Michael addition reaction of alkenyl triehloroacetates catalyzed by dibutyltin dimethoxide

Article abstract of DOI:10.1246/cl.2008.1092

The Michael addition of alkenyl trichloroacetates to p-ben-zoquinone was achieved using dibutyltin dimethoxide as a catalyst in a mixed solvent consisting of THF and MeOH. Various monoalkylated benzoquinone derivatives were obtained from cyclic and acyclic trichloroacetates in moderate yield, trans-β-Nitrostyrene was also a favorable electrophile in this catalytic process, which gave an expected Michael adduct. Copyright

Full text of DOI:10.1246/cl.2008.1092

1092
Chemistry Letters Vol.37, No.10 (2008)
Michael Addition Reaction of Alkenyl Trichloroacetates
Catalyzed by Dibutyltin Dimethoxide
Akira Yanagisawa,Ã1 Youhei Izumi,2 and Takayoshi Arai1
1Department of Chemistry, Graduate School of Science, Chiba University, Chiba 263-8522
2Graduate School of Science and Technology, Chiba University, Chiba 263-8522
(Received July 14, 2008; CL-080691; E-mail: ayanagi@faculty.chiba-u.jp)
The Michael addition of alkenyl trichloroacetates to p-ben-
Table 1. Catalytic Michael addition of various alkenyl tri-
chloroacetates 1 to p-benzoquinone (2)a
zoquinone was achieved using dibutyltin dimethoxide as a cata-
lyst in a mixed solvent consisting of THF and MeOH. Various
monoalkylated benzoquinone derivatives were obtained from
cyclic and acyclic trichloroacetates in moderate yield. trans-ꢀ-
Nitrostyrene was also a favorable electrophile in this catalytic
process, which gave an expected Michael adduct.
OCOCCl3
O
Bu2Sn(OMe)2 (6 mol%)
O
R3
+
O
O
R1
MeOH (10 equiv)
THF, rt, 1 h
R1
O
R2
R2 R3
3
1
2
Entry
Alkenyl trichloroacetate
Product
Yield/%b
OCOCCl3
1c
2
3a
3a
3b
43
46
42
The Michael addition of enolates to ꢁ,ꢀ-unsaturated
carbonyl compounds is a beneficial method to prepare 1,5-dike-
tones.1 Since the 1,5-dicarbonyl moiety is not only found in
many natural products, but is also capable of being transformed
into ꢀ-hydroxycyclohexanones and other useful compounds,
efficient ways of obtaining this structure are desired for organic
synthesis.2 Numerous examples of the Lewis acid-catalyzed
Mukaiyama-type Michael addition of silyl enolates to enones
have so far been reported,3 however the method has difficulty
in applying to acid-labile substrates. We report here a novel
conjugate addition reaction of alkenyl trichloroacetates to
Michael acceptors catalyzed by dibutyltin dimethoxide under
almost neutral reaction conditions (Scheme 1).
1a
1a
OCOCCl3
3
1b
OCOCCl3
4
3c
39
1c
OCOCCl3
5
6
3d
3e
23
35
1d
OCOCCl3
1e
We have previously shown that dibutyltin dimethoxide
[Bu2Sn(OMe)2] behaves as a catalyst in aldol reaction of alkenyl
trichloroacetates with aldehydes in the presence of methanol.4
In this reaction, a nucleophilic attack of methoxide ion of the
tin reagent to the alkenyl esters efficiently generates the corre-
sponding tin enolates. We envisioned that this tin dimethoxide
might promote the Michael addition reaction of alkenyl tri-
chloroacetates to ꢁ,ꢀ-unsaturated carbonyl compounds via a
formation of tin enolates.5 Thus, we initially examined the
reaction of cyclohexanone-derived alkenyl trichloroacetate 1a
with chalcone in the presence of a stoichiometric amount of
Bu2Sn(OMe)2 at room temperature for 2 h, however the targeted
Michael adduct was not obtained at all. Then, we tested various
Michael acceptors and among them, p-benzoquinone (2) showed
remarkable reactivity toward an in situ generated tin enolate, and
unexpected monosubstituted benzoquinone derivative 3a, which
is considered to be formed by the Michael addition reaction and
subsequent oxidation by coexisting p-benzoquinone (2), was
obtained in 43% yield (Entry 1, Table 1). Furthermore, the same
compound was given in moderate yield under the influence of a
catalytic amount of the tin methoxide and an excess amount of
(E/Z = 1/4)
aAn alkenyl trichloroacetate 1 (1.1 equiv) reacted with 1 equiv of p-benzo-
quinone (2). bIsolated yield based on 2 (1 mmol). cThe reaction was
performed using 100 mol % of Bu2Sn(OMe)2 without MeOH for 2 h.
MeOH6 (Entry 2). According to this catalytic procedure, various
alkenyl trichloroacetates 1b–1e were transformed into the corre-
sponding benzoquinone derivatives 3b–3e (Entries 3–6).7 Not
only cyclic substrates 1a–1d, but acyclic 1e also afforded the ad-
duct 3e. Use of fully substituted 1-trichloroacetoxycyclohexene
1d resulted in a lower yield (Entry 5). Noteworthy is the fact that
a significant amount of hydroquinone formed in these reactions,
for example, the reduced compound was isolated in 43% yield in
the case of Entry 2, which is good evidence for occurrence of the
above-mentioned oxidation of the Michael adduct by p-benzo-
quinone (2). However, even when 1a was treated with 2 equiv
of 2, the isolated yield of 3a was not improved (38% yield based
on 1a).
A plausible catalytic mechanism of the Michael addition re-
action is shown in Figure 1. First, an alkenyl trichloroacetate 1
reacts with Bu2Sn(OMe)2 generating the dibutylmethoxytin eno-
late 4 and methyl trichloroacetate. Then, conjugate addition of
the tin enolate 4 to p-benzoquinone (2) occurs to produce the
tin enolate of Michael adduct 5. Protonation of 5 by MeOH af-
fords the Michael product 6 as an intermediate and regenerates
the tin dimethoxide. Finally, oxidation of 6 with p-benzoquinone
(2) results in the formation of the benzoquinone derivative 3
OCOCCl3
R3
O
EWG
cat. Bu2Sn(OMe)2
EWG
EWG
+
R1
EWG
R1
MeOH−THF, rt
R2 R3
R2
Scheme 1. Dibutyltin dimethoxide catalyzed conjugate addi-
tion reaction of alkenyl trichloroacetates to Michael acceptors.
Copyright Ó 2008 The Chemical Society of Japan

Chemistry Letters Vol.37, No.10 (2008)
1093
to give monosubstituted benzoquinones in moderate yields
owing to the Michael addition and subsequent oxidation. In
the reaction of ꢀ-nitrostyrene, a typical Michael adduct is
predominantly formed. These procedures are operationally sim-
ple employing readily available chemicals and can be performed
under almost neutral conditions.
OSnBu2(OMe)
O
O
O
OSnBu2(OMe)
R3
2
R1
R1
R2 R3
4
R2
O
5
MeOCOCCl3
MeOH
O
O
This work was supported by a Grant-in-Aid for Scientific
Research on Priority Areas ‘‘Advanced Molecular Transforma-
tions of Carbon Resources’’ from the Ministry of Education,
Culture, Sports, Science and Technology, Japan.
OCOCCl3
R3
O
Bu2Sn(OMe)2
R1
R1
R2 R3
R2
1
6
O
O
This paper is dedicated to Professor Ryoji Noyori on the
occasion of his 70th birthday.
2
HO
O
OH
7
References and Notes
1
For recent examples of Michael addition of enolates, see: a) S.
Harada, N. Kumagai, T. Kinoshita, S. Matsunaga, M. Shibasaki,
J. Am. Chem. Soc. 2003, 125, 2582. b) K. Miura, T. Nakagawa,
A. Hosomi, Synlett 2003, 2068. c) K. Miura, T. Nakagawa, A.
Hosomi, Synlett 2005, 1917. d) T. Nakagawa, H. Fujisawa, Y.
Nagata, T. Mukaiyama, Bull. Chem. Soc. Jpn. 2005, 78, 236.
e) T. Tozawa, Y. Yamane, T. Mukaiyama, Chem. Lett. 2006,
35, 56. f) T. Tozawa, Y. Yamane, T. Mukaiyama, Chem. Lett.
2006, 35, 360. g) T. Mukaiyama, H. Nagao, Y. Yamane, Chem.
Lett. 2006, 35, 916. h) M. Agostinho, S. Kobayashi, J. Am. Chem.
Soc. 2008, 130, 2430. i) S. Kobayashi, T. Tsubogo, S. Saito, Y.
Yamashita, Org. Lett. 2008, 10, 807. j) A. Takahashi, H. Yanai,
T. Taguchi, Chem. Commun. 2008, 2385.
O
R1
R2 R3
O
3
Figure 1. A plausible reaction mechanism for the Michael
addition of alkenyl trichloroacetates 1 to p-benzoquinone (2)
catalyzed by Bu2Sn(OMe)2.
Table 2. Michael addition of alkenyl trichloroacetate 1a to
a
trans-ꢀ-nitrostyrene (8) promoted by Bu2Sn(OMe)2
OCOCCl3
O
Ph
Bu2Sn(OMe)2
2
3
For representative reviews, see: a) C. H. Heathcock, in Compre-
hensive Organic Synthesis, ed. by B. M. Trost, I. Fleming, C. H.
Heathcock, Pergamon, Oxford, 1991, Vol. 2, p. 133. b) M. E.
Jung, in Comprehensive Organic Synthesis, ed. by B. M. Trost,
I. Fleming, M. F. Semmelhack, Pergamon, Oxford, 1991,
Vol. 4, p. 1.
NO2
NO2
+
Ph
additive, solvent
1a
8
9
Bu2Sn(OMe)2
/mol %
Temp
/ꢀC
Yield
/%b
Entry
Solvent
Additive
1
2
3
4
5
6
100
100
100
20
THF
DMF
THF
DMF
DMF
THF
rt
rt
—
—
63
79
93
38
28
28
a) X. Wang, S. Adachi, H. Iwai, H. Takatsuki, K. Fujita, M.
Kubo, A. Oku, T. Harada, J. Org. Chem. 2003, 68, 10046.
b) D. Liu, S. Hong, E. J. Corey, J. Am. Chem. Soc. 2006, 128,
8160. c) N. Takenaka, J. P. Abell, H. Yamamoto, J. Am. Chem.
Soc. 2007, 129, 742. d) H. Yang, S. Kim, Synlett 2008, 555.
A. Yanagisawa, T. Sekiguchi, Tetrahedron Lett. 2003, 44, 7163.
For Michael addition reactions of organotin enolates, see: a) I.
Shibata, Y. Mori, H. Yamasaki, A. Baba, H. Matsuda, Tetra-
hedron Lett. 1993, 34, 6567. b) I. Shibata, M. Nishio, A. Baba,
H. Matsuda, J. Chem. Soc., Chem. Commun. 1993, 1067. c) I.
Shibata, K. Yasuda, Y. Tanaka, M. Yasuda, A. Baba, J. Org.
Chem. 1998, 63, 1334. d) M. Yasuda, N. Ohigashi, I. Shibata,
A. Baba, J. Org. Chem. 1999, 64, 2180. e) M. Yasuda, Y.
Matsukawa, K. Okamoto, T. Sako, N. Kitahara, A. Baba, Chem.
Commun. 2000, 2149. f) M. Yasuda, N. Ohigashi, A. Baba,
Chem. Lett. 2000, 1266. g) M. Yasuda, K. Chiba, N. Ohigashi,
Y. Katoh, A. Baba, J. Am. Chem. Soc. 2003, 125, 7291. h) M.
Yasuda, Y. Shigeyoshi, I. Shibata, A. Baba, Synthesis 2005, 233.
In the absence of MeOH, the reaction did not occur catalytically.
General procedure for the preparation of 3: Alkenyl trichloroace-
tate 1 (1.1 mmol) and p-benzoquinone (2, 1.0 mmol) were
dissolved in dry THF (3 mL) under argon atmosphere and then
dibutyltin dimethoxide (0.06 mmol) was added to the resulting
solution at room temperature. To the mixture was added drop-
wise MeOH (10 mmol). After being stirred for 1 h at this temper-
ature, the mixture was treated with MeOH (2 mL), brine (2 mL),
and solid KF (ca. 1 g) at ambient temperature for 30 min. The
resulting precipitate was filtered off. Then, the filtrate was dried
over Na2SO4 and concentrated in vacuo after filtration. The re-
sidual crude product was purified by column chromatography
on silica gel to give the benzoquinone derivative 3.
À20
rt
Bu4NBr (1 equiv)
—
20
20
rt
À20
MeOH (5 equiv)
Bu4NBr (1 equiv)
MeOH (5 equiv)
4
5
aAlkenyl trichloroacetate 1a (1.1 equiv) reacted with 1 equiv of trans-ꢀ-ni-
trostyrene (8). bIsolated yield based on 8.
accompanied by hydroquinone (7).
Next, we attempted the tin methoxide-catalyzed Michael
addition of alkenyl trichloroacetate 1a to ꢀ-nitrostyrene (8)
and the results are summarized in Table 2. First, we studied sol-
vent effect in the stoichiometric reaction and found that DMF
was superior to THF for obtaining the desired Michael adduct
9 in satisfactory yield (Entries 1 and 2). However, the reaction
took place more effectively in THF even at À20 ꢀC when tetra-
butylammonium bromide was used as an additive (Entry 3).5f As
a consequence, two kinds of solvent system (DMF, and THF
with Bu4NBr) were applied to the catalytic version, however,
the reactions were sluggish even in the presence of MeOH
(Entries 5 and 6) and highest yield (38% yield) was attained
when the reaction was performed in DMF without MeOH
(Entry 4).
6
7
In summary, we have demonstrated an application of
Bu2Sn(OMe)2 as a catalyst for the conjugate addition of alkenyl
trichloroacetates to Michael acceptors. The catalytic reaction
with p-benzoquinone proceeds smoothly at room temperature
Published on the web (Advance View) October 5, 2008; doi:10.1246/cl.2008.1092