A short and efficient synthesis of 3-spiro-α-methylene-γ- butyrolactone oxindolones from isomerised bromo derivatives of Morita-Baylis-Hillman adducts

Article abstract of DOI:10.1055/s-0028-1083549

A short and efficient synthesis of α-methylene-γ-butyrolactone- 3-spirooxindolones by the reaction of isomerised bromo derivatives of Morita-Baylis-Hillman adducts of isatin and formaldehyde followed by acid-catalysed lactonisation has been achieved. The oxindolidino allyl bromide has been used for the first time for the allylation of aldehydes to afford a 2-oxindolidino homoallylic alcohol which on acid-catalysed lactonisation delivered the title compounds in excellent yield. Synthetic transformation of the spirolactone oxindole is demonstrated with the preparation of an oxirane derivative and a second Morita-Baylis-Hillman adduct. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0028-1083549

LETTER
2763
A Short and Efficient Synthesis of 3-Spiro-a-methylene-g-butyrolactone
Oxindolones from Isomerised Bromo Derivatives of Morita–Baylis–Hillman
Adducts
Synthesis of
3
o
a
-met
n
hylene-
g
-bu
n
tyrolactone
O
u
xindolones samy Shanmugam,* Baby Viswambharan
Chemical Sciences and Technology Division, National Institute for Interdisciplinary Science and Technology (NIIST),
Thiruvananthapuram 695 019, Kerala, India
Fax +91(471)2491712; E-mail: shanmu196@rediffmail.com
Received 2 June 2008
mildness.21 Allylindium reagents generated in situ are at-
tractive candidates as nucleophilic partners in carbonyl al-
lylation to produce homoallylic alcohols due to their
functional group tolerance and low toxicity.22
Abstract: A short and efficient synthesis of a-methylene-g-butyro-
lactone-3-spirooxindolones by the reaction of isomerised bromo de-
rivatives of Morita–Baylis–Hillman adducts of isatin and
formaldehyde followed by acid-catalysed lactonisation has been
achieved. The oxindolidino allyl bromide has been used for the first
time for the allylation of aldehydes to afford a 2-oxindolidino ho-
moallylic alcohol which on acid-catalysed lactonisation delivered
the title compounds in excellent yield. Synthetic transformation of
the spirolactone oxindole is demonstrated with the preparation of an
oxirane derivative and a second Morita–Baylis–Hillman adduct.
O
OH
HO
OMe
H
H
N
MeO
O
NH
H
H
O
Key words: isatin, allylindium, Morita–Baylis–Hillman adduct,
lactonisation, spirolactone oxindoles
N
H
O
N
MeO
Me
chitosenine
alstonisine
Oxindoles derivatised at C3 as spirocarbo- and heterocy-
clics, spirolactones, and spirocyclic ethers are elegant tar-
gets in organic synthesis due to their significant biological
activities.1 These spirooxindole derivatives have served as
potential synthons for the synthesis of alkaloids, drug in-
termediates and pharmaceuticals (Figure 1).2 Hence, a
number of synthetic routes has been developed for the
preparation of these structural frameworks.3–7 Medium-
size lactones and macrolides with a-methylene-g-butyro-
lactone backbone are known for the treatment of antitu-
mour, phytotoxic and antibacterial activities.8 Bioactive
natural products such as napalilactone and pathylactone A
isolated from the soft coral Paralemnalia thyrsoides are
reported to be Ca2+ antagonists and are the first g-spirolac-
tone norsesquiterpenoids from a marine organism
(Figure 1).9 Consequently, there has been considerable in-
terest in developing efficient methods for the synthesis of
spirolactones.10–17
HO
O
O
O
O
R
OH
O
O
R = OH, pathylactone A
R = Cl, napalilactone
lambertellol A and B
Figure 1 Natural products with 3-spirooxindoles and spirolactones
as core structures
As part of our research on MBH chemistry,23–25 particular-
ly for the construction of novel spirooxindoles,26–30 we en-
visaged the synthesis of 3-spirolactone-2-oxindoles from
the isomerised bromo derivatives of MBH adducts of isatin
using indium metal and aqueous formaldehyde according
to the retrosynthetic analysis outlined in Scheme 1. The
synthetic flexibility of isatin and its derivatives has led to
the extensive use of this compound in synthetic organic
chemistry.31 Herein we report the synthesis of the title
compounds via a reaction of bromo isomerised MBH ad-
ducts of isatin as allylindium reagents with formaldehyde
followed by acid-catalysed lactonisation.
Morita–Baylis–Hillman (MBH) adducts and their deriva-
tives such as halides, acetates, and ethers play an impor-
tant role as synthons for the synthesis of a wide spectrum
of natural products.18 Metal-mediated reactions are well
known in the myriad of C–C bond-forming reactions. In-
dium metal has played a significant role in many reactions
such as Barbier-type allylation to amines19 and aldehydes,
elimination, coupling, reduction.20 The use of indium met-
al in organic synthesis has attracted the attention of organ-
ic chemists due to its water tolerance, low basicity and
This study was initiated with isomerisation of the MBH
adducts of N-methylisatin 1 as shown in Scheme 2. Thus,
adduct 1 in refluxing benzene with excess of aqueous HBr
afforded the E- and Z-isomer 2 and 3 in moderate yield.
The reaction in toluene did not improve the yield of the
products. However, reactions in chloroform and carbon
tetrachloride gave slightly better yields. Finally, opti-
SYNLETT 2008, No. 18, pp 2763–2768
1
4
.1
1
.2
0
0
8
Advanced online publication: 16.10.2008
DOI: 10.1055/s-0028-1083549; Art ID: D19607ST
© Georg Thieme Verlag Stuttgart · New York

2764
P. Shanmugam, B. Viswambharan
LETTER
O
CO2Me
R1
R1
R1
O
CO2Me
OH
acid-catalysed
lactonisation
aq HCHO
In2Br3
3
O
O
N
R2
O
N
R2
N
R2
A
B
C
In0
R1
CO2Me
Br
R1
HO
CO2Me
isomerisation
HBr
O
N
R2
O
N
R2
E
D
Scheme 1 Retrosynthetic analysis
Table 1 Isomerisation of MBH Adduct with Aqueous HBr under
Various Conditions
mised reaction condition was found as follows. A slurry of
1 made with silica gel and aqueous HBr was irradiated in
a microwave oven (SAMSUNG, model: CE 118KF) for
five minute to give a mixture of E- and Z-isomer 2 and 3
in 56% combined yield and these isomers were separated
by column chromatography. The results are presented in
Table 1.
Entry Conditionsa
Yield (%)
2(E) 3(Z)
1
2
3
4
5
6
benzene, 80 °C
17
19
20
37
38
19
17
17
6
toluene, 90 °C
The allylic bromides 2 and 3 on reaction with indium met-
al were found to be suitable nucleophilic partners for the
allylation of carbonyl compounds to produce homoallylic
derivatives. But the reaction of E-isomer 2 and indium
metal in DMF with paraformaldehyde for three hours fol-
lowed by acidification (dilute HCl) yielded a mixture of E
and Z trisubstituted alkenes 4 and 5. However, when 40%
aqueous formaldehyde was used as carbonyl partner, the
desired homoallylic alcohol 6 was obtained in 30% yield
and a mixture of 4 and 5. To improve the yield of 6, an ex-
tended reaction time (6 h) was used and saturated ammo-
nium chloride was used for quenching the reaction to
afford homoallylic alcohol derivative 6 in 78% yield
(Scheme 3). The structure of compound 6 was determined
toluene, montmorillonite K10, 90 °C
CCl4, H2SO4 (cat.), 90 °C
CHCl3, H2SO4 (cat.), 60 °C
10
19
mw,b 70% PL,c silica gel (60–120 mesh), 5 min, 37
40 °C
a An excess of aq HBr was used.
b SAMSUNG, model: CE 118KF.
c PL = power level.
methyl protons of oxindole nitrogen and the ester group.
Two mutually coupled doublets at d = 3.78–3.81 and at
d = 4.13–4.17 with a coupling constant J = 11.4 Hz and a
broad singlet at d = 1.70 were attributed to the methylene
1
from spectroscopic data. Thus, the H NMR spectrum
showed two singlets at d = 3.32 and d = 3.38 due to the
Br
MeO2C
Br
HO
CO2Me
aq HBr/neat
CO2Me
+
SiO2, 5 min, MW,
O
N
O
O
70% power level
N
N
Me
Me
Me
1
2 (E)
3 (Z)
Scheme 2 Isomerisation of the MBH adduct of N-methylisatin with HBr
Br
Z
Z
Z
Z
+
In0, r.t., CH2O
OH
+
DMF, 3–6 h
O
O
O
N
N
N
O
N
Z = CO2Me
Me
Me
Me
Me
2
4
5
6
Scheme 3 Optimisation of the homoallylation reaction
Synlett 2008, No. 18, 2763–2768 © Thieme Stuttgart · New York

LETTER
Synthesis of 3-Spiro-a-methylene-g-buyrolactone Oxindolones
2765
O
CO2Me
OH
Br
N
CO2Me
Br
CO2Me
+
O
In0, r.t., CH2O
DMF, 6 h
PTSA
benzene
O
O
N
O
O
N
N
Me
Me
Me
Me
2
3
6
7
Scheme 4 Indium-mediated homoallylation and lactonisation
Table 2 Synthesis of a-Methylene-g-butyrolactone-3-spirooxin-
doles 7 and 16–24a,b
and hydroxyl protons. The FAB mass spectrum showed a
molecular ion peak at m/z = 262.38 [M+], which further
supported the assigned structure of compound 6. For all
the allylation reactions, DMF was found to be the best sol-
vent in terms of yields after comparing the reaction with
solvents such as THF, MeCN and DMF. Acetonitrile was
found to be as good as DMF but the reaction needed long-
er time (12 h) for completion than in DMF (6 h). It is note-
worthy that the indium-mediated oxindolidino allyl
bromide has been used for the allylation of aldehyde for
the first time to prepare highly functionalised 2-oxindo-
lidino homoallylic alcohols.
Entry Substratec
1
Product
Yield (%)
78
Br
MeO2C
O
O
O
O
N
Me
N
3
Me
7
2
3
4
5
6
75
80
85
69
75
MeO2C
O
Br
F
The homoallylation reaction of the indium reagent de-
rived from isomerised bromo derivatives of the MBH ad-
ducts of isatin with various aldehydes such as
acetaldehyde, benzaldehyde and crotonaldehyde, under
optimised conditions afforded only the reduced products
4 and 5. The failure of the reaction to form 6 may be at-
tributed to the steric effects of the trisubstituted anionic
g-carbon at the oxindole moiety.
O
O
F
O
N
N
Me
Me
8
16
MeO2C
O
Br
Br
O
O
Br
Subsequently, the homoallylic alcohol derivative 6 was
subjected to lactonisation in refluxing benzene with a cat-
alytic amount of p-toluenesulfonic acid (PTSA) for 30
minutes, which afforded a-methylene-g-butyrolactone-3-
spirooxindole 7 in 78% yield (Scheme 4). Similarly, the
Z-isomer 3 was subjected to homoallylation followed by
lactonisation to afford the spirolactone 7 as a single prod-
uct. The structure of lactone 7 was assigned based on
O
N
N
Me
Me
9
17
MeO2C
O
Br
O
O
1
N
NMR studies. The H NMR spectrum showed two sin-
O
N
Me
glets at d = 5.35 and d = 6.31 corresponding to the exocy-
clic methylene protons and two mutually coupled
doublets at d = 4.41–4.44 and d = 4.68–4.71 with a cou-
pling constant J = 9.3 Hz amenable to the methylene pro-
tons of the spirolactone. In the 13C NMR spectrum, signals
at d = 168.4 and d = 175.5 showed the presence of the
amide carbonyl of the oxindole and the lactone carbonyl
group. Furthermore, the compound showed a molecular
ion peak at m/z = 230.32 [M + 1] in the FAB mass spec-
trum. It should be noted that both the Z- and the E-isomer
2 and 3 afforded lactone 7 under optimised lactonisation
condition. This may be due to the formation of geometri-
cally unstable allylindium reagent intermediate.32
Me
10
18
MeO2C
O
Br
OHC
O
O
OHC
O
N
N
Me
Me
11
19
MeO2C
O
Br
O
O
O
N
N
Ph
Ph
12
20
Synlett 2008, No. 18, 2763–2768 © Thieme Stuttgart · New York

2766
P. Shanmugam, B. Viswambharan
LETTER
Table 2 Synthesis of a-Methylene-g-butyrolactone-3-spirooxin-
doles 7 and 16–24a,b (continued)
characterised thoroughly by spectroscopic methods (IR,
1H, 13C NMR and FAB mass spectra).
Entry Substratec
7
Product
Yield (%)
80
A plausible mechanism involving an organoindium inter-
mediate is depicted in Scheme 5. Accordingly, the bromo
isomerised adduct on reaction with indium metal forms an
allylindium sesquihalide C. Nucleophilic allylation of in-
termediate C with formaldehyde will give homoallylic al-
cohol. Finally, the resulting allylic alcohol undergoes
lactonisation on acid exposure. The allylation reaction is
believed to proceed via a cyclic six-membered transition
state33 which is stabilised by a secondary interaction (a
five-membered ring chelation with the metal) between the
ester carbonyl group of the allyl bromide and the indium
metal.
MeO2C
O
Br
O
O
O
N
N
13
21
8
65
MeO2C
O
Br
O
O
O
CO2Me
To demonstrate the synthetic use of the spirolactones re-
ported herein, spirolactone 7 was transformed in to ep-
oxide 24 using m-chloroperoxybenzoic acid (MCPBA)
and potassium carbonate in dichloromethane at room tem-
perature. Interestingly, the spirolactone 19 having an alde-
hyde substituent at the aromatic ring successfully
underwent the MBH reaction with acrylonitrile/DABCO
to afford the highly functionalised spirolactone oxindole
derivative 25 (Scheme 6).
N
N
CO2Me
14
22
9
74
MeO2C
O
O
Br
O
N
O
N
O
O
O
15
O
O
23
MCPBA, CH2Cl2
a Reaction conditions: aq CH2O, DMF, r.t., 6 h.
b Reaction conditions: benzene, PTSA, 80 °C, 30 min.
c An E/Z mixture was used.
K2CO3, r.t., 30 min
55%
O
O
N
N
Me
Me
24
7
Since both the Z- and the E-isomer 2 and 3 afforded lac-
tone 7, we used a mixture of E- and Z-isomers of allyl bro-
mides of various isatin derivatives 8–15 for the rest of our
studies. Lactones 16–23 were prepared from several
isatins substituted on the aromatic ring (halides, aldehyde
and alkyl) and at nitrogen (methyl, propargyl, allyl, ben-
zyl, alkyl ester). The allyl bromide 10 with a methyl group
at the aromatic ring gave a better yield of the lactone. The
results are shown in Table 2. All new compounds were
O
O
OH
OHC
O
NC
acrylonitrile, neat
O
DABCO, 24 h
65%
O
N
O
N
Me
19
Me
25
Scheme 6 Synthetic transformations of the lactones 7 and 19
CO2Me
Br
CO2Me
Br
O
MeO
In2Br3
H
Br
3
O
In
CH2O
H
O
O
N
N
O
N
Me
Me
Me
3
allyl–indium sesquihalide C
H+
O
O
CO2Me
OH
PTSA
lactonisation
O
N
O
N
Me
Me
7
Scheme 5 A plausible mechanism for the reaction
Synlett 2008, No. 18, 2763–2768 © Thieme Stuttgart · New York

LETTER
Synthesis of 3-Spiro-a-methylene-g-buyrolactone Oxindolones
2767
(23) Shanmugam, P.; Vaithiyanathan, V.; Viswambharan, B.
Tetrahedron Lett. 2006, 47, 6851.
(24) Shanmugam, P.; Vaithiyanathan, V.; Viswambharan, B.;
Madhavan, S. Tetrahedron Lett. 2007, 48, 9190.
(25) Shanmugam, P.; Vaithiyanathan, V.; Viswambharan, B.
Aust. J. Chem. 2007, 60, 296.
(26) Shanmugam, P.; Vaithiyanathan, V.; Viswambharan, B.
Tetrahedron 2006, 62, 4342.
In conclusion, we have synthesised a number of pharma-
cologically important highly functionalised a-methylene-
g-butyrolactone-3-spirooxindoles using an organoindium
reagent generated in situ from the bromo isomerised MBH
adducts of isatin and indium.34 A plausible reaction mech-
anism has been proposed. The synthetic utility of the 3-spiro-
lactone oxindoles has been demonstrated with two
lactones. Further work on this reagent system for novel
methodologies is in progress.
(27) Shanmugam, P.; Viswambharan, B.; Madhavan, S. Org.
Lett. 2007, 9, 4095.
(28) Shanmugam, P.; Viswambharan, B.; Selvakumar, K.;
Madhavan, S. Tetrahedron Lett. 2008, 49, 2611.
(29) Shanmugam, P.; Vaithiyanathan, V. Tetrahedron 2008, 64,
Acknowledgment
3322.
P.S. thanks Prof. Dr. T. K. Chandrashekar, Director, NIIST, for pro-
viding infrastructure facilities. Financial support from the DST
(New Delhi) vide sanction No.SR/S1/OC-38/2005 is acknowled-
ged. B.V. thanks the CSIR (New Delhi) for the award of a Senior
Research Fellowship. Thanks are due to Mrs. Viji and Mrs. Soumini
Mathew for providing mass and NMR spectra.
(30) Shanmugam, P.; Vaithiyanathan, V.; Selvakumar, K.
Tetrahedron Lett. 2008, 49, 2119.
(31) Silva, J. F. M.; Garden, S. J.; Pinto, A. C. J. Braz. Chem. Soc.
2001, 12, 273.
(32) Isaac, M. B.; Chan, T.-H. Tetrahedron Lett. 1995, 36, 8957.
(33) Paquette, L. A.; Thomas, T. M. J. Am. Chem. Soc. 1996, 118,
1931.
(34) Typical Procedure: A mixture of isomerised MBH adduct
(100 mg), 40% aq formaldehyde (1.2 equiv) and indium
powder (1.6 equiv) in DMF (1 mL) was stirred at r.t. for 6 h.
After completion (TLC), the reaction was quenched with sat.
NH4Cl and stirred further for half an hour. The resulting
crude homoallylic alcohol was extracted with EtOAc, dried
and concentrated. The crude homoallylic alcohol compound
in benzene (1 mL) was subjected to lactonisation with PTSA
(0.2 equiv) under reflux for 30 min. After the completion of
the reaction (TLC), PTSA was removed by washing with
H2O. The organic layer was washed with brine, evaporated
in vacuo and then purified by silica gel column chromatog-
raphy to afford the products (65–85%).
References and Notes
(1) Marti, C.; Carreira, E. M. Eur. J. Org. Chem. 2003, 2209.
(2) Galliford, C. V.; Scheidt, K. V. Angew. Chem. Int. Ed. 2007,
46, 2.
(3) Yong, S. R.; Williams, M. C.; Pyne, S. G.; Ung, A. T.;
Skelton, B. W.; White, A. H.; Turner, P. Tetrahedron 2005,
61, 8120.
(4) Miyamoto, H.; Okawa, Y.; Nakazaki, A.; Kobayashi, S.
Angew. Chem. Int. Ed. 2006, 45, 2274.
(5) Ding, K.; Lu, Y.; Nikolovska-Coleska, Z.; Wang, G.; Qiu,
S.; Shangary, S.; Gao, W.; Qin, D.; Stuckey, J.; Krajewski,
K.; Roller, P. P.; Wang, S. J. Med. Chem. 2006, 49, 3432.
(6) Lo, M. M. C.; Neumann, C. S.; Nagayama, S.; Perlstein,
E. O.; Schreiber, S. L. J. Am. Chem. Soc. 2004, 126, 16077.
(7) Hilton, S. T.; Ho, T. C. T.; Pljevaljcic, G.; Jones, K. Org.
Lett. 2000, 2, 2639.
(8) Ogura, M.; Cordell, G. A.; Fransworth, N. R.
Phytochemistry 1978, 17, 957.
(9) Rodriguez, E.; Towers, G. H. N.; Mitchell, J. C.
Phytochemistry 1976, 15, 1573.
Spectral Data for Selected Compounds: Compound 4:
FTIR (CH2Cl2): 1613, 1715, 3004 cm–1. 1H NMR (300 MHz,
CDCl3/TMS): d = 2.65 (s, 3 H), 3.20 (s, 3 H), 3.90 (s, 3 H),
6.79–6.81 (d, 1 H, J = 7.8 Hz), 6.95–7.00 (d, 1 H, J = 7.8 Hz),
7.26–7.31 (d, 2 H, J = 7.8 Hz). MS (FAB): m/z calcd for
C13H13NO3: 231.24; found [M + 1]: 232.38. Compound 5:
FTIR (CH2Cl2): 1613, 1715, 2995 cm–1. 1H NMR (300 MHz,
CDCl3/TMS): d = 2.44 (s, 3 H), 3.23 (s, 3 H), 3.96 (s, 3 H),
6.81–6.84 (d, 1 H, J = 7.8 Hz), 7.03–7.08 (d, 1 H, J = 7.8 Hz),
7.29–7.34 (d, 1 H, J = 7.8 Hz), 7.51–7.54 (d, 1 H, J = 7.8 Hz).
MS (FAB): m/z calcd for C13H13NO3: 231.24; found [M + 1]:
232.35. Compound 6: FTIR (CH2Cl2): 1115, 1613, 1715,
2920, 3265 cm–1. 1H NMR (300 MHz, CDCl3/TMS): d =
1.70 (br s, 1 H), 3.30 (s, 3 H), 3.50 (s, 3 H), 3.78–3.81 (d,
1 H, J = 11.4 Hz), 4.13–4.17 (d, 1 H, J = 11.4 Hz), 6.26 (s,
1 H), 6.64 (s, 1 H), 6.88–6.91 (m, 1 H), 7.00–7.05 (m, 2 H),
7.20–7.30 (m, 1 H). MS (FAB): m/z calcd for C14H15NO4:
261.27; found [M + 1]: 262. 38. Compound 7: FTIR
(CH2Cl2): 1115, 1613, 1715, 1766, 2920 cm–1. 1H NMR (300
MHz, CDCl3/TMS): d =3.26 (s, 3 H), 4.41–4.44 (d, 1 H, J =
9.3 Hz), 4.68–4.71 (d, 1 H, J = 9.3 Hz), 5.35 (s, 1 H), 6.31 (s,
1 H), 6.91–6.94 (d, 1 H, J = 6.0 Hz), 7.11–7.21 (m, 2 H),
7.36–7.40 (d, 1 H, J = 6.0 Hz). 13C NMR (75 MHz, CDCl3/
TMS): d = 27.1, 54.5, 73.0, 108.2, 109.2, 109.5, 122.5,
123.2, 130.3, 137.5, 143.8, 168.47, 175.5. MS (FAB): m/z
calcd for C13H11NO3: 229.23; found [M + 1]: 230.3.
Compound 18: FTIR (CH2Cl2): 1116, 1618, 1720, 1770,
3020 cm–1. 1H NMR (300 MHz, CDCl3/TMS): d = 2.34 (s,
3 H), 3.20 (s, 3 H), 4.40–4.43 (d, 1 H, J = 9.0 Hz), 4.67–4.70
(d, 1 H, J = 9.0 Hz), 5.36 (s, 1 H), 6.36 (s, 1 H), 6.80–6.82
(d, 1 H, J = 6.0 Hz), 7.01 (s, 1 H), 7.18–7.16 (d, 1 H, J = 6.0
Hz). 13C NMR (75 MHz, CDCl3/TMS): d = 20.9, 26.7, 54.3,
72.6, 109.1, 123.7, 124.4, 129.8, 130.6, 133.5, 137.4, 141.0,
(10) Sohn, S. S.; Rosen, E. L.; Bode, J. W. J. Am. Chem. Soc.
2004, 126, 14370.
(11) Burstein, C.; Glorius, F. Angew. Chem. Int. Ed. 2004, 43,
6205.
(12) Sawant, M. S.; Nadkarni, P. J.; Desai, U. R.; Katoch, R.;
Korde, S. S.; Trivedhi, G. K. J. Chem. Soc., Perkin Trans. 1
1999, 2537.
(13) Collins, I. J. Chem. Soc., Perkin Trans. 1 1999, 1377.
(14) Nair, V.; Vellalath, S.; Poonoth, M.; Mohan, R.; Suresh, E.
Org. Lett. 2006, 8, 507.
(15) Paquette, L. A.; Bennett, G. D.; Isaac, M. B.; Chhatriwalla,
A. J. Org. Chem. 1998, 63, 1836.
(16) Paquette, L. A.; Mendez-Andino, J. Tetrahedron Lett. 1999,
40, 4301.
(17) Choudhury, P. K.; Foubelo, F.; Yus, M. Tetrahedron Lett.
1998, 39, 3581.
(18) Basavaiah, D.; Rao, A. J.; Satyanarayana, T. Chem. Rev.
2003, 103, 811.
(19) Tan, K. L.; Jacobson, E. N. Angew. Chem. Int. Ed. 2007, 46,
1315.
(20) Loh, T.-P.; Chua, G.-L. Chem. Commun. 2006, 2739.
(21) Nair, V.; Ros, S.; Jayan, C. N.; Pillai, B. S. Tetrahedron
2004, 60, 1959.
(22) Ranu, B. C. Eur. J. Org. Chem. 2000, 2347.
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2768
P. Shanmugam, B. Viswambharan
LETTER
168.32, 175.2. MS (FAB): m/z calcd for C14H13NO3: 243.25;
found [M + 1]: 244.3. Compound 19: FTIR (CH2Cl2): 1114,
1347, 1610, 1688, 1731, 1770, 2925 cm–1. 1H NMR (300
MHz, CDCl3/TMS): d = 3.32 (s, 3 H), 4.45–4.48 (d, 1 H, J =
9.0 Hz), 4.69–4.72 (d, 1 H, J = 9.0 Hz), 5.36 (s, 1 H), 6.41 (s,
1 H), 7.07–7.09 (d, 1 H, J = 6.0 Hz), 7.75 (s, 1 H), 7.92–7.94
(d, 1 H, J = 6.0 Hz), 9.91 (s, 1 H). 13C NMR (75 MHz,
CDCl3/TMS): d = 27.1, 53.9, 72.1, 105.4, 123.6, 125.0,
130.9, 132.74, 133.7, 136.6, 148.9, 167.6, 175.4, 190.1. MS
(FAB): m/z calcd for C14H11NO4: 257.24; found [M + 1]:
258.6. Compound 24: FTIR (CH2Cl2): 1613, 1715, 1750,
3004 cm–1. 1H NMR (300 MHz, CDCl3/TMS): d = 3.20 (s,
3 H), 3.37–3.41 (d, 1 H, J = 12.0 Hz), 3.81–3.85 (d, 1 H, J =
12.0 Hz), 4.25–4.28 (d, 1 H, J = 9.0 Hz), 4.78–4.82 (d, 1 H,
J = 9.0 Hz), 6.99–7.02 (d, 1 H, J = 9.0 Hz), 7.14–7.26 (m,
2 H), 7.42–7.47 (t, 1 H, J = 9.0 Hz). MS (FAB): m/z calcd for
C13H11NO4: 245.24; found [M + 1]: 246.38. Compound 25:
FTIR (CH2Cl2): 1613, 1715, 1750, 3004, 3282 cm–1. 1H
NMR (300 MHz, CDCl3/TMS): d = 1.68 (s, 1 H), 3.32 (s,
3 H), 4.45–4.48 (d, 1 H, J = 9.0 Hz), 4.69–4.72 (d, 1 H, J =
9.0 Hz), 5.36 (s, 1 H), 5.58 (s, 1 H), 5.63 (s, 1 H), 6.41 (s,
1 H), 7.06–7.09 (d, 1 H, J = 6.0 Hz), 7.75 (s, 1 H), 7.91–7.96
(d, 1 H, J = 6.0 Hz). MS (FAB): m/z calcd for C17H14N2O4:
310.30; found [M + 1]: 311.41.
Synlett 2008, No. 18, 2763–2768 © Thieme Stuttgart · New York

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