Highly regioselective addition of an ester enolate equivalent to α,β-unsaturated ketones: Selective formation of both isomers derived from 1,2- and 1,4-additions using α-stannyl ester with additives

Article abstract of DOI:10.1039/b004817h

The reaction of α-stannyl ester with α,β-unsaturated ketones in the presence of stannous chloride (SnCl₂) and chlorosilanes (Me₃SiCl or Me₂SiCl₂) gave 1,2- and 1,4-addition products, respectively.

Full text of DOI:10.1039/b004817h

Highly regioselective addition of an ester enolate equivalent to a,b-unsaturated
ketones: selective formation of both isomers derived from 1,2- and
1,4-additions using a-stannyl ester with additives
Makoto Yasuda, Yozo Matsukawa, Keishi Okamoto, Toshifumi Sako, Noriko Kitahara and Akio Baba*
Department of Applied Chemistry, Faculty of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka
565-0871, Japan. E-mail: baba@ap.chem.eng.osaka-u.ac.jp
Received (in Cambridge, UK) 15th June 2000, Accepted 26th September 2000
First published as an Advance Article on the web
The reaction of a-stannyl ester with a,b-unsaturated
ketones in the presence of stannous chloride (SnCl2) and
chlorosilanes (Me3SiCl or Me2SiCl2) gave 1,2- and 1,4-addi-
tion products, respectively.
regioselectivity was high (entry 5). Chlorotrimethylsilane gave
83% yield of products with high selectivity (entry 6). The cyclic
substrate 2d was also applied to these systems. When
Table 1 Effect of additives on regioselective addition of 1 to enone 2aa
The regioselective addition of a nucleophile to a,b-unsaturated
carbonyl compounds (1,2- or 1,4-addition) has been focused on
in modern organic syntheses. An enolate or its equivalent is
often used for the functionalised nucleophile to unsaturated
carbonyls. Heathcock reported excellent results using lithium
enolate in which either kinetic or thermodynamic conditions
effectively control the regioselectivity.1 The correlation
between the character of the metal in the enolate and the
regioselectivity was also investigated.2 We have recently
reported the 1,4-addition of organotin ketone enolate using a
high coordination method.3 An organotin ester enolate, how-
ever, has significantly different reactivity and character as
compared with an organotin ketone enolate and is not suitable
for the reaction conditions developed for ketone enolates. For
the organotin ester enolates, the equilibrium between O-
stannylated and C-stannylated forms largely lies towards the C-
stannylated species above 0 °C.4 The stannylation of lithium
ester enolate is reported to give only a C-stannylated ester
compound (the a-stannyl ester) after distillation,5 although
stannyl ketone enolate generally exists as an equilibrium
mixture of both forms.6 Since enol forms generally show higher
reactivity than keto forms, the a-stannyl ester has a lower
reactivity than ketone enolates.7,8 During our study of the
activation methodology of a-stannyl ester, we found a novel
approach to regiocontrol in the reaction of a,b-unsaturated
ketones with a-stannyl ester as an ester enolate equivalent.
First, we examined additives for the reaction of a-stannyl
ester 1 with chalcone 2a and the results are summarized in Table
1. An attempt without additives resulted in no reaction (entry 1).
The use of BF3·OEt2 as an additive was not effective at all (entry
2). TiCl4 afforded a low yield of 1,4-addition product 4a (entry
3). Recently, we have reported a carbonyl allylation system
using tributylallylictin(IV) and SnCl2 in which transmetallation
occurs to generate an active species.9,10 This activation
methodology was applied to the reaction of 1 in the presence of
SnCl2 to give b-hydroxy ester 3a in 63% yield with excellent
selectivity in 1,2-addition manner (entry 4). On the other hand,
the addition of chlorotrimethylsilane gave selectively 4a in
practical yields, which were influenced by the solvents used.
Nitromethane was the solvent of choice and gave the sole
product 4a in 95% yield (entry 6). These results encouraged us
to develop these reaction systems using a-stannyl ester for
regioselective addition to a,b-unsaturated ketones.
Table 2 Control of regioselectivity in addition of 1 to various enones 2a
Next, we explored the generality of this regiocontrolled
system using either SnCl2–MeCN or Me3SiCl–MeNO2 with
various types of enones 2a–e, and showed the results in Table
2.† Excellent regiocontrol was observed in the reaction with
phenyl ketone 2b, which has an alkyl substituent on the terminal
olefinic carbon (entries 3 and 4). In the reaction with alkyl
ketone 2c using SnCl2, the low yield of 3c in entry 5 was
ascribed to the polymerization of the starting enone, although
DOI: 10.1039/b004817h
Chem. Commun., 2000, 2149–2150
This journal is © The Royal Society of Chemistry 2000
2149

acetonitrile was used as a solvent in the reactions with 2a–d in
the presence of chlorotrimethylsilane, the same or lower yields
were observed but selectivity was not significantly affected. In
the reaction with 4-phenylbut-3-en-2-one 2e, the 1,2-adduct 3e
was obtained in good yield with perfect selectivity (entry 9).
However, the reaction using chlorotrimethylsilane did not give
selective 1,4-addition (3e/4e = 46/54, entry 10). The low
selectivity is ascribed to the conjugation of the phenyl group
with the olefinic moiety which could be kept by 1,2-addition
and broken by 1,4-addition.11 Unexpectedly, Michael adduct 4e
was favored (3e/4e = 5/95) when dichlorodimethylsilane was
used as an additive instead of chlorotrimethylsilane (entry
11).
Although the exact reaction mechanism for either course
using stannous chloride or chlorosilanes is not clear, the
regiocontrol can be explained by the following assumption at
the present stage. In the SnCl2 system, the active tin(II) species
generated by transmetallation has high Lewis acidity.9,10 The
strong interaction between carbonyl oxygen and the tin center in
the nucleophile effectively accelerates the carbostannylation.
The resulting Sn–O bond is strong enough for irreversible
reaction. In order to examine the chlorosilane system, an NMR
study was performed. The mixture of 1 and chlorotrimethyl-
silane in acetonitrile underwent transmetallation to give tri-
butylchlorostannane and silylketene acetal, as determined by
NMR.12,13 After standing for 48 h at rt, the silylketene acetal
completely disappeared and a-silyl ester was observed by
NMR.14,15 This resulting solution including silyl ester and
tributylchlorostannane was inert to chalcone 2a. These results
suggest that tributylchlorostannane would act as a Lewis acid
for Mukaiyama-type Michael addition of silylketene acetal.16
Another possibility, namely, that further transmetallation to
give stannylketene acetal from chlorostannane and silylketene
acetal, which would have high reactivity and a short life time
under the conditions employed in this procedure, is not
completely ruled out at this stage.4 The difference in active
species generated in each system causes the highly regiocon-
trolled reactions.
Culture, of the Japanese Government. Thanks are due to Mr H.
Moriguchi, Faculty of Engineering, Osaka University, for
assistance in obtaining MS spectra.
Notes and references
† Experimental procedure for the synthesis of 3: see the representative
experimental procedure in our previous paper9 (use an a-stannyl ester
instead of allylstannane). General procedure for the synthesis of 4: to a
mixture of chlorosilane (Me3SiCl or Me2SiCl2, 2.0 mmol) and an a-stannyl
ester 1 (1.2 mmol) in nitromethane (1 mL) was added a,b-unsaturated
ketones 2 (1.0 mmol) under nitrogen. The mixture was stirred for 3 h at
ambient temperature. The reaction mixture was poured into the mixed
solvent of Et2O (30 mL) and aqueous NH4F (15%; 15 mL) with vigorous
stirring for 10 min. The resulting Bu3SnF was filtered off. The filtrate was
extracted with Et2O (30 mL 3 2) and washed by aq.HCl (1 M, 20 mL 3 2)
and NaHCO3 (20 mL 3 1) and dried (MgSO4) and evaporated. The crude
reaction mixture was purified by column chromatography and recrystallisa-
tion or distillation gave pure products 4.
1 D. A. Oare and C. H. Heathcock, J. Org. Chem., 1990, 55, 157.
2 J. Bertrand, L. Gorrichon, P. Maroni and R. Meyer, Tetrahedron Lett.,
1982, 23, 3267.
3 M. Yasuda, N. Ohigashi, I. Shibata and A. Baba, J. Org. Chem., 1999,
64, 2180; M. Yasuda, K. Hayashi, Y. Katoh, I. Shibata and A. Baba,
J. Am. Chem. Soc., 1998, 120, 715.
4 O-Stannylated ketene acetal can be obtained as a kinetic product from
ketene and trialkyltin alkoxide and used at low temperature. E. Shimada,
K. Inomata and T. Mukaiyama, Chem. Lett., 1974, 689.
5 A. Zapata and C. Acunaˆ, Syn. Commun., 1984, 14, 27.
6 M. Pereyre, B. Bellegarde, J. Mendelsohm and J. Valade, J. Organomet.
Chem., 1968, 11, 97; M. Yasuda, Y. Katoh, I. Shibata, A. Baba, H.
Matsuda and N. Sonoda, J. Org. Chem., 1994, 59, 4386.
7 J. G. Noltes, F. Verbeek and H. M. J. C. Creemers, Organomet. Chem.
Synth., 1970/1971, 1, 57.
8 Enol forms generally show higher reactivity than keto forms. K.
Kobayashi, M. Kawanisi, T. Hitomi and S. Kozima, Chem. Lett., 1983,
851.
9 M. Yasuda, Y. Sugawa, A. Yamamoto, I. Shibata and A. Baba,
Tetrahedron Lett., 1996, 37, 5951.
10 M. Yasuda, M. Tsuchida and A. Baba, Chem. Commun., 1998, 563.
11 In the case of 1,4-addition to 2a, a new conjugation with another phenyl
group could appear in the resultant enolate which is first generated in
this reaction course before quenching.
The solvent effect of acetonitrile or nitromethane on yields
probably relates to their coordination ability to the concerned
active species. The additive effect of chlorosilanes on selectiv-
ity of 3e/4e is still not clear.
12 A mixed solution of 1 (1.0 mmol) and chlorotrimethylsilane (2.0 mmol)
in CD3CN (0.5 mL) in a sealed tube at rt for 10 min showed a signal
corresponding to tributylchlorostannane at 122 ppm in 119Sn NMR. The
In conclusion, regioselective addition of a-stannyl ester to
a,b-unsaturated ketones was achieved in 1,2- and 1,4-addition
manner by using stannous chloride and chlorosilanes as
additives, respectively. The transmetallation of stannyl ester
with these additives generates the key reactive intermediates
with proper selectivities. a-Stannyl esters will be attractive
functionalized nucleophiles with these activation method-
ologies because they are easy to prepare and handle and can be
stored for months owing to their moderate stability. The detailed
reaction mechanism is now under investigation and will be
reported in a full account.
1
silylketene acetal was also observed in 29Si NMR (21 ppm) and in H
NMR (3.16 and 3.12 ppm, each signal has a doublet with J = 2.7
Hz).
13 (a) G. S. Burlachenko, B. N. Khasapov, L. I. Petrovskaya, Yu. I. Baukov
and I. F. Lutsenko, Zh. Obshch. Khim., 1966, 36, 512; (b) S. E.
Denmark, R. A. Stavenger, S. B. D. Winter, K.-T. Wong and P. A.
Barsanti, J. Org. Chem., 1998, 63, 9517.
14 29Si NMR (3.5 ppm), 1H NMR (1.9 ppm).
15 The transformation from silylketene acetal to silylester is accelerated in
the presence of mercury salt (ref. 13a).
16 K. Narasaka, K. Soai and T. Mukaiyama, Chem. Lett., 1974, 1223; K.
Narasaka, K. Soai, Y. Aikawa and T. Mukaiyama, Bull. Chem. Soc.,
Jpn., 1976, 49, 779.
This work was supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Science, Sports, and
2150
Chem. Commun., 2000, 2149–2150