Bronsted acid-catalyzed three-component hosomi-sakurai reactions

Article abstract of DOI:10.1002/adsc.200800036

Aldehydes react with silyl ethers or the corresponding alcohols and allylsilanes in the presence of catalytic amounts of 2,4-dinitrobenzenesulfonic acid (DNBA) to provide a wide range of homoallylic ethers in moderate to high yields.

Full text of DOI:10.1002/adsc.200800036

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DOI: 10.1002/adsc.200800036
Brønsted Acid-Catalyzed Three-Component Hosomi–Sakurai
Reactions
Daniela Kampen,a Arnaud LadØpÞche,a Gerrit Claßen,a and Benjamin Lista,*
a
Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470 Mülheim an der Ruhr, Germany
Fax : (+49)-208-306-2999; e-mail: list@mpi-muelheim.mpg.de
Received: January 18, 2008; Published online: April 11, 2008
Dedicated to Professor Andreas Pfaltz on the occasion of his 60th birthday.
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: Aldehydes react with silyl ethers or the
corresponding alcohols and allylsilanes in the pres-
ence of catalytic amounts of 2,4-dinitrobenzenesul-
fonic acid (DNBA) to provide a wide range of ho-
moallylic ethers in moderate to high yields.
Alternatively, a direct approach to homoallylic
ethers (4) involves the combination of an aldehyde
(2) with a silyl ether or the corresponding alcohol and
an allylsilane (3) (b, Scheme 1). Catalysts that have
been employed for such three-component Hosomi–
Sakurai reactions using alkoxysilanes include Lewis
acids such as trimethylsilyl iodide (TMSI),[2] diphenyl-
boryl triflate (Ph2BOTf),[3] trimethylsilyl triflate
Keywords: allylation; Brønsted acids; homoallylic
ethers; Hosomi–Sakurai reaction; multicomponent
reactions; organocatalysis
(TMSOTf),[4,5]
(TMSOFs),[6]
trimethylsilyl
trimethylsilyl
fluorosulfonate
methanesulfonate
(TMSOMs),[7] iron chloride (FeCl3),[8] bismuth triflate
[Bi
these methods suffer from certain drawbacks includ-
(OTf)3],[9] and iron tosylate [Fe(OTs)3].[10] Some of
ACHRTEUNG ACHTREUGN
Homoallylic ethers represent valuable organic inter- ing the involvement of compounds that are corrosive,
mediates, which are amenable to further synthetic ma- difficult to handle, expensive or harmful, and the re-
nipulations. Accordingly, their preparation has attract- quirement of anhydrous conditions or low tempera-
ed considerable attention. The allylation of acetals (1) tures. Others represent rather one-pot procedures
is a useful method to generate homoallylic ethers (4) than true multicomponent reactions. A catalytic syn-
and can be mediated by several Lewis acids (a, thesis of homoallylic ethers starting from an aldehyde,
Scheme 1). However, many acetals are not commer- an alcohol, and an allylsilane is underdeveloped.[11,12]
cially available and have to be synthesized from the
We have previously developed Brønsted acid-cata-
corresponding aldehydes (2). In addition, most of lyzed Hosomi–Sakurai reactions of dimethyl and di-
these Hosomi–Sakurai reactions[1] give rise to homo- benzyl acetals with allylsilanes.[13] Here we report the
allyl methyl ethers bearing a protecting group that re- first three-component variants in which aldehydes
quires harsh conditions to be cleaved.
react with allylsilanes and either silyl ethers or their
corresponding alcohols.[14,15,16]
The key intermediate in allylations of acetals is pre-
sumably oxocarbenium ion A, which can be accessed
via acid catalysis from the acetal (1) (path a) or via
the reaction of an aldehyde (2) with a silyl ether
(path b). Alternatively, we reasoned that it should
also be possible to generate this intermediate more
conveniently from an aldehyde (2) and an alcohol
(path c). Nucleophilic attackof allyltrimethylsilane
(3) to intermediate A would furnish the desired ho-
moallylic ether (4) and Me3SiX which could initiate
further catalytic cycles (Scheme 2).
Scheme 1. a) Acid-catalyzed Hosomi–Sakurai reaction of
acetals; b) acid-catalyzed three-component Hosomi-Sakurai
reaction.
First, we investigated the reaction of benzaldehyde
(5), benzyloxytrimethylsilane (BnOTMS) or benzyl
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Brønsted Acid-Catalyzed Three-Component Hosomi–Sakurai Reactions
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Table 1. Three-component Hosomi–Sakurai reaction using
BnOTMS: variation of the aldehyde.
Entry
1
Product
Time [h]
3
Yield[a] [%]
92
2
3
4
3
91
86
81
Scheme 2. Possible Hosomi–Sakurai reaction pathways.
alcohol (BnOH), and allyltrimethylsilane (3). The
benzyl substituent has been chosen due to its function
as a conventional protecting group that can be
cleaved under mild conditions. Studies towards the
development of our previous Hosomi–Sakurai reac-
tion revealed that 2,4-dinitrobenzenesulfonic acid
(DNBA) is a powerful catalyst and acetonitrile a suit-
able solvent for the allylation of acetals. Therefore,
we kept these parameters constant. Screening of the
catalyst loading, the equivalents of the reagents, the
concentration, as well as the temperature furnished
our optimized conditions. Thus one equivalent of ben-
zaldehyde (5) reacted with two equivalents each of
the silyl ether and the allylsilane (3) in the presence
of 3 mol% of DNBA to give the desired product (6)
in 92% yield. As expected, BnOH turned out to be
less reactive and the catalyst loading had to be in-
creased to 5 mol%. In this case, three equivalents of
allyltrimethylsilane in combination with two equiva-
lents of the alcohol were required to afford homoallyl
benzyl ether 6 in 72% yield. The large amount of al-
lylsilane (3) might be rationalized by its partial con-
sumption due to a possible in situ generation of
BnOTMS from BnOH. Both variants of our multi-
component reactions were conducted at room temper-
ature. Raising or lowering the temperature did not
result in any improvement.
4
12
5
6
2
2
73
71
7
8
9
3
19
80
75
3
12
Using these newly developed conditions, we ex-
plored the scope and limitations of these two
Hosomi–Sakurai reactions. Different carbonyl com-
pounds were treated with BnOTMS and allyltrime-
thylsilane (3) in the presence of 3 mol% of DNBA to
give homoallyl benzyl ethers (7) in moderate to high
yields (Table 1). Aromatic aldehydes with electron-
donating or electron-withdrawing substituents as well
as heteroaromatic or a,b-unsaturated precursors are
tolerated. Aliphatic aldehydes bearing a secondary,
10
12
4
81
78
11
[a]
Yield of isolated product.
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Daniela Kampen et al.
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tertiary or quaternary carbon atom at the a-position days the starting aldehyde (2) could still be detected.
can be used, too. Ketones were found to be inert. Ap- Two reasons might be considered to explain the lower
parently, our conditions are not suitable for the ace- reactivity of this system. On the one hand, our condi-
talization of ketones, as acetals derived from ketones tions could be less suitable for the acetalization of al-
have been successfully employed in our previous dehydes with BnOH than with the more reactive silyl
DNBA-catalyzed allylation. The combinations of al- ether. On the other hand, allyltrimethylsilane could
dehydes (2), BnOTMS and allyltrimethylsilane (3) are be partially consumed due to a possible in situ genera-
generally clean and complete within 3 to 12 h. Only in tion of BnOTMS from BnOH. Consequently, less al-
the cases of thiophene-3-carbaldehyde and cinnamal- lylsilane might be available for the subsequent allyla-
dehyde were the reactions stopped before complete tion.
consumption of the starting material (2) to avoid the
Next, benzaldehyde (5) was treated with different
formation of undesired by-products. In the reaction of silyl ethers or their alcohols and allyltrimethylsilane
crotonaldehyde several by-products were obtained (18, R2 =H) in the presence of catalytic amounts of
and the corresponding benzyl ether (13) was isolated DNBA to provide a high diversity of homoallylic
in a relatively low yield.
ethers (19, R2 =H) (Table 3). Both unsaturated alco-
To compare the three-component reaction involv- hols/silyl ethers bearing a double bond or a triple
ing BnOTMS with the variant that employs the corre- bond and linear or branched saturated derivatives are
sponding alcohol, representative aldehydes (2) have tolerated. Aromatic alcohols/silyl ethers such as phe-
been investigated (Table 2). One aromatic, one heter- noxytrimethylsilane or phenol were found to be un-
reactive. The yields of the desired products derived
from
propargyloxy
allyloxytrimethylsilane
AHCTREUNG
(AllOTMS),
Table 2. Three-component Hosomi–Sakurai reaction using
BnOH: variation of the aldehyde.
tyloxytrimethylsilane (pentyl-OTMS) or isopropoxy-
trimethylsilane (i-PrOTMS) as well as from allyl alco-
hol (AllOH), 1-pentanol (pentyl-OH) or isopropyl al-
cohol (i-PrOH) are high. By way of contrast, homoall-
yl propargyl ether 21 was isolated in moderate yield
when propargyl alcohol (propargyl-OH) was used.
The combinations of benzaldehyde (5), silyl ethers or
their alcohols, and allyltrimethylsilane (18, R2 =H)
are generally clean and complete within 2 to 5 h.
Only the reaction of propargyl alcohol did not go to
completion. Even after prolonged stirring for two
days the starting aldehyde (5) was still detected.
Entry
1
Product
Time [h]
6
Yield[a] [%]
72
Additionally, benzaldehyde (5) was subjected to
BnOTMS or BnOH, methallyltrimethylsilane (18,
R2 =Me), and 3 or 5 mol% of DNBA (Table 3, en-
tries 9 and 10). Replacing allyltrimethylsilane (18,
R2 =H) by a substituted allyl transfer reagent (18,
R2 =Me) significantly diminished the yield of the cor-
responding homoallylic ether (19, R2 =Me).
2
3
5
6
44
31
Finally, we tested chiral sulfonic acids as catalysts
for the reaction of benzaldehyde (5), BnOTMS, and
allyltrimethylsilane (3). Commercially available cam-
phorsulfonic acid (CSA, 25) did not give any conver-
sion in dichloromethane, neither to the final product
(6) nor to the intermediate acetal. In contrast, the
more reactive binaphthalenyl disulfonic acid (26)[17]
provided the desired homoallyl benzyl ether (6) in
4
5
36
[a]
Yield of isolated product.
oaromatic, one a,b-unsaturated, as well as one ali- 80% GC yield (Scheme 3). However, no measurable
phatic precursor were subjected to BnOH, allyltrime- enantioselectivity has been achieved so far.
thylsilane (3), and 5 mol% of DNBA. While the yield
In summary, we have developed Brønsted acid-cat-
of the aromatic homoallyl benzyl ether (6) is good, alyzed three-component Hosomi–Sakurai reactions.
the products derived from thiophene-3-carbaldehyde, DNBA mediates the combination of aldehydes, alk-
cinnamaldehyde, and pivalaldehyde were isolated in
ACHTREoUNG xysilanes, and allylsilanes to provide a wide range of
moderate yields. None of these reactions went to homoallylic ethers in moderate to high yields. Fur-
completion. Even after prolonged stirring for two thermore, alcohols instead of their silyl ethers can be
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Brønsted Acid-Catalyzed Three-Component Hosomi–Sakurai Reactions
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Table 3. Three-component Hosomi–Sakurai reactions: variation of the silyl ether, the alcohol, and the allylsilane.
Entry
R1OTMS or R1OH
R2
Product
Time [h]
Yield[a] [%]
1
2
AllOTMS
AllOH
H
H
2
3
84
80
3
4
Propargyl-OTMS
Propargyl-OH
H
H
5
24
83
55
5
6
Pentyl-OTMS
Pentyl-OH
H
H
3
3
96
93
7
8
i-PrOTMS
i-PrOH
H
H
2
3
93
90
9
10
BnOTMS
BnOH
Me
Me
24
24
66
52
[a]
Yield of isolated product.
quire anhydrous conditions and can be stored under
air over a long period. Hence, it has certain advantag-
es over many Lewis acids.
Although the use of chiral sulfonic acids has so far
not led to any enantioselectivities yet, we anticipate
solutions to this problem to arise in the near future.
Experimental Section
General Procedure for the Three-Component
Hosomi–Sakurai Reaction of Aldehydes, Alkoxy-
silanes, and Allylsilanes
Scheme 3. Screening of chiral sulfonic acids.
Aldehyde 2 (1 mmol, 1.0 equiv.), an alkoxysilane (2 mmol,
2.0 equiv.), and allylsilane 18 (2 mmol, 2.0 equiv.) were
added to a solution of DNBA (8.5 mg, 0.03 mmol, 3 mol%)
in anhydrous CH3CN (1.5 mL) and stirred at room tempera-
ture for the indicated time. The mixture was poured into
brine (20 mL) and extracted with Et2O (3”50 mL). The
combined organic layers were washed with aqueous
NaHCO3 (20 mL) and brine (20 mL), dried over Na2SO4, fil-
tered and concentrated. Homoallylic ether 19 was isolated
by flash chromatography (silica, pentane/CH2Cl2 or pentane/
employed as well. Significant advantages of our pro-
cesses include: a) the use of commercially available
starting materials, b) the broad scope, c) a high diver-
sity of the products, and d) the simplicity and practic-
ability.
Most notably, DNBA is a powerful and useful cata-
lyst: a) it is very active resulting in low catalyst load-
ings, b) it is commercially available and can be used
without any further purification, c) it is inexpensive,
nontoxic, and easy to handle, and d) it does not re- Et2O).
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Daniela Kampen et al.
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1992, 57, 5790–5792; c) L. F. Tietze, C. Wulff, C.
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Rychnovsky, Org. Lett. 2002, 4, 147–150.
General Procedure for the Three-Component
Hosomi–Sakurai Reaction of Aldehydes, Alcohols,
and Allylsilanes
Aldehyde
2 (1 mmol, 1.0 equiv.), an alcohol (2 mmol,
[6] B. H. Lipshutz, J. Burgess-Henry, G. P. Roth, Tetrahe-
2.0 equiv.), and allylsilane 18 (3 mmol, 3.0 equiv.) were
added to a solution of DNBA (14.2 mg, 0.05 mmol, 5 mol%)
in anhydrous CH3CN (4.5 mL) and stirred at room tempera-
ture for the indicated time. The mixture was poured into
brine (20 mL) and extracted with Et2O (3”50 mL). The
combined organic layers were washed with aqueous
NaHCO3 (20 mL) and brine (20 mL), dried over Na2SO4, fil-
tered and concentrated. Homoallylic ether 19 was isolated
by flash chromatography (silica, pentane/CH2Cl2 or pentane/
Et2O).
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Supporting Information
[11] a) For one example using catalytic amounts of I2, see
ref.[2b]
;
b) for one example using stoichiometric
The Supporting Information comprises a general procedure
for the screening of chiral sulfonic acids as well as analytical
data for the characterization of new compounds (NMR,
HR-MS).
amounts of TMSOFs, see ref.[5]; c) for the reaction of
aldehydes, alcohols and a pentadienylsilane in the pres-
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[12] For intramolecular Sakurai reactions, see: a) M. Sugi-
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Acknowledgements
Generous support by the Max Planck Society, the DFG (Pri-
ority Program Organocatalysis SPP1179), Novartis (Young
Investigator Award to B.L.), the Fonds der Chemischen In-
dustrie (Silver Award to B.L.), and AstraZeneca (Research
Award in Organic Chemistry to B.L.) is gratefully acknowl-
edged. We thank Sebastian Hoffmann for the preparation of
chiral sulfonic acid 26.
´
955–959; c) A. P. Dobbs, S. Martinovic, Tetrahedron
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J. P. Vitale, S. D. Rychnovsky, Org. Lett. 2002, 4, 3919–
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Hosomi, Synlett 2005, 3148–3150.
[13] D. Kampen, B. List, Synlett 2006, 2589–2592.
[14] a) For the use of TfOH in mechanistic investigations of
TMSOTf-catalyzed allylations, see ref.[5c]; b) for the
synthesis of homoallylic ethers from ketones in the
presence of a mixture of TMSOTf and TfOH, see: L. F.
Tietze, K. Schiemann, C. Wegner, J. Am. Chem. Soc.
1995, 117, 5851–5852.
[15] For the synthesis of homoallylic ethers from ketones
catalyzed by TfOH, see: a) L. F. Tietze, K. Schiemann,
C. Wegner, C. Wulff, Chem. Eur. J. 1998, 4, 1862–1869;
b) L. F. Tietze, C. Wegner, C. Wulff, Eur. J. Org. Chem.
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J. Am. Chem. Soc. 2006, 128, 11483–11495.
[16] For Brønsted acid-catalyzed Hosomi-Sakurai reactions
of carbonyl compounds, see: a) K. Ishihara, A. Hasega-
wa, H. Yamamoto, Angew. Chem. 2001, 113, 4201–
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moto, Synlett 2001, 1851–1854.
[17] Chiral sulfonic acid 26 was prepared according to a
modified procedure reported by Takahashi and Fu-
kushi: K. Takahashi, K. Fukushi, Japanese Patent
132815, 2005.
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