Baylis-Hillman carbonates in organic synthesis: A convenient one-pot strategy for nitrone-spiro-oxindole frameworks

Article abstract of DOI:10.1016/j.tet.2013.07.002

A facile one-pot protocol for synthesis of nitrone-spiro-oxindole frameworks via alkylation of nitromethane with carbonates of Baylis-Hillman alcohols, derived from isatins and cyclohex-2-enone derivatives, followed by reductive cyclization is described.

Full text of DOI:10.1016/j.tet.2013.07.002

Tetrahedron 69 (2013) 7995e8001
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
BayliseHillman carbonates in organic synthesis: a convenient
one-pot strategy for nitroneespiro-oxindole frameworks
*
Deevi Basavaiah , Satpal Singh Badsara, Gorre Veeraraghavaiah
School of Chemistry, University of Hyderabad, Central University (PO), Gachibowli, Hyderabad 500 046, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 20 May 2013
Received in revised form 25 June 2013
Accepted 1 July 2013
Available online 5 July 2013
A facile one-pot protocol for synthesis of nitroneespiro-oxindole frameworks via alkylation of nitro-
methane with carbonates of BayliseHillman alcohols, derived from isatins and cyclohex-2-enone
derivatives, followed by reductive cyclization is described.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
BayliseHillman reaction
Nitrones
Spiro-oxindoles
Alkylation
Reductive cyclization
1. Introduction
adducts5 in developing useful protocols for obtaining diverse classes
of heterocyclic molecules of biological relevance we, herein, report
Inrecentyears therehas beenincreasinginterestinunderstanding
the free radical mediated oxidative damage to cells because it is
considered to be one of the major factors responsible for many dis-
eases, such as neuro-degeneration, stroke, cancers etc.1 After the
a simple one-pot methodology for synthesis of interesting class of
compounds (nitroneespiro-oxindoles) containing both spiroox-
indole and nitrone skeletons using the BayliseHillman carbonates as
starting materials.
initial studies on the applications of PBN (a-phenyl-tert-butylnitrone)
The BayliseHillman (BH) reaction6,7 occupies a special place in
the list of carbonecarbon bond forming reactions because of its
unique applications in producing highly useful densely functional-
ized molecules, which are commonly known as the BayliseHillman
adducts. Due to the presence of proximal functional groups,
BH-adducts have been extensively used in many synthetic trans-
formations and also in the synthesis of several bioactive and natural
products. There are some interesting reports on the applications of
BH-adducts and their derivatives in the synthesis of various spi-
rooxindoles8 and also few reports are available for obtaining N-oxide
derivatives.3a,9 We have recently reported the BayliseHillman
coupling between cyclohex-2-enone and isatin derivatives under
the influence of titanium tetrachloride to produce the required
BH-adducts (1).10 Based on our experience in understanding the
versatility of BH adducts we envisaged that the BayliseHillman
carbonates (2) would serve as appropriate alkylators for obtaining
the nitro-enone derivatives 3, which in turn can be transformed into
an interesting class of compounds (4) containing both the spiroox-
indole and nitrone frameworks as shown in the retro synthetic
strategy (Scheme 1).
and its derivatives for trapping free radicals in chemical systems,
research work from various leading laboratories has been directed
toward examining the utility of nitrones as spin traps in biological
systems and many significant results were achieved in this
direction.1aed,2 In fact the present day developments in synthetic and
medicinal chemistry demand the design and synthesis of appropriate
nitrone frameworks for addressing the problems of oxidative damage
to tissues.1d,3 Spirooxindole skeleton is another unique structural
organization present in several natural products and biologically ac-
tive molecules and therefore development of efficient and simple
protocols for obtaining spirooxindole derivatives represents an at-
tractive area of research in synthetic chemistry.4 It occurred to us
that molecules containing both nitrone skeleton and spirooxindole
structural units might show interesting biological activities. In con-
tinuation of our interest on applications of the BayliseHillman (BH)
* Corresponding author. Tel.: þ91 040 23134812; fax: þ91 40 23012460; e-mail
addresses: dbsc@uohyd.ernet.in, basavaiahdeevi@gmail.com (D. Basavaiah).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.07.002

7996
D. Basavaiah et al. / Tetrahedron 69 (2013) 7995e8001
Table 2
R3
O
N
R3
R3
Optimization: Alkylation of nitromethane with BH-carbonate (2a)a
O
N
R3
O2N
O
R1
R1
O
BocO
O
O
base (nucleophile)
nitromethane
O2N
N
R2
O
R2
O
3
4
N
solvent, rt
N
Me
Me
nitrone-spiro-oxindoles
alkylated products
2a
3a
Entry
Base/nucleophile
Solvent
Time (h)
Yield (%)
R3
R3
R3
R3
O
HO
O
BocO
1
2
3
4
5
6
7
DABCO
PPh3
Me2S
DMAP
DMAP
DMAP
DMAP
DCM
DCM
DCM
Toluene
CH3CN
DCM
48
48
48
48
48
12
24
N.R.
N.R.
N.R
53
R1
R1
O
N
O
N
R2
50
2
R2
BH carbonates
82b
75c
1
DCM
BH alcohols
a
All reactions were carried out on a 2.0 mmol scale of BayliseHillman carbonates
(2a) with 3.0 mmol of nitromethane in the presence of various nucleophiles (bases)
(2.0 mmol) in different solvents at room temperature under N2 atmosphere.
Scheme 1. Retro-synthetic strategy for synthesis of nitroneespiro-oxindoles.
b
Reaction was also carried out on a 4.0 mmol scale of Baylis-Hillman carbonates
2. Results and discussion
(2a) with 6.0 mmol of nitromethane in the presence of DMAP (4.0 mmol) in an-
hydrous DCM at room temperature under N2 atmosphere.
c
1.0 mmol of DMAP was used.
Accordingly we have first prepared BayliseHillman adduct (1a)
following the procedure developed in our laboratory10 via the cou-
pling of N-methylisatin and cyclohex-2-enone under the influence
of TiCl4. This allyl alcohol (1a) was converted into its carbonate
derivative (2a) by treatment with Boc2O (Table 1).11
(25e30 ꢀC) for 12h to provide [1-methylindolin-2-one]-3-spiro-30-
[20,50,60,70-tetrahydroindole 10-oxide] (4a) in 69% yield (overall
yield 57% starting from 2a).
With a view to examining the possibility of performing both the
steps in one-pot, we have treated the BayliseHillman carbonate 2a
(2 mmol) with nitromethane (3 mmol) in the presence of DMAP
(2 mmol) in DCM at room temperature for 12 h and the resulting
reaction mixture (after the solvent was removed under reduced
pressure) was subsequently treated with Fe powder (12 mmol) and
2 N HCl (2 mL) in ethanol for 12 h at room temperature to provide
the desired nitrone 4a in 59% overall yield (after usual work-up
followed by purification of the crude product, thus obtained, by
silica gel column chromatography).
Table 1
Synthesis of Boc-derivatives (2ael) of BH-alcohols (1ael)a
R3
R3
R3
R3
O
HO
O
BocO
DMAP, DCM
rt, 1 h
R1
R1
+
Boc2O
O
O
N
N
R2
R2
1a l
-
2a l
-
R1 = H, Cl, Br ; R2 = Me, Et, Bn
R3 = H, Me
71-86%
Structure of the molecule 4a was established by spectral data
Entry
BH alcohol
R1
R2
R3
Productb
Yieldc (%)
1
analysis.14 In the H NMR spectrum of 4a, C-60 methylene protons
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1g
1h
1i
H
H
H
Me
Et
Bn
Me
Et
Bn
Me
Et
Bn
Me
Me
Et
H
H
H
H
H
H
H
H
2a
2b
2c
2d
2e
2f
2g
2h
2i
72
74
83
71
78
80
79
74
76
75
86
79
appear as a multiplet at
and
2.69e2.80 are attributed to methylene protons at C-50 (or C-
70) and at C-70 (or C-50), respectively. Singlet at
3.26 arises due to
NeMe Protons. Methylene protons at C-20 appear as ABq at
4.21 &
4.47. Triplet at
5.39 is attributed to the olefinic proton at C-40.
Aromatic proton at C-7 appears as a doublet at 6.90. The
remaining three aromatic protons appear as two multiplets one at
7.08e7.18 (2H) and the other one at
7.32e7.38 (1H). 13C NMR
spectrum of 4a shows 16 signals corresponding to 16 carbons of the
d 1.71e1.92. The multiplets at d 2.08e2.27
d
Cl
Cl
Cl
Br
Br
Br
Cl
Br
Cl
d
d
d
d
9
H
10
11
12
1j
1k
1l
Me
Me
Me
2j
2k
2l
d
d
compound. Six aliphatic carbons show peaks at d
20.02(C-40), 21.28
a
All reactions were carried out on a 20.0 mmol scale of BayliseHillman alcohols
(1) with 22.0 mmol of Boc2O in the presence of DMAP (1.0 mmol) in anhydrous DCM
(see the procedure in Experimental section).
(C-5’or C-60), 24.59 (C-60 or C-50), 26.57 (NeMe carbon), 51.29 (C-30),
68.66 (C-20). Six aromatic, two olefinic and one iminium carbons
b
appear at
143.44, 143.91. Signal at
d
108.48, 122.85, 123.48, 123.86, 129.06, 130.94, 137.42,
175.95 arises due to amide carbonyl
All the compounds were obtained as solids and fully characterized.
Isolated yields were based on the BayliseHillman alcohols.
c
d
carbon (NeC]O). HRMS (ESI) shows the exact mass of
269.1290 (MþH)þ [exact mass calcd for (4a) C16H16N2O2þH
(MþH)þis 269.1290].
We have performed alkylation of nitromethane with 2a under
various conditions (Table 2). Best results were obtained when 2a
(4 mmol) was treated with nitromethane (6 mmol) in the presence
of DMAP (4 mmol) in dichloromethane (DCM) under nitrogen at-
mosphere at room temperature (25e30 ꢀC) for 12 h thus providing
the desired alkylated product, 3-nitromethyl-3-(cyclohex-2-enon-
2-yl)-1-methylindolin-2-one (3a),12 in 82% isolated yield (Table 2,
Entry 6).
We have next directed our efforts toward transformation of
nitro-enone derivative (3a) into 4a under different conditions.
In this regard we obtained encouraging results when we have
performed the reaction of 3a (2 mmol) with Fe powder/HCl
[Fe (12 mmol)/HCl (2N, 2 mL)] in EtOH13 at room temperature
This is indeed a very encouraging result. We therefore have
selected one-pot procedure to understand the generality of this
methodology. We have prepared a representative class of the
BayliseHillman adducts (1ael) from selected isatins and cyclo-
hexenone & 5,5-dimethylcyclohexenone and converted them into
their carbonate derivatives 2ael (Table 1). We have then subjected
these carbonates (2ael) first to the reaction with nitromethane and
then in situ produced alkylated products (3ael) with Fe/HCl as in
the case of 4a to produce the resulting nitroneespiro-oxindoles
(4ael) in 56e65% isolated yields (Table 3). Structures of the nitro-
neespiro-oxindoles 4b and 4j were further confirmed by their

D. Basavaiah et al. / Tetrahedron 69 (2013) 7995e8001
7997
Table 3
H
Synthesis of nitroneespiro-oxindole derivatives (4ael)a
NO2
H
H
R3
R3
O
O
O
O
O
N
7'
O
1'
R3
6'
1. DMAP, DCM
-t-BuO
-CO2
BocO
rt, 12 h, N2
R1
O
R3
2'
4
+
3'
MeNO2
R1
N
N
O
5'
O
N
Me
3
5
4'
O
2. Fe/HCl, C2H5OH
rt, 12 h
N
Me
O
N
N
N
2
R2
R1 = H, Cl, Br ; R2 = Me, Et, Bn
R
6
N
2a l
-
1
R2
56-65%
7
2a
4a-l
3 = H, Me
-DMAP
Entry
BH carbonate
R1
R2
R3
Productb
Yieldc (%)
1
2
3
4
5
6
7
8
2a
2b
2c
2d
2e
2f
2g
2h
2i
H
H
H
Me
Et
Bn
Me
Et
Bn
Me
Et
Bn
Me
Me
Et
H
H
H
H
H
H
H
H
4a
4bd
4c
4d
4e
4f
59
64
60
61
56
62
65
60
64
63
58
61
O
N
O
H
O
H
O2N
Fe/HCl
EtOH
Cl
Cl
Cl
Br
Br
Br
Cl
Br
Cl
O
O
N
Me
N
Me
3a
4g
4h
4i
9
H
10
11
12
2j
2k
2l
Me
Me
Me
4jd
4k
4l
O
O
N
O
N
OH2
OH
N
H
H
Cl
-H2O
HCl
a
All reactions were carried out on a 2.0 mmol scale of Baylis-Hillman carbonates
(2) with 3.0 mmol of nitromethane in the presence of DMAP (2.0 mmol) in anhy-
drous DCM, followed by reductive cyclization of the in situ generated nitro-enone
derivatives using Fe powder (12.0 mmol) and HCl (2 N, 2.0 mL) in EtOH (10.0 mL)
at room temperature.
O
O
O
N
Me
N
Me
N
Me
4a
Scheme 2. Plausible mechanism for synthesis of nitroneespiro-oxindoles 4.
b
All the compounds were obtained as solids and fully characterized.
Isolated yields were based on the BayliseHillman carbonates.
Structures of these compounds were further confirmed by single crystal X-ray
c
d
followed by reductive cyclization of the in situ generated nitro-
enones 3 using Fe/HCl/EtOH in encouraging yields.
data analysis.15
single crystal X-ray data analysis (Fig. 1).15 A plausible mechanism
for obtaining nitroneespiro-oxindoles (4) is presented in Scheme 2
taking 4a as a model case.
4. Experimental section
4.1. General remarks
3. Conclusions
Melting points were recorded on a Superfit (India) capillary
melting point apparatus and are uncorrected. IR spectra were
recorded on a JASCO-FT-IR model 5300 spectrometer using solid
samples as KBr plates and liquid sample as thin film between NaCl
plates. For all the compounds 1H NMR (400 or 500 MHz) and 13C
In conclusion, we have developed an efficient one-pot meth-
odology for the synthesis of nitroneespiro-oxindoles (4) via al-
kylation of nitromethane with BayliseHillman carbonates (2)
Fig. 1. ORTEP diagrams for compounds 4b & 4j.

7998
D. Basavaiah et al. / Tetrahedron 69 (2013) 7995e8001
NMR (100 MHz) spectra were recorded in deuterochloroform
(CDCl3) on a Bruker-AVANCE-400 and 500 spectrometers using
yield: 71%; Rf (50% EtOAc in hexanes) 0.40; brown solid; mp:
162e164 ꢀC; IR (KBr): 1761, 1726, 1678, 1612 cmꢁ1 1H NMR
(CDCl3, 400 MHz): 1.36 (s, 9H), 1.90e2.03 (m, 2H), 2.25e2.40 (m,
2H), 2.50e2.58 (m, 2H), 3.29 (s, 3H), 6.77 (d, 1H, J¼8.0 Hz), 7.07
(d,1H, J¼2.0 Hz), 7.28 (dd,1H, J¼2.0 & 8.4 Hz)*, 7.65 (t,1H, J¼4.4 Hz),
*one of the peak of dd merged with CHCl3 peak; 13C NMR
n
;
tetramethylsilane (TMS,
d
¼0) as an internal standard at room
d
temperature. HRMS spectra were recorded on Bruker maXis ESI-
TOF spectrometer. The X-ray diffraction measurements were car-
ried out at 298 K on a Bruker SMART APEX CCD area detector sys-
tem equipped with a graphite monochromator and a Mo-K
a
fine-
(100 MHz): d 22.06, 25.93, 26.75, 27.55, 38.48, 79.05, 83.51, 109.16,
ꢀ
focus sealed tube (l¼0.71073 A). The BayliseHillman alcohols
123.26, 127.31, 128.69, 129.93, 135.68, 144.46, 148.81, 149.79,
172.76, 195.81; HRMS (ESI) exact mass calcd for C20H22ClNO5þNa
(MþNa)þ, 414.1084; Found, 414.1087.
1ael were prepared via the reaction between cyclohex-2-enone (or
5,5-dimethylcyclohex-2-enone) with isatin derivatives under the
influence of TiCl4 following the known procedure.10
4.1.5. 5-Chloro-3-(tert-butoxycarbonyloxy)-3-(cyclohex-2-enon-2-
yl)-1-ethylindolin-2-one (2e). Reaction time: 0.5 h (0 ꢀC)þ1 h (rt);
yield: 78%; Rf (50% EtOAc in hexanes) 0.50; brown solid; mp:
4.1.1. Synthesis of 3-(tert-butoxycarbonyloxy)-3-(cyclohex-2en-on-2-
yl)-1-methylindolin-2-one (2a). Representative procedure: To a stir-
ring solution of 3-hydroxy-3-(cyclohex-2-enon-2-yl)-1-methylin-
dolin-2-one (20 mmol, 5.14 g) in anhydrous CH2Cl2 (40 mL) at
172e174 ꢀC; IR (KBr):
400 MHz):
n
1747, 1726, 1671, 1610 cmꢁ1; 1H NMR (CDCl3,
d
1.31 (t, 3H, J¼7.2 Hz), 1.34 (s, 9H), 1.87e2.03 (m, 2H),
0
ꢀC were added Boc2O (22 mmol, 4.8 g, 5.0 mL) and DMAP
2.22e2.38 (m, 2H), 2.45e2.54 (m, 2H), 3.67e3.77 (m, 1H),
3.78e3.91 (m, 1H), 6.77 (d, 1H, J¼8.0 Hz), 7.07 (d, 1H, J¼2.0 Hz), 7.23
(dd, 1H, J¼2.0 & 8.4 Hz), 7.60 (t, 1H, J¼4.4 Hz); 13C NMR (100 MHz):
(4-dimethylaminopyridine) (1.0 mmol, 0.122 g) in anhydrous
CH2Cl2 (40 mL) drop-wise slowly (over half an hour) at the same
temperature. After the addition, the stirring was continued at room
temperature (25e30 ꢀC) for 1 h. The reaction mixture was washed
with aqueous hydrochloric acid (2 N, 2 mL) followed by saturated
aqueous sodium bicarbonate solution (10 mL). Organic layer was
separated, dried over anhydrous Na2SO4 and concentrated. The
crude product, thus obtained, was purified by column chromatog-
raphy (40% ethyl acetate in hexanes) to provide the title compound
as a brown solid in 72% (5.15 g) yield. Rf (50% EtOAc in hexanes)
d
11.52, 22.01, 25.87, 27.49, 35.08, 38.43, 79.05, 83.29, 109.15,123.40,
126.97, 128.89, 129.78, 135.63, 143.54, 148.68, 149.71, 172.09,
195.65; HRMS (ESI) exact mass calcd for C21H24ClNO5þH (MþH)þ,
406.1421; Found, 406.1418.
4.1.6. 5-Chloro-3-(tert-butoxycarbonyloxy)-3-(cyclohex-2-enon-2-
yl)-1-benzylindolin-2-one (2f). Reaction time: 0.5 h (0 ꢀC)þ1 h
(rt); yield: 80%; Rf (50% EtOAc in hexanes) 0.55; white solid; mp:
0.32; mp:130e132 ꢀC; IR (KBr):
NMR (CDCl3, 400 MHz): 1.33 (s, 9H), 1.88e2.07 (m, 2H), 2.23e2.39
n
1749, 1728, 1674, 1610 cmꢁ1
;
1H
160e162 ꢀC; IR (KBr):
(CDCl3, 400 MHz): d 1.39 (s, 9H), 1.88e2.08 (m, 2H), 2.27e2.44
n ;
1758, 1728, 1672, 1610 cmꢁ1 1H NMR
d
(m, 2H), 2.46e2.61 (m, 2H), 3.30 (s, 3H), 6.85 (d, 1H, J¼8.0 Hz),
6.92e6.99 (m, 1H), 7.11 (dd, 1H, J¼0.8 & 7.2 Hz)*, 7.29e7.35 (m, 1H),
7.64 (t, 1H, J¼4.0 Hz), *not properly resolved; 13C NMR (100 MHz):
(m, 2H), 2.49e2.62 (m, 2H), 4.96 & 5.02 (ABq, 2H, J¼16.0 Hz), 6.51
(d, 1H, J¼8.0 Hz), 7.08e7.12 (m, 2H), 7.24e7.39 (m, 3H)*, 7.51
(d, 2H, J¼7.2 Hz), 7.67 (t, 1H, J¼4.0 Hz), *It contains CHCl3 peak;
d
22.09, 25.88, 26.61, 27.49, 38.52, 79.49, 83.13, 108.16, 122.14,
13C NMR (100 MHz):
d 22.16, 26.06, 27.70, 38.57, 44.96, 79.21,
122.74, 126.97, 130.11, 136.02, 145.70, 148.25, 149.77, 173.16, 195.81;
HRMS (ESI) exact mass calcd for C20H23NO5þNa (MþNa)þ,
380.1474; Found, 380.1488.
83.63, 110.50, 123.36, 127.41, 127.48, 127.53, 128.71, 128.82, 129.91,
135.56, 135.83, 143.92, 149.04, 149.98, 173.08, 195.89; HRMS (ESI)
exact mass calcd for C26H26ClNO5þH (MþH)þ, 468.1578; Found,
468.1575.
4.1.2. 3-(tert-Butoxycarbonyloxy)-3-(cyclohex-2-enon-2-yl)-1-
ethylindolin-2-one (2b). Reaction time: 0.5 h (0 ꢀC)þ1 h (rt); yield:
74%; Rf (50% EtOAc in hexanes) 0.49; brown solid; mp 140e142 ꢀC;
4.1.7. 5-Bromo-3-(tert-butoxycarbonyloxy)-3-(cyclohex-2-enon-2-
yl)-1-methylindolin-2-one (2g). Reaction time: 0.5 h (0 ꢀC)þ1 h (rt);
yield: 79%; Rf (50% EtOAc in hexanes) 0.47; brown solid; mp:
IR (KBr): n
1755, 1728, 1678, 1608 cmꢁ1; 1H NMR (CDCl3, 400 MHz):
d
1.33 (s, 9H), 1.35 (t, 3H, J¼7.2 Hz)*, 1.88e2.05 (m, 2H), 2.23e2.40
162e164 ꢀC; IR (KBr):
(CDCl3, 400 MHz): d 1.36 (s, 9H), 1.90e2.06 (m, 2H), 2.25e2.41
n ;
1759, 1726, 1678, 1610 cmꢁ1 1H NMR
(m, 2H), 2.46e2.57 (m, 2H), 3.70e3.82 (m, 1H), 3.86e3.96 (m, 1H),
6.86 (d, 1H, J¼7.6 Hz), 6.91e6.98 (m, 1H), 7.11 (dd, 1H, J¼0.8 &
7.2 Hz), 7.27e7.33 (m, 1H), 7.62 (t, 1H, J¼4.0 Hz), *one of the peak
(m, 2H), 2.49e2.58 (m, 2H), 3.28 (s, 3H), 6.73 (d, 1H, J¼8.0 Hz), 7.20
(d, 1H, J¼2.0 Hz), 7.42 (dd, 1H, J¼2.0 & 8.0 Hz), 7.64 (t, 1H, J¼4.0 Hz);
merged with singlet at
d
1.33; 13C NMR (100 MHz):
d
11.59, 22.03,
13C NMR (100 MHz):
d 22.07, 25.95, 26.76, 27.57, 38.48, 78.97, 83.60,
25.80, 27.42, 34.86, 38.47, 79.49, 82.86, 108.13, 121.78, 122.90,
127.13, 129.92, 135.99, 144.78, 148.04, 149.67, 172.44, 195.57; HRMS
(ESI) exact mass calcd for C21H25NO5þNa (MþNa)þ, 394.1630;
Found, 394.1634.
109.73, 114.57, 125.96, 129.01, 132.88, 135.67, 144.94, 148.94, 149.79,
172.71, 195.92; HRMS (ESI) exact mass calcd for C20H22BrNO5þNa
(MþNa)þ, 458.0579; Found, 458.0584.
4.1.8. 5-Bromo-3-(tert-butoxycarbonyloxy)-3-(cyclohex-2-enon-2-
yl)-1-ethylindolin-2-one (2h). Reaction time: 0.5 h (0 ꢀC)þ1 h (rt);
yield: 74%; Rf (50% EtOAc in hexanes) 0.53; brown solid; mp:
4.1.3. 3-(tert-Butoxycarbonyloxy)-3-(cyclohex-2-enon-2-yl)-1-
benzylindolin-2-one (2c). Reaction time: 0.5 h (0 ꢀC)þ1 h (rt); yield:
83%; Rf (50% EtOAc in hexanes) 0.60; white solid; mp: 124e126 ꢀC;
174e176 ꢀC; IR (KBr):
400 MHz):
n
1758,1725,1676,1605 cmꢁ1; 1H NMR (CDCl3,
IR (KBr):
n
1758, 1735, 1683, 1612 cmꢁ1; 1H NMR (CDCl3, 400 MHz):
d
1.33 (t, 3H, J¼7.2 Hz), 1.36 (s, 9H), 1.89e2.06 (m, 2H),
d
1.40 (s, 9H), 1.86e2.10 (m, 2H), 2.25e2.46 (m, 2H), 2.49e2.62 (m,
2.25e2.41 (m, 2H), 2.49e2.56 (m, 2H), 3.69e3.80 (m, 1H),
3.81e3.94 (m, 1H), 6.75 (d, 1H, J¼8.0 Hz), 7.21 (d, 1H, J¼2.0 Hz), 7.41
(dd, 1H, J¼2.0 & 8.4 Hz), 7.62 (t, 1H, J¼4.0 Hz); 13C NMR (100 MHz):
2H), 5.05 (s, 2H), 6.63 (d,1H, J¼8.0 Hz), 6.89e6.98 (m,1H), 7.11e7.20
(m, 2H), 7.25e7.32 (m, 1H), 7.33e7.41 (m, 2H), 7.57 (d, 2H, J¼7.2 Hz),
7.69 (t, 1H, J¼4.0 Hz); 13C NMR (100 MHz):
d
22.14, 25.96, 27.61,
d 11.61, 22.11, 25.99, 27.60, 35.17, 38.53, 79.07, 83.47, 109.77, 114.31,
38.57, 44.79, 79.60, 83.11, 109.43, 122.19, 122.84, 127.05, 127.22,
127.36, 128.54, 129.98, 135.94, 136.14, 145.22, 148.34, 149.93, 173.40,
195.74; HRMS (ESI) exact mass calcd for C26H27NO5þH (MþH)þ,
434.1967; Found, 434.1968.
126.20, 129.33, 132.80, 135.74, 144.13, 148.83, 149.79, 172.11, 195.81;
HRMS (ESI) exact mass calcd for C21H24BrNO5þNa (MþNa)þ,
472.0736; Found, 472.0740.
4.1.9. 5-Bromo-3-(tert-butoxycarbonyloxy)-3-(cyclohex-2-enon-2-
yl)-1-benzylindolin-2-one (2i). Reaction time: 0.5 h (0 ꢀC)þ1 h (rt);
yield: 76%; Rf (50% EtOAc in hexanes) 0.61; yellow solid; mp:
4.1.4. 5-Chloro-3-(tert-butoxycarbonyloxy)-3-(cyclohex-2-enon-2-
yl)-1-methylindolin-2-one (2d). Reaction time: 0.5 h (0 ꢀC)þ1 h (rt);

D. Basavaiah et al. / Tetrahedron 69 (2013) 7995e8001
7999
170e172 ꢀC; IR (KBr):
(CDCl3, 400 MHz): 1.39 (s, 9H), 1.91e2.08 (m, 2H), 2.28e2.44 (m,
n
1753, 1730, 1672, 1605 cmꢁ1
;
1H NMR
54.36, 76.54, 108.65, 122.90, 124.83, 127.70, 129.11, 134.70, 143.80,
149.38, 175.22, 197.69; HRMS (ESI) exact mass calcd for
C
d
2H), 2.49e2.62 (m, 2H), 4.96 & 5.02 (ABq, 2H, J¼16.0 Hz), 6.47
(d, 1H, J¼8.4 Hz), 7.21 (d, 1H, J¼2.0 Hz), 7.23e7.30 (m, 2H)*,
7.31e7.36 (m, 2H), 7.51 (d, 2H, J¼7.2 Hz), 7.67 (t, 1H, J¼4.0 Hz), *It
16H16N2O4þH (MþH)þ, 301.1188; Found, 301.1191.
4.1.14. Synthesis of [1-methylindolin-2-one]-3-spiro-30-[20,50,60,70-
tetrahydroindole 10-oxide] (4a). To
stirring solution of 3-
contains CHCl3 peak; 13C NMR (100 MHz):
d
22.15, 26.06, 27.71,
a
38.56, 44.94, 79.12, 83.65, 111.03, 114.79, 126.05, 127.41, 127.48,
128.71, 129.17, 132.81, 135.52, 135.84, 144.42, 149.05, 149.98, 172.97,
195.89; HRMS (ESI) exact mass calcd for C26H26BrNO5þH (MþH)þ,
512.1073; Found, 512.1069.
nitromethyl-3-(cyclohex-2-enon-2-yl)-1-methylindolin-2-one 3a
(2.0 mmol, 0.600 g) in ethanol (10 mL) at room temperature
(25e30 ꢀC) were added Fe powder (12.0 mmol, 0.672 g) and 2 N HCl
(2.0 mL). After stirring at room temperature (25e30 ꢀC) for 12 h the
reaction mixture was diluted with ethyl acetate (20 mL) and stirred
for a few minutes and filtered to remove iron impurities. The res-
idue was washed with ethyl acetate (20 mL). The combined organic
layer was dried over anhydrous Na2SO4. Solvent was evaporated
and the crude product thus obtained was subjected to column
chromatography (silica gel, 2% EtOH in EtOAc) to provide 4a in 69%
(0.370 g) isolated yield as a brown solid. Rf (20% EtOH in ethyl ac-
4.1.10. 5-Chloro-3-(tert-butoxycarbonyloxy)-3-(5,5-dimethyl-cyclo-
hex-2-enon-2-yl)-1-methylindolin-2-one (2j). Reaction time: 0.5 h
(0 ꢀC)þ1 h (rt); yield: 75%; Rf (50% EtOAc in hexanes) 0.58; yellow
solid; mp: 158e160 ꢀC; IR (KBr): 1752, 1736, 1676, 1615, cmꢁ1; 1H
n
NMR (CDCl3, 400 MHz): d 0.99 (s, 3H), 1.02 (s, 3H), 1.36 (s, 9H), 2.15
& 2.18 (ABq, 2H, J¼16.0 Hz), 2.42 (d, 2H, J¼4.4 Hz), 3.28 (s, 3H), 6.77
(d, 1H, J¼8.4 Hz), 7.07 (d, 1H, J¼2.0 Hz), 7.27 (dd, 1H, J¼2.0 & 8.4 Hz),
etate) 0.35; mp:180e182 ꢀC; IR (KBr):
NMR (CDCl3, 400 MHz): 1.71e1.92 (m, 2H)*, 2.08e2.27 (m, 2H),
n ;
1718, 1610, 1587 cmꢁ1 1H
7.51 (t, 1H, J¼4.4 Hz); 13C NMR (100 MHz):
d
26.83, 27.61, 27.96,
d
28.17, 33.79, 39.96, 52.10, 79.07, 83.62, 109.24, 123.13, 127.40,
128.70, 130.03, 134.73, 144.56, 146.58, 149.82, 172.69, 196.15; HRMS
(ESI) exact mass calcd for C22H26ClNO5þNa (MþNa)þ, 442.1397;
Found, 442.1397.
2.69e2.80 (m, 2H), 3.26 (s, 3H), 4.21 & 4.47 (ABq, 2H, J¼14.0 Hz),
5.39 (t, 1H, J¼4.4 Hz), 6.90 (d, 1H, J¼8.0 Hz), 7.08e7.18 (m, 2H),
7.32e7.38 (m, 1H), *It contains moisture peak; 13C NMR (100 MHz):
d
20.02, 21.28, 24.59, 26.57, 51.29, 68.66, 108.48, 122.85, 123.48,
123.86, 129.06, 130.94, 137.42, 143.44, 143.91, 175.95; HRMS (ESI)
exact mass calcd for C16H16N2O2þH (MþH)þ, 269.1290; Found,
269.1290.
4.1.11. 5-Bromo-3-(tert-butoxycarbonyloxy)-3-(5,5-dimethylcycl-
ohex-2-enon-2-yl)-1-methylindolin-2-one (2k). Reaction time: 0.5 h
(0 ꢀC)þ1 h (rt); yield: 86%; Rf (50% EtOAc in hexanes) 0.56; yellow
solid; mp: 140e142 ꢀC; IR (KBr):
n
1750, 1732, 1682, 1618,
4.1.15. [1-Methylindolin-2-one]-3-spiro-30-[20,50,60,70-tetrahy-
droindole 10-oxide] (4a). Representative one-pot procedure: To
a stirring solution of 3-(tert-butoxycarbonyloxy)-3-(cyclohex-2-
enon-2-yl)-1-methylindolin-2-one (2a) (2.0 mmol, 0.715 g) and
nitromethane (3.0 mmol, 0.183 g, 0.16 mL) in anhydrous CH2Cl2
(5 mL) at room temperature (25e30 ꢀC) was added DMAP
(2.0 mmol, 0.244 g). After stirring at the same temperature for 12 h
under N2 atmosphere, the solvent was removed under reduced
pressure. The resulting residue was dissolved in ethanol (10 mL)
and Fe powder (12.0 mmol, 0.672 g) and 2 N HCl (2.0 mL) were
added. After stirring at room temperature (25e30 ꢀC) for 12 h the
reaction mixture was diluted with ethyl acetate (20 mL) and stirred
for a few minutes and filtered to remove iron impurities. The res-
idue was washed with ethyl acetate (20 mL). The combined organic
layer was dried over anhydrous Na2SO4. Solvent was evaporated
and the crude product thus obtained was subjected to column
chromatography (silica gel, 2% EtOH in EtOAc) to provide 4a in 59%
(0.319 g) isolated yield as brown solid.
1605 cmꢁ1 1H NMR (CDCl3, 400 MHz):
; d 0.99 (s, 3H), 1.02 (s, 3H),
1.36 (s, 9H), 2.15 & 2.20 (ABq, 2H, J¼16.0 Hz), 2.42 (d, 2H, J¼4.4 Hz),
3.28 (s, 3H), 6.74 (d, 1H, J¼8.4 Hz), 7.20 (d, 1H, J¼2.0 Hz), 7.43 (dd,
1H, J¼2.0 & 8.0 Hz), 7.51 (t, 1H, J¼4.4 Hz); 13C NMR (100 MHz):
d
26.80, 27.61, 27.92, 28.21, 33.79, 39.95, 52.09, 78.97, 83.63, 109.77,
114.58, 125.82, 129.03, 132.93, 134.73, 145.04, 146.58, 149.80, 172.57,
196.15; HRMS (ESI) exact mass calcd for C22H26BrNO5þH (MþH)þ,
464.1073; Found, 464.1074.
4.1.12. 5-Chloro-3-(tert-butoxycarbonyloxy)-3-(5,5-dimethylcycl-
ohex-2-enon-2-yl)-1-ethylindolin-2-one (2l). Reaction time: 0.5 h
(0 ꢀC)þ1 h (rt); yield: 79%; Rf (50% EtOAc in hexanes) 0.64; brown
solid; mp: 168e170 ꢀC; IR (KBr):
n
1750, 1676, 1610 cmꢁ1; 1H NMR
(CDCl3, 400 MHz):
d
0.99 (s, 3H), 1.02 (s, 3H), 1.33 (t, 3H, J¼7.2 Hz),
1.36 (s, 9H), 2.16 & 2.20 (ABq, 2H, J¼16.0 Hz), 2.39 & 2.45 (dABq, 2H,
J¼4.4 & 15.2 Hz), 3.68e3.80 (m, 1H), 3.81e3.94 (m, 1H), 6.79 (d, 1H,
J¼8.4 Hz), 7.06 (d, 1H, J¼2.0 Hz), 7.22 (dd, 1H, J¼8.4 & 2.4 Hz)*, 7.50
(t, 1H, J¼4.4 Hz), *It contains CHCl3 peak; 13C NMR (100 MHz):
Note: The spectral (IR, 1H, & 13C NMR, HRMS) data of this
product (4a) was identical with that of the compound, obtained in
a two-step protocol (Section 4.1.14).
d
11.63, 27.63, 28.09, 33.79, 35.21, 39.99, 52.13, 79.16, 83.48, 109.30,
123.35, 127.15, 129.01, 129.95, 134.81, 143.74, 146.47, 149.81,
172.10, 196.04; HRMS (ESI) exact mass calcd for C23H28ClNO5þNa
(MþNa)þ, 456.1554; Found, 456.1558.
4.1.16. [1-Ethylindolin-2-one]-3-spiro-30-[20,50,60,70-tetrahydroindole
10-oxide] (4b). Reaction time: 12 hþ12 h; yield: 64%; Rf (20% EtOH
4.1.13. Synthesis of 3-nitromethyl-3-(cyclohex-2-enon-2-yl)-1-
methylindolin-2-one (3a). To a stirring solution of 3-(tert-butox-
ycarbonyloxy)-3-(cyclohex-2-enon-2-yl)-1-methylindolin-2-one
(2a) (4.0 mmol, 1.430 g) and nitromethane (6.0 mmol, 0.366 g,
0.33 mL) in anhydrous DCM (10 mL) was added DMAP (4.0 mmol,
0.488 g) at room temperature (25e30 ꢀC). After stirring for 12 h at
room temperature under N2 atmosphere, solvent was removed and
crude product thus obtained was purified by column chromatog-
raphy (40% EtOAc in hexanes) to provide the desired product in 82%
yield (0.985 g) as a white solid. Rf (50% EtOAc in hexanes) 0.29; mp:
in ethyl acetate) 0.45; brown solid; mp: 162e164 ꢀC; IR (KBr):
n
1709, 1612, 1583 cmꢁ1 1H NMR (CDCl3, 400 MHz):
; d 1.31 (t, 3H,
J¼7.2 Hz), 1.72e1.94 (m, 2H)#, 2.08e2.28 (m, 2H), 2.75 (t, 2H,
J¼6.8 Hz), 3.69e3.92 (m, 2H), 4.22 & 4.48 (ABq, 2H, J¼14.0 Hz), 5.37
(t, 1H, J¼4.4 Hz), 6.92 (d, 1H, J¼8.0 Hz), 7.07e7.12 (m, 1H), 7.14e7.19
(m,1H), 7.31e7.37 (m,1H),* #It contains moisture peak. *Unresolved
dd; 13C NMR (100 MHz):
d 12.52, 20.00, 21.26, 24.59, 34.97, 51.22,
68.53, 108.60, 123.01, 123.25, 123.67, 128.97, 131.25, 137.58, 142.46,
143.95, 175.49; HRMS (ESI) exact mass calcd for C17H18N2O2þNa
(MþNa)þ, 305.1266; Found, 305.1232.
140e142 ꢀC; IR (KBr):
(CDCl3, 400 MHz): 1.84e2.06 (m, 2H), 2.30e2.55 (m, 4H), 3.31 (s,
n
1709, 1676, 1630, 1610 cmꢁ1
;
1H NMR
Crystal data for 4b: Empirical formula, C17H18N2O2; formula
weight, 282.33; crystal color, habit: colorless, block; crystal di-
mensions, 0.36ꢂ0.28ꢂ0.25 mm3; crystal system, triclinic; lattice
d
3H), 5.03 & 5.60 (ABq, 2H, J¼13.6 Hz), 6.88 (d, 1H, J¼8.0 Hz), 6.94 (t,
ꢀ
ꢀ
1H, J¼4.4 Hz), 7.00e7.09 (m, 1H), 7.28e7.36 (m, 1H), 7.50 (dd, 1H,
type, primitive; lattice parameters, a¼8.4050(6) A, b¼8.7609(6) A,
J¼0.8 & 7.6 Hz); 13C NMR (100 MHz):
d
21.87, 26.39, 26.71, 39.22,
c¼11.2366(8) A;
a
¼92.5970(10);
b
¼109.0770(10); ¼108.3070(10);
g
ꢀ

8000
D. Basavaiah et al. / Tetrahedron 69 (2013) 7995e8001
3
V¼732.23(9) A ; space group, P-1; Z¼2; Dcald¼1.281 g/cm3;
13C NMR (100 MHz):
d 20.13, 21.46, 24.82, 26.87, 51.44, 68.65,
ꢀ
ꢀ
F000¼300;
l
(Mo-Ka)¼0.71073 A; R (Iꢃ2s1)¼0.0493, wR2¼0.1453.
110.08, 116.10, 124.37, 126.38, 132.08, 133.05, 137.05, 142.67, 143.96,
175.52; HRMS (ESI) exact mass calcd for C16H15BrN2O2þNa
(MþNa)þ, 369.0215; Found, 369.0184.
Detailed X-ray crystallographic data is available from the Cam-
bridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2
1EZ, UK (for compound 4b CCDC # 923595).
4.1.22. [1-Ethyl-5-bromoindolin-2-one]-3-spiro-30-[20,50,60,70-tetra-
hydroindole 10-oxide] (4h). Reaction time: 12 hþ12 h; yield : 60%; Rf
(20% EtOH in ethyl acetate) 0.49; brown solid; mp: 182e184 ꢀC; IR
4.1.17. [1-Benzylindolin-2-one]-3-spiro-30-[20,50,60,70-tetrahy-
droindole 10-oxide] (4c). Reaction time: 12 hþ12 h; yield: 60%; Rf
(20% EtOH in ethyl acetate) 0.48; white solid; mp: 162e164 ꢀC; IR
(KBr):
n ; d 1.29
1715, 1605, 1589 cmꢁ1 1H NMR (CDCl3, 400 MHz):
(KBr) :
n
1709, 1616, 1589 cmꢁ1
;
1H NMR (CDCl3, 400 MHz):
(t, 3H, J¼7.2 Hz), 1.74e1.94 (m, 2H)#, 2.12e2.29 (m, 2H), 2.75 (t, 2H,
J¼6.8 Hz), 3.67e3.88 (m, 2H), 4.19 & 4.47 (ABq, 2H, J¼14.4 Hz), 5.38
(t, 1H, J¼4.8 Hz), 6.80 (d, 1H, J¼8.4 Hz), 7.29 (d, 1H, J¼2.0 Hz), 7.46
(dd, 1H, J¼8.4 & 2.0 Hz), #It contains moisture peak; 13C NMR
d
1.73e1.96 (m, 2H)#, 2.09e2.30 (m, 2H), 2.76 (t, 2H, J¼6.8 Hz), 4.26
& 4.54 (ABq, 2H, J¼14.0 Hz), 4.77 & 5.09 (ABq, 2H, J¼15.6 Hz), 5.40
(t, 1H, J¼4.4 Hz), 6.79 (d, 1H, J¼8.0 Hz), 7.03e7.09 (m, 1H), 7.16 (dd,
1H, J¼0.8 & 7.2 Hz)*, 7.18e7.23 (m, 1H), 7.26e7.38 (m, 5H), #It
contains moisture peak. *unresolved dd; 13C NMR (100 MHz):
(100 MHz):
d 12.69, 20.20, 21.53, 24.90, 35.41, 51.45, 68.63, 110.24,
115.96, 124.18, 126.63, 132.07, 133.51, 137.33, 141.79, 144.01, 175.17;
HRMS (ESI) exact mass calcd for C17H17BrN2O2þNa (MþNa)þ,
383.0371; Found, 383.0364.
d
20.02, 21.28, 24.67, 43.97, 51.29, 68.74, 109.46, 122.93, 123.48,
123.62, 127.11, 127.69, 128.70, 128.93, 130.98, 135.23, 137.68, 142.53,
143.75, 176.05; HRMS (ESI) exact mass calcd for C22H20N2O2þNa
(MþNa)þ, 367.1422; Found, 367.1406.
4.1.23. [1-Benzyl-5-bromoindolin-2-one]-3-spiro-30-[20,50,60,70-tetra-
hydroindole 10-oxide] (4i). Reaction time: 12 hþ12 h; yield: 64%; Rf
(20% EtOH in ethyl acetate) 0.59; white solid; mp: 186e188 ꢀC; IR
4.1.18. [1-Methyl-5-chlorolindolin-2-one]-3-spiro-30-[20,50,60,70-tet-
rahydroindole 10-oxide] (4d). Reaction time: 12 hþ12 h; yield : 61%;
Rf (20% EtOH in ethyl acetate) 0.43; brown solid; mp: 202e204 ꢀC;
(KBr):
d
n ;
1715, 1610, 1589 cmꢁ1 1H NMR (CDCl3, 400 MHz):
1.75e1.95 (m, 2H)#, 2.12e2.31 (m, 2H), 2.76 (t, 2H, J¼6.8 Hz), 4.23
IR (KBr):
n
1720, 1610, 1589 cmꢁ1
;
1H NMR (CDCl3, 400 MHz):
& 4.53 (ABq, 2H, J¼14.0 Hz), 4.75 & 5.06 (ABq, 2H, J¼15.6 Hz), 5.41
(t, 1H, J¼4.4 Hz), 6.66 (d, 1H, J¼8.4 Hz), 7.24e7.36 (m, 7H)*. #It
contains moisture peak. *It contains CHCl3 peak; 13C NMR
d
1.74e1.94 (m, 2H), 2.11e2.28 (m, 2H), 2.75 (t, 2H, J¼6.8 Hz), 3.25
(s, 3H), 4.19 & 4.47 (ABq, 2H, J¼14.0 Hz), 5.40 (t, 1H, J¼4.4 Hz), 6.83
(d, 1H, J¼8.0 Hz), 7.15 (d, 1H, J¼2.0 Hz), 7.32 (dd, 1H, J¼2.0 & 8.0 Hz);
(100 MHz):
d 20.08, 21.40, 24.84, 44.23, 51.37, 68.66, 111.08, 116.10,
13C NMR (100 MHz):
d
20.12, 21.46, 24.81, 26.90, 51.52, 68.61,109.61,
124.11, 126.36, 127.19, 128.01, 128.94, 131.91, 133.04, 134.86, 137.24,
141.68, 143.75, 175.56; HRMS (ESI) exact mass calcd for
C22H19BrN2O2þH (M þH)þ, 423.0708; Found, 423.0704.
123.68, 124.53, 128.93, 129.19, 132.66, 137.04, 142.18, 144.13, 175.63;
HRMS (ESI) exact mass calcd for C16H15ClN2O2þH (MþH)þ,
303.0900; Found, 303.0900.
4.1.24. [1-Methyl-5-chloroindolin-2-one]-3-spiro-30-[60,60-dimethyl-
20,50,60,70-tetrahyroindole 10-oxide] (4j). Reaction time: 12 hþ12 h;
yield: 63%; Rf (20% EtOH in ethyl acetate) 0.52; white solid; mp:
4.1.19. [1-Ethyl-5-chlorolindolin-2-one]-3-spiro-30-[20,50,60,70-tetra-
hydroindole 10-oxide] (4e). Reaction time: 12 hþ12 h; yield: 56%; Rf
(20% EtOH in ethyl acetate) 0.46; brown solid; mp 154e156 ꢀC; IR
186e188 ꢀC; IR (KBr):
400 MHz):
n ;
1722, 1588 cmꢁ1 1H NMR (CDCl3,
(KBr):
n
1713, 1607, 1585 cmꢁ1
;
1H NMR (CDCl3, 500 MHz):
d
1.29
d
1.03 (s, 3H), 1.06 (s, 3H), 2.00 & 2.07 (dABq, 2H, J¼4.8 &
(t, 3H, J¼7.0 Hz), 1.76e1.94 (m, 2H)#, 2.12e2.28 (m, 2H), 2.75 (t, 2H,
J¼7.0 Hz), 3.68e3.78 (m, 1H), 3.79e3.88 (m, 1H), 4.19 & 4.47 (ABq,
2H, J¼14.0 Hz), 5.38 (t, 1H, J¼4.5 Hz), 6.85 (d, 1H, J¼8.0 Hz), 7.15 (d,
1H, J¼2.0 Hz), 7.30 (dd, 1H, J¼2.0 & 8.5 Hz), #It contains moisture
18.0 Hz), 2.55 (s, 2H)*, 3.25 (s, 3H), 4.22 & 4.49 (ABq, 2H, J¼14.0 Hz),
5.29 (t, 1H, J¼4.8 Hz), 6.84 (d, 1H, J¼8.4 Hz), 7.14 (d, 1H, J¼2.0 Hz),
7.33 (dd, 1H, J¼2.0 & 8.0 Hz), *It may be unresolved ABq; 13C NMR
(100 MHz):
d 26.97, 28.55, 28.64, 30.96, 34.91, 39.33, 51.33, 69.16,
peak; 13C NMR (100 MHz):
d
12.68, 20.22, 21.53, 24.90, 35.42, 51.52,
109.66, 122.37, 123.58, 129.03, 129.26, 132.73, 136.47, 142.27, 144.35,
175.67; HRMS (ESI) exact mass calcd for C18H19ClN2O2þH (MþH)þ,
331.1213; Found, 331.1209.
68.64, 109.74, 123.87, 123.94, 128.79, 129.15, 133.17, 137.40, 141.31,
143.87, 175.26; HRMS (ESI) exact mass calcd for C17H17ClN2O2þH
(MþH)þ, 317.1057; Found, 317.1056.
Crystal data for 4j: Empirical formula, C18H19ClN2O2; formula
weight, 330.80; crystal color, habit: colorless, block; crystal
dimensions, 0.32ꢂ0.24ꢂ0.12 mm3; crystal system, monoclinic;
4.1.20. [1-Benzyl-5-chlorolindolin-2-one]-3-spiro-30-[20,50,60,70-tet-
rahydroindole 10-oxide] (4f). Reaction time: 12 hþ12 h; yield: 62%;
Rf (20% EtOH in ethyl acetate) 0.56; white solid; mp: 100e102 ꢀC; IR
ꢀ
lattice type, centrosymmetric; lattice parameters, a¼15.6727(8) A,
ꢀ
ꢀ
b¼10.8206(5) A, c¼19.7503(11) A;
a¼90.00;
b¼103.779(5);
3
1715, 1610, 1583 cmꢁ1
;
1H NMR (CDCl3, 400 MHz):
g
¼90.00; V¼3253(3) A ; space group, C2/c; Z¼8; Dcald¼1.351 g/cm3;
ꢀ
(KBr):
n
1.68e1.88 (m, 2H)#, 2.06e2.24 (m, 2H), 2.69 (t, 2H, J¼6.8 Hz), 4.15
F000¼1392;
l
(Mo-Ka)¼0.71073 A; R (Iꢃ2s1)¼0.0459, wR2¼0.1167.
ꢀ
d
& 4.45 (ABq, 2H, J¼14.0 Hz), 4.68 & 4.99 (ABq, 2H, J¼15.6 Hz), 5.34
(t, 1H, J¼4.4 Hz), 6.63 (d, 1H, J¼8.4 Hz), 7.07 (d, 1H, J¼2.0 Hz), 7.11
(dd, 1H, J¼2.0 & 8.4 Hz), 7.17e7.31 (m, 5H)*, #It contains moisture
Detailed X-ray crystallographic data is available from the Cambridge
Crystallographic Data Centre,12 Union Road, Cambridge CB2 1EZ, UK
(for compound 4j CCDC # 923596).
peak. *It contains CHCl3 peak; 13C NMR (100 MHz):
d 19.93, 21.28,
24.70, 44.10, 51.32, 68.44, 110.53, 123.52, 124.35, 127.07, 127.86,
128.72, 128.80, 128.91, 132.46, 134.79, 137.05, 141.08, 143.94, 175.56;
HRMS (ESI) exact mass calcd for C22H19ClN2O2þH (MþH)þ,
379.1213; Found, 379.1210.
4.1.25. [1-Methyl-5-bromoindolin-2-one]-3-spiro-30-[60,60-dimethyl-
20,50,60,70-tetrahydroindole 10-oxide] (4k). Reaction time: 12 hþ12 h;
yield: 58%; Rf (20% EtOH in ethyl acetate) 0.55; white solid;
mp:194e196 ꢀC; IR (KBr):
400 MHz):
n
1704, 1616, 1578 cmꢁ1; 1H NMR (CDCl3,
d
1.03 (s, 3H), 1.06 (s, 3H), 2.05 & 2.07 (dABq, 2H, J¼4.8 &
4.1.21. [1-Methyl-5-bromoindolin-2-one]-3-spiro-30-[20,50,60,70-tetra-
hydroindole 10-oxide] (4g). Reaction time: 12 hþ12 h; yield: 65%; Rf
(20% EtOH in ethyl acetate) 0.44; brown solid; mp: 198e200 ꢀC; IR
18.0 Hz), 2.47e2.62 (m, 2H)*, 3.24 (s, 3H), 4.21 & 4.49 (ABq, 2H,
J¼14.0 Hz), 5.29 (t, 1H, J¼4.8 Hz), 6.79 (d, 1H, J¼8.0 Hz), 7.28 (d, 1H,
J¼2.0 Hz), 7.48 (dd, 1H, J¼2.0 & 8.4 Hz), *Unresolved ABq; 13C NMR
(KBr):
n
1716, 1604, 1585 cmꢁ1
;
1H NMR (CDCl3, 400 MHz):
(100 MHz) d 26.97, 28.56, 28.71, 30.99, 34.96, 39.39, 51.30, 69.24,
d
1.76e1.93 (m, 2H), 2.11e2.28 (m, 2H), 2.75 (t, 2H, J¼6.0 Hz), 3.24
110.15, 116.23, 122.30, 126.37, 132.19, 133.17, 136.52, 142.80, 144.30,
175.59; HRMS (ESI) exact mass calcd for C18H19BrN2O2þH (MþH)þ,
375.0708; Found, 375.0712.
(s, 3H), 4.19 & 4.46 (ABq, 2H, J¼14.0 Hz), 5.40 (t, 1H, J¼4.4 Hz), 6.78
(d,1H, J¼8.4 Hz), 7.28 (d,1H, J¼2.0 Hz), 7.47 (dd,1H, J¼2.0 & 8.4 Hz);

D. Basavaiah et al. / Tetrahedron 69 (2013) 7995e8001
8001
4.1.26. [1-Ethyl-5-chloroindolin-2-one]- 3-spiro-30-[60,60-dimethyl-
20,50,60,70-tetrahydroindole 10-oxide] (4l). Reaction time: 12 hþ12 h;
yield: 61%; Rf (20% EtOH in ethyl acetate) 0.59; white solid; mp:
Chem. Commun. 2005, 2621e2623; (i) Marti, C.; Carreira, E. M. Eur. J. Org. Chem.
2003, 2209e2219.
5. (a) Basavaiah, D.; Reddy, D. M. Org. Biomol. Chem. 2012, 10, 8774e8777; (b)
Basavaiah, D.; Devendar, B.; Aravindu, K.; Veerendhar, A. Chem.dEur. J. 2010, 16,
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Basavaiah, D.; Lenin, D. V.; Devendar, B. Tetrahedron Lett. 2009, 50, 3538e3542;
(e) Basavaiah, D.; Devendar, B.; Lenin, D. V.; Satyanarayana, T. Synlett 2009,
411e416; (f) Basavaiah, D.; Roy, S. Org. Lett. 2008, 10, 1819e1822; (g) Basavaiah,
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Pandiaraju, S. Chem. Commun. 1998, 1639e1640.
184e186 ꢀC; IR (KBr):
500 MHz):
n ;
1704, 1605, 1582 cmꢁ1 1H NMR (CDCl3,
d
1.02 (s, 3H), 1.07 (s, 3H), 1.29 (t, 3H, J¼7.5 Hz), 2.00 &
2.07 (dABq, 2H, J¼4.5 & 18.0 Hz), 2.54 (s, 2H)*, 3.68e3.88 (m, 2H),
4.22 & 4.50 (ABq, 2H, J¼14.5 Hz), 5.26 (t, 1H, J¼4.5 Hz), 6.84 (d, 1H,
J¼8.5 Hz), 7.14 (d, 1H, J¼2.0 Hz), 7.31 (dd, 1H, J¼2.0 & 8.0 Hz),
*Unresolved ABq; 13C NMR (100 MHz):
d 12.65, 28.53, 28.64, 30.94,
34.90, 35.38, 39.33, 51.25, 69.07, 109.76, 121.87, 123.67, 128.76,
129.15, 133.13, 136.70, 141.30, 144.14, 175.19; HRMS (ESI) exact mass
calcd for C19H21ClN2O2þH (MþH)þ, 345.1370; Found, 345.1377.
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maty, F. J. Org. Chem. 2009, 74, 2004e2007; (j) Khamri, S.; Amri, H. Tetrahedron
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Acknowledgements
We thank DST (New Delhi) for funding this project. S.S.B. thanks
CSIR and DST (New Delhi) for research fellowships. G.V. thanks CSIR
(New Delhi) for his fellowship. We thank UGC for support and
providing some instrumental facilities. We thank the national sin-
gle crystal X-ray and HRMS facility funded by DST. We also thank
Professors T.P. Radhakrishnan and S. Pal, School of Chemistry,
University of Hyderabad, for helpful discussions regarding X-ray
data analysis.
Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.07.002.
8. (a) Basavaiah, D.; Badsara, S. S.; Sahu, B. C. Chem.dEur. J. 2013, 19, 2961e2965;
(b) Chen, G.-Y.; Zhong, F.; Lu, Y. Org. Lett. 2012, 14, 3955e3957; (c) Wang, Y.; Liu,
L.; Zhong, N.-J.; Wang, D.; Chen, Y.-J. J. Org. Chem. 2012, 77, 4143e4147; (d)
Zhong, F.; Han, X.; Wang, Y.; Lu, Y. Angew. Chem., Int. Ed. 2011, 50, 7837e7841;
(e) Deng, H.-P.; Wei, Y.; Shi, M. Org. Lett. 2011, 13, 3348e3351; (f) Peng, J.;
Huang, X.; Jiang, L.; Cui, H.-L.; Chen, Y.-C. Org. Lett. 2011, 13, 4584e4587; (g) Tan,
B.; Candeias, N. R.; Barbas, C. F., III. J. Am. Chem. Soc. 2011, 133, 4672e4675; (h)
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11. Preparation of carbonates of the BH adducts, derived from aldehydes and alkyl
acrylate, is reported in the literature (see Ref: Feng, J.; Lu, X.; Kong, A.; Han, X.
Tetrahedron 2007, 63, 6035e6041.) We have prepared the carbonates 2 fol-
lowing a similar procedure.
References and notes
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was recently reoprted by Lu and co-workers (Ref. 8b).
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14. One of the referees has suggested to present a brief discussion on character-
ization of structure of one of the nitroneespiro-oxindole derivatives using
spectral data. This is a very nice suggestion and we thank the referee for the
same. Accordingly we present a brief discussion on the characterization of 4a
using spectral data.
15. Detailed X-ray crystallographic data is available from the CCDC, 12 Union
Road, Cambridge CB2 1EZ, UK for compounds 4a (CCDC # 923595) and 4j
(CCDC # 923596).
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