Preparation of substituted allyl acetates and sulfones from Baylis-Hillman adducts in ionic liquid media

Article abstract of DOI:10.1016/S0040-4039(03)01073-6

Reactions of potassium acetate and the sodium salt of p-toluenesulfinic acid with acetates of Baylis-Hillman adducts produce substituted allyl acetates and allyl sulfones respectively. Ionic liquids are utilized in place of conventional solvents.

Full text of DOI:10.1016/S0040-4039(03)01073-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 4673–4675
Preparation of substituted allyl acetates and sulfones from
Baylis–Hillman adducts in ionic liquid media
George W. Kabalka,a,b,* Bollu Venkataiaha and Gang Donga
aDepartment of Chemistry, The University of Tennessee, 611 Buehler Hall, Knoxville, TN 37996-1600, USA
bDepartment of Radiology, The University of Tennessee Medical Center, 1924 Alcoa Highway, Knoxville, TN 37920-6999, USA
Received 14 March 2003; revised 22 April 2003; accepted 25 April 2003
Abstract—Reactions of potassium acetate and the sodium salt of p-toluenesulfinic acid with acetates of Baylis–Hillman adducts
produce substituted allyl acetates and allyl sulfones respectively. Ionic liquids are utilized in place of conventional solvents.
© 2003 Published by Elsevier Science Ltd.
There has been rapid growth in the use of room tem-
perature ionic liquids as reaction media for organic
transformations because they are air and moisture sta-
ble and can be used to replace volatile solvents.1 Ionic
liquids containing 1-alkyl-3-methylimidazolium cations
are electrochemically stable, have negligible vapor pres-
sure, and are chemically and thermally stable. They are
useful as media for reactions of polar substrates which
do not readily dissolve in conventional organic
solvents.1,2
We first examined the reaction of methyl 3-acetoxy-3-
phenyl-2-methylenepropanoate with potassium acetate
in various ionic liquids as well as conventional solvents
(Table 1). Interestingly, the reaction proceeded well in
ionic liquids, whereas little reaction occurred in conven-
tional solvents (Table 1). The best results were obtained
when
butylmethylimidazolium
tetrafluoroborate
(BmimBF4) was used as the reaction media.
In order to establish the generality of the reaction, we
utilized various Baylis–Hillman acetate adducts (1 in
The Baylis–Hillman reaction is an important car-
bonꢀcarbon bond forming route which has been used in
the synthesis of a variety of compounds.3 For example,
acetates of Baylis–Hillman adducts have been utilized
to prepare trisubstituted alkenes.3 As part of our stud-
ies of organic reactions in ionic liquid media,4 we
examined the use of organoboronates as nucleophiles in
reactions with acetates of Baylis–Hillman adducts.5
When potassium acetate was used as a base, we noted
a product which formed via SN2% substitution of the
original acetate.6 For example, methyl 3-acetoxy-3-
phenyl-2-methylenepropanoate was converted to
methyl (E)-2-(acetoxymethyl)-3-phenylprop-2-enoate in
high yields (Scheme 1). Previously the isomerization of
acetates of Baylis–Hillman adducts required catalysts
such as TMSOTf,7a DABCO7b or montmorillonite K10
clay.7c The present method utilizes simple protocols and
provides high yields in an environmentally benign
system.
Scheme 1.
Table 1. Reaction of KOAc with 3-acetoxy-3-phenyl-2-
methylenepropanoate in various solvents (Scheme 1)
Entry
Solvent
Isolated yield (%)
1
2
3
4
BmimBr
92
95
52
0
BmimBF4
BmimPF6
Methanol
Ethanol
5
0
6
THF
0
7
Dioxane
0
8
9
10
Acetonitrile
DMF
Recycled BmimBF4
8
43
94
* Corresponding author. Tel.: 865-974-3260; fax: 865-974-2997;
e-mail: kabalka@utk.edu
0040-4039/03/$ - see front matter © 2003 Published by Elsevier Science Ltd.
doi:10.1016/S0040-4039(03)01073-6

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G. W. Kabalka et al. / Tetrahedron Letters 44 (2003) 4673–4675
Table 2) that had been prepared according to literature
procedures.7 Similar reactions were observed for both
ester and nitrile derivatives but stereochemical directive
effects were reversed.3,7 Although no mechanistic studies
have been carried out, related stereochemical reversals
have been attributed to differences in the relative stabil-
ities of the transition states.3e E:Z ratios in all cases were
greater than 9:1 (Table 2). The stereochemistry of the
when R is alkyl (Table 2). However, this is not a
limitation when the reaction is carried out using the
sodium salt of p-toluenesulfinic acid (Table 3). The
product allylsulfones are important intermediates in
organic synthesis8 and are generally prepared by dis-
placement of halides by sodium arenesulfinates.9 The
structures of the allylsulfones were established by com-
paring the 1H NMR spectra values10 of olefin and
methylene protons with those of related compounds.7,9a
The products were also prepared from known allyl
acetates.11 For example reactions of methyl (E)-2-(acet-
oxymethyl)-3-phenylprop-2-enoate (2a) with p-toluene-
sulfinic acid sodium salt in the presence of Pd(PPh3)4
and triphenylphosphine gave (Z)-(2-methoxycarbonyl-
styryl)tolylsulfone (4a). The preparation of substituted
allylsulfones from Baylis–Hillman acetate adducts has
not been reported.
1
products was assigned on the basis of the H NMR
chemical shift values of the olefinic protons by compari-
son with the values reported in the literature.7
We applied the method to the preparation of allyl
sulfones by allowing Baylis–Hillman acetate adducts to
react with the sodium salt of p-toluenesulfinic acid. It is
interesting to note that the reaction of acetates of
Baylis–Hillman adducts with KOAc does not occur
a
Table 2. Reaction of acetates of Baylis–Hillman adducts (1) with KOAc in BmimBF4
R
Z
Product
Yield (%)b
E:Z ratioc
Phenyl
COOMe
COOMe
COOMe
COOMe
COOMe
CN
2a
2b
2c
2d
2e
3a
3b
3c
95
92
92
93
0
91
92
0
96.4
94:6
91:9
100
4-Chlorophenyl
3-Nitrophenyl
4-Nitrophenyl
Octyl
Phenyl
4-Chlorophenyl
Octyl
95:5
96:4
CN
CN
a All reactions were carried out at 50°C for 2 h.
b Isolated yields.
c E/Z ratio determined by 1H NMR.
a
Table 3. Reaction of acetates of Baylis–Hillman adducts (1) with TolSO2Na in BmimBF4
R
Z
Productb
Yield (%)c
E/Z ratiod
Phenyl
COOMe
COOMe
COOMe
COOMe
COOMe
CN
4a
4b
4c
4d
4e
5a
5b
5c
97
96
96
95
90
94
95
91
3:97
5:95
8:92
10:90
6:94
92:8
94:6
95:5
4-Chlorophenyl
3-Nitrophenyl
4-Nitrophenyl
Octyle
Phenyl
4-Chlorophenyl
CN
CN
Octyle
a Reactions were carried out at 40°C for 90 min.
b All structures were characterized by NMR spectroscopy and elemental analyses.
c Isolated yields.
d E/Z ratio determined by 1H NMR.
e Reaction time was 3 h.

G. W. Kabalka et al. / Tetrahedron Letters 44 (2003) 4673–4675
4675
Reaction yields are very high. Product isolation can be
achieved by distillation but, for convenience, we
extracted the product using diethyl ether. Pure products
were obtained and the ionic liquid can be reused with-
out loss in reaction yield (Table 1, entry 10). No
catalyst is required and the procedure is very straight-
forward. In conclusion, we have developed an environ-
mentally benign procedure for the transformation of
acetates of Baylis–Hillman adducts into trisubstituted
alkenes using ionic liquids as reaction media.
5. The results of these studies will be published in due
course.
6. When potassium thioacetate was used, (Z)-(2-
methoxycorbonyl)cinnamyl thioacetate was obtained in
92% yield.
7. (a) Basavaiah, D.; Muthukumaran, K.; Sreenivasulu, B.
Synthesis 2000, 545; (b) Manson, P. H.; Esmile, N. D.
Tetrahedron 1994, 41, 12001; (c) Shanmugam, P.; Singh,
P. R. Synlett 2001, 1314.
8. (a) Patai, S.; Rapport, Z.; Stirling, C. The Chemistry of
Sulfones and Sulfoxides; Wiley: New York, 1988; (b)
Wrobel, Z. Tetrahedron 1998, 54, 2607; (c) Quiclet-Sire,
B.; Seguin, S.; Zard, S. Z. Angew. Chem., Int. Ed. 1998,
37, 2864; (d) Kim, S.; Lim, C. J. Angew. Chem., Int. Ed.
2002, 41, 3265.
General experimental procedure:
A mixture of the acetate of the Baylis–Hillman adduct
(1 mmol) and BmimBF4 (500 mg) was placed in a 10 ml
round-bottomed flask followed by addition of potas-
sium acetate or sodium p-toluenesulfinate (1.5 mmol).
The mixture was stirred at the appropriate temperature
until the reaction was complete (TLC), the product
extracted into diethyl ether (3×5 ml), and purified by
column chromatography (hexane and ethyl acetate).
The ionic liquid was dried under vacuum and reused.
9. (a) Colombani, D.; Navarro, C.; Degueil-Castaing, M.;
Maillard, B. Synth. Commun. 1991, 21, 1482; (b) Cheng,
W.-C.; Halm, C.; Evarts, J. B.; Olmstead, M. M.; Kurth,
M. J. J. Org. Chem. 1999, 64, 8557.
10. In the crude 1H NMR spectrum of 4, the b-vinylic
proton, cis to the ester group (Z-isomer) appears at l
7.09 and a minor peak for the E-isomer appears at l 6.08
when R is alkyl. Similarly, the same proton appears at l
7.90 and l 6.85 for Z- and E-isomers, respectively, when
R is aryl. Purification of the major isomer is readily
achieved by column chromatography. Spectral data for
Acknowledgements
We wish to thank the US Department of Energy and
the Robert H. Cole Foundation for financial support.
1
4a: H NMR (250 MHz, CDCl3); l 2.36 (3H, s, Ar-CH3),
3.60 (3H, s, -COOCH3), 4.47 (2H, s, -CH2-SO2-Ar), 7.25
(2H d, J=8.0 Hz, Ar-H) 7.30–7.45 (5H, m, Ar-H), 7.68
(2H, d, J=8.0 Hz, Ar-H), 7.90 (1H, s, vinylic H; (Z)-iso-
mer); 13C NMR: l 21.3, 52.1, 54.8, 120.8, 126.9, 127.5,
128.4, 128.7, 129.4, 133.3, 136.9, 144.5, 145.7 and 166.6.
In the crude 1H NMR spectrum of 5, the a-vinylic proton
trans to the nitrile group (E-isomer) appears at l 6.33
and a minor peak for Z-isomer appears at l 6.60 when R
is alkyl. Similarly, the same proton appears at l 7.08 and
l 7.48 for the E- and Z-isomers, respectively, when R is
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1
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