Efficient and practical catalytic vinylogous aldol reaction of dioxinone-derived silyl dienol ethers with aromatic aldehydes

Article abstract of DOI:10.1016/j.tetlet.2006.10.084

Vinylogous Mukaiyama-aldol reaction was realized by use of dioxinone-derived silyl dienol ethers and various aldehydes in the presence of highly catalytic amounts of bismuth triflate. The reaction proceeds rapidly and affords the corresponding β-hydroxy-1

Full text of DOI:10.1016/j.tetlet.2006.10.084

Tetrahedron Letters 47 (2006) 9089–9092
Efficient and practical catalytic vinylogous aldol reaction of
dioxinone-derived silyl dienol ethers with aromatic aldehydes
Thierry Ollevier,* Valerie Desyroy, Cristian Catrinescu and Raphael Wischert
De´partement de chimie, Universite´ Laval, Que´bec (Que´bec), Canada G1K 7P4
Received 27 September 2006; accepted 16 October 2006
Available online 7 November 2006
Abstract—Vinylogous Mukaiyama-aldol reaction was realized by use of dioxinone-derived silyl dienol ethers and various aldehydes
in the presence of highly catalytic amounts of bismuth triflate. The reaction proceeds rapidly and affords the corresponding
b-hydroxy-1,3-dioxin-4-ones in very good to excellent yields (up to 98%).
ꢀ 2006 Elsevier Ltd. All rights reserved.
b-Hydroxy ketones and esters are extremely important
compounds as biologically active molecules.1 The deve-
lopment of new methods for the preparation of aldols is
therefore an important area of synthetic efforts. The
vinylogous Mukaiyama-aldol reaction provides a rapid
route of such compounds by fast connection of a car-
bonyl framework to the c carbon of a dienolate.2 Over
the past years, many elegant enantioselective versions
of this reaction have been described, using high catalytic
amount of various chiral mediators.3 However, to our
knowledge, all non enantioselective examples up to
now have employed Lewis acids such as TiCl4, BF3ÆOEt2
or SiCl4.4 Yet, moisture sensitivity and the high cost of
these catalysts restrict their use. In addition, all reported
racemic reactions used the Lewis acid in stoichiometric
amount or even in excess.4 In view of the versatile
synthetic utility of b-hydroxy-1,3-dioxin-4-ones, for
example, for the synthesis of 4-hydroxy-2-pyrones via
the oxidation of the hydroxyl group,4c there is clearly
a need for practical, and efficient conditions that involve
a bench-stable catalyst, used in very low loading.
Friedel–Crafts reactions,9 Fries and Claisen rearrange-
ments,10 and Sakurai reactions.11 Bismuth triflate
[Bi(OTf)3] is particularly attractive due to its commercial
availability or ease of preparation from commercial
cheap starting materials.12 Bismuth triflate was reported
by Dubac as very efficient for the Mukaiyama-aldol
reaction with silyl enol ethers.13 However, the vinylo-
gous Mukaiyama-aldol has never been investigated with
Bi(OTf)3Æ4H2O as a catalyst.
As a part of our ongoing interest in bismuth(III)-
catalyzed condensation reactions,14 we report herein a
bismuth(III)-catalyzed vinylogous Mukaiyama-aldol
reaction with 2,2-dimethyl-6-methylene-4-(trimethyl-
silyloxy)-1,3-diox-4-ene 2b. Aldols are obtained effi-
ciently in the presence of 1 mol % of Bi(OTf)3Æ4H2O.
The Bi(OTf)3Æ4H2O (3 mol %) catalyzed reaction of silyl
ketene acetal 2a with benzaldehyde led to the expected
product as a mixture of silylated aldol 3 and aldol 4 in
moderate to good yields (Scheme 1, entries 1 and 2).
The need for fluoride-mediated deprotection of silylated
aldol 3 in aldol 4 motivated us to use TMS derivative 2b
instead of 2a for easier work-up of the reaction mixture
(aq HCl, THF, 22 ꢁC, 2 h). As shown in Table 1, the for-
mation of the corresponding aldol 4 from readily avail-
able ketene acetal 2b was achieved in good yield and
complete c-regioselectivity (entries 3–9). Because of the
better yield obtained for our model reaction, diethyl-
ether was selected as the solvent of choice with 1 mol %
Bi(OTf)3Æ4H2O (compare entries 7–8 with 4–5). Only
1.5 equiv of the reagent were required to ensure
complete conversion (Table 1, compare entries 5–8 with
Bismuth compounds provide a good alternative due to
low toxicity, low cost, and good stability.5 Bismuth(III)
salts have been reported as effective catalysts for an
array of synthetic transformations: opening of epox-
ides,6 Mannich-type reactions,7 formation of acetals,8
Keywords: Bismuth; Bismuth(III) triflate; Aldol; Lewis acid; Silyl
dienolate; Vinylogous.
*
Corresponding author. Tel.: +1 418 656 5034; fax: +1 418 656
7916; e-mail: thierry.ollevier@chm.ulaval.ca
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.10.084

9090
T. Ollevier et al. / Tetrahedron Letters 47 (2006) 9089–9092
Bi(OTf)3•4H2O
(x mol %)
O
O
O
R'3SiO
Ph
O
O
HO
O
O
+
+
Ph
H
OSiR'3
O
Ph
O
1
2
3
4
2a (OSi
t-BuMe2)
2b (OSiMe3)
Scheme 1.
Table 1. Bi(OTf)3 catalyzed vinylogous Mukaiyama-aldol reaction of benzaldehydea
Entry
2 (equiv)
x
Conditions
Yield 3a (%)
Yield 4b (%)
1
2
3
4
5
6
7
8
9
2a (1.2)
2a (1.5)
2b (1.2)
2b (1.2)
2b (1.5)
2b (1.5)
2b (1.5)
2b (1.5)
2b (1.5)
3
3
3
3
3
3
3
1
Et2O, À78 ꢁC, 8 h
CH2Cl2, À78 ꢁC, 7.5 h
Et2O, À78 ꢁC, 5.5 h
CH2Cl2, À78 ꢁC, 3 h
CH2Cl2, À78 ꢁC, 4 h
THF, À78 ꢁC, 4 h
Et2O, À78 ꢁC, 4 h
Et2O, À78 ꢁC, 4 h
Et2O, À78 ꢁC, 4 h
43
75
—
—
—
—
—
—
—
21
6
75
82
98
75
89
95
93
0.5
a Conditions: x mol % Bi(OTf)3Æ4H2O, À78 ꢁC, then 10% aq HCl, THF, 22 ꢁC, 2 h.
b Isolated yield.
1) 1 mol % Bi(OTf)3•4H2O
Et2O, -78 ˚C, 1-2 h
O
O
O
HO
O
O
+
R
H
2) HCl, THF/H2O
OSiMe3
R
O
1
2b
4
Scheme 2.
Table 2. Bi(OTf)3 catalyzed vinylogous Mukaiyama-aldol reaction of
3–4). More interestingly, from a preparative point of
view, the drastic reduction of the catalyst loading (down
to 0.5 mol %) did not cause any appreciable decrease of
yield (Table 1, entry 9).
various aldehydesa
Entry
1
1
Compound
Yield 4b (%)
CHO
4b
86
The addition of silyl ketene acetal 2b to various alde-
hydes 1 proceeded readily employing Bi(OTf)3Æ4H2O
as the Lewis acid (Scheme 2, Table 2).15 Generally,
excellent yields of b-hydroxy-1,3-dioxin-4-ones were
obtained with 1.5 equiv of TMS-derived silyl ketene
acetal 2b and 0.01 equiv of Bi(OTf)3Æ4H2O at À78 ꢁC
in Et2O. Aromatic aldehydes as well as an a,b-unsatu-
rated aldehyde reacted smoothly to give the correspond-
ing b-hydroxy-1,3-dioxin-4-ones 4 in high yield (Table 2,
entries 1–10). Electron-rich p-, m-, or o-methoxybenz-
aldehyde led to the desired product in excellent yield
(Table 2, entries 3–5). The reaction worked well with a
variety of aldehydes including those bearing an elec-
tron-withdrawing group, and the expected product 4
was obtained with excellent yields (Table 2, entries 6–8).
In addition, heteroaromatic aldehyde such as furfural
can also serve as a substrate in this reaction, giving the
corresponding aldol in a moderate yield (Table 2,
entry 9). Conjugated aldehydes were good substrates
as well (Table 2, entry 10). Aliphatic aldehydes lead to
a poor yield of the aldol due to incomplete conversion
(Table 2, entries 11 and 12).
Me
CHO
Me
2
3
4c
4d
90
91
CHO
MeO
CHO
4
5
4e
4f
96
93
OMe
CHO
OMe
CHO
6
7
4g
4h
98
97
Cl
CHO
In summary, we have found that the vinylogous
Mukaiyama-aldol reaction proceeds smoothly with
F3C

T. Ollevier et al. / Tetrahedron Letters 47 (2006) 9089–9092
9091
Table 2 (continued)
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metry 2000, 11, 3187.
Entry
1
Compound
Yield 4b (%)
CHO
8
4i
74c
4. (a) Sato, M.; Sugita, Y.; Abiko, Y.; Kaneko, C.
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mane, H.; Le Roux, C. Eur. J. Org. Chem. 2004, 2517;
(c) Leonard, N. M.; Wieland, L. C.; Mohan, R. S.
Tetrahedron 2002, 58, 8373.
6. (a) Ogawa, C.; Azoulay, S.; Kobayashi, S. Heterocycles
2005, 66, 201; (b) Ollevier, T.; Lavie-Compin, G. Tetra-
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O2N
O
CHO
9
4j
73
CHO
10
11
4k
4l
80
Ph
35d
CHO
CHO
12
4m
28d
a Conditions: 1.5 equiv silyl ketene acetal 2b, 1 mol % Bi(OTf)3Æ4H2O,
Et2O, À78 ꢁC, then 10% aq HCl, THF, 22 ꢁC, 2 h.
b Isolated yield.
c 2 h, À78 ꢁC then 2 h, 22 ꢁC.
d Unoptimized conditions.
´
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dioxinone-derived silyl ketene acetal and a catalytic
amount of Bi(OTf)3Æ4H2O. This method offers several
advantages including mild reaction conditions, highly
catalytic (1%) process, and no formation of by-products.
Because of its numerous benefits, the Bi(OTf)3Æ4H2O
protocol should find utility in the synthesis of biologi-
cally active compounds.
´
9. (a) Le Roux, C.; Dubac, J. Synlett 2002, 181; (b) Repichet,
S.; Le Roux, C.; Dubac, J.; Desmurs, J. R. Eur. J. Org.
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Synlett 2004, 2794; (b) Ollevier, T.; Mwene-Mbeja, T. M.
Tetrahedron Lett. 2006, 47, 4051; (c) Ollevier, T.; Mwene-
Mbeja, T. M. Synthesis, in press.
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Acknowledgments
This work was financially supported by the Natural
Sciences and Engineering Research Council of Canada
´ ´
(NSERC), the Fonds Quebecois de la Recherche sur la
Nature et les Technologies (FQRNT, Quebec, Canada),
the Canada Foundation for Innovation, Universite La-
´
Marko, I. E. Org. Lett. 2002, 4, 47–50; (e) Sreekanth, P.;
Park, J. K.; Kim, J. W.; Hyeon, T.; Kim, B. M. Catal.
Lett. 2004, 96, 201–204; (f) Choudary, B. M.; Chidara, S.;
Raja Sekhar, C. V. Synlett 2002, 1694–1696; (g) Ollevier,
T.; Li, Z. Org. Biomol. Chem., in press.
´
´
val, and Merck. V.D. thanks NSERC for a postgraduate
scholarship. We thank Rhodia (Lyon, France) for gen-
erous gift of chemicals.
´
12. (a) Repichet, S.; Zwick, A.; Vendier, L.; Le Roux, C.;
Dubac, J. Tetrahedron Lett. 2002, 43, 993; (b) Lab-
`
rouillere, M.; Le Roux, C.; Gaspard, H.; Laporterie, A.;
Dubac, J.; Desmurs, J. R. Tetrahedron Lett. 1999, 40, 285;
(c) Torisawa, Y.; Nishi, T.; Minamikawa, J.-i. Org.
Process Res. Dev. 2001, 5, 84; (d) Bi(OTf)3Æ4H2O has
been prepared from BiPh3 according to Ref. 12c.
References and notes
13. Le Roux, C.; Ciliberti, L.; Laurent-Robert, H.; Laporte-
rie, A.; Dubac, J. Synlett 1998, 1249.
1. Shiina, I. In Modern Aldol Reactions; Mahrwald, R., Ed.;
Wiley-VCH: Weinheim, 2004; Vol. 2, pp 105–166.
2. (a) Mukaiyama, T.; Banno, K.; Narasaka, K. J. Am.
Chem. Soc. 1974, 96, 7503; For reviews of catalytic
Mukaiyama-aldol reactions: (b) Mukaiyama, T.; Matsuo,
J.-i. In Modern Aldol Reactions; Mahrwald, R., Ed.;
Wiley-VCH: Weinheim, 2004; Vol. 1, pp 127–160;
(c) Carreira, E. M. In Comprehensive Asymmetric Cataly-
sis I–III; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.;
Springer-Verlag: Berlin, Germany, 1999; Vol. 3, pp 997–
1065.
14. For a review of bismuth-mediated Mannich and aldol
reactions, see: (a) Ollevier, T.; Desyroy, V.; Nadeau, E.
ARKIVOC (Gainesville, FL, U.S.) 2007, 10, 10; (b)
Ollevier, T.; Desyroy, V.; Debailleul, B.; Vaur, S. Eur. J.
Org. Chem. 2005, 4971–4973.
15. General procedure for the bismuth-catalyzed vinylogous
Mukaiyama-aldol reaction. Under an inert atmosphere
of argon, the aldehyde (0.5 mmol) was stirred with
Bi(OTf)3Æ4H2O (0.005 mmol) in 0.5 mL of dry Et2O at
22 ꢁC for 0.5 h. After cooling down to À78 ꢁC, the silyl
ketene acetal (0.75 mmol) in 0.5 mL of dry Et2O was
added dropwise to the solution. The mixture was stirred at
À78 ꢁC until the reaction was completed as indicated by
TLC. The reaction was diluted with THF (1 mL),
quenched with 10% aqueous HCl and stirred for 2 h.
3. For a review, see: (a) Denmark, S. E.; Heemstra, J. R., Jr.;
Beutner, G. L. Angew. Chem., Int. Ed. 2005, 44, 4682;
(b) Singer, R. A.; Carreira, E. M. J. Am. Chem. Soc. 1995,
117, 12360; (c) Kruger, J.; Carreira, E. M. J. Am. Chem.
¨
Soc. 1998, 120, 837; (d) Denmark, S. E.; Beutner, G. L.

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T. Ollevier et al. / Tetrahedron Letters 47 (2006) 9089–9092
The crude reaction mixture was then extracted with
vacuum (rotatory evaporator). The crude product was
purified by column chromatography (eluent hexane/ethyl
acetate). The spectral data of the aldols match with those
reported in the literature.3e,4c,d
3 · 10 mL of diethyl ether. The organic phase was washed
with water, then with saturated aqueous sodium chloride,
dried over magnesium sulfate, and concentrated under