An efficient method for the chemoselective synthesis of acylals from aromatic aldehydes using bismuth triflate

Article abstract of DOI:10.1016/S0040-4039(01)01756-7

Aromatic aldehydes are smoothly converted into the corresponding acylals in good yields in the presence of 0.10 mol% Bi(OTf)₃·xH₂O. Ketones are not affected under the reaction conditions. The highly catalytic nature of bismuth triflate and the fact that it is relatively non-toxic, easy to handle and insensitive to small amounts of air and moisture makes this procedure especially attractive for large-scale synthesis.

Full text of DOI:10.1016/S0040-4039(01)01756-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 8133–8135
An efficient method for the chemoselective synthesis of acylals
from aromatic aldehydes using bismuth triflate
Marc D. Carrigan, Kyle J. Eash, Matthew C. Oswald and Ram S. Mohan*
Department of Chemistry, Illinois Wesleyan University, Bloomington, IL 61701 USA
Received 15 August 2001; revised 31 August 2001; accepted 6 September 2001
Abstract—Aromatic aldehydes are smoothly converted into the corresponding acylals in good yields in the presence of 0.10 mol%
Bi(OTf)3·xH2O. Ketones are not affected under the reaction conditions. The highly catalytic nature of bismuth triflate and the fact
that it is relatively non-toxic, easy to handle and insensitive to small amounts of air and moisture makes this procedure especially
attractive for large-scale synthesis. © 2001 Elsevier Science Ltd. All rights reserved.
Acylals (geminal diacetates) have often been used as
protecting groups for carbonyl compounds because
they are stable to neutral and basic conditions.1,2
Hence, methods for their synthesis have received con-
Scheme 1.
siderable attention. Some of the reagents and catalysts
that have been developed for this purpose include sulfu-
ric acid,2 triflic acid,3 PCl3,4 TMSCl–NaI,5 ZnCl2,6 I2,7
Bismuth triflate, Bi(OTf)3·xH2O is much more efficient
than Sc(OTf)3 and Cu(OTf)2 as a catalyst for this
anhydrous ferrous sulfate,8 FeCl3,9 and NBS.10 Several
inorganic heterogeneous catalysts have also been devel-
oped as catalysts for synthesis of acylals.11 Lewis acids
such as Cu(OTf)2 (2.5 mol%)12 and Sc(OTf)3 (2 mol%)13
are also efficient for this conversion. Many of these
reagents are highly corrosive and difficult to handle
while copper and scandium triflate are rather expensive.
Recently, bismuth compounds have attracted attention
because of their low toxicity, low cost and relative
insensitivity to air and small amounts of moisture.14 In
a recent study aimed at investigating bismuth triflate
catalyzed acetylations of phenols, we observed that
when 4-hydroxybenzaldehyde was reacted with acetic
anhydride in the presence of Bi(OTf)3·xH2O, not only
was the phenol converted to the corresponding acetate
but the aldehyde moiety was also converted to the
corresponding acylal. This observation prompted us to
investigate the utility of bismuth triflate as a catalyst for
conversion of aldehydes to acylals.
conversion. Only 0.1 mol% of Bi(OTf)3·xH2O is needed
to effect reaction. We recently reported the use of
bismuth triflate as a catalyst for rearrangement of
epoxides to aldehydes and ketones.15 Bismuth triflate
has also been used as a catalyst for Friedel–Crafts
acylations,16 sulfonylations,17 Diels–Alder reactions,18
and aza-Diels–Alder reactions.19 Although Bi(OTf)3 is
not commercially available it can be easily synthesized
as the tetrahydrate at a relatively low cost.20 The exper-
imental procedure for synthesis of acylals is straightfor-
ward and involves stirring the aldehyde and acetic
anhydride as a solution in acetonitrile.21 A wide variety
of aromatic aldehydes underwent smooth reaction to
give the corresponding acylal in good yield (Table 1). It
should also be noted that this reaction can be carried
out under solvent free conditions.22
Aliphatic aldehydes (entries 8–10) reacted sluggishly in
acetonitrile but rapid reaction occurred under solvent
free conditions. However, the product yield was lower
than those obtained with aromatic aldehydes. We
attribute the lower yield to the formation of some
We wish to report that bismuth triflate is a highly
efficient catalyst for the conversion of aromatic alde-
hydes to acylals (Scheme 1).
1
unidentifiable by-products. H and 13C NMR spectral
Keywords: acylals; acylation; bismuth and compounds; protecting
groups.
* Corresponding author. Fax: (309) 5563864; e-mail: rmohan@
titan.iwu.edu
analysis of the crude product from aliphatic aldehydes
(entries 8 and 9) showed peaks in the olefininc region,
but the by-products were not consistent with the corre-
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01756-7

8134
M. D. Carrigan et al. / Tetrahedron Letters 42 (2001) 8133–8135
Table 1. Formation of acylals from aldehydes using Bi(OTf)3·xH2O
a
Superscript against entry c refers to literature reference for product.
b
Method A: 3 equiv. of (CH3CO)2O, CH3CN, 0.1 mol% Bi(OTf)3·xH2O. Method B: 1.5 equiv. of (CH3CO)2O, no solvent, 0.1 mol%
Bi(OTf)3·xH2O.
c Refers to yield of isolated product.
d
Crude product was estimated to be >98% by 1H and 13C NMR spectroscopy and GC analyses, and hence it was not purified further.
Purified by flash column chromatography.
Purified by recrystallization from hexanes.
e
f
g Reaction carried out under reflux.
h
After 5 h at room temperature, less than 10% conversion to product had occurred.

M. D. Carrigan et al. / Tetrahedron Letters 42 (2001) 8133–8135
8135
sponding enol acetates that would result if the acylal
underwent an elimination reaction. Ketones proved
resistant to the reaction conditions and no diacetate
formed even under reflux conditions. The chemoselectiv-
ity of this method was demonstrated using acetylben-
zaldehyde (entry 14). Smooth conversion of the aldehyde
to the diacetate was observed while the ketone function-
ality remained unaffected (Scheme 2).
Makone, S. S.; Kulkarni, S. P. Monatshefte Chem. 2000,
131, 417.
12. Chandra, K. L.; Saravanan, P.; Singh, V. K. Synlett 2000,
359.
13. Aggarwal, V. K.; Fonquerna, S.; Vennall, G. P. Synlett
1998, 849.
14. (a) Reglinski, J. In Chemistry of Arsenic, Antimony and
Bismuth; Norman, N. C., Ed.; Blackie Academic and
Professional: New York, 1998; pp. 403–440; (b) Marshall,
J. A. Chemtracts 1997, 1064–1075; (c) Suzuki, H.; Ikegami,
T.; Matano, Y. Synthesis 1997, 249; (d) Organobismuth
Chemistry; Suzuki, H.; Matano, Y., Ed.; Elsevier: Amster-
dam, 2001.
15. Bhatia, K. A.; Eash, K. J.; Leonard, N. M.; Oswald, M.
C.; Mohan, R. S. Tetrahedron Lett. 2001, 42, 8129–8132.
16. (a) Labrouille`re, M.; Le Roux, C.; Gaspard, H.; Laporterie,
A.; Dubac, J. Tetrahedron Lett. 1997, 38, 8871; (b) Re´pichet,
S.; Le Roux, C.; Dubac, J.; Desmurs, J. R. Eur. J. Org.
Chem. 1998, 2743.
Scheme 2.
In summary, a new highly catalytic and chemoselective
method has been developed for conversion of aromatic
aldehydes to acylals using bismuth triflate. Advantages
of this method include: (1) the use of an inexpensive and
relatively non-toxic catalyst (2) high catalytic efficiency
and (3) the observed chemoselectivity.
17. Re´pichet, S.; Le Roux, C.; Hernandez, P.; Dubac, J. J. Org.
Chem. 1999, 64, 6479.
18. (a) Garrigues, B.; Gonzaga, F.; Robert, H.; Dubac, J. J.
Org. Chem. 1997, 62, 4880; (b) Robert, H.; Garrigues, B.;
Dubac, J. Tetrahedron Lett. 1998, 39, 1161.
19. Laurent-Robert, H.; Garrigues, B.; Dubac, J. Synlett 2000,
1160.
20. Labrouille`re, M.; Le Roux, C.; Gaspard, H.; Laporterie,
A.; Dubac, J.; Desmurs, J. R. Tetrahedron Lett. 1999, 40,
285.
Acknowledgements
21. Method A: A solution of benzaldehyde (5.00 g, 0.0471 mol)
in acetonitrile (15 mL) was stirred as acetic anhydride (14.44
g, 0.141 mol) and Bi(OTf)3·xH2O (31 mg, 4.71×10−5 mol)
were added. The reaction progress was monitored by TLC.
After 45 min, 10% NaHCO3 (15 mL) was added and the
mixture was stirred for 5 min. The mixture was extracted
with ether (2×40 mL) and the combined organic layers were
washed with saturated aqueous NaHCO3 until basic, H2O
(2×25 mL), saturated NaCl (25 mL) and dried (Na2SO4).
The solvents were removed on a rotary evaporator to give
8.91 g (91%) of benzylidene diacetate that was determined
The authors wish to acknowledge funding by the National
Science Foundation (RUI grant). We also wish to thank
Dr. C. Le Roux (CNRS, Universite´ Paul-Sabatier) for
useful comments on the synthesis of bismuth triflate.
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1
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22. Caution: An exothermic reaction ensues upon addition of
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26. The product has been reported before (Ref. 11e) but spectral
1
data were not given. H NMR (270 MHz, CDCl3): l 2.11
(s, 6H), 2.29 (s, 3H), 7.11 (d, 2H, J=8.6 Hz), 7.53 (d, 2H,
J=8.6 Hz), 7.66 (s, 1H). 13C NMR (CDCl3, 67.5 MHz)
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CDCl3): l 2.12 (s, 6H), 2.60 (s, 3H), 7.60 (d, 2H, J=8.4
Hz), 7.69 (s, 1H), 7.98 (d, 2H, J=8.4 Hz). 13C (67.5 MHz,
CDCl3): 20.68, 26.60, 88.86, 126.84, 128.46, 137.90, 139.88,
168.55, 197.34. Mp: 56–59°C. Anal. calcd for C13H14O5: C,
62.39; H, 5.64. Found: C, 62.28; H, 5.48.