Allylation of acetals and ketals with allyltrimethylsilane catalyzed by the mixed Lewis acid system AlBr3/CuBr

Article abstract of DOI:10.1016/j.tetlet.2004.04.183

The synthesis of homoallyl ethers from various acetals and a cyclic ketal with allyltrimethylsilane catalyzed by aluminum bromide in the presence of trimethylaluminum as a desiccant is described. We found that the addition of a catalytic amount of copper(

Full text of DOI:10.1016/j.tetlet.2004.04.183

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 5301–5304
Allylation of acetals and ketals with allyltrimethylsilane catalyzed
by the mixed Lewis acid system AlBr /CuBr
q
3
*
Michael E. Jung and Andreas Maderna
Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Drive, East,
Los Angeles, CA 90095-1569, USA
Received 6 March 2004; revised 30 April 2004; accepted 30 April 2004
Abstract—The synthesis ofhomoallyl ethers fr om various acetals and a cyclic ketal with allyltrimethylsilane catalyzed by aluminum
bromide in the presence oftrimethylaluminum as a desiccant is described. We of und that the addition ofa catalytic amount of
copper(I) bromide accelerates the allylation reactions to afford the homoallyl ether derivatives in good to excellent yield.
ꢀ
2004 Elsevier Ltd. All rights reserved.
The synthesis ofhomoallyl ethers by the allylation of
acetals and ketals with allylsilanes is a valuable C–C
bond formation and is commonly applied in organic
OMe
OMe
TMS
OMe
+
1
synthesis. Usually, these reactions require the presence
2
Scheme 1.
4
ofa Lewis acid promoter or catalyst, such as TiCl ,
3
4
TMSOTf, and others. We have recently reported the
use ofa 10:1 mixture ofAlBr /AlMe as an efficient
3
3
Table 1. Reaction conditions for the allylation of benzaldehyde
dimethyl acetal with allyltrimethylsilane
Lewis acid promoter system for the synthesis of a ste-
rically demanding Diels–Alder adduct, which served as
an advanced intermediate in the synthesis ofa tricyclic
a
b
c
Entry
AlBr
(
3
/AlMe
3
Temp
(ꢁC)
Time
(h)
Yield
(%)
mol %)
5
BCD analogue ofouabain. We proposed that a small
1
2
3
4
5
6
7
8
100
50
10
10
6
)78
)78
)78
)78 fi RT
)78 fi RT
)78 fi RT
)78 fi RT
RT
2
2
98
94
28
92
83
82
56
0
amount ofAlMe
the reaction. This paper describes a new application of
the mixed Lewis acid system AlBr /AlMe , namely the
3
eliminated any HX formed during
7
3
3
48
48
148
148
48
synthesis ofhomoallyl ethers by the reaction ofacetals
and ketals with allyltrimethylsilane.
3
1
0
3 3
The ability ofthe AlBr /AlMe mixture to act as a Lewis
a
acid promoter or catalyst was studied on the allylation
ofbenzaldehyde dimethyl acetal with allyltrimethyl-
silane, which we used as a model reaction (Scheme 1).
In a typical experiment, a solution of2 mmol acetal and 2 mmol silane
in 7 mL anhydrous DCM was cooled to )78 ꢁC with stirring under
argon. Then, AlMe
3
(2 M solution in toluene) was added, followed by
the addition ofAlBr
3
(1 M/CH Br ). The reaction mixture was
2
2
allowed to warm to room temperature and was stirred for the time
indicated.
Table 1 describes the yields ofthe product as a uf nc-
tion ofthe mole-equivalents ofLewis acid used, the
b
c
All experiments were performed with a 6:1 ratio of AlBr
GC conversion.
3 3
/AlMe .
temperature and the reaction time. Ifstoichiometric or
sub-stoichiometric amounts ofa 6:1 mixture ofAlBr
AlMe are used (entries 1 and 2), the reaction is com-
plete after 2 h of stirring at )78 ꢁC with a high yield of
product. If10 mol % ofthe Lewis acid mixture is used
(entries 3 and 4), the reaction needs to be warmed to
Keywords: Allylation; Acetals; Ketals; Lewis acid catalysis; Copper
bromide.
3
/
q
3
Supplementary data associated with this article can be found, in the
online version, at doi:10.1016/j.tetlet.2004.04.183
*
Corresponding author. Tel.: +1-310-8257954; fax: +1-310-2063722;
e-mail: jung@chem.ucla.edu
0
040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.04.183

5302
M. E. Jung, A. Maderna / Tetrahedron Letters 45 (2004) 5301–5304
Table 2. Product formation as a function of the AlBr
3
/AlMe
3
ratio
Table 3. Comparison ofproduct yields a ft er 1 h ofreaction time with
with a constant overall catalyst loading of6%
and without the addition ofCuBr
a
b
a
b;c
Entry
AlBr
3
/AlMe
3
Yield (%)
Entry
Substrate
Product
Yield
b
(%)
Yield (%)
CuBr
c
1
2
3
4
5
6
7
100:0
90:10
85:15
75:25
50:50
25:75
0:100
45
no CuBr added
85
83
62
42
17
3
OMe
OMe
OMe
1
52
77
OMe
OMe
a
2
3
6
36
16
93
81
The reaction conditions are the same as those described under foot-
note a ofTable 1, with a constant overall catalyst loading of6% and
6
OMe
4
8 h stirring at room temperature.
b
c
GC conversion, except entry 1.
Isolated yield.
OMe
OMe
OMe
Reactions were carried out as described in footnote a of Table 1,
using 10 mol % ofa 10:1 mixture ofAlBr /AlMe . The reactions were
a
room temperature and stirred for 48 h to go to com-
pletion.
3
3
stirred for 1 h at room temperature and then analyzed by GC. All
reactions were still incomplete.
GC conversion.
b
c
The amount ofcatalyst can be lowered to 6, 3, and
10 mol % ofCuBr was suspended in anhydrous DCM prior to the
addition ofthe substrates and the catalyst mixture.
1
mol % (entries 5, 6, and 7) but the reaction takes longer
and the yields start to decrease. In a control experiment
entry 8, Table 1), the starting materials were stirred
(
without the presence ofthe Lewis acid; no product
formation was observed.
were analyzed by GC after 1 h of stirring at room tem-
perature. The results impressively demonstrate the
ability ofCuBr to enhance the per of rmance ofthe cat-
alytic mixture, which is most evident in the case ofthe
alkyl-substituted derivatives (entries 2 and 3).
We next examined the influence ofthe ratio ofAlBr
3
/
AlMe on the reaction outcome. For this purpose we
3
conducted the allylation ofour model reaction under the
same reaction conditions with a constant overall catalyst
loading of6%, but with different AlBr
The results are listed in Table 2.
3
/AlMe
3
ratios.
As we have demonstrated earlier, the catalytic allylation
ofbenzaldehyde dimethyl acetal does not require the
presence ofCuBr, and the corresponding aromatic
homoallyl ether can be isolated in 92% yield after 24 h
stirring at room temperature using 10 mol % ofAlBr 3/
3
The data show that AlBr alone (entry 1) gave the
product in only 45% isolated yield. We also observed an
unidentified precipitate, which was formed early on
during the reaction. Ifthe catalyst mixture contained
AlMe (Table 1, entry 4). However, in the presence of
3
CuBr the same reaction is faster and is complete after
only 3 h at room temperature. In the case ofthe less
reactive alkyl derivatives, longer reaction times with
10% AlBr /AlMe alone did not significantly improve
1
0–15% AlMe
was formed and the product yields were the highest
3
entries 2 and 3). Upon further lowering of the AlBr /
3
, no precipitate in the reaction mixture
(
3
3
AlMe
AlMe
3
3
ratio the yields decreased (entries 4, 5, and 6).
without AlBr did not give the product in note-
the yields shown in Table 3 and the presence ofCuBr
was necessary to obtain high yield ofthe product. At
present, we cannot give a detailed explanation on how
CuBr acts as a catalytic promoter. Presumably, the
catalytically active system is a mixed aluminum–copper
species.
3
worthy yield (entry 7). These results indicate that a small
amount ofAlMe added to AlBr is ofsignificant benefit
for the catalytic process, presumably due to scavenging
any HBr, which is present or is formed in the reaction
3
3
mixture. However, ifthe content ofAlMe
3
is further
increased, the product yields decrease. We generally
found that AlBr /AlMe ratios between 6:1 and 10:1
gave the best catalytic results.
In Table 4 are listed the results for the allylation of
various substrates. For all reactions, CuBr was used as a
cocatalyst. The comparison ofentries 1 and 2 reveals
that the bromo substituent in acetal 2a leads to a
decreased reaction rate, compared to that ofthe un-
substituted acetal 1a. The allylation ofthe para-meth-
oxy-substituted acetal 3a was unsuccessful and only the
formation of higher molecular weight species was indi-
cated by GC analysis, presumably due to polymerization
ofan alkylated para-quinone methide cation. The alkyl-
substituted derivatives 4a and 5a (entries 4 and 5) gave
the corresponding homoallyl ethers in comparatively
short reaction times, with a lower yield for the cyclic
ketal 5a. For the bromo substituted acetal 6a, the use of
20 mol % CuBr and 20 mol % AlBr /AlMe was neces-
3
3
With this information in hand, we investigated the
allylation ofother acetals and ketals. In case ofalkyl
derivatives (Table 3, entries 2 and 3), we observed a
conspicuously reduced product yield compared to our
model reaction. Upon screening ofvarious additives fo r
enhanced catalytic activity, we were surprised to find
that CuBr significantly increases the formation of the
allylated products. Table 3 compares the yields ofthe
product ofour model system (entry 1) and two alkyl
derivatives (entries 2 and 3) with and without the
addition of10 mol % CuBr to the AlBr /AlMe catalytic
3
3
3
3
6
mixture (10 mol %, 10:1 ratio). The reaction mixtures
sary to obtain an adequate yield of 6b, reflecting the

M. E. Jung, A. Maderna / Tetrahedron Letters 45 (2004) 5301–5304
Table 4. Allylation ofvarious substrates using optimized reaction conditions
5303
a
b
Entry
Substrate
Product
Time (h)
3
Yield (%)
100
OMe
OMe
OMe
1
a
a
1b
1
OMe
OMe
OMe
2
3
24
25
100
0
2
Br
2b Br
OMe
OMe
OMe
3a MeO
3b MeO
OMe
OMe
4
b
4
a
6
4
5
6
6
2
1
98
81
OMe
OMe
OMe
5a
5b
OMe
OMe
OMe
6
b
Br
c
6a Br
24
84
OMe
OMe
OMe
7
8
7a
7b
8b
46
48
83
OMe
NC
OMe
NC
8a
d
76
OMe
In a typical experiment, a suspension of0.2 mmol CuBr, 2.0 mmol acetal and 2.6 mmol silane in 5.0 mL anhydrous DCM was cooled to )78 ꢁC with
stirring under argon. Then, 20.0 lmol AlMe (2 M solution in toluene) was added, followed by the addition of 0.2 mmol AlBr (1 M/CH Br ). The
reaction mixture was allowed to warm to room temperature and was stirred for the time indicated. All reaction mixtures were quenched with aq
NaHCO prior to work-up, except for 6b and 8b where NEt was used instead. All reactions were monitored by GC and stopped after the complete
OMe
a
3
3
2
2
3
3
1
13
disappearance ofthe starting materials. The products were characterized by H NMR, C NMR, and IR spectroscopy.
Isolated yield.
b
c
2
0 mol % CuBr and 20 mol % AlBr
3
/AlMe
3
were used.
d
The product is 90% clean by GC and NMR. CAUTION: The product has a strong unpleasant odor!
decreased reactivity ofthe acetal uf nction in 6a due to
the electron-withdrawing bromine substituent. With
acetals, ketals, and allyltrimethylsilane, namely a system
comprised ofAlBr , AlMe , and CuBr. The exact cat-
alytically active component is unknown, but is believed
3
3
1
0 mol % ofCuBr and 10 mol % AlBr
3
/AlMe
3
, only 50%
of 6b was obtained (data not shown). An interesting case
is the cyano-substituted acetal 8a in which both the
nitrile group and the acetal function can competitively
coordinate to the Lewis acid catalyst during the reac-
tion. We observed that the reaction has an induction
period ofseveral hours in which no product of rmation
could be detected. This might point toward a preferred
initial binding ofthe catalyst to the nitrile group, with
subsequent binding to the acetal and allylation. For the
to be a mixed Al–Cu species. AlMe acts as a desiccant
3
scavenging unwanted HBr from the reaction mixture.
Acknowledgements
The authors thank the National Science Foundation
(CHE-0314591) for financial support.
7
purification of 6b and 8b it is necessary to quench the
reaction mixtures with triethylamine prior to the aque-
ous work-up. To the best ofour knowledge, the
described example (entry 8) is the first example ofa
successful Lewis acid-catalyzed allylation of an acetal
having a peripheral functionality present in the mole-
cule, emphasizing the potential value ofour new method
in synthetic chemistry.
References and notes
1
2
. For reviews see: (a) Mukaiyama, T.; Murakami, M.
Synthesis 1987, 1043–1054; (b) Yamamoto, Y.; Asao, N.
Chem. Rev. 1993, 93, 2207.
. Hosomi, A.; Endo, M.; Sakurai, H. Chem. Lett. 1976, 941–
9
42.
3. (a) Tsunoda, T.; Suzuki, M.; Noyori, R. Tetrahedron Lett.
1980, 21, 71–74; (b) Murata, S.; Suzuki, M.; Noyori, R.
In summary, we have disclosed a new and potent Lewis
acid catalyst for the synthesis of homoallyl ethers from

5304
M. E. Jung, A. Maderna / Tetrahedron Letters 45 (2004) 5301–5304
J. Am. Chem. Soc. 1980, 102, 3248; (c) Zerth, H. M.;
Leonard, N. M.; Mohan, R. S. Org. Lett. 2003, 5, 55–57.
. (AlCl , BF O): Hosomi, A.; Endo, M.; Sakurai, H.
· Et
Chem. Lett. 1978, 499; (Trityl perchlorate, Ph BOTf):
Mukaiyama, T.; Nagaoka, H.; Murakami, M.; Ohshima,
M. Chem. Lett. 1985, 977–980; (Montmorillonite): Kawai,
M.; Onaka, M.; Izumi, Y. Chem. Lett. 1986, 381–384;
5. Jung, M. E.; Davidov, P. Angew. Chem., Int. Ed. 2002, 41,
4125–4128.
6. Spectroscopic data for 6b: H NMR (500 MHz, CDCl
5.7 (m, 1H, CH@C), 5.1 (m, 2H, CH @C), 3.4 (m, 6H,
CH , CH Br, CH–O), 2.4 (m, 2H, CH
(126 MHz, CDCl ): d 133.3 (CH@C), 118.2 (CH
(CH–O), 57.3 (CH ), 36.8 (CH –allyl), 33.9 (C–Br); IR
1
4
3
3
2
3
): d
2
2
1
3
3
2
2
–allyl); C NMR
@C), 79.5
3
2
3
2
(
TMSI): Sakurai, H.; Sasaki, K.; Hosomi, A. Tetrahedron
Lett. 1981, 22, 745–748; (TiCp (OTf) ): Hollis, T. H.;
Robinson, N. P.; Whelan, J.; Bosnich, B. Tetrahedron Lett.
993, 34, 4309–4312; (BiBr ): Komatsu, N.; Domae, T.;
Wada, M. Tetrahedron Lett. 1997, 38, 7215–7218;
Bi(OTf) ): Wieland, L. C.; Zerth, H. M.; Mohan, R. S.
Tetrahedron Lett. 2002, 43, 4597–4600; (TMSNTf ): Ishii,
A.; Kotera, O.; Saeki, T.; Mikami, K. Synlett 1997, 1145–
146; (Sc(OTf) ): Yadav, J. S.; Subba Reddy, B. V.; Srihari,
P. Synlett 2001, 673–675.
(neat): m 3077, 2979, 2930, 2825, 1641, 1433, 1339, 1095,
À1
2
2
994, 919 cm
.
1
7. Spectroscopic data for 8b: H NMR (500 MHz, CDCl
5.7 (m, 1H, CH@C), 5.0 (m, 2H, CH @C), 3.3 (m, 4H), 2.4
(m, 2H), 2.3 (m, 1H), 2.2 (m, 1H), 1.8 (m, 1H), 1.7 (m, 1H);
3
): d
1
3
2
1
3
(
3
C NMR (126 MHz, CDCl
(CN), 117.9 (CH @C), 78.0 (CH–O), 56.9 (CH
(CH –allyl), 29.3 (C–CN), 13.2 (C–CCN); IR (neat): m 3078,
3
): d 133.3 (CH@C), 119.7
2
2
3
), 37.0
2
1
3
2979, 2934, 2828, 2246, 1641, 1441, 1358, 1094, 997,
À1
918 cm
.