Synthesis of homoallyl ethers via allylation of acetals in ionic liquids catalyzed by trimethylsilyl trifluoromethanesulfonate

Article abstract of DOI:10.1021/ol0271739

(Matrix presented) The chemoselective allylation of acetals using allyltrimethylsilane in ionic liquids is catalyzed by TMS triflate (5.0-20.0 mol %). The reaction proceeds smoothly at room temperature to afford the corresponding homoallyl ether in good y

Full text of DOI:10.1021/ol0271739

ORGANIC
LETTERS
2003
Vol. 5, No. 1
55-57
Synthesis of Homoallyl Ethers via
Allylation of Acetals in Ionic Liquids
Catalyzed by Trimethylsilyl
Trifluoromethanesulfonate
Herbert M. Zerth, Nicholas M. Leonard,† and Ram S. Mohan*
Laboratory for EnVironment Friendly Organic Synthesis, Department of Chemistry,
Illinois Wesleyan UniVersity, Bloomington, Illinois 61701
rmohan@iwu.edu
Received October 25, 2002
ABSTRACT
The chemoselective allylation of acetals using allyltrimethylsilane in ionic liquids is catalyzed by TMS triflate (5.0−20.0 mol %). The reaction
proceeds smoothly at room temperature to afford the corresponding homoallyl ether in good yield. Since the ionic liquids are easily recovered
and recycled, they are a useful alternative to dichloromethane, which is the commonly used solvent for allylations.
Of all the organic reactions, carbon-carbon bond-forming
reactions rank among the most important. Of particular
interest are Lewis acid-catalyzed carbon-carbon bond-
forming reactions since there is a wide range of selectivity
and catalytic behavior among various Lewis acids. The
allylation of acetals using organosilicon reagents has attracted
much attention as a useful method to generate homoallyl
ethers. Several catalysts have been used to effect this
transformation. These include TiCl4,1 AlCl3,2 BF3‚Et2O,2 trityl
perchlorate,3 diphenylboryl triflate,3 montmorillonite,4 Pb/
Al,5 trimethylsilyl bis(fluorosulfonyl)imide,6 (CH3)4SiI,7
TMSOTf,8 TiCp2(CF3SO3)2,9 CF3COOH,10 BiBr3,11 trimeth-
ylsilyl bis(trifluoromethanesulfonyl)amide [TMSNTf2],12
Sc(OTf)3,13 indium metal,14 and Bi(OTf)3.15 While most of
these allylations require an activated alkene such as allyl-
trimethylsilane, other allyl group sources such as allyl
bromide,2 and lithium n-butyltriallylborate16 have also been
used. Most of these methods require the use of chlorinated
organic solvents such as CH2Cl2 and often inconveniently
low temperatures. With increasing environmental concerns,
it is imperative that new “environment friendly” solvents be
developed and used.17 Room temperature ionic liquids are
becoming increasingly popular as solvents in organic syn-
thesis for several reasons.18 They are practically nonvolatile
and hence do not the pose the risks associated with volatile
organic compounds. In addition, they are nonflammable and
† Current address: University of California, Irvine.
(1) Hosomi, A.; Masahiko, E.; Sakurai, H. Chem. Lett. 1976, 941.
(2) Hosomi, A.; Endo, M.; Sakurai, H. Chem. Lett. 1978, 499.
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Lett. 1985, 980.
(11) Komatsu, N.; Uda, M.; Suzuki, H.; Takahashi, T.; Domae, T.; Wada,
M. Tetrahedron Lett. 1997, 38, 7215.
(4) Kawai, M.; Onaka, M.; Izumi, Y. Chem. Lett. 1986, 381.
(5) Tanaka, H.; Yamashita, S.; Ikemoto, Y.; Torii, S. Tetrahedron Lett.
1988, 14, 1721.
(6) Trehan, A.; Vij, A.; Walia, M.; Kaur, G.; Verma, R. D.; Trehan, S.
Tetrahedron Lett. 1993, 34, 7335.
(7) Sakurai, H.; Sasaki, K.; Hosomi, A. Tetrahedron Lett. 1981, 22, 745.
(8) Tsunoda, T.; Suzuki, M.; Noyori, R. Tetrahedron Lett. 1980, 21, 71.
(9) Hollis, T. K.; Robinson, N. P.; Whelan, J.; Bosnich, B. Tetrahedron
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(13) Yadav, J. S.; Subba Reddy, V. B.; Srihari, P. Synlett 2001, 673.
(14) (a) Yadav, J. S.; Subba Reddy, B. V.; Reddy, G. S. K. K.
Tetrahedron Lett. 2000, 41, 2695. (b) Kwon, J. S.; Pae, A. N.; Choi, K.;
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43, 4597.
(16) Hunter, R.; Tomlinson, G. D. Tetrahedron Lett. 1989, 30, 2013.
(17) Garrett R. L.; DeVito, S. C. In Designing Safer Chemicals; American
Chemical Society Symposium Series 640; American Chemical Society:
Washington, DC, 1996; Chapter 1.
10.1021/ol0271739 CCC: $25.00 © 2003 American Chemical Society
Published on Web 12/10/2002

Scheme 1
Table 1. TMS Triflate Catalyzed Allylation of Acetals in
[bmim][PF6]a and [bmim][OTf]a
can be recycled easily without any significant loss in activity.
Often, unexpected or improved reactivity is seen in ionic
liquids. The allylation of carbonyl compounds in ionic liquids
to yield homoallyl alcohols has been reported.19 We now
report that the TMS triflate catalyzed chemoselective ally-
lation of acetals in ionic liquids, butylmethylimidazolium
hexafluorophosphate, [bmim][PF6], 1 and butylmethylimi-
dazolium triflate, [bmim][OTf], 2 affords the corresponding
homoallyl ethers in good yields (Scheme 1).20
The product is isolated by extraction with ether, and the
ionic liquid can be reused after drying at 70 °C under
vacuum. This procedure works well at room temperature and
avoids the use of chlorinated compounds, such as CH2Cl2,
that are typically used as solvents for allylation of acetals.
The results are summarized in Table 1. The reaction progress
was followed by TLC. Some of the acetals are not completely
soluble in the ionic liquid, and hence, it is important to stir
the reaction mixture well. In none of the cases was there
any evidence of the formation of the diallylated product. In
the case of cinnamaldehyde dimethyl acetal (entry 5), it was
especially important to ensure that the ionic liquid was dry.21
Otherwise, considerable amounts (20-50%) of cinnamal-
a Ionic liquids were purchased from Acros Chemical Co. b Literature
reference for the product. c Reaction progress was followed by TLC. d Refers
to yield of isolated, purified product. All products were at least 98% pure
1
by H and 13C NMR and GC analysis. e 5 mol % TMSOTf used.
dehyde formed during the course of the reaction. It has been
reported that with TiCl4 as the activator, the reaction of
cinnamaldehyde dimethyl acetal with allyltrimethylsilane
gives only the diallylated product.2 Even at low temperatures
(-78 °C) the monoallylated product was not formed. Similar
results were obtained when allylation of cinnamaldehyde
dimethylacetal was carried out using allyl bromide in the
presence of AlBr3.5 In contrast, we did not observe any
diallylated product using TMSOTf as the catalyst in [bmim]-
[PF6] or [bmim][OTf] and the monoallylated product was
obtained in good yield in both the ionic liquids. No
diallylation product is observed when the allylation is carried
out using TMSOTf in CH2Cl2 as the solvent.8 When the
allylation of cinnamaldehyde dimethyl acetal was attempted
neat, the results were not reproducible and in most trials, an
exothermic reaction occurred leading to the formation of
black tar. The chemoselective allylation of 2,2′-diethoxy-
acetophenone 3 in [bmim][OTf] proceeded smoothly to
afford the corresponding homoallyl ether 4 (Scheme 2).23
(18) For reviews on ionic liquids, see: (a) Wasserscheid, P.; Keim, W.
Angew. Chem., Int. Ed. 2000, 39, 3772. (b) Welton, T. Chem. ReV. 1999,
99, 2071-2083. (c) Gordon, C. M. Appl. Catal. A: General 2001, 222,
101-117. (d) Butler, R. Chem. Ind. (London) 2001, 17, 532. (e) Wasser-
scheid, P. Nachr. Chem. 2001, 49, 12-16.
(19) (a) Gordon, C. M.; Ritchie, C. Green Chem. 2002, 4, 124. (b) Law,
M. C.; Wong, K.-Y.; Chan, T. H. Green Chem. 2002, 4, 161.
(20) Typical procedure: A flame-dried 25 mL round-bottomed flask
was charged with the ionic liquid (1.5 mL, 2.05 g of [bmim][PF6] or 1.94
g of [bmim][OTf] and heptanal dimethyl acetal (0.50 g, 3.12 mmol).
Allyltrimethylsilane (0.463 g, 0.645 mL, 4.06 mmol, 1.3 equiv) was added
with a syringe followed by TMS triflate (0.035 g, 0.030 mL, 0.156 mmol,
5.0 mol %), and the mixture was magnetically stirred vigorously for 45
min. The reaction mixture was extracted with ether (4 × 20 mL), and the
combined ether extracts were washed with 10% aqueous Na2CO3 (25 mL)
and saturated NaCl (15 mL) and dried (Na2SO4). The solvent was removed
on a rotary evaporator to yield 0.500 g of a pale yellow liquid that was
further purified by flash chromatography to yield 0.42 g (79%) of a colorless
liquid identified as the corresponding homoallyl ether (98% pure by GC,
1H NMR and 13C NMR). The recovered ionic liquid (typical recovery )
1.95 g) was dried at 70 °C (0.1 mmHg) for 4 h (as described in ref 22)
1
prior to use in the next allylation. Based on H NMR analysis, there was
no evidence of either ionic liquid in the ether layer or any organic product
in the ionic liquid.
(21) For allylation of cinnamaldehyde acetal, the ionic liquid was stirred
with solid K2CO3 (0.5 g per 3 mL of ionic liquid) for 20 min, extracted
with ethyl acetate, and dried (Na2SO4), and the solvent was removed on a
rotary evaporator. The ionic liquid was further dried by heating at 70 °C
(0.1 mmHg) for 4 h. The potassium carbonate treatment removes any HF
that might be formed by hydrolysis of the [bmim][PF6]. Over the course of
several weeks, we did not see any evidence of hydrolysis of the ionic liquid
[bmim][PF6], such as etching of the glassware.
(22) The ionic liquids were dried as follows after each run: The recovered
ionic liquid was stirred over powdered activated 4 Å sieves for 12 h,
dissolved in ethyl acetate, and filtered, and the solvent was removed on a
rotary evaporator. The ionic liquid was further dried by heating at 70 °C
(0.1 mmHg) for 4 h.
56
Org. Lett., Vol. 5, No. 1, 2003

were due to any trace halides in the ionic liquids, one would
expect allyaltion to proceed in the absence of TMSOTf.
Similar results were obtained with the recycled ionic liquids
(no added TMSOTf). The ionic liquid was easily recycled.22
To determine the efficiency of recycling, the allylation of
p-chlorobenzaldehyde dimethyl acetal was studied (Table 3).
For each subsequent run, the recovered ionic liquid was used.
Scheme 2
Table 3. Recycling of [bmim][PF6]: Allylation of
p-Chlorobenzaldehyde Dimethyl Acetal
Thus, the acetal moiety can be selectively allylated over the
carbonyl group.
When the same reaction was carried out in CH2Cl2, the
allylation was very slow and less than 40% product resulting
from allylation of the acetal formed after 24 h. With 5 mol
% Bi(OTf)3 as the catalyst in CH2Cl2, no reaction was
observed.15 This example illustrates that ionic liquids are not
a mere substitute for volatile organicssrather, they can
significantly influence the outcome of the reaction. In Table
2, yields of allylation of four acetals using four different
gc yield of
% recovery (by mass)
trial no.
of ionic liquid
1
2
3
4
85
84
88
88
95
95
95
96
In summary, this work demonstrates a new environment
friendly and mild method for the chemoselective allylation
of acetals using catalytic amounts of TMS triflate in ionic
liquids as solvents. The solvent can be easily recycled, thus
allowing allylations to be carried out in non-chlorinated
solvents.
Table 2. Allylation of Acetals Using Allyltrimethylsilane in
Various Solvents
Acknowledgment. We acknowledge funding by the
National Science Foundation (RUI grant). R.M. acknowl-
edges The Camille and Henry Dreyfus Foundation for a
Teacher-Scholar Award and thanks Illinois Wesleyan
University for an Artistic and Scholarly grant in partial
support of this project.
Supporting Information Available: Experimental details
and spectral data for all products. This material is available
free of charge via the Internet at http://pubs.acs.org.
a Data from refs 1 and 2. b Data from ref 8. c Date from ref 15. d Reaction
carried out in [bmim][PF6].
OL0271739
(23) IR (neat): 3084, 2985, 2873, 1692, 1593, 1439, 1111 cm-1 1H
.
NMR (CDCl3, 270 MHz): δ 1.18 (3 H, apparent triplet), 2.56 (2 H, apparent
triplet), 3.50 (2 H, 16 line multiplet), 4.56 (1 H, apparent multiplet), 5.06
(2 H, multiplet), 5.83 (1 H, multiplet), 7.49 (3 H. multiplet), 8.05 (2 H,
multiplet). 13C NMR (CDCl3, 67.5 MHz, 11 peaks): δ 15.2, 37.5, 65.6,
82.9, 117.6, 128.5, 128.7, 133.3, 133.5, 135.2, 200.3. Anal. Calcd for
C13H16O2: C, 76.44; H, 7.90. Found: C, 76.48; H, 7.89. HRMS: m/e
205.122289 (M + 1), C13H16O2 requires 205.12296 (M + 1).
(24) Barentsen, H. M.; Sieval, A. B.; Cornelisse, J. Tetrahedron 1995,
51, 7495.
methods are compared. It can be seen that allylations in
CH2Cl2 using TMSOTf or TiCl4 require inconveniently low
temperatures while allylation in ionic liquids can be carried
out at room temperature.
If the ionic liquid was used alone (no added TMSOTf),
almost no allylation was observed. If the observed catalysis
Org. Lett., Vol. 5, No. 1, 2003
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