Efficient Br?nsted acid catalyzed Hosomi-Sakurai reaction of acetals

Article abstract of DOI:10.1055/s-2006-950444

Acetals react with allyltrimethylsilane in the presence of a catalytic amount of sulfonic acids to give the corresponding homoallylic ethers in high yields. The scope of the reaction is broad and both aromatic as well as aliphatic acetals can readily be u

Full text of DOI:10.1055/s-2006-950444

LETTER
2589
Efficient Brønsted Acid Catalyzed Hosomi–Sakurai Reaction of Acetals
Organocatalytic
H
a
osomi–Saku
n
r
ai Reaction
i
of
A
cetals la Kampen, Benjamin List*
Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470 Mülheim an der Ruhr, Germany
Fax +49(208)3062999; E-mail: list@mpi-muelheim.mpg.de
Received 31 July 2006
Me
Abstract: Acetals react with allyltrimethylsilane in the presence of
a catalytic amount of sulfonic acids to give the corresponding ho-
moallylic ethers in high yields. The scope of the reaction is broad
and both aromatic as well as aliphatic acetals can readily be used.
O
MeOH
SiMe3
X
R
H
3
2
OMe
OMe
Key words: Hosomi–Sakurai reaction, acetals, organocatalysis,
Brønsted acid catalysis, allylsilanes
R
1
HX
OMe
X
SiMe3
R
Acetals are useful intermediates in organic synthesis and
undergo coupling reactions with different nucleophiles
via carbon–carbon bond formation. Successfully used nu-
cleophiles include silyl enol ethers, allyl transfer reagents,
vinyl ethers, and also common olefins as well as cyanide
sources. A valuable example is the Hosomi–Sakurai
reaction1 of acetals with allyltrimethylsilane,2 which
furnishes homoallylic ethers. Catalysts that have been
employed for this transformation include Lewis acids
such as NbCl5/AgClO4,3 AlBr3/CuBr,4 FeCl3,5 TMSOTf,6
OMe
4
R
MeOH
5
MeOSiMe3
+
6
Scheme 1
Table 1 Catalyst Screening for the Allylation of Acetal 1a
Bi(OTf)3,7
Sc(OTf)3,8
BiBr3,9
TMSNTf2,10
OMe
OMe
TMSN(SO2F)2,11 TiCp2(CF3SO3)2,12 montmorillonite,13
trityl perchlorate,14 diphenylboryl triflate,14 and TMSI.15
Alternatively, stoichiometric Lewis acidic activators that
have been used include TiCl4,16 AlCl3,17 BF3·Et2O,17,18
liquid SO2,19 and CuBr/microwave.20 Several of these
methods suffer from drawbacks such as the involvement
of compounds that are corrosive, difficult to handle, ex-
pensive, or toxic. Others require strictly anhydrous condi-
tions or less practical reaction temperatures. Surprisingly,
Brønsted acids have not been studied for this important
reaction despite their great potential as easily tunable,
economic, and environmentally acceptable catalysts.21,22
We reasoned that a catalytic cycle could be readily initiat-
ed via the reaction of a strong Brønsted acid (HX) with an
acetal (1) to give an oxonium ion (2). Its reaction with
allyltrimethylsilane (3) would lead to the silicon-stabi-
lized carbocation (4). This intermediate in turn should
readily collapse to the desired product (5) and volatile
methoxytrimethylsilane (6) upon reaction with methanol,
generated in the initializing step of the catalytic cycle
(Scheme 1).23
Acid Catalyst
MeCN
SiMe3
+
Ph
Ph
OMe
1a
5a
3
(1.5 equiv)
Entry Acid
Amount Temperature Time
Conversiona
(%)
catalyst
(mol%)
(h)
21
21
3
1
2
3
4
5
6
7
8
9
PPA
10
10
10
5
r.t.
20
25
PPA
60 °C
r.t.
TFA
TFA
CSA
>99
60
r.t.
21
24
12
15
2
10
r.t.
40
p-TsOH 10
r.t.
>99
>99
95b
>99
p-TsOH
H2SO4
3
2
2
r.t.
r.t.
DNBA
r.t.
2
a Conversion was determined by GC.
b By-products were formed.
SO3H
SO3H
O
P
PhO
PhO
OH
O2N
NO2
O
SO3H
PPA
CSA
p-TsOH
DNBA
SYNLETT 2006, No. 16, pp 2589–2592
0
4
.1
0
.2
0
0
6
Advanced online publication: 22.09.2006
DOI: 10.1055/s-2006-950444; Art ID: G21706ST
© Georg Thieme Verlag Stuttgart · New York

2590
D. Kampen, B. List
LETTER
With this reaction design in mind, we have studied several powerful catalyst for the reaction. Compared to sulfuric
different Brønsted acids for the reaction of benzaldehyde acid, which is also an active catalyst, it mediates the
acetal 1a with allylsilane 3 to give homoallylic ether 5a allylation very cleanly without by-product formation and
(Table 1). In initial experiments, acetonitrile was found to was therefore chosen for further studies. Lowering the
be the best solvent. While the modestly acidic diphenyl catalyst loading from 2 mol% to 1 mol% significantly
phosphate) (PPA) gave some conversion (entries 1 and 2), reduced the turnover and increasing the temperature did
stronger acids such as trifluoroacetic acid (TFA; entries 3 not result in any improvement. Consequently, 2 mol% of
and 4) and in particular sulfonic acids as well as sulfuric DNBA was used in subsequent experiments.
acid (entries 5–9) proved to be much more useful.
Dinitrobenzenesulfonic acid (DNBA) turned out to be a
conditions, we have explored the scope of the reaction
After identifying an active catalyst and suitable reaction
Table 2 Substrate Scope of the Brønsted Acid Catalyzed Hosomi–Sakurai Reaction of Acetals
DNBA
(2 mol%)
OMe
MeO OMe
R1 R2
SiMe3
+
R1
R2
MeCN, r.t.
1
5
3
(1.5 equiv)
Entry
Acetal
Product
Time (h)
Yield (%)
OMe
OMe
Ar
OMe
Ar
Ar = Ph
1
2
3
4
1
1
2
3
99
95
90
93
Ar = p-BrC6H4
Ar = p-MeOC6H4
Ar = p-O2NC6H4
OMe
OMe
5
6
2
2
7
8
7
3
3
1
2
84
87
96
53a
64a
85
88
78
87
n-Hex
n-Hex
OMe
OMe
OMe
c-Hex
OMe
OMe
c-Hex
OMe
7
BnO
BnO
OMe
OMe
OMe
8
Br
Br
OMe
OMe
OMe
9
NC
NC
OMe
OMe
OMe
10
11
12
13
MeOOC
MeOOC
OMe
OMe
MeOOC
MeOOC
OMe
OMe
OMe
OMe
Ph
Ph
OMe
OMe
OMe
Ph
Ph
Ph
OMe
MeO OMe
Ph
OMe
14
15
1
2
82
91
MeO
OMe
MeO
a Reduced yield due to volatility of the product.
Synlett 2006, No. 16, 2589–2592 © Thieme Stuttgart · New York

LETTER
Organocatalytic Hosomi–Sakurai Reaction of Acetals
2591
(Table 2). Upon treating acetals 1 with 1.5 equivalents of the use of both aromatic and aliphatic substrates c) its high
allyltrimethylsilane (3) in the presence of 2 mol% of tolerance towards diverse functional groups, d) its sim-
DNBA at room temperature in acetonitrile, the corre- plicity and practicability, e) its use of an inexpensive and
sponding homoallylic ethers 5 were obtained in high non-toxic Brønsted acid, and f) its low catalyst loading.
yields. It turned out that the selected reaction conditions We are currently extending this methodology to alterna-
are broadly useful for a variety of different substrates. tive variants and substrate classes.
Both aromatic acetals (entries 1–4) with electron-rich or
electron-poor aryl substituents, as well as simple un-
branched or branched aliphatic acetals (entries 5 and 6)
can be used with similar efficiencies. Functional groups
that are tolerated include a benzyl ether (entry 7), an alkyl
bromide (entry 8), a nitrile (entry 9), two esters (entries 10
and 11), and an a,b-unsaturated acetal. Remarkably, even
ketone-derived acetals (‘ketals’) can be employed with
good results (entries 14 and 15). The reactions are gener-
ally clean and chemoselective and possible products of
hydrolysis or aldolization were not detected in the crude
mixture. The best result was achieved with benzaldehyde
acetal (entry 1), which provided the corresponding
homoallylic ether in nearly quantitative yield after only
one hour. While in almost all cases full conversion to the
desired product was obtained after 2 to 3 hours, the
allylation of the bromo (entry 8) as well as the cyano
(entry 9) substituted aliphatic acetals was less efficient
(85% conversion according to GC after 8 hours and 7
hours, respectively). In addition, the volatility of the cor-
responding ethers contributed to the moderate isolated
yields (53% and 64%) in these cases. It has been reported
that the Hosomi–Sakurai reaction of cinnamaldehyde
dimethyl acetal with allyltrimethylsilane mediated by
stoichiometric amounts of TiCl4 gave only the diallylated
product.16 In contrast, we did not observe any diallylated
compound. Although the allylation of cinnamaldehyde
acetal has been expected to give a mixture of regioiso-
meric products resulting from either direct or vinylogous
nucleophilic attack of the presumed oxonium ion, DNBA
catalyzes the formation of the homoallylic ether regio-
specifically (entry 13). Compared to the present Hosomi–
Sakurai reaction of acetals, the allylation of benzaldehyde
under the same conditions was found to be extremely
slow. Even after 21 hours less than 20% of the corre-
sponding homoallylic silyl ether was formed.
General Procedure for the Hosomi–Sakurai Reaction
Acetal 1 (1.5 mmol, 1.0 equiv) and allyltrimethylsilane (3; 0.36 mL,
2.25 mmol, 1.5 equiv) were added to a solution of DNBA (8.5 mg,
0.03 mmol, 0.02 equiv) in anhydrous MeCN and stirred at r.t. for
1–8 h. The mixture was poured into brine (50 mL) and extracted
with Et2O (2 × 50 mL). The combined organic layers were washed
with aqueous NaHCO3 (10 mL) and brine (10 mL), dried over
Na2SO4, filtered and concentrated. The homoallylic ether 5 was
isolated by flash chromatography (SiO2, pentane–Et2O).
Acknowledgment
We thank Degussa, Saltigo, and Wacker for the donation of chemi-
cals and Novartis for a Young Investigator award to BL. Our work
was supported by the Max-Planck-Gesellschaft, the Deutsche
Forschungsgemeinschaft (Priority Program 1179 Organocatalysis),
and the Fonds der Chemischen Industrie. Technical assistance by
Marianne Hannappel is gratefully acknowledged.
References and Notes
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Finally, a benzyl acetal (7) has also been studied. Subject-
ing acetal 7 to our reaction conditions provided the syn-
thetically useful benzyl homoallylic ether 8 in good yield
(Equation 1).
DNBA
(2 mol%)
OBn
OBn
OBn
SiMe3
+
Ph
Ph
MeCN, r.t.
2 h, 97%
7
8
3
(1.5 equiv)
Equation 1
In summary, we have developed a highly efficient
Brønsted acid catalyzed allylation of acetals using allyl-
trimethylsilane. Significant advantages of our process
include: a) its high yields, b) its broad scope, allowing for
(16) Hosomi, A.; Masahiko, E.; Sakurai, H. Chem. Lett. 1976, 9,
941.
Synlett 2006, No. 16, 2589–2592 © Thieme Stuttgart · New York

2592
D. Kampen, B. List
LETTER
(17) Hosomi, A.; Endo, M.; Sakurai, H. Chem. Lett. 1978, 5, 499.
(18) (a) Lucero, C. G.; Woerpel, K. A. J. Org. Chem. 2006, 71,
2641. (b) Hathaway, S. J.; Paquette, L. A. J. Org. Chem.
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(19) Mayr, H.; Gorath, G.; Bauer, B. Angew. Chem., Int. Ed.
Engl. 1994, 33, 788.
(20) Jung, M. E.; Maderna, A. J. Org. Chem. 2004, 69, 7755.
(21) (a) For an example of using TfOH, see: Denmark, S. E.;
Wilson, T. M. J. Am. Chem. Soc. 1989, 111, 3475. (b) For
the use of Tf2NH and HN(SO2F)2 in related reactions, see:
Kuhnert, N.; Peverley, J.; Robertson, J. Tetrahedron Lett.
1998, 39, 3215. (c) Kaur, G.; Kaushik, M.; Trehan, S.
Tetrahedron Lett. 1997, 38, 2521.
(22) (a) For the use of Tf2NH in the Hosomi–Sakurai reaction of
carbonyl compounds, see: Ishihara, K.; Hiraiwa, Y.;
Yamamoto, H. Synlett 2001, 1851. (b) For an example of
Brønsted acid catalyzed Hosomi–Sakurai reaction of
carbonyl compounds, see: Ishihara, K.; Hasegawa, A.;
Yamamoto, H. Synlett 2002, 1299. (c) Cossy, J.; Lutz, F.;
Alauze, V.; Meyer, C. Synlett 2002, 45. (d) Ishihara, K.;
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(e) Kaur, G.; Manju, K.; Trehan, S. Chem. Commun. 1996,
581.
(23) As suggested by a reviewer, the reaction may also be
promoted by the in situ generated TMS sulfonate. For an
example, see ref. 22a.
Synlett 2006, No. 16, 2589–2592 © Thieme Stuttgart · New York