Diacetoxyiodobenzene-mediated oxidative addition of 1,3-dicarbonyl compounds to olefins: An efficient one-pot synthesis of 2,3-dihydrofuran derivatives

Article abstract of DOI:10.1016/S0040-4039(03)01644-7

A variety of olefins react with -dicarbonyl compounds at 0°C in the presence of diacetoxyiodobenzene to afford highly substituted 2,3-dihydrofuran derivatives in good to excellent yields.

Full text of DOI:10.1016/S0040-4039(03)01644-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 6729–6731
Diacetoxyiodobenzene-mediated oxidative addition of
1,3-dicarbonyl compounds to olefins: an efficient one-pot
synthesis of 2,3-dihydrofuran derivatives
N. N. Karade,a,* S. G. Shirodkar,b M. N. Patil,a R. A. Potrekarb and H. N. Karadeb
aSchool of Chemical Sciences, S.R.T.M. University, Nanded 431606, India
bNetaji Subhash Chandra Bose College, Nanded 431606, India
Received 14 May 2003; revised 9 June 2003; accepted 27 June 2003
Abstract—A variety of olefins react with -dicarbonyl compounds at 0°C in the presence of diacetoxyiodobenzene to afford highly
substituted 2,3-dihydrofuran derivatives in good to excellent yields.
© 2003 Published by Elsevier Ltd.
The dihydrofuran ring system is found prevalently at
the central position of diverse classes of naturally
occurring and biologically active heterocycles.1 A num-
ber of syntheses of dihydrofurans are available which
offer a variety of intermediates and reaction condi-
tions.2 The majority of synthetic approaches have been
accomplished via ionic3 or radical4 pathways through
oxidative addition of 1,3-dicarbonyl compounds to
appropriate olefins. Although all of these methodolo-
gies afford the dihydrofuran moiety in a reasonable
yield, simple and efficient synthetic approaches still
remain scarce.5
Mechanistically, the formation of dihydrofuran deriva-
tives may proceed through the initial reaction of the
fairly electrophilic DIB with the nucleophilic enol form
of the 1,3-dicarbonyl compound to give the intermedi-
ate 2. The tendency of intermediate 2 to expel iodoben-
zene converts the initial electron rich active methylene
carbon into an electron deficient centre.6a Car-
bonꢀcarbon bond formation is then established by trap-
ping of the alkene to form
a relatively stable
carbocation 3 which is attacked by the oxygen lone pair
to form a cyclic product 4. Finally, the acetate anion
abstracts an acidic hydrogen from 4 to give the 2,3-
dihydrofuran derivative 1c (Scheme 2).
Recently there has been considerable growth in the
application of hypervalent iodine reagents for carrying
out synthetic organic transformations.6 Diace-
toxyiodobenzene, (DIB) is a hypervalent iodine reagent
which is readily available, frequently used in several
oxidative transformations.7 In this communication, we
wish to report the use of DIB in the oxidative addition
of 1,3-dicarbonyl compounds to olefins to afford func-
tionalised dihydrofuran derivatives.
In order to assess the generality of the methodology,
DIB-mediated oxidative addition was carried out with
some representative alkenes and 1,3-dicarbonyl com-
pounds. The results are summarised in Table 1. Aro-
matic olefins such as styrene (entry 1), cinnamyl acetate
(entries 2, 9 and 12) and indene (entry 3) underwent
oxidative addition to form the corresponding dihydro-
furan derivatives in good to excellent yields. Simple
alkenes such as allyl chloride (entry 5) and 1-methylcy-
clohexene (entries 6 and 10) were rather unreactive and
We initiated the study by investigating the reaction of
dimedone 1a with styrene 1b in the presence of DIB.
When the above reaction mixture in acetonitrile was
stirred at 0°C for 1.5 h, the 2,3-dihydrofuran derivative
1c was indeed formed in 71% yield (Scheme 1).8
* Corresponding author. Fax: 91(2462) 229245; e-mail: nnkarade@
rediffmail.com
Scheme 1.
0040-4039/$ - see front matter © 2003 Published by Elsevier Ltd.
doi:10.1016/S0040-4039(03)01644-7

6730
N. N. Karade et al. / Tetrahedron Letters 44 (2003) 6729–6731
Scheme 2.
Table 1. Oxidative addition of b-dicarbonyl compounds to olefins using iodobenzenediacetate in CH3CN at 0°C
a
Yields refer to isolated products.
b All the products gave satisfactory spectral data.3,4
c Relative stereochemistry of compounds 2c, 3c, 6c, 8c, 9c, 10c and 12c was not determined.

N. N. Karade et al. / Tetrahedron Letters 44 (2003) 6729–6731
6731
gave the corresponding products in inferior yields. The
References
reaction between electron deficient olefins such as ethyl
acrylate (entry 7), ethyl cinnamate (entry 8) and dimedone
was also studied. Since the success of dihydrofuran
formation involves trapping of the relatively ‘stable
carbocation’ intermediate, no product formation
occurred in the case of ethyl acrylate. However, ethyl
cinnamate underwent regioselective addition to dimedone
to form the dihydrofuran in 52% yield.
1. (a) Lee, J.; Li, J.-H.; Oya, S.; Snyder, J. K. J. Org.
Chem. 1992, 57, 5301; (b) Jacobi, P. A.; Selnick, H. G.
J. Org. Chem. 1990, 55, 202; (c) Lipshutz, B. H. Chem.
Rev. 1986, 86, 795.
2. (a) Fukude, Y.; Shiragami, H.; Utimoto, K.; Nozaki, H.
J. Org. Chem. 1991, 56, 5816; (b) Shishido, K.; Umi-
moto, K.; Shibuya, M. Heterocycles 1990, 31, 597; (c)
Tanis, S. P.; McMills, M. C.; Scahill, T. A.; Klooster-
man, D. A. Tetrahedron Lett. 1990, 31, 1977; (d) Dan-
heiser, R. L.; Stormer, E. J.; Koyama, H.; Yamashita,
D. S.; Klade, C. A. J. Am. Chem. Soc. 1989, 111, 4407.
3. (a) Lee, Y. R.; Suk, J. Y. Tetrahedron 2002, 58, 2359;
(b) Aso, N.; Ojida, A.; Yang, G.; Cha, O. J.; Osawa, E.;
Kamematsu, K. J. Org. Chem. 1993, 58, 3960.
4. (a) Nair, V.; Mathew, J.; Radhakrishnan, K. V. J.
Chem. Soc., Perkin Trans. 1 1996, 1487; (b) Iqbal, J.;
Bhatia, B.; Nayyar, N. K. Tetrahedron 1991, 47, 6457.
5. (a) Harwood, L. M.; Jones, G.; Pickard, J.; Thomas, R.
M.; Watkin, D. J. Chem. Soc., Chem. Commun. 1990,
605; (b) Jung, M. E.; Street, L. J. J. Am. Chem. Soc.
1994, 106, 8327; (c) Sternbach, D. D.; Rossana, D. M.
Tetrahedron Lett. 1982, 23, 303.
6. (a) Varvoglis, A.; Spyroudis, S. Synlett 1997, 221; (b)
Stang, P. J.; Zhdankin, V. V. Chem. Rev. 1996, 96, 1123;
(c) Stang, P. J. Angew Chem., Int. Ed. Engl. 1992, 31,
274.
7. (a) Kotali, A.; Harris, P. A. J. Heterocycl. Chem. 1996,
33, 605; (b) Kotali, A. Tetrahedron Lett. 1994, 36, 6753;
(c) Varella, E. A.; Varvoglis, A. Synth. Commun. 1991,
21, 531.
In a separate report, the synthesis of dihydrofuran from
iodonium ylides of b-diketones and alkenes in the pres-
ence of Cu(acac)2 yields complex mixtures of inseparable
products under thermal conditions.9 The yields of dihy-
drofurans are very low in the case of the single electron
oxidant [CAN and Mn(OAc)3]-mediated oxidative addi-
tion of b-dicarbonyl compounds to styrene derived
olefins.4 This is due to the susceptibility of styrenic olefins
to polymerisation and therefore, an excess of the olefin
is needed. Thus it appears that the present methodology
is quite advantageous in comparison to single electron
oxidants and iodonium ylide procedures.
In conclusion, we have developed an efficient DIB-medi-
ated oxidative addition of b-dicarbonyl compounds to
olefins resulting in a one-pot synthesis of highly substi-
tuted dihydrofuran derivatives. We hope that the present
methodology will be a useful synthetic entry in the use
of DIB for carbonꢀcarbon bond forming reactions.
General procedure: To a magnetically stirred solution of
dimedone (3 mmol) and styrene (3 mmol) in acetonitrile
(15 ml) was introduced diacetoxyiodobenzene (3 mmol).
The reaction mixture was stirred at 0°C for 1.5 h and the
progress of the reaction was monitored by TLC. After
completion of reaction, the mixture was washed with
water (10 ml), extracted with CH2Cl2 and dried over
anhydrous sodium sulphate. Removal of the solvent and
subsequent silica gel chromatography afforded the pure
product 1c in 71% yield.
8. Spectral data of 6,6-dimethyl-2-phenyl-2,3,4,5,6,7-hexahy-
dro-1-benzofuran-4-one 1c: 1H NMR (300 MHz;
CDCl3): lH 1.08 (6H, s), 2.05 (2H, s), 2.18 (2H, s), 3.61
(2H, d, J=5.9 Hz), 5.29 (1H, t, J=5.9 Hz), 7.12–7.38
(5H, m). 13C NMR: lc 196.3, 160.4, 135.3, 132.0, 129.7,
128.2, 127.0, 75.7, 39.4, 31.8, 29.4, 21.7. IR (cm−1, KBr):
3012, 2957, 2843, 1712, 1604, 1468, 1254, 1095, 793.
Anal calcd for C16H18O2: C, 79.33; H, 7.43. Found: C,
79.36; H, 7.41.
9. (a) Asouti, A.; Hadjiarapoglou, L. P. Tetrahedron Lett.
1998, 39, 9073 and references cited therein; (b) Alexiou,
I.; Gogonas, E. P.; Hadjiarapoglou, L. P. Synlett 1999,
12, 1925.
Acknowledgements
We are thankful to UGC, New Delhi for support of this
work.