A novel, efficient, and selective cleavage of acetals using bismuth(III) chloride

Article abstract of DOI:10.1246/cl.2000.1074

Treatment of acetals with bismuth(III) chloride in methanol provides a simple, convenient and chemoselective process for deprotection, and the parent aldehyde or ketone was obtained in high yield. The acetals have been cleaved selectively in the presence of silyl, benzyl and tetrahydropyranyl ethers.

Full text of DOI:10.1246/cl.2000.1074

1074
Chemistry Letters 2000
A Novel, Efficient, and Selective Cleavage of Acetals Using Bismuth(III) Chloride
Gowravaram Sabitha,* R. Satheesh Babu, E. Veakata Reddy, and J. S . Yadav
Organic Division I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
(Received May 1, 2000; CL-000423)
Treatment of acetals with bismuth(III) chloride in methanol
provides a simple, convenient and chemoselective process for
deprotection, and the parent aldehyde or ketone was obtained in
high yield. The acetals have been cleaved selectively in the
presence of silyl, benzyl and tetrahydropyranyl ethers.
Acetals are most frequently used protecting groups for car-
bonyl functionality in organic synthesis. The deprotection of
these groups into aldehydes and ketones is an important trans-
formation and usually accomplished by aqueous acid hydrolysis
using several acids such as hydrochloric acid, acetic acid, oxalic
acid, p-toluenesulfonic acid, trifluoroacetic acid etc. Other
methods include using Lewis acids,2 oxidative conditions,3
phosphorus-based reagents4 and silicon-based reagents.5
Recently (trimethylsilyl) bis(fluorosulfinyl)imide6 and thiourea7
have been employed for the effective cleavage of these groups.
Many of these procedures suffer from one or more drawbacks
such as lack of selectivity due to strong acidic conditions, oxi-
dizing nature, non commercially available reagent and unsatis-
factory yields. Although all these procedures have their own
advantages, there is still a great need to develop an efficient
method which is non acidic, anhydrous and mild to cleave the
acetals selectively in presence of other ether linked protecting
groups.
Over recent years, the catalytic activity of bismuth(III)
derivatives as Lewis acids has been demonstrated in several
reactions such as cyanation and allylation of carbonyl com-
pounds,8 Friedel–Crafts,9 enoxysilanes,10 allylsilanes,11 cross
aldol and Michael reactions. Mukaiyama,12 carbonyl-ene13
reactions and carbonyl Diels–Alder reactions14 reveal the exclu-
sive importance of bismuth(III) salts over other Lewis acids.15
We herein report a simple, efficient and selective method for
the cleavage of acetals using bismuth(III) chloride as catalyst.
Even though bismuth(III) halides16 have been known for thioace-
talization, it is justified here to note that we have made a system-
atic study on the deprotection of acetals and found high selectivi-
ty over the other ether linked protecting groups.
Thus, a mixture of benzaldehyde dimethylacetal (entry 1, 1
Copyright © 2000 The Chemical Society of Japan

Chemistry Letters 2000
1075
eq), bismuth chloride (0.5 eq) and methanol (5 mL) was stirred
at room temperature for 30 min, on completion, (monitored by
thin layer chromatography) the reaction mixture was subjected
to usual workup which yielded 92% of the deprotected product.
A wide range of acetals has been subjected to cleavage by this
procedure with bismuth chloride to provide the corresponding
aldehydes and ketones in good yields (Table 1). It was
observed that the cleavage of these groups was faster in
methanol rather than in dichloromethane. However, 1,3-diox-
olanes of aliphatic compounds required reflux conditions to
accelerate the reaction.
With these results, we have extended our studies on doubly
protected acid-sensitive substrates for making the procedure
more effective. Silyl ethers with acetals (entries 9, 10, 11) were
subjected to the cleavage procedure and observed the selective
cleavage of acetal group only. Similarly THP ethers of acetal
(entries 12, 13) and benzylic ethers of the acetal (entries 14, 15)
were also converted to the singly protected compounds without
any noticeable deprotection of the other protecting groups.
In conclusion, we have developed a new and efficient
selective method for the deprotection of acetals using BiCl3, an
inexpensive, commercially available and non-toxic reagent.
Moreover, the selectivity of the procedure under mild Lewis
acid conditions may find application in organic synthesis.
4
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References and Notes
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17 General Procedure: To an acetal (1 mmol) in MeOH (5
mL), BiCl3 (0.5 mmol) was added and stirred for the speci-
fied time and conditions (Table l). On completion, MeOH
was removed under reduced pressure and ice was added to
quench the catalyst. The reaction mixture was extracted
with dichloromethane (3 × 10 mL). The combined organic
layers were washed with water and dried over Na2SO4.
The solvent was removed under reduced pressure, and sub-
jected to further purification by column chromatography to
give the corresponding aldehyde or ketone.
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IICT Communication No. 4S57