Lewis base catalyzed Michael reaction between ketene silyl acetals and α,β-unsaturated carbonyl compounds

Article abstract of DOI:10.1246/cl.2003.56

Catalytic Michael reaction between trimethylsilyl enolates and α,β-unsaturated carbonyl compounds by using a Lewis base such as lithium benzamide or lithium succimide in a DMF solvent proceeded smoothly to afford the corresponding Michael adducts.

Full text of DOI:10.1246/cl.2003.56

56
Chemistry Letters Vol.32, No.1 (2003)
Lewis Base Catalyzed Michael Reaction between Ketene Silyl Acetals
and ꢀ,ꢁ-Unsaturated Carbonyl Compounds
Teruaki Mukaiyama,Ã Takashi Nakagawa, and Hidehiko Fujisawa#
The Kitasato Institute, Center for Basic Research, TCI, 6-15-5 Toshima, Kita-ku, Tokyo 114-0003
(Received October 4, 2002; CL-020853)
Catalytic Michael reaction between trimethylsilyl enolates
In the first place, a reaction of chalcone and 1 in DMF was
and ꢀ,ꢁ-unsaturated carbonyl compounds by using a Lewis base
such as lithium benzamide or lithium succimide in a DMF solvent
proceeded smoothly to afford the corresponding Michael adducts.
tried in the presence of a catalytic amount of lithium diphenyl-
amide or lithium pyrroridone, and the Michael adduct was
afforded in 52% or 68% yield, respectively. Of the amides
screened, lithium benzamide 2 then turned out to be the most
effective Lewis base for the acceleration of the reaction.
Surprisingly, the lithium succimide 3 also catalyzed the reaction
and the Michael adduct was obtained in high yield even though
pKa value of N–H bond of its precursor was much lower than that
of above three precursors, which was measured in DMSO12
(Scheme 1). In the absence of the catalyst, on the other hand, the
Michael adduct was not obtained at all.
Silyl enolates are stable enolate equivalents and can be
isolated by distillation. However, their utility in synthetic organic
chemistry has not fully been developed because of their weakly
nucleophilic character. Since a crossed aldol reaction between
aldehydes and silyl enolates promoted by Lewis acids such as
titanium tetrachloride was reported from our laboratory,1 silyl
enolates are recognized as convenient and useful nucleophiles
and have frequently been employed in constructing carbon
skeleton. Recently, activation of silyl enolates under neutral or
nonacidic conditions is studied intensively: for example, Den-
mark et al. and Hosomi and co-workers reported methods of using
silyl enolates having an enhanced Lewis acidic silicon atom, by
which the interaction between Lewis bases is increased.2 In our
previous paper, it was reported that the lithium diphenylamide or
lithium pyrrolidone was an effective Lewis base catalyst for the
activation of a simple silyl enolate such as trimethylsilyl enolate
in a dimethylformamide (DMF) or pyridine solvent under
nonacidic conditions.3 In this communication, we would like to
report a catalytic Michael reaction between trimethylsilyl
enolates and ꢀ,ꢁ-unsaturated carbonyl compounds by using
Lewis base catalysts in order to prove the usefulness of the Lewis
base catalysts.
2 (10 mol%)
DMF, −45 oC, 3 h
OSiMe3
O
+
OMe
Ph
Ph
or 3 (10 mol%)
DMF, 0 oC, 2.5 h
(1.4 eq)
1
Me3SiO
Ph
Ph
O
O
Ph
O
1N HClaq
THF, rt
OMe
Ph
OMe
99% (catalyst 2)
90% (catalyst 3)
Li
N
O
Li
O
O
Ph
N
H
2
3
Scheme 1.
Although the Michael reaction is one of the most important
methods for carbon–carbon bond formation, side reactions such
as self-condensations of substrates, proton transfers, and con-
comitant 1,2-additions often occur in conventional Michael
reactions which are carried out under basic conditions.4 Such
undesired reactions can be conquered by using silyl enol ethers as
the functional equivalents of Michael donors. This type of
reaction has become very popular ever since the Michael reaction
between ꢀ,ꢁ-unsaturated ketones and silyl enolates promoted by
Lewis acid was reported from our laboratory.5 Also, fluoride ion
catalyzed reactions of sily enol ethers6 or silyl ketene acetals,7
and a reaction of dimethyl(trifloxy)silyl enol ethers with ꢀ,ꢁ-
unsaturated ketones8 have been shown. In the latter case, silyl
enolates smoothly reacted with ꢀ,ꢁ-unsaturated ketones even in
the absence of catalysts. In addition, reactions of silyl ketene
acetals with ꢀ,ꢁ-unsaturated carbonyl compounds have been
carried out in DMSO9 or nitromethane7 at room temperature and
in acetonitrile at 55 ꢀC10 or under high pressure.11 Some of these
methods, however, were found to have synthetic limitations: i.e.,
when trimethylsilyl enolate derived from methyl isopropionate 1
was used, the reactivity decreased and, therefore, reaction
temperature must be elevated.11
Next, the reactions of trimethylsilyl enolate with various
Michael acceptors were tried by using 2 or 3 as a catalyst. The
results are summarized in Table 1. Bulky silyl enolate 1 smoothly
reacted with various Michael acceptors to give the corresponding
Michael adducts in high yields at low temperature. When the
acceptors having active hydrogens at the ꢀ position of carbonyl
moiety were used, 3 proved to be a very effective Lewis base
catalyst; that is, the reaction proceeded smoothly by using such
weak base catalyst 3 and gave the corresponding Michael adducts
in high yield (Entry 9), while the yield was very poor when the
same reaction was carried out by using 2 at room temperature
because 2 behaved as a brꢀnsted base in DMF (Entry 8). From a
synthetic point of view, the present Lewis base catalyzed reaction
has a remarkable advantage in forming Michael adducts
especially when Michael acceptors of having basic functions in
the same molecules were used. Expectedly, reactions proceeded
smoothly and the corresponding Michael adducts were afforded
in high yields in the above cases (Entry 10–13).
The lithium benzamide 2 catalyzed Michael reaction was
further tried by using several silyl enolates (see Table 2). When
sterically hindered triethylsilyl enolate derived from methyl
Copyright Ó 2003 The Chemical Society of Japan

Chemistry Letters Vol.32, No.1 (2003)
57
Table 1.
proceeded via the activation of trimethylsilyl enolate by forming
hypervalent silicate between Lewis bases and the silicon atom of
enolate.3 Further, the reactivities were slightly decreased when
trimethylsilyl enolates derived from methyl propionate were used
as a substrate. Similar phenomenon was observed also in the
Michael reaction carried out in DMSO in the absence of a
catalyst.9 When the E enolate was allowed to react with
cyclopentenone at 0.23 mol dmÀ3, the corresponding Michael
adduct was afforded in high yield (Entry 3).
Thus, a new catalytic Michael reaction between trimethylsi-
lyl enolates and ꢀ,ꢁ-unsaturated carbonyl compounds was
established under nonacidic conditions by using lithium benz-
amide 2 or lithium succimide 3 in a DMF solvent. Further
expansion of this reaction is now in progress.
1) Catalyst (10mol%)
DMF, Temp, Time
OSiMe3
OMe
Michael Acceptor
+
Product
2) 1N HClaq
THF, rt
1 (1.4 eq)
Temp /oC
Yielda /%
Catalyst
Entry
Michael acceptor
Time /h
cyclopentenone
cyclopentenone
cyclohexenone
methyl vinyl ketone
O
2
3
2
2
−45
−45
−45
−45
3
91
88
94
90
1
2
3
4
3
3
3
5
2
0
3
85
42
75
40
83
6
7
8
9
2
2
2
3
−45
0
rt
3
3
3
3
O
This work was supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Science, Sports and
Culture, Japan.
rt
O
10
11
2
3
3
4
−45
−45
83
97
References and Notes
N
O
#
1
A doctor course student of Science University of Tokyo.
T. Mukaiyama, K. Banno, and K. Narasaka, J. Am. Chem.
Soc., 96, 7503 (1974).
0
0
12
13
2
3
3
92
91
3.5
N
2
3
S. E. Denmark and R. A. Stavenger, Acc. Chem. Res., 33, 432
(2000); K. Miura, T. Nakagawa, and A. Hosomi, J. Am. Chem.
Soc., 124, 536 (2002).
H. Fujisawa and T. Mukaiyama, Chem. Lett., 2002, 182; H.
Fujisawa and T. Mukaiyama, Chem. Lett., 2002, 858; T.
Mukaiyama, H. Fujisawa, and T. Nakagawa, Helv. Chim.
Acta, 2002, in press.
methyl acrylate
−45
0
14
2
5
65
All reactions were carried out at 0.11 mol dm . aYield was determined by
1H-NMR analysis (270 MHz) using 1,1,2,2-tetrachloroethane as an internal
standard.
-3
4
E. D. Bergmann, D. Ginsburg, and R. Rappo, in ‘‘Organic
Reactions,’’ ed. by R. Adams, Wiley, New York (1959),
Vol. 10, pp 179–555; H. O. House, in ‘‘Modern Synthetic
Reactions,’’ 2nd ed., ed. by W. A. Benjamin, Menlo Park,
California (1972), p 595; P. Perlmutter, ‘‘Conjugate Addition
Reactions in Organic Synthesis,’’ Pergamon Press, Oxford
(1992).
Table 2.
1) 2 (10 mol%), DMF
O
Conc., −45 °C, 3 h
Ketene Silyl Acetals
(1.4 eq)
+
Product
2) 1N HClaq, THF, rt
Conc. / mol dm−3 Yielda / %
syn : anti
Entry
1
Ketene silyl acetals
5
6
K. Narasaka, K. Soai, and T. Mukaiyama, Chem. Lett., 1974,
1223; K. Narasaka, K. Soai, Y. Aikawa, and T. Mukaiyama,
Bull. Chem. Soc. Jpn., 49, 779 (1976); K. Saigo, M. Osaki, and
T. Mukaiyama, Chem. Lett., 1976, 163.
J. Boyer, R. J. P. Corriu, R. Perz, and C. Reye, J. Organomet.
Chem., 184, 157 (1980); J. Boyer, R. J. P. Corriu, R. Perz, and
C. Reye, Tetrahedron, 39, 117 (1983).
T. V. Rajan Babu, J. Org. Chem., 49, 2083 (1984).
S. Kobayashi and K. Nishio, J. Org. Chem., 58, 2647 (1993).
´
Y. Genisson and L. Gorrichon, Tetrahedron Lett., 41, 4881
(2000).
OSiEt3
46
0.11
OMe
OSiMe3
0.11
0.23
0.11
0.23
59
85b
1 : 1
1 : 1
1 : 1
1 : 1
2
3
4
5
(E : Z = 5 : 1)
OMe
OSiMe3
60
41b,c
(E : Z = 1 : 9)
7
8
9
OMe
aYield was determined by 1H-NMR analysis (270 MHz) using 1,1,2,2-
tetrachloroethane as an internal standard. bIsolated yield. cCompound 4 was
O
afforded as a by-product (13% yield).
O
10Y. Kita, J. Segawa, J. Haruta, H. Yasuda, and Y. Tamura, J.
Chem. Soc., Perkin Trans. 1, 1982, 1099.
11 R. A. Bunce, M. F. Schlecht, W. G. Dauben, and C. H.
Heathcock, Tetrahedron Lett., 24, 4943 (1983); Y. Yama-
moto, K. Maruyama, and K. Matsumoto, Tetrahedron Lett.,
25, 1075 (1984).
CO2Me
4
12 F. G. Bordwell, Acc. Chem. Res., 21, 456 (1988); F. G.
Bordwell, J. C. Branca, D. L. Hughes, and W. N. Olmstead, J.
Org. Chem., 45, 3305 (1980).
isopropionate was employed in place of the above trimethylsilyl
enolate 1, the corresponding Michael adduct was obtained only in
46% yield (Entry 1). This result indicated that the reaction