An efficient protection of carbonyls and deprotection of acetals using decaborane

Article abstract of DOI:10.1016/S0040-4039(02)00387-8

Carbonyls were efficiently converted to the corresponding dimethyl acetals at room temperature using trimethyl orthoformate and 1 mol% of decaborane under a nitrogen atmosphere. In turn, acetals were deprotected to the corresponding carbonyls using 1 mol% of decaborane in aqueous THF chemoselectively.

Full text of DOI:10.1016/S0040-4039(02)00387-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 2699–2703
An efficient protection of carbonyls and deprotection of acetals
using decaborane
Seung Hwan Lee, Ji Hee Lee and Cheol Min Yoon*
Graduate School of Biotechnology, Korea University, Seoul, South Korea
Received 3 December 2001; revised 20 February 2002; accepted 25 February 2002
Abstract—Carbonyls were efficiently converted to the corresponding dimethyl acetals at room temperature using trimethyl
orthoformate and 1 mol% of decaborane under a nitrogen atmosphere. In turn, acetals were deprotected to the corresponding
carbonyls using 1 mol% of decaborane in aqueous THF chemoselectively. © 2002 Elsevier Science Ltd. All rights reserved.
Protection of carbonyls and deprotection of acetals (or
ketals) are two of the most important reactions in
organic chemistry and many methods have been devel-
oped for these reactions.1 Although a lot of conven-
chemoselective and efficient Lewis acid catalyst in the
conversions between carbonyls and acetals. Here, we
wish to describe the protection of carbonyls to acetals
and the deprotection of acetals to carbonyls using a
catalytic amount of decaborane (Scheme 1).
tional catalysts including acid catalysts1,2 and Sc(NTf)3
3
have been reported for the protection of carbonyls into
dimethyl acetals, the search for a new catalyst is still
actively pursued due to the problems such as difficulty
in handling the reagent, poor chemoselectivity and lim-
ited examples.3 For deprotection of dimethyl acetals
into carbonyls, many acid catalysts such as protic and
Lewis acid catalysts have been developed.1,4 However,
many of these methods involve the use of corrosive
reagents and elevated temperature. Several mild meth-
ods have also been developed for the conversion of
acetals and ketals into carbonyls.5 Although a selective
method6 has also been reported, a mild and neutral
method which would effect the selective cleavage of
acetals (or ketals) is still required.
Various aldehydes and ketones were efficiently con-
verted to the corresponding dimethyl acetals in the
presence of trimethyl orthoformate using a catalytic
amount of decaborane in anhydrous methanol at room
temperature under a nitrogen atmosphere and the
results are shown in Table 1.14 Yields of these reactions
are almost quantitative in most cases. Decaborane (1
mol%) was used in all of the cases except for acetophe-
none (2 mol% decaborane). The reaction seemed to
proceed through an oxonium ion intermediate (Scheme
2). The formation of any side product resulting from
reduction
of
carbonyls10c,d
and
reductive
etherification10b was not observed probably because
acetalization might be much faster than the two reac-
tions. Even if 30 mol% of decaborane was used, any
other product related to reductive etherification and
reduction of carbonyls was not formed at all. Decabo-
rane (and/or its decomposed intermediate) as a Lewis
acid catalyst might activate the carbonyl group via
coordination and make the oxygen of the hemiacetal a
good leaving group. Decaborane decomposes slowly in
methanol. It is not clear at this moment whether all
kinds of decomposed species of decaborane in addition
Decaborane7 is a commercially available white solid
that decomposes slowly in air. Typical known reactions
of decaborane include adduct formation and ortho-
carborane8 preparation for BNCT. Decaborane as a
reducing reagent in organic synthesis has been reported,
but was inefficient due to its low reactivity in hexane
even at high temperature.9 By changing the solvent
system to protic solvents, the reducing power of decab-
orane was increased to be efficient for reductive etherifi-
cation and reductive amination.10 As a result of an
ongoing study, decaborane was found to be a mild,
Keywords: carbonyls; acetals; protection; decaborane; chemoselective.
* Corresponding author. Fax: +82-2-3290-3433; e-mail: cmyoon@
korea.ac.kr
Scheme 1.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00387-8

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S. H. Lee et al. / Tetrahedron Letters 43 (2002) 2699–2703
Table 1. Acetalization of carbonyls to acetals using decaborane in methanol
to decaborane have a catalytic activity or not,11 but it is
under investigation. Trimethyl orthoformate (3 equiv.)
is a water scavenger that shifts the equilibrium to the
side of the products. The several acid-sensitive function-
alities such as MOM (entry 11), PMB (entry 12),
methylenedioxy (entry 13) and TBDPS (entry 14)
remained intact under our reaction conditions. It has
been reported that the electron-withdrawing sub-
stituents at the alpha position to the carbonyl enhance
the rate of acetal formation and electron donating
groups (such as phenyl or conjugated) and retard acetal
formation under acid-catalytic conditions.12 However,
under our conditions, aromatic aldehydes with electron
donating groups (entries 7–9 and 11–14) and conju-
gated aldehyde (entry 10) were converted to dimethyl
acetal within a few minutes. Dimethyl acetalization of
aromatic aldehydes with a nitro group (known as an
activating group for the acetal formation reaction) at
meta or para positions (entries 5 and 6) and acetophe-
none (entry 15) was relatively slow. This result might be
evidence that the oxonium ion generation step from
carbonyl is a slow process as shown in Scheme 2. The
oxonium ion generated from the benzaldehyde with the
electron withdrawing group is quite unstable and
results in a slow process for the formation of acetals.
The acetophenone acetal formation is slow because
hemiacetal formation is a slow process resulting from
the steric hindrance to the methanol approach. The
Scheme 2.

S. H. Lee et al. / Tetrahedron Letters 43 (2002) 2699–2703
2701
by a triple bond (entry 12) was subjected to the reaction
conditions, no aldehyde was formed even after 6 h
stirring at reflux. No reaction was observed with the
cyclic acetal of 3-bromobenzaldehyde (entry 13) and the
starting material was recovered quantitatively after 2 h
stirring at rt. Acetals of nonconjugated aldehyde
(entries 14 and 15) and benzaldehyde acetals with an
electron withdrawing group such as cyano (entry 16) or
nitro (entries 17 and 18) were resistant against depro-
tection under these conditions. The deprotection of
these acetals did not proceed at all and substrates were
recovered completely. Benzaldehyde dimethyl acetals
were cleaved selectively in the presence of other acid
labile protecting groups such as MOM (entry 8), PMB
(entry 9), methylenedioxy (entry 10) and TBDPS (entry
11). THP ether of phenol and aliphatic alcohol survived
under our reaction conditions within 6 h (entries 19 and
20).
electron donating group stabilized the oxonium ion,
helping it to form fast and thus increased the reaction
rate. The benzophenone (entry 17) was not acetalized at
all under our conditions. Our method is also effective
for the preparation of diethyl acetal of carbonyls. The
treatment of benzaldehyde with 3 equiv. of triethyl
orthoformate in absolute ethanol using 1 mol% of
decaborane gave diethyl acetal in 96% isolated yield
(entry 18).
The acetals and ketals in aqueous THF using decabo-
rane were deprotected to give the corresponding car-
bonyls and the results are shown in Table 2.15 The
experiment was conducted in a solution of water and
tetrahydrofuran (1:1) in the presence of decaborane (1
mol%). Dimethyl acetals of aromatic aldehydes (entries
1–4) and conjugated aldehyde (entry 5) underwent
smooth deprotection at room temperature in a rela-
tively fast rate to give the corresponding aldehydes in
high yields. Ketals of aromatic ketone (entry 6) and
aliphatic ketone (entry 7) are efficiently deprotected to
give ketones under these conditions. However, conjuga-
tion with a triple bond did not assist the deprotection
of aldehyde acetals. When the diethyl acetal conjugated
Deprotection can apply to the selective reduction of
carbonyls13 by coupling with reduction in a consecutive
way and one example is shown in Scheme 3. A solution
of dimethyl acetal of benzaldehyde and hydrocin-
namaldehyde in the presence of 1 mol% of decaborane
Table 2. Hydrolysis of acetals to carbonyls using decaborane in aqueous THF

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S. H. Lee et al. / Tetrahedron Letters 43 (2002) 2699–2703
Scheme 3.
in aqueous THF was stirred for 10 min and then 1
equiv. of sodium borohydride was added. The reaction
was monitored by TLC using a solution of ethyl acetate
and hexane (1:10). After 10 min stirring at rt and the
usual work-up followed by column chromatography,
benzyl alcohol was obtained in 94% isolated yield and
hydrocinnamaldehyde dimethyl acetal was recovered
intact in 91% yield.
Commun. 1992, 979; (d) Ford, K. L.; Roskamp, E. J.
Tetrahedron Lett. 1992, 33, 1135.
6. (a) Eash, K. J.; Pulia, M. S.; Wieland, L. C.; Mohan, R.
S. J. Org. Chem. 2000, 65, 8399; (b) Ko, K.-Y.; Park,
S.-T. Tetrahedron Lett. 1999, 40, 6025; (c) Sabitha, G.;
Bbu, R. S.; Reddy, V.; Yadav, J. S. Chem. Lett. 2000,
1074; (d) Gautier, E. C. L.; Graham, A. E.; Mckillop, A.;
Standen, S. P.; Taylor, R. J. K. Tetrahedron Lett. 1997,
38, 1881.
In conclusion, the carbonyls were efficiently converted
to the corresponding dimethyl acetals at room tempera-
ture using trimethyl orthoformate as a water scavenger
and decaborane as a Lewis acid catalyst under a nitro-
gen atmosphere. The advantage of this methodology is
that it is simple, mild and efficient. Acetals and ketals
were efficiently deprotected to the corresponding car-
bonyls using a catalytic amount of decaborane in
aqueous THF. The deprotection condition is chemose-
lective against aliphatic and cyclic acetals, and acid
labile protecting groups such as THP, TBDPS and
MOM.
7. Review of structure and properties: (a) Campbell, Jr. In
Press in Boron Chemistry; Steinberg, M., Ed.; Macmillan:
New York, 1964; Vol. 1, p. 173; (b) Lipscomb, W. N.
Science 1977, 196, 1047; (c) Muetterties, E. I. Boron
Hydride Chemistry; Academic Press: New York, 1975; (d)
Decaborane was purchased from Katchem Ltd., E. Kras-
nohorske 6 110 00 PRAHA 1 and used without any
further purification.
8. For reviews: (a) Hawthorne, M. F.; Angew. Chem., Int.
Ed. Engl. 1993, 32, 950; (b) Solloway, A. H.; Tjarks, W.;
Barnum, B. A.; Rong, F.-G.; Barth, R. F.; Codogni, I.
M.; Wilson, J. G. Chem. Rev. 1998, 98, 1515.
9. Tanaka, T.; Matsuda, T.; Kimijima, K.; Iwasaki, Y. Bull.
Chem. Soc. Jpn. 1978, 51, 1259.
10. (a) Reductive amination: Bae, J. W.; Cho, Y. J.; Lee, S.
H.; Maing Yoon, C. O.; Yoon, C. M. Chem. Commun.
2000, 1857; (b) Reductive etherification: Lee, S. H.; Park,
Y. J.; Yoon, C. M. Tetrahedron Lett. 1999, 40, 6049; (c)
Ketone reduction: Bae, J. W.; Lee, S. H.; Jung, Y. J.;
Maing Yoon, C. O.; Yoon, C. M. Tetrahedron Lett. 2001,
42, 2137; (d) Aldehyde reduction: Lee, S. H.; Yoon, C.
M., unpublished result.
Acknowledgements
This work was supported by Korea Research Founda-
tion Grant (KRF-2001-015-DP0302).
11. Decaborane solution in methanol has a catalytic power
even after 10 h stirring at rt: benzaldehyde turned into
dimethyl acetal within 10 min in the prepared solution at
rt.
12. Clerici, A.; Pastori, N.; Porta, O. Tetrahedron 1998, 54,
15679 and references cited therein.
References
1. Greene, T. W.; Wuts, P. G. M. Protective Groups in
Organic Synthesis, 3rd ed.; John Wiley & Sons: New
York, 1991; p. 188.
2. (a) Perio, B.; Dozias, M. J.; Jacquault, P.; Hamelin, J.
Tetrahedron Lett. 1997, 38, 7867; (b) Tateiwa, J.; Hori-
uchi, H.; Uemura, S. J. Org. Chem. 1995, 60, 4039; (c)
Clerici, A.; Pastori, N.; Porta, O. Tetrahedron 1998, 54,
15679; (d) Karimi, B.; Ashtiani, A. M. Chem. Lett. 1999,
1199.
13. Selective reduction of carbonyl groups: Gemal, A. L.;
Luche, J.-L. J. Org. Chem. 1979, 44, 4187.
14. Typical procedure for dimethyl acetalization of carbonyl:
To a solution of benzaldehyde (100 mg, 0.942 mmol) and
trimethyl orthoformate (0.3 ml, 2.827 mmol) in anhy-
drous methanol (4.7 ml) was added decaborane (1.2 mg,
1 mol%) and the resulting solution was stirred at room
temperature under nitrogen. The reaction was monitored
by TLC (ethyl acetate: n-hexane=1:4). After 5 min, the
reaction was quenched by adding saturated aqueous
K2CO3 (10 ml) and extracted with methylene chloride (10
ml×3). Then, the organic layer was washed with water
followed by saturated NaCl solution and dried over
anhydrous sodium sulfate. The solvent was removed
under reduced pressure to give benzaldehyde dimethylac-
etal as a colorless liquid in high yield (92%).
3. Ishihara, K.; Karumi, Y.; Kubota, M.; Yamamoto, H.
Synlett 1996, 839.
4. (a) Kametani, T.; Kondoh, H.; Honda, T.; Ishizone, H.;
Suzuki, Y.; Mori, W. Chem. Lett. 1989, 901; (b) Sen, S.
E.; Roach, S. L.; Boggs, J. K.; Ewing, G. J.; Magrath, J.
J. Org. Chem. 1997, 62, 6684.
5. (a) Marko, I. E.; Ates, A.; Gautier, A.; Leroy, B.;
Plancher, J.-M.; Quesnel, Y.; Vanherck, J.-C. Angew.
Chem., Int. Ed. 1999, 38, 3207; (b) Johnstone, C.; Kerr,
W.; Scott, J. Chem. Commun. 1996, 341; (c) Tanemura,
K.; Suzuki, T.; Horaguchi, T. J. Chem. Soc., Chem.

S. H. Lee et al. / Tetrahedron Letters 43 (2002) 2699–2703
2703
15. Typical experimental for deprotection of acetal: To a
solution of benzaldehyde dimethyl acetal (0.2 ml, 1.31
mmol) in a solution of THF and water (1:1, 0.2 M)
was added decaborane (1.6 mg, 1 mol%). The reaction
was monitored by TLC using a solution of ethyl ace-
tate and n-hexane (1:4). After 2 min stirring at rt, the
reaction mixture was quenched with saturated sodium
bicarbonate solution (5 ml), and extracted with ethyl
acetate (10 ml). The organic layer was washed with
water (10 ml×3) and dried over anhydrous magnesium
sulfate. After concentration followed by column chro-
matography on a short silica gel pad using a solution
of ethyl acetate and hexane (1:10), benzaldehyde was
obtained in 94% yield.