Iron(III) chloride-catalyzed effective allylation reactions of aldehydes with allyltrimethylsilane

Article abstract of DOI:10.1016/S0040-4039(02)02107-X

Iron(III) chloride-catalyzed allylation reactions of a variety of aldehydes with allyltrimethylsilane proceeded efficiently and smoothly to afford the corresponding homoallyl alcohols in high to excellent yields. This novel method could be suitable especi

Full text of DOI:10.1016/S0040-4039(02)02107-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 8959–8962
Iron(III) chloride-catalyzed effective allylation reactions of
aldehydes with allyltrimethylsilane
Tsutomu Watahiki and Takeshi Oriyama*
Faculty of Science, Ibaraki University, Bunkyo, Mito 310-8512, Japan
Received 11 September 2002; revised 24 September 2002; accepted 26 September 2002
Abstract—Iron(III) chloride-catalyzed allylation reactions of a variety of aldehydes with allyltrimethylsilane proceeded efficiently
and smoothly to afford the corresponding homoallyl alcohols in high to excellent yields. This novel method could be suitable
especially for the allylation of sterically hindered aliphatic aldehydes. © 2002 Elsevier Science Ltd. All rights reserved.
Lewis acid catalyzed allylations of aldehydes with
allylic metal reagents are an important carbon-carbon
bond forming reaction, since they give synthetically
useful homoallyl alcohols.1 Among various allylic metal
reagents, allyltrialkylsilanes are inexpensive and non-
toxic compounds compared to allylstannanes, and
many allylation reactions using allylsilanes have been
developed.2 In these reactions, traditional Lewis acids
such as TiCl4, BF3·OEt2, and SnCl4 have been generally
used, though stoichiometric or near-stoichiometric
amounts of Lewis acid were required to perform the
reaction completely for the reason that the alcohol
oxygen atom coordinates tightly to the Lewis acid.3
Recently, various rare earth metal triflates such as
Sc(OTf)3, La(OTf)3, and Yb(OTf)3 were known to be
utilized as Lewis acid catalysts to promote the allyla-
tion reactions.4 However, these cases involve some
annoying problems: (1) use of very expensive Lewis
acids; (2) longer reaction time; (3) lower yields of
allylation products in the case of aliphatic aldehydes;
and (4) substrate limitation, and so on. Therefore, we
have been interested in developing a highly efficient and
widely applicable allylation reaction using an inexpen-
sive Lewis acid catalyst.
Initially, we examined the reaction of benzaldehyde
with 2 equiv. of allyltrimethylsilane in the presence of 5
mol% of anhydrous FeCl3 in MeNO2 at room temper-
7
ature; however, the corresponding homoallyl alcohol
was scarcely obtained (Table 1, Run 1), because over-
allylation products, such as 1 and 2 (Fig. 1),4c,8 were
formed in moderate yields (48 and 18%, respectively).
To control the reactivity of this allylation reaction, we
tested the reaction temperature. Predictably, the yields
of desired product could be improved and the forma-
tion of side products suppressed by lowering the reac-
Table 1. The effect of reaction temperature
Run
Temp. (°C)
Time (h)
Yielda (%)
1
2
3
4
rt
2
2
1
1
0
54
66
69
0
−20
−29
Iron is an abundant, cheap, and benign element which
exists in nature, and many reactions using iron salts
have been developed recently in organic synthesis.5
Nevertheless, an FeCl3-catalyzed allylation reaction has
not been reported so far.6 Herein we wish to report a
highly efficient and convenient procedure for the allyla-
tion of various aldehydes with allyltrimethylsilane in
the presence of a catalytic amount of FeCl3.
a Combined yields of alcohol and silyl ether.
* Corresponding author.
Figure 1. Over-allylation products.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02107-X

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T. Watahiki, T. Oriyama / Tetrahedron Letters 43 (2002) 8959–8962
Table 2. The effect of solvent
Representative and successful examples for the synthe-
ses of various homoallyl alcohols from aromatic and
aliphatic aldehydes are collected in Table 3.9 Electron-
deficient aromatic aldehydes were allylated in excellent
yields (Runs 1–6). However, in the case of electron-rich
aromatic aldehydes such as p-anisaldehyde and p-tolu-
aldehyde, over-allylation occurred via a stabilized ben-
zylic cation (Run 8–11). In contrast, FeCl3 catalyzed
reaction of acetal with allylsilane gave satisfactory
result. That is, the corresponding allylated product was
obtained in 92% yield by the treatment of p-anisalde-
hyde dimethyl acetal with allyltrimethylsilane promoted
by 5 mol% FeCl3 (Scheme 2). In general, it is antici-
pated that the allylation of an aliphatic aldehyde is
more difficult than that of an aromatic aldehyde
because of the higher electron density of the carbonyl
group. Fortunately, aliphatic aldehydes could be allyl-
ated in high yields with only 5 mol% of FeCl3 at room
temperature (Runs 12–17). Especially, it should be
noted that sterically hindered aldehydes, such as
diphenylacetaldehyde and trimethylacetaldehyde, which
branched at the a-position to the carbonyl group, were
transformed smoothly into the corresponding homoal-
lyl alcohols in excellent yields (Runs 14–17). Further-
more, we also investigated the diastereoselective
allylation of aldehyde having a chiral center (Run 15).
Although the stereoselectivity was not satisfactory
(syn:anti=1.8:1) considering Cram’s rule, this was
almost equal to the results reported so far on the
allylation promoted by TiCl4, BF3·OEt2, and SnCl4.10
Run
x (equiv.)
Solvent
Time (h)
Yielda (%)
1
2
3
4
5
6
2
2
2
2
1.5
1.1
MeNO2
CH2Cl2
MeCN
THF
MeNO2
MeNO2
1
1
4
4
1
66
33
0
0
81
55
16
a Combined yields of alcohol and silyl ether.
Scheme 1. Allylation of benzaldehyde catalyzed by FeCl3.
In conclusion, we have presented a highly efficient and
powerful method for the allylation of aldehyde with
allyltrimethylsilane catalyzed by FeCl3. This reaction
took place smoothly using only 5 mol% of FeCl3 and
could be applied to a broad range of aldehydes and,
especially, very hindered aliphatic aldehydes could be
allylated efficiently at room temperature. Additionally,
FeCl3 is a very cheap Lewis acid, so this method can be
utilized for an economical allylation reaction. These
features show that this new method is very practical
and will be applicable to the synthesis of various com-
plex natural products.
tion temperature. It was found that the reaction pro-
ceeded smoothly at −20°C and the desired allylation
product was given in 66% yield (Run 3).
Next, we investigated the effect of solvents and the
loading of allyltrimethylsilane, and these experimental
results are shown in Table 2. In the case of using
CH2Cl2, the corresponding allylation product was
obtained in lower yield (Run 2). On the other hand,
when MeCN and THF were used as a solvent, no
reaction occurred (Runs 3 and 4). Thus, MeNO2 turned
out to be the most effective solvent in this reaction.
Additionally, when the reaction was carried out with
1.5 equivalents of allylsilane, the reaction proceeded
very cleanly compared to using 2 equiv. of allylsilane
(Run 5). As depicted in the Scheme 1, by shortening the
reaction time (0.5 h) and with the treatment of 1N HCl
solution for desilylation after allylation, the corre-
sponding homoallyl alcohol could be isolated in excel-
lent yield (92%).
Acknowledgements
T.W. thanks the Sasakawa Scientific Research Grant
from The Japan Science Society for generous financial
support.
Scheme 2. Allylation of p-anisaldehyde dimethyl acetal catalyzed by FeCl3.

T. Watahiki, T. Oriyama / Tetrahedron Letters 43 (2002) 8959–8962
8961
Table 3. Allylation of various aldehydes
M. Tetrahedron Lett. 1983, 24, 2865; (c) Denmark, S. E.;
Henke, B. R.; Weber, E. J. J. Am. Chem. Soc. 1987, 109,
2512; (d) Nishigaichi, Y.; Takuwa, A.; Jodai, A. Tetra-
hedron Lett. 1991, 32, 2383; (e) Yanagisawa, A.;
Morodome, M.; Nakashima, H.; Yamamoto, H. Synlett
1997, 1309.
References
1. For leading review, see: (a) Yamamoto, Y.; Asao, N.
Chem. Rev. 1993, 93, 2207; (b) Masse, C. E.; Panek, J. S.
Chem. Rev. 1995, 95, 1293; (c) Marshall, J. A. Chem. Rev.
1996, 96, 31. (d) Fleming, I.; Barbero, A.; Walter, D.
Chem. Rev. 1997, 97, 2063.
4. Allylation of aldehydes with allylsilanes: (a) Aggarwal, V.
K.; Vennall, G. P. Tetrahedron Lett. 1996, 37, 3745; (b)
Yang, Y.; Wang, M.; Wang, D. Chem. Commun. 1997,
1651; (c) Aggarwal, V. K.; Vennall, G. P. Synthesis 1998,
1822. With allylstannanes: (d) Hachiya, I.; Kobayashi, S.
J. Org. Chem. 1993, 58, 6958; (e) Aspinall, H. C.; Brown-
ing, A. F.; Greeves, N.; Ravenscroft, P. Tetrahedron Lett.
1994, 35, 4639; (f) Aspinall, H. C.; Greeves, N.; McIver,
E. G. Tetrahedron Lett. 1998, 39, 9283; (g) Aspinall, H.
C.; Bissett, J. S.; Greeves, N.; Levin, D. Tetrahedron Lett.
2002, 43, 319. With allylgermane: (h) Akiyama, T.; Iwai,
J.; Sugano, M. Tetrahedron 1999, 55, 7499.
5. (a) Iranpoor, N.; Salehi, P. Synthesis 1994, 1152; (b)
Christoffers, J. J. Chem. Soc., Perkin Trans. 1 1997, 3141;
(c) Barton, D. H. R.; Hill, D. R.; Hu, B. Tetrahedron
Lett. 1997, 38, 1711; (d) Salehi, P.; Iranpoor, N.; Behba-
hani, F. K. Tetrahedron 1998, 54, 943; (e) Sen, S. E.;
2. (a) Hollis, T. K.; Robinson, N. P.; Whelan, J.; Bosnich,
B. Tetrahedron Lett. 1993, 34, 4309; (b) Maeta, H.;
Nagasawa, T.; Handa, Y.; Takei, T.; Osamura, Y.;
Suzuki, K. Tetrahedron Lett. 1995, 36, 899; (c) Gauthier,
D. R.; Carreira, E. M. Angew. Chem. 1996, 108, 2521;
Angew. Chem. Int. Ed. Engl. 1996, 35, 2363; (d) Kaur, G.;
Manju, K.; Trehan, S. Chem. Commun. 1996, 581; (e)
Komatsu, N.; Uda, M.; Suzuki, H. Tetrahedron Lett.
1997, 38, 7215; (f) Marx, A.; Yamamoto, H. Angew.
Chem. Int. Ed. 2000, 39, 178; (g) Yasuda, M.; Onishi, Y.;
Ito, T.; Baba, A. Tetrahedron Lett. 2000, 41, 2425; (h)
Yadav, J. S.; Chand, P. K.; Anjaneyulu, S. Tetrahedron
Lett. 2002, 43, 3783.
3. (a) Hosomi, A.; Sakurai, H. Tetrahedron Lett. 1976,
1295; (b) Hayashi, T.; Kabeta, K.; Hamachi, I.; Kumada,

8962
T. Watahiki, T. Oriyama / Tetrahedron Letters 43 (2002) 8959–8962
Roach, S. L.; Smith, S. M.; Zhang, Y. Z. Tetrahedron
8. (a) Ishii, A.; Kotera, O.; Saeki, T.; Mikami, K. Synlett
1997, 1145; (b) Fang, X.; Watkin, J. G.; Warner, B. P.
Tetrahedron Lett. 2000, 41, 447.
Lett. 1998, 39, 3969; (f) Sharma, G. V. M.; Mahalingam,
A. K.; Nagarajan, M.; Ilangovan, A.; Radhakrishna, P.
Synlett 1999, 1200; (g) Barrett, I. C.; Langille, J. D.;
Kerr, M. A. J. Org. Chem. 2000, 65, 6268; (h) Chibiryaev,
A. M.; Kimpe, N. D.; Tkachev, A. V. Tetrahedron Lett.
2000, 41, 8011; (i) Yus, M.; Pastor, I. M.; Gomis, J.
Tetrahedron 2001, 57, 5799; (j) Sharma, G. V. M.;
Kumar, K. R.; Sreenivas, P.; Krishna, P. R.; Chorghade,
M. S. Tetrahedron: Asymmetry 2002, 13, 687; (k) Vidari,
G.; Beszant, S.; Merabet, J. E.; Bovolenta, M.; Zanoni,
G. Tetrahedron Lett. 2002, 43, 2687.
9. A typical experimental procedure is as follows (Table 3,
Run 1): To a solution of FeCl3 (5.4 mg, 0.033 mmol) in
MeNO2 (1.0 ml) were added allyltrimethylsilane (159 ml,
1.00 mmol) and a solution of benzaldehyde (76.3 mg,
0.66 mmol) in MeNO2 (1.0 ml) at −20°C under argon
atmosphere. After stirring the reaction mixture for 0.5 h,
1N HCl (2.0 ml) was added and the reaction was allowed
to warm to room temperature. The resultant mixture was
stirred for an additional 0.5 h and poured into saturated
sodium hydrogencarbonate. The organic materials were
extracted with Et2O and dried over anhydrous magne-
sium sulfate. The solvent was evaporated and 1-phenyl-3-
buten-1-ol (90.0 mg, 92%) was isolated by thin-layer
chromatography on silica gel (ether:hexane=1:1). The
6. Nucleophilic additions of allylic metal reagents promoted
by stoichiometric amounts of FeCl3: (a) Denmark, S. E.;
Weber, E. J. Helv. Chim. Acta. 1983, 66, 1655; (b)
Denmark, S. E.; Weber, E. J.; Wilson, T. M.; Willson, T.
M. Tetrahedron 1989, 45, 1053; (c) Kang, K.-T.; Kim, S.
S.; Lee, J. C.; U, J. S. Tetrahedron Lett. 1992, 33, 3495;
(d) Kuroda, C.; Koshio, H.; Koito, A.; Sumiya, H.;
Murase, A.; Hirono, Y. Tetrahedron 2000, 56, 6441.
7. FeCl3 was purchased from Aldrich Company.
1
product gave satisfactory H NMR and IR spectra.
10. (a) Heathcock, C. H.; Kiyooka, S.; Blumenkopf, T. A. J.
Org. Chem. 1984, 49, 4214; (b) Davis, A. P.; Jaspars, M.
J. Chem. Soc., Perkin Trans. 1 1992, 2111.