Bismuth triflate catalyzed Mukaiyama aldol reaction in an ionic liquid

Article abstract of DOI:10.1002/ejoc.200500621

We have developed an efficient, bismuth triflate catalyzed Mukaiyama aldol reaction. The reaction proceeds rapidly and affords the corresponding β-hydroxy carbonyl compound in moderate to very good yields (up to 92%). Wiley-VCH Verlag GmbH & Co. KGaA, 200

Full text of DOI:10.1002/ejoc.200500621

SHORT COMMUNICATION
DOI: 10.1002/ejoc.200500621
Bismuth Triflate Catalyzed Mukaiyama Aldol Reaction in an Ionic Liquid
[a]
[a]
[a]
[a]
Thierry Ollevier,* Valerie Desyroy, Blandine Debailleul, and Sophie Vaur
Keywords: Aldol / Bismuth / Green chemistry / Ionic liquid / Mukaiyama aldol reactions
We have developed an efficient, bismuth triflate catalyzed
Mukaiyama aldol reaction. The reaction proceeds rapidly
and affords the corresponding β-hydroxy carbonyl compound
in moderate to very good yields (up to 92%).
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2005)
The development of new methods for the synthesis of β- product isolation. Interestingly, bismuth triflate has already
hydroxy carbonyl compounds is an important area of syn- been reported as catalyst in ionic liquids for Friedel–Crafts
[
17]
[18]
thetic efforts. β-Hydroxy ketones and esters are extremely acylation,
epoxide opening,
and heterocycle forma-
[
1]
[19]
important compounds as biologically active molecules.
The Lewis acid mediated reactions of aldehydes with silyl
tion.
As a part of our ongoing interest in bismuth()-cata-
enolates are among the most efficient for the synthesis of lyzed condensation reactions, we report herein a bis-
β-hydroxy carbonyl compounds.[ Therefore, the develop- muth()-catalyzed Mukaiyama aldol reaction in the ionic
2a]
ment of new catalytic methods for their preparation is of liquid
1-butyl-3-methylimidazolium
tetrafluoroborate
first importance in organic synthesis. Catalytic Mukaiyama ([Bmim]BF ), as an alternative to dichloromethane. β-Hy-
4
aldol reactions have been reported by several groups as an droxy ketones and esters are obtained efficiently in the pres-
efficient method to prepare aldols.[ Synthetic methods in- ence of 10 mol% of Bi(OTf) ·nH O (with 1 Ͻ n Ͻ 4).
2b]
3
2
volving lanthanide triflates as catalysts for Mukaiyama al-
Initially, we screened various conditions for the Mukai-
dol reactions have been reported.[ High catalytic activity, yama aldol reaction of benzaldehyde (1a) and (1-phenylvi-
3]
moisture and air tolerance make lanthanide triflates attract- nyloxy)trimethylsilane (2a) in the presence of Bi(OTf)3·
ive catalysts. However, the high cost of these catalysts re- nH O (Table 1). The effect of the catalyst loading was ex-
2
stricts their use.
amined in the test reaction, using [Bmim]BF4 at 25 °C.
Bismuth compounds, too, have attracted recent attention When the reaction was carried out with 10 mol% of Bi-
[
4]
due to their low toxicity, low cost, and good stability. Bis- (OTf) ·nH O, the product was obtained with the best yield
3
2
muth salts have been reported as catalysts for Mannich-type (3-hydroxy-1,3-diphenylpropan-1-one, 86%; silylated 3-hy-
reactions, opening of epoxides, allylation of imines, al- droxy-1,3-diphenylpropan-1-one: 6%) (Table 1, Entry 1).
[5]
[6]
[7]
[
8]
[9]
dol reactions, formation and deprotection of acetals,
Several examples of Bi(OTf) -catalyzed Mukaiyama al-
3
[10]
[11]
Friedel–Crafts reactions,
Diels–Alder reactions,
Fries
dol reactions with various silyl enolates are summarized in
Table 1. Several silyl enol ethers derived from aromatic
ketones were treated with benzaldehyde (1a) in the presence
of 10 mol% of Bi(OTf) ·nH O. The corresponding β-hy-
[
12]
[13]
rearrangements, Claisen rearrangements, and intramol-
ecular Sakurai cyclizations.[ Bi(OTf)3 is particularly at-
tractive because it is commercially available or can be easily
prepared from commercially available starting materials.
Bismuth triflate has been reported by Dubac as efficient
catalyst for the Mukaiyama aldol reaction in dichlorometh-
ane. However, organic solvents, and in particular chlori-
nated solvents, have some drawbacks associated with vola-
tility and toxicity. In this context, ionic liquids are becom-
ing increasingly popular as solvents in organic synthesis for
14]
3
2
[
15]
droxy ketones 3a–d were obtained in moderate to very good
yields (Table 1, Entries 1–4). Trimethyl(prop-1-en-2-yloxy)
silane (2e) afforded β-hydroxy ketone 3e in moderate yield
Table 1, Entry 5). The silyl enol ether 2f derived from cy-
clopentanone afforded the corresponding β-hydroxy ketone
f with a good yield (Table 1, Entry 6). Silyl ketene acetals
[
8a]
(
3
were also treated with benzaldehyde (1a) under the same
conditions. The trimethylsilylketene acetal 2g of phenyl ace-
tate afforded the β-hydroxy ester 3g with a moderate yield
[
16]
various reasons.
They are practically nonvolatile, non-
flammable and can be recycled easily without any signifi-
cant loss in activity. In addition, one can take advantage of
the unique solubility properties of ionic liquids to facilitate
(Table 1, Entry 7). Thioester 3h was obtained using the
same conditions, albeit with poor syn/anti selectivity
(
Table 1, Entry 8).
Next, various aldehydes were tested and the results are
[
a] Département de Chimie, Université Laval,
Québec (Québec), Canada G1K 7P4
E-mail: thierry.ollevier@chm.ulaval.ca
summarized in Table 2. (1-Phenylvinyloxy)trimethylsilane
Eur. J. Org. Chem. 2005, 4971–4973
© 2005 Wiley-VCH Verlag GmbH & Co. KgaA, Weinheim
4971

T. Ollevier, V. Desyroy, B. Debailleul, S. Vaur
SHORT COMMUNICATION
Table 1. Bi(OTf)
benzaldehyde (1a) and silyl enolates.
3
-catalyzed Mukaiyama aldol reaction involving
Table 2. Bi(OTf)
various aldehydes and (1-phenylvinyloxy)trimethylsilane (2a).
3
-catalyzed Mukaiyama aldol reaction involving
[a]
[a]
[
(
[
5
a] Conditions: benzaldehyde (1a) (1.0 equiv.), silyl enolate
2 equiv.), Bi(OTf) ·nH (0.10 equiv.), concentration 2 .
b] Isolated yield. [c] Including TMS-protected aldol product. [d] A
0:50 mixture of syn/anti stereoisomers was obtained. [e] 4 equiv.
3
2
O
=
[
a] Conditions: aldehyde (1.0 equiv.), (1-phenylvinyloxy)trimethyl-
silane (2a) (2 equiv.), Bi(OTf) ·nH O (0.10 equiv.), concentration =
. [b] Isolated yield.
3
2
2
of silyl enol ether were used. [f] A 55:45 mixture of syn/anti stereo-
isomers was obtained. [g] A 61:39 mixture of syn/anti stereoisomers
was obtained.
study of the recycling is still in progress and the detailed
results will be disclosed soon in a full paper.
was chosen as the silyl enol ether partner. Generally, moder-
ate to very good yields of β-hydroxy ketone 3 were obtained
with 2 equiv. of (1-phenylvinyloxy)trimethylsilane (2a) and
In summary, we have found that the Mukaiyama aldol
reaction in an ionic liquid proceeds smoothly with silyl eno-
lates and a catalytic amount of Bi(OTf) ·nH O. This
3
2
0
.10 equiv. of Bi(OTf) ·nH O at 25 °C in [Bmim]BF . Aro-
3 2 4
method offers several advantages including mild reaction
conditions, green solvent chemistry, and no formation of
by-products. The β-hydroxy carbonyl compound is easily
purified. Because of its numerous benefits, the Bi(OTf)3·
matic aldehydes reacted smoothly to give the corresponding
β-hydroxy ketone derivatives 3 (Table 2, Entries 1–5). The
reaction worked well with a variety of aldehydes including
those bearing an electron-withdrawing group, and the cor-
responding β-hydroxy ketone 3 was obtained with moderate
to very good yields (Table 2, Entries 1–4). Electron-rich p-
methoxybenzaldehyde led to the desired product in moder-
ate yield (Table 2, Entry 5). Aliphatic aldehydes reacted
with (1-phenylvinyloxy)trimethylsilane (2a) under the same
conditions and afforded the corresponding β-hydroxy
ketones 3 in moderate yield (Table 2, Entries 6 and 7). Re-
placing the aldehyde by a ketone has not been successful as
no conversion was observed in the reaction of acetophe-
none with (1-phenylvinyloxy)trimethylsilane (2a).
nH O protocol should find utility in the synthesis of biolo-
2
gically active compounds. Development of other Bi(OTf)3·
nH O-catalyzed condensation reactions and related mech-
2
anistic studies will be reported in due course.
Experimental Section
General Procedures: Infrared spectra were recorded with an FT IR
–
1
1
13
19
spectrometer and are reported in cm . H, C, and F NMR
spectra were recorded with a 400 MHz NMR spectrometer in
1
CDCl
3
. For H NMR, tetramethylsilane (TMS) served as internal
In view of “green chemistry”, reuse of solvent is prefera-
ble. In the reaction of benzaldehyde (1a) with (1-phenylvi-
nyloxy)trimethylsilane (2a), the ionic liquid and the Lewis
acid were recovered after extracting the product with di-
1
3
standard (δ = 0 ppm). For C NMR, CDCl
3
was used as internal
standard (δ = 77.0 ppm) and spectra were obtained with complete
19
proton decoupling. For F NMR, CFCl
3
was used as internal
standard (δ = 0 ppm). The ionic liquid, 1-butyl-3-methylimidaz-
ethyl ether. Successive reuse of the recovered ionic liquid in olium tetrafluoroborate ([Bmim]BF ) was stirred under vacuum
4
the same reaction afforded the products in good yield. The (0.1 Torr, 1 h) prior to use.
4972
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© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2005, 4971–4973

Bismuth Triflate Catalyzed Mukaiyama Aldol Reaction in an Ionic Liquid
SHORT COMMUNICATION
General Procedure for the Mukaiyama Aldol Reaction: Under ar-
gon, the aldehyde (0.50 mmol) and silyl enolate (1.0 mmol) were
43, 7891–7893; c) T. Ollevier, G. Lavie-Compin, T. Ba, Recent
Development in Bismuth(III) Catalysis: Ring Opening of Epox-
ides with Aromatic Amines and Allylation of in situ Formed Im-
ines with Allylsilanes, Proceedings of the 13th European Sym-
posium on Organic Synthesis, Cavtat-Dubrovnik, September,
added dropwise successively to a solution of Bi(OTf)
3 2
·nH O
(
0.10 mmol) in 0.25 mL of dry [Bmim]BF . The mixture was stirred
4
at room temperature until the reaction was completed as indicated
by TLC. The reaction mixture was extracted with diethyl ether. The
ethereal phase was concentrated under vacuum (rotary evaporator).
The crude product was purified by silica gel chromatography
10–15, 2003, Monduzzi Eds., Bologna, 2004, p. 51–54.
[
[
7] T. Ollevier, T. Ba, Tetrahedron Lett. 2003, 44, 9003–9005.
8] a) C. Le Roux, L. Ciliberti, H. Laurent-Robert, A. Laporterie,
J. Dubac, Synlett 1998, 1249–1251; b) C. Le Roux, H. Gas-
pard-Iloughmane, J. Dubac, J. Jaud, P. Vignaux, J. Org. Chem.
1993, 58, 1835–1839; c) M. Wada, M. Takeichi, T. Matsumoto,
Bull. Chem. Soc. Jpn. 1991, 64, 990–994; d) H. Ohki, M. Wada,
K. Akiba, Tetrahedron Lett. 1988, 29, 4719–4722.
(hexane/ethyl acetate, 85:15–95:5). β-Hydroxy carbonyl compounds
3a–o accord exactly with those that have been previously reported
in the literature.
[
9] a) N. M. Leonard, M. C. Oswald, D. A. Freiberg, B. A. Nattier,
R. C. Smith, R. S. Mohan, J. Org. Chem. 2002, 67, 5202–5207;
b) M. D. Carrigan, D. Sarapa, R. C. Smith, L. C. Wieland,
R. S. Mohan, J. Org. Chem. 2002, 67, 1027–1030.
Acknowledgments
This work was financially supported by the Natural Sciences and
Engineering Research Council of Canada (NSERC), the Fonds
Québécois de la Recherche sur la Nature et les Technologies
[10] a) C. Le Roux, J. Dubac, Synlett 2002, 181–200; b) J. R. De-
smurs, M. Labrouillère, C. Le Roux, H. Gaspard, A. Laport-
erie, J. Dubac, Tetrahedron Lett. 1997, 38, 8871–8874; c) S.
Répichet, C. Le Roux, J. Dubac, J. R. Desmurs, Eur. J. Org.
Chem. 1998, 2743–2746.
(FQRNT, Québec, Canada), the Canada Foundation for Innova-
tion (CFI), and Université Laval. V. D. thanks NSERC for a post-
graduate scholarship. S. V. thanks the Office Franco-Québécois
pour la Jeunesse (OFQJ) for a scholarship. We thank Rhodia
[
11] a) B. Garrigues, A. Oussaid, J. Organomet. Chem. 1999, 585,
2
2
53–255; b) H. Laurent-Robert, B. Garrigues, J. Dubac, Synlett
000, 1160–1162.
(
(
Lyon, France) for a generous gift of triflic acid and Sidech s.a.
Tilly, Belgium) for bismuth oxide.
[
12] T. Ollevier, V. Desyroy, M. Asim, M. C. Brochu, Synlett 2004,
2794–2796.
[
[
13] T. Ollevier, T. M. Mwene-Mbeja, Synlett, submitted.
14] a) B. Leroy, I. E. Markó, Org. Lett. 2002, 4, 47–50; b) B. Leroy,
I. E. Markó, Tetrahedron Lett. 2001, 42, 8685–8688.
[
1] I. Shiina, in: Modern Aldol Reactions (Ed.: R. Mahrwald),
Wiley-VCH, Weinheim, 2004, vol. 2, p. 105–166.
[15] a) S. Répichet, A. Zwick, L. Vendier, C. Le Roux, J. Dubac,
Tetrahedron Lett. 2002, 43, 993–995; b) M. Labrouillère, C.
Le Roux, H. Gaspard, A. Laporterie, J. Dubac, J. R. Desmurs,
Tetrahedron Lett. 1999, 40, 285–286; c) Y. Torisawa, T. Nishi,
J.-i. Minamikawa, Org. Process Res. Dev. 2001, 5, 84–88; d) M.
Peyronneau, C. Arrondo, L. Vendier, N. Roques, C. Le Roux,
[
2] a) T. Mukaiyama, K. Banno, K. Narasaka, J. Am. Chem. Soc.
1
974, 96, 7503–7509; for reviews of catalytic Mukaiyama aldol
reactions, see: b) T. Mukaiyama, J. Matsuo, in: Modern Aldol
Reactions (Ed.: R. Mahrwald), Wiley-VCH, Weinheim, 2004,
vol. 1, p. 127–160; c) E. M. Carreira, in: Comprehensive Asym-
metric Catalysis I-III (Eds.: E. N. Jacobsen, A. Pfaltz, H. Yam-
amoto), Springer-Verlag, Berlin, Germany, 1999, vol. 3, p. 997–
3 2
J. Mol. Catal. A2004, 211, 89–91; e) Bi(OTf) ·nH O has been
2 3
prepared from Bi O
according to ref.[
15a]
1
065.
[16] a) Ionic Liquids in Organic Synthesis (Eds: P. Wasserscheid, T.
Welton), Wiley-VCH, Weinheim, 2003; b) for a review on ionic
liquids, see: S. Luo, Y. Peng, B. Zhang, P. Wang, J. Cheng, Curr.
Org. Synth. 2004, 1, 405–429.
[17] S. Gmouh, H. Yang, M. Vaultier, Org. Lett. 2003, 5, 2219–
2222.
[
3] a) S. Kobayashi, M. Sugiura, H. Kitagawa, W. W. L. Lam,
Chem. Rev. 2002, 102, 2227–2302; b) S. Kobayashi, T. Hamada,
S. Nagayama, K. Manabe, Org. Lett. 2001, 3, 165–167; c) S.
Kobayashi, I. Hachiya, T. Takahori, Synthesis 1993, 371–373;
d) S. Kobayashi, I. Hachiya, Tetrahedron Lett. 1992, 33, 1625–
1628.
[18] M. M. Khodaei, A. R. Khosropour, K. Ghozati, Tetrahedron
Lett. 2004, 45, 3525–3529.
[
4] a) Organobismuth Chemistry (Eds.: H. Suzuki, Y. Matano), El-
sevier, Amsterdam, 2001; b) H. Gaspard-Iloughmane, C.
Le Roux, Eur. J. Org. Chem. 2004, 2517–2532; c) N. M. Leo-
nard, L. C. Wieland, R. S. Mohan, Tetrahedron 2002, 58, 8373–
[19] a) M. M. Khodaei, A. R. Khosropour, M. Jowkar, Synthesis
2005, 1301–1304; b) J. S. Yadav, B. V. S. Reddy, P. N. Reddy,
Chem. Lett. 2004, 33, 1436–1437; c) J. S. Yadav, B. V. S. Reddy,
B. Eeshwaraiah, M. K. Gupta, Tetrahedron Lett. 2004, 45,
5873–5876; d) J. S. Yadav, B. V. S. Reddy, P. N. Reddy, M. S.
Rao, Synthesis 2003, 1387–1390.
8397.
[
5] a) T. Ollevier, E. Nadeau, J. Org. Chem. 2004, 69, 9292–9295;
b) T. Ollevier, E. Nadeau, Adv. Synth. Catal., submitted.
[
6] a) T. Ollevier, G. Lavie-Compin, Tetrahedron Lett. 2004, 45,
Received: August 16, 2005
Published Online: October 19, 2005
49–52; b) T. Ollevier, G. Lavie-Compin, Tetrahedron Lett. 2002,
Eur. J. Org. Chem. 2005, 4971–4973
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