Directed ortho-metalation, a new insight into organosodium chemistry

Article abstract of DOI:10.1002/1521-3773(20020118)41:2<340::AID-ANIE340>3.0.CO;2-D

Finely dispersed metallic sodium in combination with an alkyl chloride RCcan replace organolithium reagents in the ortho-metalation of aromatic compounds (see scheme). The in situ generated base is consumed as soon as it is formed, which avoids Wurtz coupling, the usual side reaction, and the handling and storage of highly reactive alkyl sodium bases. Reaction conditions are mild, the reaction is easy to scale up, and the reagents needed are inexpensive.

Full text of DOI:10.1002/1521-3773(20020118)41:2<340::AID-ANIE340>3.0.CO;2-D

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sodium.[2±6] Under classical conditions, organohalides react
with sodium to give mainly Wurtz coupling products.
[
3] a) N. A. Paras, D. W. C. MacMillan, J. Am. Chem. Soc. 2001, 123, 4370;
b) S. Hanessian, V. Pham, Org. Lett. 2000, 2, 2975; c) for a recent
review on asymmetric synthesis with organic catalysts see P. I. Dalko,
L. Moisan, Angew. Chem. 2001, 113, 3841; Angew. Chem. Int. Ed. 2001,
[7, 8]
Moreover, alkylsodium compounds show poor stability,
especially in ethereal solvents.[
9, 10]
As a consequence, in spite
4
0, 3726.
4] E. Emori, T. Arai, H. Sasai, M. Shibasaki, J. Am. Chem. Soc. 1998, 120,
043 ± 4044.
5] S. Colonna, A. Re, H. Wynberg, J. Chem. Soc. Perkin Trans. 1 1981,
47.
[
[
[
[
[
[
of the low cost of metallic sodium and the sometimes
4
[11]
demonstrated interesting reactivity,
alkylsodium com-
pounds have not been considered so far as valuable organo-
metallic reagents in organic synthesis.
5
6] a) H. Wynberg, Top. Stereochem. 1986, 16, 87; b) H. Hiemstra, H.
Wynberg, J. Am. Chem. Soc. 1981, 103, 417.
Herein we report on a straightforward and efficient one-pot
ortho-metalation procedure relying on the generation of
sodiated organic bases from RCl and a stoichiometric amount
of metallic sodium in the presence of aromatic substrates.[
Under these conditions, handling and storage of alkylsodium
compounds is avoided and ortho-metalation is favored over
7] K. Suzuki, A. Ikegawa, T. Mukaiyama, Bull. Chem. Soc. Jpn. 1982, 55,
3
277.
8] M. Ostendorf, S. van der Neut, F. P. J. T. Rutges, H. Hiemstra, Eur. J.
Org. Chem. 2000, 105.
9] a) F. Toda, K. Tanaka, J. Sato, Tetrahedron: Asymmetry 1993, 4, 17 7 1;
b) A. Ito, K. Konishi, T. Aida, Tetrahdron Lett. 1996, 37, 2585; c) K.
Nishimura, M. Ono, Y. Nagaoka, K. Tomioka, J. Am. Chem. Soc. 1997,
12]
[13]
usual coupling and solvolysis side reactions.
1
19, 12974.
1
,3-Dimethoxybenzene (1,3-DMB), known to undergo
[
[
[
10] For a highly diastereoselective reduction of (R)-3-(p-tert-butylphe-
nylsulfanyl)cyclohexan-1-one see: K. Suzuki, A. Ikegawa, T. Mu-
kaiyama, Chem. Lett. 1982, 899.
[14]
ortho-metalation with alkyllithium bases in good yields,
was selected as a model substrate to investigate the scope of
the reaction with alkylsodium compounds [Eq. (1)]. Several
parameters, including solvent, temperature, and the nature of
the organohalide, were varied (Table 1). All reactions were
quenched by addition of dry-ice, and the yield of acid [see
Eq. (1)] was considered as indicative of the metalation
11] For conversion of thioethers to ketones see: a) A. D. Lebsack, L. E.
Overman, R. J. Valentekovich, J. Am. Chem. Soc. 2001, 123, 4851;
b) R. D. Little, S. O. Myong, Tetrahedron Lett. 1980, 21, 3339.
12] a) Y. Chen, S.-K. Tian, L. Deng, J. Am. Chem. Soc. 2000, 122, 9542;
b) C. Choi, S.-K. Tian, L. Deng, Synthesis 2001, 1737; c) S.-K. Tian, L.
Deng, J. Am. Chem. Soc. 2001, 123, 6195; d) Y. Chen, L. Deng, J. Am.
Chem. Soc. 2001, 123, 11302; e) J. Hang, S.-K. Tian, L. Tang, L. Deng,
J. Am. Chem. Soc. 2001, 123, 12696.
[15]
efficiency.
Na
COOH
O
O
1) CO2
Na sand
O
O
O
O
(1)
+
RX, solvent
3
2) H O
Directed ortho-Metalation, a New Insight into
Organosodium Chemistry**
Table 1. Influence of some parameters on the directed ortho-sodiation of
1,3-DMB [Eq. (1)].[
a]
Arnaud Gissot, Jean-Michel Becht,
Jean Roger Desmurs, Virginie P e¬ v e¡ re, Alain Wagner,*
and Charles Mioskowski*
Entry
RX
Solvent
T [8C]
Yield [%]
70
1
2
3
4
1-chlorooctane
2-chloropropane
2-bromopropane
chlorobenzene
1-chlorooctane
1-chlorooctane
toluene
toluene
toluene
toluene
20
20
0
20
20
[
b]
8
From laboratory to industrial scale, the use of strong
organoalkali metal bases is almost exclusively restricted to
alkyllithium derivatives.[1] They are commercially available as
21
35[
c]
[
d]
5
6
7
Et
2
O or THF
45 or 86
30 or 28
THF or toluene
toluene 110
À 15
1
±2m solutions, quite stable and easily generated from
1-chlorooctane
20
alkylhalides and lithium. In contrast, the synthesis of alkylso-
dium compounds is much more troublesome and requires
high-speed mechanical stirring, low temperatures, and excess
[
a] The sodium sand was obtained by dispersing melted sodium under
vigorous mechanical stirring; see Experimental Section. [b] Tˆ room
temperature or 08C. [c] 2,6-dimethoxybiphenyl was also isolated in 35%
yield.[
16, 17]
2 4 2
[d] Me SO instead of CO used as electrophile.
[
*] Dr. A. Wagner, Dr. C. Mioskowski, A. Gissot, J.-M. Becht
Laboratoire de Synth e¡ se Bio-organique
In the presence of 1-chlorooctane (or 1-chloropropane) 2,6-
dimethoxybenzoic acid was obtained in 70% yield (entry 1),
comparable to the yield of classical nBuLi metalations.
When the reaction was conducted in a two-step manner, that
is, when the alkylsodium compound was synthesized prior to
the addition of 1,3-DMB, only trace amounts (<1%) of
carboxylic acid were detected. The sterically hindered neo-
Universit e¬ Louis Pasteur de Strasbourg
UMR 7514, Facult e¬ de Pharmacie
7
6
4, route du Rhin ± B. P. 24
7401 Illkirch cedex (France)
[14]
Fax : (‡33)3-9024-4306
E-mail: Wagner@bioorga.u-strasbg.fr
Mioskowski@bioorga.u-strasbg.fr
Dr. J. R. Desmurs, Dr. V. P e¬ v e¡ re
Rhodia Chimie Fine
pentyl chloride did not give any metalation product, and
8
6
5, Avenue des fr e¡ res Perret
9192 St-Fons Cedex (France)
[3a]
secondary chloroalkanes gave poor results (entry 2).
As
expected, primary bromoalkanes were too reactive toward
sodium, even at low temperature. Yet, secondary bromoal-
kanes, with a lower tendency to undergo Wurtz coupling, gave
the desired acid in moderate yield (entry 3).
[
**] We thank the Minist e¡ re de la Recherche et de l×Enseignement for
MRE grants to A. Gissot and J.-M. Becht. We are also grateful to Prof.
Manfred Schlosser, Lausanne, and Dr. Matteo Zanda, Milan, Italy, for
helpful suggestions.
340
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Although alkylsodium compounds react with ethereal
Similar trends were observed with 1,4-DMB and anisole.
No acid was formed in toluene or THF until micronized
sodium dispersion was used (entries 3 and 4). The slow
metalation of anisole might account for the modest 45% yield
[
10]
solvents much faster than alkyllithium compounds, reac-
tion (1) was efficiently conducted not only in toluene, but also
in THF and to a lesser extent in diethyl ether (entries 1 and 5).
The thermal instability of alkylsodium compounds[ did not
prevent the reaction using melted sodium to give the metal-
ation product in 20% yield (entry 7). This result emphasizes
the exceptional thermal stability of 2,6-dimethoxyphenylso-
dium. At À158C, 2,6-dimethoxybenzoic acid was formed in
modest yields (entry 6). In this case, part of the chlorooctane
remained unreacted, and no improvement was achieved by
increasing the reaction time.
18]
[26]
obtained.
Heterocyclic systems known to easily undergo a-metal-
ation, such as thiophene and benzofuran, were successfully
[
27]
metalated using sodium sand dispersion (entries 5 and 6).
Not surprisingly,[ other aromatic compounds bearing elec-
tron-withdrawing groups, like oxazolines, secondary and
tertiary amides, invariably failed to undergo metalation.[
In these cases, metallic sodium reacts with the aromatic ring to
form complex mixtures even prior to the addition of the
chlorooctane.
28]
12b, 29]
Noteworthy, under optimized conditions, that is, slow
addition of 1.2 equiv of pure 1-chlorooctane at room temper-
ature to a mixture of the aromatic substrate and 2.6 equiv of
sodium in toluene, the reaction was successfully carried out on
a 1-kg scale.
Since only few reports exist on the reactivity of sodiated
carbanions the ortho-sodiated anion was quenched with
various electrophiles. The results proved to be comparable
The three-component heterogeneous ortho-metalation pre-
sented here involves a complex set of equilibria. The desired
path will be followed as soon as the aromatic derivative to be
metalated will efficiently trap the in situ formed alkylsodium
compound. In other words, the extent of side reactions
indebted to the alkylsodium compound, that is homo-coupling
and solvolysis, has to be minimized. This holds as long as the
substrate bears a readily labile hydrogen as in the case of
thiophene or benzofuran (see Table 3, entries 5 and 6).
Nevertheless, the substrate acidity alone cannot account for
our experimental results as studies by Schlosser and Maggi of
the relative rates of the metalation of the DMB isomers
with s-butyllithium in THF gave the order 1,4- > 1,3- ꢀ 1,2-
DMB.[
to those reported for conventional commercially available
organolithium bases,[
19±23]
with yields ranging from 52 to 86%
(
Table 2).
Table 2. Reaction of various electrophiles with 2,6-dimethoxyphenylso-
dium.
Entry Electrophile Yield [%][a] Entry Electrophile Yield [%][a]
30]
1
2
3
DMF
B(OMe)
52 ( ± )
4
5
6
PhCH
2
Br
75 (57[21])
1,3-DMB is the only substrate that reacts with the sodium
70[ (57[19])
b]
Me
Me
S
2
SO
4
75 (85
86 (76
[22]
)
)
3
2
sand dispersion, although 1,4-DMB undergoes proton ab-
straction with ease. Hence, an additional parameter that
influences the whole process has to be taken into account. We
believe the ortho-metalation step takes place on the metallic
surface within the coordination sphere of the alkylsodium
molecules progressively formed (Scheme 1), whereby the
[c]
[23]
Me
3
SiCl
76 (83[20])
2
[
a] Yields from other publications in brackets. [b] 2,6-Dimethoxyphenylso-
dium was added dropwise to a trimethylborate solution in toluene. [c] With
THF as solvent.
We then tried to extend the scope of our method to other
aromatic ethers. 1,2-DMB failed to react under the optimized
conditions given above (Table 3, entry 1). Only nonylbenzene
arising from solvent metalation was obtained.[ Changing the
solvent from toluene to THF resulted in a complex reaction
mixture. When 1-chlorooctane was added over a 3 h period to
disfavor Wurtz coupling, the yield was brought to 20%
Na
OMe
24]
stable in
solution
OMe
solvolysis
R
Wurtz-type
products
sol
R
(
entry 1). To further favor the heterogeneous reaction, hence
chlorooctane sol
Na
the formation of the alkylsodium compound, finely divided
micronized sodium was tested.[25] Under these conditions, 1,2-
[
R-Na]n sol
OMe
OMe
DMB underwent clean metalation affording the correspond-
ing carboxylic acid in 80% yield (entry 2).
ads
chlorooctane ads
R
A
ads + R-Na ads
metallic surface
R
Na
B
Scheme 1. Proposed mechanism for the directed ortho-sodiation of
aromatic ethers.
Table 3. Sodiation of other substrates in the presence of 1-chlorooctane.
Entry Aromatic compound Sodium dispersion[a] Solvent Yield [%]
1
2
3
4
5
6
1,2-DMB
1,2-DMB
1,4-DMB
anisole
thiophene
benzofuran
sand
toluene
0, 20[b]
substrate is driven onto the surface as a result of its affinity for
Na . Literature and our experimental data strongly support
micronized
micronized
micronized
sand
toluene 80
toluene 88
toluene 25, 45[
toluene 90
toluene 85
‡
this hypothesis. If the abilities of lithiated and of sodiated
alkyl bases to coordinate to aromatic ethers are assumed to be
similar, anisole binds weakly to an alkylsodium compound
whereas 1,3-DMB and an alkylsodium compound form a
b]
sand
[
a] The micronized dispersion in toluene is commercially available from
[31]
strong complex. 1,3-DMB bears a labile hydrogen and binds
Aldrich. [b] This yield was obtained when diluted 1-chlorooctane was
added slowly.
‡
[30, 32]
Na tightly,
ortho-metalation on the sodium surface will
Angew. Chem. Int. Ed. 2002, 41, No. 2
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341

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be highly favored, and the reaction will proceed even with
sodium sand. Interestingly, 1,3-DMB forms a strong complex
with Na as the reaction can be successfully carried out in
Typical metalation procedure: The aromatic substrate (1 equiv) was added
to the sodium dispersion (2.6 equiv) at room temperature. A small portion
(
roughly one tenth of 1.3 equiv) of the alkyl halide was added drop-wise to
‡
initiate the reaction. The reaction initiated within 2 ± 5 min and was
characterized by a slight increase of the temperature. The remaining alkyl
halide was then added at constant temperature (if necessary, the reaction
was cooled). Metalation was monitored by the slow disappearance of
sodium and was usually complete within one to two hours. The electrophile
was finally added to the mixture at room temperature and allowed to react
for a period ranging from two to ten hours depending on the electrophile.
weakly coordinating solvents such as THF or diethylether
‡
(
Table 1, entries 5 and 6).[33,34] In contrast, anisole binds Na
[26]
weakly and reacts very slowly with strong bases. As a result,
the amount of anisole on the sodium sand surface is low, and
alkylsodium molecules will be slowly released in the solution.
While Wurtz-type products (nonylbenzene and hexadecane)
will form in toluene, alkylsodium compounds will decompose
rapidly in THF and no ortho-metalation is observed.
Since both 1-chlorooctane and anisole compete for the
occupation of the metallic surface, complex A will more likely
form if the specific area of the metal is increased and/or if the
chlorooctane concentration is kept negligible, that is, when
the amount of B is made as low as possible (Scheme 1;
Table 3, entry 4).[
Received: July 25, 2001
Revised: November 5, 2001 [Z17600]
[1] For general references on organoalkali metal reagents see a) M.
Schlosser, Organometallics in Synthesis, Wiley, New York, 1996,
chap. 1 and 2; b) R. G. Jones, H. Gilman, Chem. Rev. 1954, 54, 835.
[
2] For general reviews on alkylsodium compounds see a) M. Schlosser,
Angew. Chem. 1964, 76, 258; Angew. Chem. Int. Ed. Engl. 1964, 3, 362;
b) M. Schlosser, Angew. Chem. 1964, 76, 124; Angew. Chem. Int. Ed.
Engl. 1964, 3, 287; c) R. A. Benkeser, D. J. Foster, D. M. Sauve, J. F.
Nobis, Chem. Rev. 1957, 57, 867.
35]
The behavior of 1,2- and 1,4-DMB lies between these two
extreme cases; they show intermediate reactivity toward the
sodium/alkylchloride metalation system. 1,4-DMB is meta-
[
3] For examples see a) A. A. Morton, J. B. Davidson, R. J. Best, J. Am.
Chem. Soc. 1942, 64, 2239; b) P. G. Gassman, D. S. Patton, J. Am.
Chem. Soc. 1968, 90, 7276; c) M. Schlosser, J. Hartmann, M. St‰hle, J.
Kramar, A. Walde, A. Mordini, Chimia 1986, 40, 306; d) M. St‰hle, R.
Lehmann, J. Kramar, M. Schlosser, Chimia 1985, 39, 229; e) J.
Einhorn, J. L. Luche, Tetrahedron Lett. 1986, 27, 501; f) D. H. R.
Barton, F. S. Guziec, I. Shahak, J. Chem. Soc. Perkin Trans. 1 1974,
lated very efficiently,[ while its affinity for Na is close to
30]
‡
that of anisole. On the other hand, 1,2-DMB coordinates to
‡
[32b]
Na quite strongly
but reacts very slowly with strong
bases.[ Low reactivity and low affinity prevent ortho-metal-
30]
ation in the presence of sodium sand (Table 3, entry 1).
Nevertheless, the reaction proceeds with ease when the
specific area of sodium is increased (Table 3, entries 2 and 3).
Besides, the low reactivity of secondary chloroalkanes and
the failure of the reaction at low temperature can be ascribed
to the fact that the disruption of the sodium particles into
1
794.
[
4] a) Ref. [3a]; b) W. L. Carothers, D. D. Coffman, J. Am. Chem. Soc.
1929, 51, 588; c) A. A. Morton, J. B. Davidson, R. J. Best, J. Am.
Chem. Soc. 1942, 64, 2240; d) A. A. Morton, G. M. Richardson, J. Am.
Chem. Soc. 1940, 62, 123.
[
[
[
5] a) H. Gilman, R. L. Bebb, J. Am. Chem. Soc. 1939, 61, 109; b) H.
Gilman, R. V. Young, J. Am. Chem. Soc. 1935, 57, 1121; c) W. Schlenk,
J. Holtz, Ber. Dtsch. Chem. Ges. 1917, 50, 269.
6] Their reactivity was shown to depend on the method employed for
their synthesis, see A. A. Morton, J. T. Massengale, J. Am. Chem. Soc.
smaller aggregates caused by the heat released during the
alkylsodium formation is inhibited.[
36]
The formation of
secondary alkylsodium compounds is much less exothermi-
[
3a]
c, so the metallic surface is more and more shielded as NaCl
is progressively formed on it; the result of this is a poor
metalation efficiency (Table 1, entries 2 and 6). This hypoth-
esis is corroborated by the unaltered aspect of the sodium
dispersion at the end of the reaction.
1
940, 62, 120.
7] Historically, alkylsodium compounds were prepared from different
sources, see a) J. A. Wanklyn, Justus Liebigs Ann. Chem. 1858, 107,
125; b) F. S. Acree, Am. Chem. J. 1903, 29, 588; c) W. Schlenk, J.
Appendrodt, A. Michael, A. Thal, Ber. Dtsch. Chem. Ges. 1914, 47,
4
73; d) W. Schlenk, E. Marcus, Ber. Dtsch. Chem. Ges. 1914, 47, 1664;
In conclusion, we have demonstrated that alkylsodium
compounds are synthetically useful reagents. Our process
requires only inexpensive and readily available reagents.
Transportation, storage, and handling of sensitive and danger-
ous organolithium bases are also avoided. This sodium/
chlorooctane-mediated metalation opens new prospects for
the metalation of aromatic ethers and heterocycles in
laboratories and in the industry.[ Investigations are currently
underway to extend the strategy to the metalation of aromatic
derivatives containing electron-withdrawing groups.
e) W. Schlenk, J. Holtz, Ber. Dtsch. Chem. Ges. 1917, 50, 262; f) K.
Hess, H. Munderloch, Ber. Dtsch. Chem. Ges. 1918, 51, 37 7 ; g) H.
Gilman, R. V. Young, J. Am. Chem. Soc. 1936, 58, 315; h) R. L.
Letsinger, J. G. Traynham, J. Am. Chem. Soc. 1948, 70, 3342; i) L.
Lochmann, J. Pospisil, D. Lim, Tetrahedron Lett. 1966, 257; j) U.
Azzeno, T. Denurra, G. Melloni, A. M. Piroddi, J. Org. Chem. 1990,
5
5, 5386; k) E. Weiss, Angew. Chem. 1993, 105, 1565; Angew. Chem.
Int. Ed. Engl. 1993, 32, 1501.
[8] A. Wurtz, Justus Liebigs Ann. Chem. 1855, 96, 364.
9] See ref. [4b,c].
37]
[
[
[
10] Alkylsodium compounds react very rapidly with ethereal solvents to
afford sluggish reaction mixtures: a) P. Schorigin, Ber. Dtsch. Chem.
Ges. 1910, 43, 1938; b) P. Schorigin, Ber. Dtsch. Chem. Ges. 1908, 41,
2711.
11] a) Ref. [5a]; b) H. Gilman, H. A. Pacevitz, O. Baine, J. Am. Chem.
Soc. 1940, 62, 1514.
[12] Reviews on ortho-metalation: a) V. Snieckus, Bull. Soc. Chim. Fr.
1988, 67; b) V. Snieckus, Chem. Rev. 1990, 90, 879.
[13] Examples of ortho-metalations using essentially pure solutions of
alkylsodium compounds can be found in ref. [2c] and references
therein.
[14] R. Levine, J. R. Sommers, J. Org. Chem. 1974, 39, 3559.
[15] H. Gilman, H. A. Pacevitz, J. Am. Chem. Soc. 1940, 62, 1301.
[16] Under optimized conditions, the biphenyl derivative was obtained in
72% yield.
Experimental Section
Preparation of the sodium dispersion: The quantity of sodium needed was
cut off in small pieces from metal sticks, washed with hexane, and
immediately added to dry toluene (35 mL per g Na) under inert atmos-
phere in a three-necked flask equipped with a condenser, a mechanical
stirrer and a dropping funnel. The temperature was raised to 1108C under
gentle stirring until the metal fusion was complete (a uniformly bright
metal was obtained). The mixture was then cooled to room temperature
under vigorous stirring until a finely divided sodium dispersion was
obtained. The dispersion usually consisted of small round gray particles of
roughly 1 mm size.
342
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
1433-7851/02/4102-0342 $ 17.50+.50/0
Angew. Chem. Int. Ed. 2002, 41, No. 2

COMMUNICATIONS
[
17] This reaction has already been observed: G. Ehrhart, Chem. Ber. 1963,
6, 2042.
18] a) Ref. [4b]; b) A. A. Morton, H. A. Newey, J. Am. Chem. Soc. 1942,
4, 2242.
Palladium-Catalyzed Regio- and
9
Diastereoselective Tandem Silastannylation/
Allyl Addition of Allene Aldehydes and Allene
Ketones: Synthesis of cis Cyclopentanols and
Cyclohexanols**
[
6
[
[
19] D. Q. Quan, Bull. Soc. Chim. Fr. 1973, 2, 767.
20] G. P. Crowther, R. J. Sundberg, A. M. Sarpeshkar, J. Org. Chem. 1984,
4
9, 4657.
[
21] F. J. Brown, P. E. Bernstein, L. A. Cronk, D. L. Dosset, K. C. Hebbel,
J. Med. Chem. 1989, 32, 820.
Suk-Ku Kang,* Young-Hwan Ha, Byung-Soo Ko,
Yoongho Lim, and Jihyun Jung
[22] P. Jacob, A. T. Shulgin, Synth. Commun. 1981, 11, 957.
[23] J. P. Lambooy, J. Am. Chem. Soc. 1956, 78, 7 7 1.
[24] a) Ref. [3a]; b) Ref. [11b]; c) A. A. Morton, G. M. Richardson, J. Am.
Chem. Soc. 1941, 63, 327.
To achieve economically useful transformations in organic
synthesis it would be desirable if multistep bond formations
and/or bond cleavages could be facilitated with a single
catalyst in one pot at a constant temperature. Such a process
would minimize the amount of chemicals, the production of
[
[
25] The micronized sodium dispersion refers to sodium dust <100 mm.
26] a) Ref. [5a]; b) A. A. Morton, E. J. Lanpher, J. Org. Chem. 1958, 23,
1
639.
[
27] a) H. W. Gschwend, H. R. Rodriguez, Org. React. 1979, 26, 1; b) J. W.
Schick, H. D. Hartough, J. Am. Chem. Soc. 1948, 70, 286.
waste, and the processing time.[ In this regard, Jeong et al.
1, 2]
[3]
[
[
[
[
28] E. Alonso, D. J. Ramon, M. Yus, Tetrahedron 1998, 54, 13629.
29] H. W. Gschwend, A. Hamdan, J. Org. Chem. 1975, 40, 2008.
30] M. Schlosser, R. Maggi, Tetrahedron Lett. 1999, 40, 8797.
31] 1,3-DMB and anisole disrupt butyllithium oligomers in C
,3-DMB forms a stable complex, free and complexed anisole coexist
in solution: W. Bauer, P. von R. Schleyer, J. Am. Chem. Soc. 1989, 111,
191.
reported allylation/Pauson ± Khand reactions with two artifi-
cial catalysts in a one-pot procedure. Subsequently, Evans
et al.[ developed the allylation/Pauson ± Khand reaction in a
tandem sequence with a Rh complex as the only catalyst.
4]
8 8
D . While
1
[5]
Recently, Shibasaki and co-workers reported a one-pot
7
synthesis of b-cyanohydrin from olefins mediated by a Zr
catalyst.
‡
[
32] a) Ref. [31]; b) in addition, the binding energies for Na ± 1,2-dime-
‡
thoxyethane and Na ± dimethylether in the gas phase were measured
and calculated; the affinity is stronger in the case of the cyclic bridged
chelate (39.4 and 17.6 kcalmol , respectively): T. B. McMahon, G.
Ohanessian, Chem. Eur. J. 2000, 6, 2931.
The palladium-catalyzed addition of silylstannanes to
allenes is known and the palladium- or platinum-catalyzed
À1
[6]
addition of allylstannanes to aldehydes was reported by
Yamamoto et al.[ However, to the best of our knowledge,
the transition metal catalyzed addition of allylstannanes to
ketones has not yet been successful. Our ongoing studies into
[
33] For examples see: a) M. Vos, F. J. J. de Kanter, M. Schakel, N. J. R.
van Eikema Hommes, G. W. Klumpp, J. Am. Chem. Soc. 1987, 109,
7, 8]
2
187; b) E. Wehman, J. T. B. H. Jastrzebski, J. M. Ernsting, D. M.
Grove, G. van Koten, J. Organomet. Chem. 1988, 353, 145.
34] a) H. J. Reich, B. O. Gudmundsson, J. Am. Chem. Soc. 1996, 118, 6074;
b) H. J. Reich, W. S. Goldenberg, A. W. Sanders, C. C. Tzschucke,
Org. Lett. 2001, 3, 33.
35] The fact that very slow addition of the chlorooctane led to some
product formation ruled out the hypothesis that the higher reactivity
observed with the micronized dispersion is a consequence of a
different origin of the sodium dispersions. For the preparation and
reactivity of metals see: P. Cintas, Activated Metals in Organic
Chemistry, CRC, Boca Raton, FL, USA, 1993.
[
[
[9]
the use of allene substrates in organic synthesis led us to
believe that allene aldehydes and allene ketones are good
substrates for palladium-catalyzed silastannylations. In a
tandem reaction, the resulting allylstannanes would be good
candidates for carbonyl allyl addition with a single palladium
catalyst at a constant temperature (Scheme 1).
The results of the tandem silastannylation/carbonyl allyl
addition of allene aldehydes and allene ketones to form cis
[
36] The composition of these aggregates was analyzed: A. A. Morton,
A. E. Brachman, J. Am. Chem. Soc. 1954, 76, 2980.
37] a) A. Wagner, C. Mioskowski, A. Gissot, J. R. Desmurs, S. Jost
cyclopentanols[
10]
are summarized in Table 1. In finding
[
(
Rhodia Chimie), WO 0064905, 2000; b) V. P e¬ v e¡ re, J. R. Des-
murs, C. Mioskowski, A. Wagner, A. Gissot (Rhodia Chimie),
WO 9959941, 1999.
SiMe3
O
SiMe3
H
Pd0
SnBu3
Pd0
X
X
X
O
Me3SiSnBu3
n
OH
n
n
R
R
R
Scheme 1. Tandem silastannylation/allyl addition of allene aldehydes and allene
ketones (n ˆ 1, 2; R ˆ H, CH ; X ˆ NTs, O, C(CO Et) , etc.).
3
2
2
[
*] Prof. Dr. S.-K. Kang, Y.-H. Ha, B.-S. Ko
Department of Chemistry and BK-21 School of Molecular Science
Sungkyunkwan University
Suwon 440-746 (Korea)
Fax : (‡82)31-290-7079
E-mail: skkang@chem.skku.ac.kr
Prof. Dr. Y. Lim, J. Jung
Department of Applied Biology and Chemistry
Konkuk University
Seoul 143-701 (Korea)
[
**] This work was supported by the National Research Laboratory
Project administrated by the Ministry of Science and Technology and
KOSEF-CMDS.
Supporting information for this article is available on the WWW under
http://www.angewandte.com or from the author.
Angew. Chem. Int. Ed. 2002, 41, No. 2
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
1433-7851/02/4102-0343 $ 17.50+.50/0
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