18N2O7Na [M + Na]+: 481.1012;
found: 481.1002.
(2'R,4'R,5'R)-5'-nitro-4'-phenyl-2'-(o-tolyl)-2',4',5',6'-
tetrahydrospiro[indene-2,3'-pyran]-1,3-dione (3k):To a solution of 2k (0.1
mmol, 24.8 mg) and cesium carbonate (0.3 mmol, 97.7 mg) in chloroform
(3 mL), nitroallylic alcohol 1a (0.2 mmol, 35.8 mg) was added at room
temperature. The reaction mixture was stirred at room temperature for 6
h. Yield: 86 % (22 mg). White solid; m.p. 168-169 0C. 1H NMR (400 MHz,
CDCl3): = 7.26 (d, J = 7.2 Hz, 1 H), 7.48-7.43 (m, 3 H), 7.21-7.19 (m,
1H), 7.15-7.13 (m, 2 H), 7.08-7.00 (m, 3 H), 6.87-6.83 (m, 3 H), 6.41-
6.34 (m, 1 H), 5.32 (s, 1 H), 4.85 (dd, J = 11.2, 4.8 Hz, 1 H), 4.39 (d, J =
12.4 Hz, 1 H), 4.2 (t, J = 10.8 Hz, 1 H), 2.26 (s, 3 H) ppm. 13C NMR (100
MHz, CDCl3)  = 198.9, 198.5, 143.1, 135.5, 135.2, 134.7, 133.1, 130.8,
129.0, 128.6, 128.5, 128.2, 127.4, 125.9, 122.5, 122.4, 81.3, 80.5, 70.7,
63.8, 49.4,19.3. IR (neat): cm-1= 2926, 2864, 1731, 1691, 1598, 1552,
1452, 1356, 1248, 1090, 753. HRMS (ESI): m/z calcd. for C26H22NO5 [M
+ H]+: 428.1498; found: 428.1498.
4-((2'R,4'R,5'R)-5'-nitro-1,3-dioxo-4'-phenyl-1,2',3,4',5',6'-
hexahydrospiro[indene-2,3'-pyran]-2'-yl)benzonitrile (3g):To a solution of
2g (0.1 mmol, 25.9 mg) and cesium carbonate (0.3 mmol, 97.7 mg) in
chloroform (3 mL), nitroallylic alcohol 1a (0.2 mmol, 35.8 mg) was added
at room temperature. The reaction mixture was stirred at room
temperature for 10 h. Yield: 93 % (41 mg). White solid; m.p. 192-194 0C.
1H NMR (400 MHz, CDCl3): = 7.55-7.49 (m, 4 H), 7.31 (d, J = 8.4 Hz, 2
H), 7.22 (d, J = 8.4 Hz, 2 H), 7.09-7.00 (m, 5 H), 6.25-6.20 (m, 1 H), 5.11
(s, 1 H), 4.87 (dd, J = 10.8, 4.8, Hz, 1 H), 4.33 (d, J = 12 Hz, 1 H), 4.19
(t, J = 10.8 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3)  = 198.9, 198.3,
142.4, 141.5, 140.4, 136.1, 135.8, 132.6, 131.9, 128.8, 128.7, 128.6,
127.5, 122.7, 122.6, 112.6, 82.8, 80.7, 70.1, 63.4, 49.2. IR (neat): cm-1=
2920, 2227, 1102, 1456, 1591, 1350, 1700, 1547, 1250, 770, 699.
HRMS (ESI): m/z calcd. for C26H19N2O5 [M + H]+: 439.1294; found:
439.1294.
(2'S,4'R,5'R)-2'-(furan-2-yl)-5'-nitro-4'-phenyl-2',4',5',6'-
tetrahydrospiro[indene-2,3'-pyran]-1,3-dione (3l):To a solution of 2l (0.1
mmol, 22.4 mg) and cesium carbonate (0.3 mmol, 97.7 mg) in chloroform
(3 mL), nitroallylic alcohol 1a (0.2 mmol, 35.8 mg) was added at room
temperature. The reaction mixture was stirred at room temperature for 48
1
h. Yield: 45 % (10 mg). Pale green solid; m.p. 174-176 0C. H NMR (400
MHz, CDCl3): = 7.73 (d, J = 7.2 Hz, 1 H), 7.61-7.54 (m, 4 H), 7.11 (d, J
= 7.2 Hz, 2 H), 7.07-7.00 (m, 4 H), 6.89 (d, J = 2.4 Hz, 1 H), 6.30-6.23
(m, 1 H), 6.00-5.98 (m, 1 H), 5.10 (s, 1 H), 4.82 (dd, J = 10.8, 4.8, Hz, 1
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201801709
European Journal of Organic Chemistry
FULL PAPER
H), 4.28 (d, J = 12 Hz, 1 H), 4.16 (t, J = 10.8 Hz, 1 H) ppm. 13C NMR
(100 MHz, CDCl3)  = 198.9, 197.5, 147.8, 142.6, 142.5, 141.4, 135.6,
135.3, 132.6, 128.7, 128.7,128.4, 122.8, 114.0, 80.8, 77.8, 70.3, 61.8,
49.0. IR (neat): cm-1 = 2928, 2860, 1735, 1696, 1590, 1556, 1450, 1352,
1245, 1099, 749. HRMS (ESI): m/z calcd. for C23H17NO6Na [M + Na]+:
426.0954; found: 426.0953.
(2'R,4'R,5'R)-4'-(4-methoxyphenyl)-5'-nitro-2'-phenyl-2',4',5',6'-
tetrahydrospiro[indene-2,3'-pyran]-1,3-dione (3q):To a solution of 2a (0.1
mmol, 23.4 mg) and cesium carbonate (0.3 mmol, 97.7 mg) in chloroform
(3 mL), nitroallylic alcohol 1e (0.2 mmol, 41.8 mg) was added at room
temperature. The reaction mixture was stirred at room temperature for 8
1
h. Yield: 77 % (34 mg). Pale green solid; m.p. 172-174 0C. H NMR (400
MHz, CDCl3): = 7.54-7.44 (m, 4 H), 7.07-6.95 (m, 7 H), 6.59-6.56 (m, 2
H), 6.27-6.21 (m, 1 H), 5.03 (s, 1 H), 4.84 (dd, J = 10.8, 4.8, Hz, 1 H),
4.30 (d, J = 11.6 Hz, 1 H), 4.18 (t, J = 10.8 Hz, 1 H), 3.59 (s, 3 H) ppm.
13CNMR (100 MHz, CDCl3)  = 199.7, 198.8, 159.2, 142.8, 141.8, 135.5,
135.3, 129.9, 128.6, 128.1, 126.6, 125.1, 122.6, 122.4, 114.1, 84.1, 81.4,
70.3, 64.1, 55.0, 48.4. IR (neat): cm-1= 2926, 1732, 1694, 1590, 1548,
1452, 1356, 1248, 1181, 1099, 812, 756, 700. HRMS (ESI): m/z calcd.
for C26H21NO6Na [M + Na]+: 466.1267; found: 466.1258.
(2'S,4'R,5'R)-5'-nitro-4'-phenyl-2'-(thiophen-2-yl)-2',4',5',6'-
tetrahydrospiro[indene-2,3'-pyran]-1,3-dione (3m):To a solution of 2m
(0.1 mmol, 24.0 mg) and cesium carbonate (0.3 mmol, 97.7 mg) in
chloroform (3 mL), nitroallylic alcohol 1a (0.2 mmol, 35.8 mg) was added
at room temperature. The reaction mixture was stirred at room
temperature for 48 h. Yield: 21 % (5 mg). Pale brown solid; m.p. 178-180
0C. 1H NMR (400 MHz, CDCl3): = 7.63 (d, J = 6.4 Hz, 1 H), 7.57 (d, J =
2.0 Hz, 1 H), 7.53-7.51 (m, 2 H), 7.11-7.09 (m, 2 H), 7.06-6.99 (m, 3 H),
6.96-6.95 (m, 1 H), 6.72 (d, J = 3.6 Hz, 1 H), 6.61-6.58 (m, 1 H), 6.31-
6.24 (m, 1 H), 5.37 (s, 1 H), 4.85 (dd, J = 10.8, 4.8, Hz, 1 H), 4.31 (d, J =
12 Hz, 1 H), 4.19 (t, J = 10.8 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3) 
= 199.5, 198.4, 168.1, 142.9, 141.8, 137.0, 135.6, 135.4, 132.8, 128.7,
128.6, 128.4, 126.3, 126.1, 125.9, 122.7, 122.6, 80.8, 80.5, 70.4, 63.6,
49.1. IR (neat): cm-1= 2932, 2862, 1738, 1692, 1594, 1551, 1454, 1358,
1241, 1156, 1095, 754. HRMS (ESI): m/z calcd. for C23H17NO5SNa [M +
Na]+: 442.0725; found: 442.0728.
(2'R,4'R,5'R)-4'-(4-(benzyloxy)phenyl)-5'-nitro-2'-phenyl-2',4',5',6'-
tetrahydrospiro [indene-2,3'-pyran]-1,3-dione (3r):To a solution of 2a (0.1
mmol, 24.8 mg) and cesium carbonate (0.3 mmol, 97.7 mg) in chloroform
(3 mL), nitroallylic alcohol 1f (0.2 mmol, 57 mg) was added at room
temperature. The reaction mixture was stirred at room temperature for 12
1
h. Yield: 90 % (47 mg). Pale green solid, m.p. 134-136 0C. H NMR (400
MHz, CDCl3): = 7.54-7.43 (m, 4 H), 7.30-7.26 (m, 4 H), 7.07-6.94 (m, 8
H), 6.65 (d, J = 8.8 Hz, 2 H), 6.27-6.20 (m, 1 H), 5.03 (s, 1 H), 4.88-4.82
(m, 3 H), 4.30 (d, J = 12 Hz, 1 H), 4.18 (t, J = 10.8 Hz, 1 H) ppm. 13C
NMR (100 MHz, CDCl3)  = 199.7, 198.7, 158.5, 142.8, 141.8, 136.5,
135.5, 135.3, 135.2, 129.9, 128.5, 128.5, 128.1, 127.9, 127.3, 126.6,
125.4, 122.6, 122.4, 115.2, 115.0, 84.0, 81.4, 70.3, 69.8, 64.1, 48.4. IR
(neat): cm-1= 2918, 2850, 1736, 1692, 1591, 1546, 1452, 1251, 1108,
810, 761, 745, 692. HRMS (ESI): m/z calcd. for C32H25NO6Na [M +Na]+:
542.1580; found: 542.1585.
(2'R,4'R,5'R)-4'-(4-fluorophenyl)-5'-nitro-2'-phenyl-2',4',5',6'-
tetrahydrospiro[indene-2,3'-pyran]-1,3-dione (3n):To a solution of 2a (0.1
mmol, 23.4 mg) and cesium carbonate (0.3 mmol, 97.7 mg) in chloroform
(3 mL), nitroallylic alcohol 1b (0.2 mmol, 39.4 mg) was added at room
temperature. The reaction mixture was stirred at room temperature for 4
h. Yield: 77 % (33 mg). Off white solid; m.p. 150-152 0C. 1H NMR (400
MHz, CDCl3): = 7.54-7.46 (m, 4 H), 7.13-7.09 (m, 2 H), 7.07-7.07 (m, 2
H), 7.02-6.96 (m, 3 H), 6.75 (t, J = 8.8 Hz, 2 H), 6.28-6.21 (m, 1 H), 5.03
(s, 1 H), 4.86 (dd, J = 10.8, 4.8, Hz, 1 H), 4.35 (d, J = 12 Hz, 1 H), 4.18
(t, J = 10.8 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3)  = 199.5, 198.5,
163.6, 161.1, 142.7, 141.7, 135.7, 135.5, 135.1, 130.6, 130.5, 129.0,
128.7, 128.1, 126.6, 122.7, 122.4, 115.8, 115.6, 84.1, 81.2, 70.2, 64.0,
48.3. IR (neat): cm-1= 2952, 2851, 1738, 1702, 1592, 1547, 1454, 1350,
1244, 1105, 844, 759, 697. HRMS (ESI): m/z calcd. for C25H19FNO5 [M +
H]+: 432.1247; found: 432.1247.
(2'R,4'R,5'R)-4'-(3-methoxyphenyl)-5'-nitro-2'-phenyl-2',4',5',6'-
tetrahydrospiro[indene-2,3'-pyran]-1,3-dione (3s):To a solution of 2a (0.1
mmol, 23.4 mg) and cesium carbonate (0.3 mmol, 97.7 mg) in chloroform
(3 mL), nitroallylic alcohol 1g (0.2 mmol, 41.8 mg) was added at room
temperature. The reaction mixture was stirred at room temperature for 8
h. Yield: 63 % (28 mg). Off white solid; m.p. 144-145 0C. 1H NMR (400
MHz, CDCl3): = 7.55-7.44 (m, 4 H), 7.07 (d, J = 6.4 Hz, 2 H), 7.02-6.93
(m, 4 H), 6.69 (d, J = 7.6 Hz, 1 H), 6.64 (d, J = 2 Hz, 1 H), 6.55-6.52 (m,
1 H), 6.30-6.24 (m, 1 H), 5.04 (s, 1 H), 4.86 (dd, J =10.8, 6, 4.8, Hz, 1 H),
4.33 (d, J = 11.6 Hz, 1H), 4.18 (t, J = 10.8 Hz, 1H), 3.64 (s, 3H) ppm. 13
C
NMR (100 MHz, CDCl3)  = 199.8, 198.7, 159.4, 135.5, 135.2, 134.6,
129.6, 128.6, 128.1, 126.6, 122.6, 122.3, 121.0, 114.5, 114.1, 84.0, 81.1,
70.3, 63.8, 55.1, 49.0. IR (neat): cm-1= 1740, 1583, 1701, 2920, 2970,
1163, 1542, 1357, 1452, 1249, 869, 761, 753, 695. HRMS (ESI): m/z
calcd. for C26H21NO6Na [M + Na]+: 466.1267; found: 466.1262.
(2'R,4'R,5'R)-4'-(4-bromophenyl)-5'-nitro-2'-phenyl-2',4',5',6'-
tetrahydrospiro[indene-2,3'-pyran]-1,3-dione (3o):To a solution of 2a (0.1
mmol, 23.4 mg) and cesium carbonate (0.3 mmol, 97.7 mg) in chloroform
(3 mL), nitroallylic alcohol 1c (0.2 mmol, 51.6 mg) was added at room
temperature. The reaction mixture was stirred at room temperature for 6
h. Yield: 60 % (24 mg).Off white solid; m.p. 168-170 0C. 1H NMR (400
MHz, CDCl3): = 7.55-7.48 (m, 3 H), 7.16-7.13 (m, 4 H), 7.10-6.95 (m, 6
H), 6.26-6.20 (m, 1 H), 5.04 (s, 1 H), 4.84 (dd, J = 10.4, 4.8, Hz, 1 H),
4.33 (d, J = 12 Hz, 1 H), 4.19 (t, J = 10.8 Hz, 1 H) ppm. 13C NMR (100
MHz, CDCl3)  = 199.8, 198.4, 141.8, 135.9, 135.4, 134.0, 131.8, 128.9,
128.2, 128.1, 122.9, 122.4, 82.4, 80.8, 70.4, 63.7, 49.6. IR (neat): cm-1=
2952, 2921, 2854, 1736, 1699, 1594, 1546, 1458, 1350, 1247, 1096,
802, 764, 692, 580. HRMS (ESI): m/z calcd. for C25H19NO5Br [M + H]+:
492.0447; found: 492.0448.
4-((2'R,4'R,5'R)-5'-nitro-1,3-dioxo-2'-phenyl-1,2',3,4',5',6'-
hexahydrospiro[indene-2,3'-pyran]-4'-yl)benzonitrile (3t):To a solution of
2a (0.1 mmol, 23.4 mg) and cesium carbonate (0.3 mmol, 97.7 mg) in
chloroform (3 mL), nitroallylic alcohol 1h (0.2 mmol, 40.8 mg) was added
at room temperature. The reaction mixture was stirred at room
temperature for 4 h. Yield: 53 % (23 mg). Pale green solid; m.p. 146-
1480C. 1H NMR (400 MHz, CDCl3): = 7.56-7.50 (m, 4 H), 7.33 (d, J =
8.4 Hz, 3 H), 7.23 (d, J = 8.4 Hz, 2 H), 7.10-7.00 (m, 4 H), 6.30-6.22 (m,
1 H), 5.24 (s, 1 H), 4.86 (dd, J = 10.8, 4.8, Hz, 1 H), 4.35 (d, J = 12 Hz, 1
H), 4.20 (t, J = 10.8 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3)  = 199.7,
198.4, 142.7, 141.4, 140.6, 136.1, 135.9, 132.5, 131.8, 128.9, 128.6,
128.4, 127.7, 122.9, 122.5, 111.9, 81.8, 80.6, 70.4, 61.9, 49.3. IR (neat):
cm-1= 2922, 2226, 1108, 1454, 1590, 1351, 1704, 1546, 1251, 776, 690.
HRMS (ESI): m/z calcd. for C26H19N2O5 [M + H]+: 439.1294; found:
439.1295.
(2'R,4'S,5'R)-4'-(2,4-dichlorophenyl)-5'-nitro-2'-phenyl-2',4',5',6'-
tetrahydrospiro[indene -2,3'-pyran]-1,3-dione (3p):To a solution of 2a (0.1
mmol, 24.8 mg) and cesium carbonate (0.3 mmol, 97.7 mg) in chloroform
(3 mL), nitroallylic alcohol 1d (0.2 mmol, 49.6 mg) was added at room
temperature. The reaction mixture was stirred at room temperature for 12
h. Yield: 47 % (26 mg). Pale yellow solid; m.p. 122-124 0C. 1H NMR (400
MHz, CDCl3): = 7.62-7.48 (m, 4 H), 7.23 (d, J = 2 Hz, 1 H), 7.20 (d, J =
8.4 Hz, 1 H) 7.08-7.05 (m, 2 H), 7.02-6.93 (m, 4 H), 6.16-6.09 (m, 1 H),
5.11-5.08 (m, 2 H), 4.87 (dd, J = 10.8, 4.8, Hz, 1 H), 4.23 (t, J = 10.4 Hz,
1 H) ppm. 13C NMR (100 MHz, CDCl3)  = 200.0, 196.7, 142.7, 141.5,
136.1, 135.7, 134.8, 134.7, 130.5, 130.2, 129.3, 128.7, 128.1, 127.4,
126.7, 122.9, 122.4, 84.4, 81.8, 70.1, 63.0, 43.6. IR (neat): cm-1= 2924,
2850, 1742, 1704, 1250, 1592, 1546, 1468, 1351, 1097, 846, 821, 766,
742. HRMS (ESI): m/z calcd. for C25H17Cl2NO5Na [M + Na]+: 504.0381;
found: 504.0382.
Gram Scale preparation for the synthesis of (2'R,4'R,5'R)-5'-nitro-
2',4'- diphenyl-2',4',5',6'-tetrahydrospiro[indene-2,3'-pyran]-1,3-dione
(3a):To a solution of benzylidene-1,3-indanedione 2a (4.27 mmol, 1.0
gm) and cesium carbonate (12.82 mmol, 4.17 gm) in chloroform (10 mL),
MBH alcohol 1a (8.54 mmol, 1.52 gm) was added at room temperature.
The reaction mixture was allowed to stir at room temperature, monitored
by TLC until the completion of the reaction. The crude mixture was
extracted with dichloromethane (3x10 mL), later washed with brine
solution, dried over Na2SO4 and concentrated under reduced pressure.
Crude compound was purified by flash column chromatography on silica
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201801709
European Journal of Organic Chemistry
FULL PAPER
gel (5 %, ethyl acetate in hexane) to afford product 3a.Yield: 83 % (1.46
gm).
[10] A. Rai, L. D. S. Yadav, Tetrahedron 2012, 68, 2459-2464.
[11] M. Bakthadoss, N. Sivakumar, A. Devaraj, P. V. Kumar, RSC Adv.
2015, 5, 93447-93451.
[12] B. C. Hong, D. J. Lan, N. S. Dange, G. H. Lee, J. H. Liao, Eur. J.
Org. Chem. 2013, 2472-2478.
[13] D. C. Cruz, R. Mose, C. V. Gomez, S. V. Torbensen, M. S. Larsen,
K. A. Jorgensen, Chem. Eur. J. 2014, 20, 11331-11335.
[14] S. Singh, A. Srivastava, S. M. Mobin, S. Samanta, RSC Adv. 2015,
5, 5010-5014.
Acknowledgments
The authors gratefully acknowledge Department of Science and
Technology (DST), SERB, New Delhi for providing financial
support under Fast track scheme (SB/FT/CS/079-2014). We
thank Dr. Bharat Kumar Tripuramallu for providing X-ray Crystal
Data. We also thank School of Chemistry, University of
Hyderabad for HRMS and control experiments. We are indebted
to Vignan’s Foundation for Science, Technology and Research
for providing Central Instrumentation facilities at CoExAMMPC.
[15] Y. M. Chen, M. Amireddy, K. Chen, Tetrahedron 2014, 70, 9064-
9069.
[16] a) E. K. Reddy, C. Remya, A. M. Sajith, K.V. Dileep, C.
Sadasivan, S. Anwar, RSC Adv. 2016, 6, 77431-77439; b) W.-Y.
Huang, S. Anwar, K.Chen, Chem. Rec. 2017, 17, 363-381.
[17] For reactions using 2-benzylidene-1,3-indanedione refer: a) D. B.
Ramachary, K. Anebouselvy, N. S. Chowdari, and C. F. III.
Barbas, J. Org. Chem. 2004, 69, 5838-5849; b) A. Russo, S.
Meninno, C. Tedesco and A. Lattanzi, Eur. J. Org. Chem. 2011,
5096-5103; c) U. Das, Y-L. Tsai, W. Lin, Org. Biomol. Chem. 2013,
11, 44-47; d) Y. Han, Y. Zhu, P.Zhang, W. Li, P. Li, Chemistry
Select 2017, 2, 11380-11383; e) E. Li, L. Liang, P. Xie, Org. Lett.
2013, 15, 3138-3141; f) K. B. Manjappa, Y-T.Peng, W-F, Zhang,
D-Y. Yang, Tetrahedron 2016, 72, 853-861; g) D. B. Ramachary,
T. P. Reddy, A. S. Kumar, Org. Biomol. Chem. 2016, 14, 6517-
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Keywords: Spiro Compounds; Nucleophilic addition; Ambiphile;
C-C Coupling; Cycloaddition
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10.1002/ejoc.201801709
European Journal of Organic Chemistry
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[31] CCDC 1841114 for 3a contains the supplementary crystallographic
data for this paper. This data can be obtained free of charge from
The
www.ccdc.cam.ac.uk/data_request/cif.
[32] TLC of the reaction mixture showed formation of only 2a.
Cambridge
Crystallographic
Data
Centre
via
[33] Among all the solvents screened, only CHCl3 was ideal solvent for
one pot synthesis of 3a.
[34] Controlled experiments were carried out by mixing 2a and 1a at
room temperature and allowed to stir for 30 min before cooling the
reaction mixture, followed by addition of various electrophiles.
Kinetic products C, D and E were detected using HRMS by
periodically analyzing the crude reaction mixture every 30 min
using HRMS.
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10.1002/ejoc.201801709
European Journal of Organic Chemistry
FULL PAPER
FULL PAPER
Spiropyrans
Veera Babu Gudise, Poorna
Chandrasekhar Settipalli, Eeda Koti
Reddy and Shaik Anwar*
Page No. – Page No.
Functionalized tetrahydrospiropyran derivatives can be easily accessed
regioselectively by use of nitrostyrene derived MBH alcohols and 2-arylidene-1,3-
indanediones in high chemical yields (upto 93% yield). The synthetic utility of MBH
alcohol as an ambident substarte towards the synthesis of spirocyclic skeletons is
noteworthy.
Oxa Michael-Michael Reaction of
MBH Alcohol and 2-arylidene-1,3-
indanedione: Regioselective Formal
[4+2] Cycloaddition Towards
Tetrahydrospiropyran Scaffolds
*Nitrostyrene Derived Emm Bee Hch Alcohol
This article is protected by copyright. All rights reserved.