Allylation reactions of carbonyl compounds using an organosilicon reagent in aqueous media

Article abstract of DOI:10.1039/b300535f

Allylation reactions of carbonyl compounds such as aldehydes and reactive ketones using allyltrimethoxysilane in aqueous media proceeded smoothly in the presence of 5 mol% of a CdF₂-terpyridine complex; the presence of the ligand plays an impor

Full text of DOI:10.1039/b300535f

Allylation reactions of carbonyl compounds using an organosilicon
reagent in aqueous media
Naohiro Aoyama, Tomoaki Hamada, Kei Manabe and Shu¯ Kobayashi*
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033,
Japan. E-mail: skobayas@mol.f.u-tokyo.ac.jp
Received 15th January 2003, Accepted 11th February 2003
First published as an Advance Article on the web 27th February 2003
Allylation reactions of carbonyl compounds such as alde-
hydes and reactive ketones using allyltrimethoxysilane in
aqueous media proceeded smoothly in the presence of 5
mol% of a CdF2–terpyridine complex; the presence of the
ligand plays an important role for the catalytic activity; the
catalyst was easily recovered and reused without loss of
activity.
the effect of water. The reaction catalyzed by CdF2–3f in
anhydrous THF gave only a trace amount of the product. This
result shows that water is essential for this catalytic system.
With the optimized reaction conditions, this catalyst was
applied to allylation of various aldehydes and ketones (Table
3).† In most aldehydes, their allylated adducts were obtained in
Table
1
Metal fluorides-catalyzed allylation reactions using
allyltrimethoxysilane in the presence of 3aa
Allylation reactions of carbonyl compounds, which afford
synthetically useful homoallylic alcohols, have been a subject
of extensive investigations.1 Recently, development of allyla-
tion reactions in aqueous media has attracted great attention,
because dehydrative drying of the substrates and solvents is not
required, and unique reactivity and selectivity are often
observed.2 In the allylations in aqueous media, highly reactive
allyltins have been often used in many cases.3 On the other
hand, allylsilanes are generally preferable reagents compared to
allyltins due to their low toxicity and simple removal of silicon
by-products. However, as far as we know, there is no report on
allylation reactions of simple carbonyl compounds in aqueous
media using allylsilanes,4 because allylsilanes are generally less
reactive than allyltins. To solve this problem, we decided to
develop ligand-accelerated catalysts. Quite recently, we have
reported that some ligands accelerate metal-catalyzed allylation
reactions using allyltributyltin in aqueous media to realize high
reactivity and even enantioselectivity.5 Herein, we report
allylation reactions using allyltrimethoxysilane in aqueous
media. This is the first example of allylation reaction of simple
carbonyl compounds using an organosilicon reagent in aqueous
media. In this reaction system, remarkable acceleration by
ligands is observed, and allylation of aldehydes and reactive
ketones proceeds smoothly.
Entry
MFn
Yield (%)
Entry
MFn
Yield (%)
1
2
3
4
BiF3
SnF2
InF3
ZnF2
5
10
7
trace
5
6b
7
CdF2
CuF
CuF2
AgF
51
23
48
44
8
a All reactions were carried out with aldehyde 1 (1 equiv.) and allyl-
trimethoxysilane 2 (1.5 equiv.). b CuF was prepared by mixing CuCl and
TBAF in THF at rt, for 30 min.
Table 2 Allylation reactions catalyzed by CdF2–ligand 3 using allyl-
trimethoxysilanea
At first, we selected allyltrimethoxysilane as an allylating
agent6 because it would be activated by the fluoride anion more
easily than allyltrimethysilane. In fact, two groups reported
allylation reactions using a combination of the fluoride anion and
allyltrimethoxysilane in organic solvents.7 We aimed at ligand-
acceleration and chose N,NA-dibenzylethylenediamine (3a) as a
representative ligand, and various metal fluorides were screened
under mild conditions (H2O/THF = 1+9, 30 °C) (Table 1). As a
result, the metal fluorides of soft metal cations such as CdF2,
CuF2, CuF, and AgF gave the allylated product in moderate
yields. Among these metal fluorides, CdF2 gave the best yield.
Other metal fluorides (MgF2, SrF2, ScF3, LaF3, TiF4, ZrF4, HfF4,
FeF3, and NiF2) and other cadmium salts (CdCl2, Cd(ClO4)2) did
not work at all. These results suggest that both the cadmium
cation and the fluoride anion are crucial for the catalysis.
Next, we examined the effect of ligands in the allylation
reaction catalyzed by 5 mol% of CdF2 (Table 2). The reaction
was found to be remarkably accelerated by 3a; the reaction
without 3a gave only 5% yield (entry 1). We tested the ligands
which worked effectively in the case of allyltributyltin (entries
2–4).5 Among them, 2,9-dimethyl-1,10-phenanthroline (3c)
gave higher yield compared with 3a or N,N,NA,NB,NB-pentame-
thyldiethylenetriamine (3b). Interestingly, 1,10-phenanthroline
(3d) and 6,6A-dimethyl-2,2A-bipyridine (3e) were not effective
(entries 5, 6). After further investigations, 2,2A:6A,2B-terpyridine
(3f) was found to be the best ligand (entry 7). We then examined
Entry
Ligand 3
Yield (%)
1
2
—
5
36
3
4
42
82
5
6
16
2
7
93
a All reactions were carried out with aldehyde 1 (1 equiv.) and allyl-
trimethoxysilane 2 (1.5 equiv.).
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CHEM. COMMUN., 2003, 676–677
This journal is © The Royal Society of Chemistry 2003

Table 3 Allylation reactions catalyzed by CdF2–3f using allyltrimethoxy-
silanea
Scheme 1 Reuse of the catalyst
Entry
1
1
Yield (%)
81
investigations on diastereo- and enantioselective allylation
reactions of allyltrimethoxysilane in aqueous media using this
catalyst and elucidation of the mechanism of the ligand-
accelerated allylation are currently in progress in our labo-
ratory.
This work was partially supported by CREST and SORST,
Japan Science and Technology Corporation (JST), and a Grant-
in-Aid for Scientific Research from Japan Society of the
Promotion of Science.
2
3
99
99
4
5
96
82
Notes and references
6
72
† A typical experimental procedure is described for the reaction of
benzaldehyde with allyltrimethoxysilane using the CdF2–3f catalyst. To a
clear solution of CdF2 (2.3 mg) and 3f (3.5 mg) in H2O (0.15 mL) was added
THF (1.35 mL). To this suspension were added benzaldehyde (31.9 mg) and
allyltrimethoxysilane (72.2 mg, 1.5 equiv.) successively. The mixture was
stirred at 30 °C for 9 h and diluted with water (5 mL). The aqueous layer was
extracted with CH2Cl2 three times, and the organic layer was washed with
satd. NaCl and dried over Na2SO4. The solvents were evaporated after
filtration. The residual crude product was purified by preparative TLC on
silica gel to give the pure product as a colorless oil (42.4 mg, 93% yield).
7b
8b
86
32
a The reactions were carried out with aldehyde
allyltrimethoxysilane 2 (1.5 equiv.). b Allyltrimethoxysilane 2 (3 equiv.)
1 (1 equiv.) and
was used and reaction time was 24 h.
1 Y. Yamamoto and N. Asao, Chem. Rev., 1993, 93, 2207.
2 For reviews, see: (a) C. J. Li and T. H. Chan, Organic Reactions in
Aqueous Media, John Wiley & Sons, New York, 1997; (b) Organic
Synthesis in Water, ed. P. A. Grieco, Blackie Academic & Professional,
London, 1998.
3 For example, see: (a) I. Hachiya and S. Kobayashi, J. Org. Chem., 1993,
58, 6958; (b) S. Kobayashi, T. Wakabayashi and H. Oyamada, Chem.
Lett., 1997, 831; (c) A. Yanagisawa, H. Inoue, M. Morodome and H.
Yamamoto, J. Am. Chem. Soc., 1993, 115, 10356; (d) T. P. Loh and J. Xu,
Tetrahedron Lett., 1999, 40, 2431; (e) A. MacCluskey, Green Chem.,
1999, 167; (f) I. Shibata, N. Yoshimura, M. Yabu and A. Baba, Eur. J.
Org. Chem., 2001, 3207.
4 Wang et al. reported Sc(OTf)3-catalyzed allylation of reactive aldehydes
with allyltrimethylsilane in H2O–CH3CN at high temperature: (a) M. W.
Wang, Y. J. Chen, L. Liu, D. Wang and X. L. Liu, J. Chem. Res., 2000,
80; Sakurai et al. suggested that allylation of aldehydes with allyltri-
fluorosilanes in the presence of hydroxy compounds and triethylamine
could be carried out even in the presence of water. However, no
experimental result was shown (b) M. Kira, K. Sato and H. Sakurai, J.
Am. Chem. Soc., 1990, 112, 257.
high yields (entries 1–5), and reactive ketones such as benzyl
pyruvate and 4A-nitroacetophenone also gave the allylated
products in high yields (entries 6, 7). On the other hand,
unreactive ketones such as acetophenone afforded the product
in lower yield (entry 8).
Considering the toxicity of cadmium compounds, it is
desirable to recover and reuse the cadmium catalyst. In the
present catalytic system using CdF2 and 3f, the recovery and
reuse of the cadmium complex was performed by extraction
with water (4 times) after diluting the reaction mixture with
ether. ICP-MS determination of the cadmium amount in the
organic phase showed that more than 99.99% cadmium was
extracted with water. After concentrating the aqueous phase, the
catalyst was recovered and reused without loss of catalytic
activity (Scheme 1).
In conclusion, we have developed allylation reactions
catalyzed by CdF2–terpyridine using allyltrimethoxysilane in
aqueous media. This unique ligand-accelerated catalytic system
gave the corresponding products of various aldehydes and
reactive ketones in high yields. Although the mechanism of the
cadmium-catalyzed allylation including the ligand acceleration
has not been clarified yet, to the best of our knowledge, this is
the first example of an allylation reaction using an allyl-
trimethoxysilane in aqueous media. It is noteworthy that toxic
tin reagents are not needed for the synthesis and that the catalyst
was easily recovered and reused without loss of activity. Further
5 (a) S. Kobayashi, N. Aoyama and K. Manabe, Synlett, 2002, 483; (b) S.
Kobayashi, N. Aoyama and K. Manabe, Chirality, 2003, 15, 124.
6 (a) K. Sato, M. Kira and H. Sakurai, J. Am. Chem. Soc., 1989, 111, 6429;
(b) A. Hosomi, S. Kohra, K. Ogata, T. Yanagi and Y. Tominaga, J. Org.
Chem., 1990, 55, 2415.
7 For combinations of metal fluorides and allyltrimethoxysilane, see: (a) A.
Yanagisawa, H. Kageyama, Y. Nakatsuka, K. Asakawa, Y. Matsumoto
and H. Yamamoto, Angew. Chem., Int. Ed., 1999, 38, 3701; (b) S.
Yamasaki, K. Fujii, R. Wada, M. Kanai and M. Shibasaki, J. Am. Chem.
Soc., 2002, 124, 6536. For a combination of a metal fluoride and
allyltrimethylsilane, see (c) D. R. Gauthier, Jr. and E. M. Carreira,
Angew. Chem., Int. Ed. Engl., 1996, 35, 2363.
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