Potassium fluoride-induced 1,4-elimination of o-[(trimethylsilyl)methyl] benzyl acetates: A versatile generation of o-quinodimethanes

Article abstract of DOI:10.1246/cl.2005.728

o-Quinodimethane interemediate was generated from o-[(trimethylsilyl) methyl]benzyl acetate with potassium fluoride. The o-quinodimethane in hand reacted with electron-deficient olefins, affording [4+2] cycloadducts, tetrahydronaphthalenes. Copyright

Full text of DOI:10.1246/cl.2005.728

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Chemistry Letters Vol.34, No.5 (2005)
Potassium Fluoride-induced 1,4-Elimination of o-[(Trimethylsilyl)methyl]benzyl Acetates:
A Versatile Generation of o-Quinodimethanes
Ryoichi Kuwanoꢀ and Takenori Shige
Department of Cheistry, Graduate School of Sciences, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581
(Received February 24, 2005; CL-050238)
o-Quinodimethane interemediate was generated from o-
KF
SiMe3
OCMe
O
+
[(trimethylsilyl)methyl]benzyl acetate with potassium fluoride.
The o-quinodimethane in hand reacted with electron-deficient
olefins, affording [4+2] cycloadducts, tetrahydronaphthalenes.
DMF
CO2Me
CO2Me
1a
100 °C, 3 h
2a
88% yield
Scheme 2.
Cycloaddition of olefins to o-quinodimethane1 intermedi-
ates has offered a versatile and straightforward access to
1,2,3,4-tetrahydronaphthalene skeletons.2 A variety of methods
for in situ generation of o-quinodimethane have been devel-
oped,3–7 and have been utilized for the syntheses of steroids8
and other natural products to date.9 In particular, fluoride-in-
duced 1,4-elimination from ꢀ0-heterosubstituted ꢀ-silyl-o-xy-
lenes is an important and versatile method for the preparation
of o-quinodimethane.10–13 The 1,4-elimination occurred under
mild conditions compared with other methods, e.g. thermal
ring-opening of benzocyclobutenes.14 The generation of o-qui-
nodimethane from the ꢀ-silyl-o-xylenes, however, has been con-
ducted in the presence of either tetrabutylammonium fluoride or
cesium fluoride, which are expensive and hard to handle in air
because of their hygroscopicity.
Herein, we report a new protocol for the generation of o-qui-
nodimethanes via 1,4-elimination of o-(silylmethyl)benzylic
acetates (1).12,15 Potassium fluoride, which is handled with ease
in air and is an inexpensive fluoride source,16 was employed for
the induction of 1,4-elimination. The o-quinodimethenes reacted
with electron-deficient olefins to give the corresponding tetrahy-
dronaphthalenes 2 (Scheme 1).
DMF. Lewis basicity of DMF may assist the activation of C–
Si bond by KF.20
When 1a was treated with KF in the absence of any dieno-
phile, a mixture of spiro-di-o-xylylene 3 and [2,2]orthocyclo-
phane 4 was obtained as seen in Scheme 3. Although the forma-
tion of 4 might result from thermally forbidden [4,4] cycloaddi-
tion of o-quinodimethane, the observation is consistent with
Errede’s results.21
KF
3 (42%)
4 (14%)
1a
+
DMF
100 °C
Scheme 3.
The o-quinodimethane intermediate generated from 1a re-
acted with acrylonitrile as well as with methyl acrylate, and
the cycloaddition product 2b was obtained in high yield
(Table 1, Entry 1). Unexpectedly, acrolein was not so reactive
toward the o-qunodimethane intermediate (Entry 2). The reac-
tions of electron-deficient trans-olefins, trans-benzalacetone,
and dimethyl fumarate, afforded [4+2] cycloadducts 2d and
2e in good yields, respectively (Entries 3 and 4). In contrast,
no cycloaddition of o-quinodimethane was observed when cis-
olefins such as maleic anhydride and dimethyl maleate were em-
ployed as a dienoplile.22 Use of acetylenedicarboxylate resulted
in a complex mixture.22 The reaction of 4-methyl-o-quinodime-
thane precursor 1b with methyl acrylate gave a mixture of two
regioisomeric [4+2] cycloadducts with no selectivity (Entry 5).
The o-quinodimethane precursor 1a was prepared with ace-
tylation of benzylic alcohol 5, which was readily synthesized
from o-methylbenzyl alcohol.11b We attempted the one-pot gen-
eration of o-quinodimethane from 5 (Scheme 4). After 5 was
treated with acetic anhydride, methyl acrylate and KF were add-
ed to the resulting solution containing 1a. Heating the mixture at
100 ꢁC for 1 h produced 2a in 66% yield.23
F–
EWG
Si
OCMe
O
EWG
1
2
o-quinodimethane
EWG: electron-withdrawing group
Scheme 1.
A mixture of o-[(trimethylsilyl)methyl]benzyl acetate (1a)
with methyl acrylate in DMF was heated at 100 ꢁC in the pres-
ence of KF. The resulting mixture afforded methyl 1,2,3,4-tetra-
hydronaphthalene-2-carboxylate (2a) in 88% yield (Scheme 2).17
When tetrabutylammonium fluoride was used as a fluoride
source, 2a was obtained in trace amount (2%), and 2-methylben-
zyl acetate resulting from protodesilylation was generated in
50% yield.18 The desired product 2a was formed by use of KF
even at room temperature (26% at 48 h), while the reaction af-
forded 2-methylbenzyl acetate in 40% yield.19 This observation
may indicate that the KF-induced activation of silyl group occurs
even at room temperature but the following 1,4-elimination of
the acetoxy group seems to compete with the protodesilylation.
No consumption of 1a was observed in any solvents other than
In summary, we have developed a new method for generat-
ing o-quinodimethane intermediates from 1. Potassium fluoride,
which is an inexpensive and tractable fluoride source, was em-
ployed to activate the silyl group and induced 1,4-elimination
providing the reactive intermediate. The o-quinodimethane in
Copyright ꢀ 2005 The Chemical Society of Japan

Chemistry Letters Vol.34, No.5 (2005)
729
Table 1. Cycloaddition of o-quinodimethane with dienophilesa
Nakatsuka, and T. Saegusa, J. Am. Chem. Soc., 102, 863 (1980).
b) Y. Ito, M. Nakatsuka, and T. Saegusa, J. Am. Chem. Soc.,
104, 7609 (1982). c) Y. Ito, Y. Amino, M. Nakatsuka, and T.
Saegusa, J. Am. Chem. Soc., 105, 1586 (1983).
Entry
1
Dienophile
Product (yield/%)b
SiMe3
OCMe
11 Generation from ꢀ-silyl-ꢀ0-sulfonyl-o-xylenes: a) B. D.
Lenihan and H. Shechter, Tetrahedron Lett., 35, 7505 (1994).
b) B. D. Lenihan and H. Shechter, J. Org. Chem., 63, 2072
(1998).
12 SiO2-induced generation of o-quinodimethane from ꢀ-silyl-ꢀ0-
acetoxy-o-xylenes: A. R. Beard, S. J. Hazell, J. Mann, and C.
Palmer, J. Chem. Soc., Perkin Trans. 1, 1993, 1235.
13 Acid-induced generation of o-quinodimethane from ꢀ-stannyl-
ꢀ0-hydroxy-o-xylenes: H. Sano, H. Ohtsuka, and T. Migita,
J. Am. Chem. Soc., 110, 2014 (1988).
14 Examples: a) W. Oppolzer, J. Am. Chem. Soc., 93, 3833 (1971).
b) T. Kametani, M. Tsubuki, Y. Shiratori, Y. Kato, H. Nemoto,
M. Ihara, K. Fukumoto, F. Satoh, and H. Inoue, J. Org. Chem.,
42, 2672 (1977).
15 I. Fleming, I. T. Morgan, and A. K. Sarkar, J. Chem. Soc.,
Perkin Trans. 1, 1998, 2749.
1
2b (81)
CN
CN
O
1a
2c
3
2c (26)
CHO
CHO
Ph
Ph
2d (63)
COMe
COMe
CO2Me
MeO2C
4
2e (77)
CO2Me
CO2Me
SiMe3
OCMe
2f (68)d
CO2Me
5c
Me
CO2Me
Me
O
1b
aReactions were conducted on a 1 mmol scale in DMF (20 mL)
16 The costs of fluoride sources are as follows: TBAF (1.0 M THF
solution), ¥37,400/mol; CsF, ¥25,519/mol; KF, ¥581/mol
(from Aldrich).
b
at 100 ꢁC for 3 h. 1/dienophile/KF was 1/1.25/1.5. Isolated
c
yield. The reactions were conducted for 1 h. dYield of the
mixture of methyl 5- and 6-methyl-1,2,3,4-tetrahydronaphtha-
lene-2-carboxylates (ca. 1:1).
17 Procedure of the reaction of 1a with methyl acrylate is as fol-
lows: Under nitrogen atmosphere, 1a (241 mg, 1.02 mmol)
and methyl acrylate (109 mg, 1.26 mol) were added to a suspen-
sion of KF (88 mg, 1.51 mmol) in dry DMF (20 mL). The mix-
ture was stirred at 100 ꢁC for 3 h. After cooling, the mixture was
diluted with water and was extracted with hexane. The organic
layer was washed with brine, was dried with MgSO4, and was
evaporated under reduced pressure. The residue was purified
with a flash column chromatography on silica gel (EtOAc/
hexane = 1/5), giving 2a (170 mg, 88%): 1H NMR (400
MHz, CDCl3, TMS) ꢁ 1.86 (dddd, J ¼ 6:6, 10.8, 13.0,
23.9 Hz, 1H), 2.17–2.25 (m, 1H), 2.70–2.79 (m, 1H), 2.79–
2.93 (m, 2H), 2.95–3.06 (m, 2H), 3.73 (s, 3H), 7.06–7.13 (m,
4H); 13C {1H} NMR (100 MHz, CDCl3) ꢁ 25.8, 28.5, 31.6,
39.9, 51.7, 125.7, 125.8, 128.8, 129.0, 134.8, 135.6, 175.8.
lit. S.-i. Inaba, R. M. Wehmeyer, M. W. Forkner, and R. D.
Rieke, J. Org. Chem., 53, 339 (1988).
1. Ac2O, pyridine, cat. DMAP
SiMe3
OH
2. KF, H2C=CHCO2Me
CO2Me
5
2a
66% yield
Scheme 4. One-pot synthesis of tetrahydronaphthalene from 3.
hand reacted with electron-deficient dienophiles to give tetrahy-
dronaphthalenes.
This work was partly supported by the Sumitomo
Foundation and a Grant-in-Aid for Young Scientist (A)
(no. 16685011) from MEXT.
References and Notes
1
18 The reaction was conducted in dry DMF (5 mL) at 80 ꢁC. The
rest of 1a was converted into 3 and 4. The water contained in
TBAF solution might cause the protodesilylation. The reaction
employing KF under the identical conditions gave 2a in 70%
yield.
M. P. Cava and D. R. Napier, J. Am. Chem. Soc., 79, 1701
(1957).
2
Reviews: a) J. L. Charlton and M. M. Alauddin, Tetrahedron,
43, 2873 (1987). b) J. L. Segura and N. Martin, Chem. Rev.,
99, 3199 (1999).
19 The remaining 1a was recovered.
3
M. P. Cava and A. A. Deana, J. Am. Chem. Soc., 81, 4266
(1959).
K. Alder and M. Fremery, Tetrahedron, 14, 190 (1961).
P. G. Sammes and S. M. Mellows, J. Chem. Soc., Chem.
Commun., 1971, 21.
F. Jung, M. Molin, R. Van der Elzen, and T. Durst, J. Am.
Chem. Soc., 96, 935 (1974).
T. Tuschka, K. Naito, and B. Rickborn, J. Org. Chem., 48, 70
(1983).
Review: H. Nemoto and K. Fukumoto, Tetrahedron, 54, 5425
(1998).
Recent examples: a) Y. Matsuya, K. Sasaki, M. Nagaoka, H.
Kakuda, N. Toyooka, N. Imanishi, H. Ochiai, and H. Nemoto,
J. Org. Chem., 69, 7989 (2004). b) K. C. Nicolaou and
D. L. F. Gray, J. Am. Chem. Soc., 126, 607 (2004).
20 S. Kobayashi and K. Nishio, J. Org. Chem., 59, 6620 (1994).
21 The pathway of the [4+4] cycloaddition might involve the
formation of a biradical intermediate: L. A. Errede, J. Am.
Chem. Soc., 83, 949 (1961).
4
5
22 Many examples of reactions of o-quinodimethanes with maleic
anhydride and acetylenedicarboxylates have been reported.10,13
23 Procedure of the one-pot transformation of 5 into 2a is as fol-
lows: Under nitrogen atmosphere, pyridine (95 mg, 1.20 mmol)
and acetic anhydride (114 mg, 1.12 mmol) were added to a so-
lution of 5 (193 mg, 0.99 mmol) and 4-(dimethylamino)pyri-
dine (1.5 mg, 12 mmol) in dry DMF (2 mL). The mixture was
stirred at room temperature for 3 h. After DMF (18 mL), KF
(87 mg, 1.50 mmol), and methyl acrylate (118 mg, 1.37 mmol)
were added, the mixture was stirred at 100 ꢁC for 1 h. The re-
sulting mixture was purified according to the protocol described
in note 17, giving 2a (125 mg, 66%).
6
7
8
9
10 Generation from ꢀ-silyl-ꢀ0-ammonium-o-xylenes: a) Y. Ito, M.
Published on the web (Advance View) April 16, 2005; DOI 10.1246/cl.2005.728