Dimethylsulfoxide-iodine catalysed deprotection of 2′- allyloxychalcones: Synthesis of flavones

Article abstract of DOI:10.1016/j.tetlet.2004.12.041

A new one-pot method is described for the removal of O-allyl protecting groups under oxidative conditions at neutral pH. 2′-Allyloxychalcones undergo deprotection and subsequent oxidative cyclisation to give flavones. The general applicability of the reagent has been studied.

Full text of DOI:10.1016/j.tetlet.2004.12.041

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 1573–1574
Dimethylsulfoxide–iodine catalysed deprotection of
20-allyloxychalcones: synthesis of flavones
Pradeep D. Lokhande,* Sachin S. Sakate, Kiran N. Taksande and Beena Navghare
The Center For Advanced Studies, Department of Organic Chemistry, University of Pune, Pune 411007, India
Received 2 October 2004; revised 20 November 2004; accepted 8 December 2004
Available online 22 January 2005
Abstract—A new one-pot method is described for the removal of O-allyl protecting groups under oxidative conditions at neutral
pH. 20-Allyloxychalcones undergo deprotection and subsequent oxidative cyclisation to give flavones. The general applicability
of the reagent has been studied.
Ó 2005 Published by Elsevier Ltd.
The DMSO–I2 reagent has been used in the oxidative
cyclisation of 20-hydroxychalcones to flavones1 and the
oxidation of pyrazolines to pyrazoles,2 isoxazolines to
isoxazoles3 and flavanones to flavones.4 A comparison
of the reported methods showed the DMSO–I2 reagent
to be particularly useful in the synthesis of flavones from
20-hydroxychalcones. Under these conditions the reac-
tion temperature is fairly high and the iodine does not
cause any side reactions. Naturally occurring flavonoids
contain free phenolic–OH groups or methoxy groups as
substituents. Therefore, the protection of phenolic
groups is an important step in the synthesis of chal-
cones,5a flavanones,5b and flavones.6 The allyl-protect-
ing group has been shown to be useful for the
protection of phenolic functions7 due to its ready avail-
ability and stability under acidic and basic conditions.8
Several methods have been developed for the removal
of allyl groups under different conditions; these include
DDQ,9 NaBH4/I2,10 NBS/hm,11 (TBA)2S2O8,12 OsO4,
14
NMO/NaIO4,13 Pd(PPh3)4/NaBH4
and Me3SiCl/
NaI.15 These systems, however, have several drawbacks
such as the instability of the reagent, nasty smells, long
reaction times, high cost of the reagent16 and competi-
tive side reactions.17 The ready availability as well as
the ease of handling of the DMSO–I2 reagent provides
a particular advantage of the present system.
We herein report an efficient procedure for the cleavage of
20-allyloxychalcones containing benzyl and methoxy pro-
tection using the DMSO–I2 reagent (Scheme 1). Cleavage
reactions using a stoichiometric amount of I2 gave excel-
lent yields (85–98%) of flavones within 30 min. 20-
Hydroxychalcones were not isolated from the reaction.
The results obtained are summarised in Table 1.
R2
R3
R4
R2
R1
O
I2
- DMSO
R3
R4
O
R1
°
130 C, 30 min.
O
O
1
2
Scheme 1.
Keywords: Allylchalcones; Deprotection; Flavones.
*
Corresponding author. Tel.: +91 020 25696061; fax: +91 020 25691728; e-mail: pdlokhande@rediffmail.com
0040-4039/$ - see front matter Ó 2005 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2004.12.041

1574
P. D. Lokhande et al. / Tetrahedron Letters 46 (2005) 1573–1574
Table 1.
Entry
R1
R2
R3
R4
Yield of 2 (%)
a
b
c
d
e
f
H
H
H
CH3
CH3
CH3
Cl
86
89
92
85
97
92
90
87
93
88
85
H
OCH3
OCH3
OCH3
OCH3
H
H
OCH3
H
H
H
OCH3
H
H
Cl
Cl
H
g
h
i
NO2
H
H
H
Cl
H
OCH3
OCH3
H
OCH2Ph
OCH2Ph
OCH2Ph
OCH2Ph
OCH3
H
NO2
H
j
H
k
H
H
3. Gaikwad, D. D. M. Phil. Thesis, 2003, University of Pune,
Pune.
The typical experimental procedure is as follows:
4. Wasim, F.; Jawaid, I.; Manachanda, W.; Shaidawora, R.
W. J. Chem. Res. (S) 1984, 9, 298.
5. (a) Wall, M. E.; Woni, C. M.; Sparacino, C. M.; Kim, N.
C. Org. Biomol. Chem. 2003, 1, 168; (b) Kardar, M. N.;
Rasheed, M.; Ali, S. T. Helv. Chim. Acta 2003, 86,
2164.
6. Hostehmann, K.; Msonthi, J. D.; Antus, S.; Szikszai-kiss,
A.; Kurtan, T.; Terreaux, G.; Ferrari, J. Helv. Chim. Acta
2003, 86, 2768.
7. Bodo, B.; Caux, C.; Reddy, M. K. Chem. Pharm. Bull.
2003, 51, 854.
To a solution of compound 1a (248 mg, 1 mmol) in
DMSO (5 mL) was added I2 (254mg, 1 mmol) and the
reaction mixture was heated in an oil bath at 130 °C
for 30 min. After cooling, the reaction mixture was di-
luted with water and the iodine was removed by washing
with a saturated solution of sodium thiosulfate. The
product 2a was then extracted with ethyl acetate
and purified by column chromatography (hexane/ethyl
acetate, 9:1)
8. Green, T. W.; Wuts, P. G. Protective Groups In Organic
Synthesis, 3rd ed.; John Wiley: New York, 1999.
9. Yadav, J. S.; Chandrashekhar, S.; Sumita, G.; Kachake,
R. Tetrahedron Lett. 1996, 37, 6603.
10. Thomas, R. M.; Mohan, G. H.; Iyengar, D. S. Tetrahe-
dron Lett. 1996, 38, 4721.
11. Diaz, R. R.; Melagarejo, C. R.; Espinosa, M. T. P. L.;
Cubero, I. I. J. Org. Chem. 1994, 59, 7928.
12. Kim, Y. H.; Park, M. Y.; Yang, S. G. Synlett 2002, 3,
492.
The present work provides an efficient deallylation pro-
cedure, which uses a weak oxidising agent under neutral
conditions. The mild conditions, compatibility with
other functional groups and easy handling of the reagent
constitute advantages of the present procedure. It may
provide a new entry into the synthesis of naturally
occurring flavonoids.
References and notes
13. Bundle, D. R.; Kitov, P. I. Org. Lett. 2001, 3, 2835.
14. Zhu, J.; Bigot, A.; Bourdet, S.; Beugelmans, R. Tetrahe-
dron Lett. 1994, 35, 4349–4350.
15. Ahmed, K.; Laxman, E.; Venugopal Rao, N. Tetrahedron
Lett. 1999, 40, 371–372.
16. Kitamur, M.; Tanaka, S.; Yashimura, M. J. Org. Chem.
2002, 67, 4975.
17. Ozaki, S.; Hirofuji, H.; Akiyama, T. Tetrahedron Lett.
1991, 32, 1321–1324.
1. Ghiya, B. G.; Soni, P. A.; Doshi, A. G. Ind. J. Chem. (B)
1986, 25B, 759; Hoshino, Y.; Takeno, N. Cancer Res.
1999, 59, 578; Patonay, T.; Cavaleiro, J. A. S.; Levai, A.;
Silva, A. M. S. Heterocycl. Commun. 1997, 3, 223.
2. Waghmare, B. Y. M. Phil. Thesis, 1998, University of
Pune, Pune; Lokhande, P. D.; Waghmare, B. Y. Ind. J.
Chem. (B) January 2005.