Pyridinium poly(hydrogen fluoride)-assisted cleavage of acetals and ketals

Article abstract of DOI:10.1016/S0040-4039(01)00808-5

Acetals, including ketals, were smoothly cleaved by the action of pyridinium poly(hydrogen fluoride) without addition of water or an alcohol in an anhydrous solvent.

Full text of DOI:10.1016/S0040-4039(01)00808-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 4641–4643
Pyridinium poly(hydrogen fluoride)-assisted cleavage of
acetals and ketals
Yutaka Watanabe,* Youko Kiyosawa, Akiko Tatsukawa and Minoru Hayashi
Department of Applied Chemistry, Faculty of Engineering, Ehime University, Matsuyama 790-8577, Japan
Received 23 March 2001; revised 23 April 2001; accepted 11 May 2001
Abstract—Acetals, including ketals, were smoothly cleaved by the action of pyridinium poly(hydrogen fluoride) without addition
of water or an alcohol in an anhydrous solvent. © 2001 Elsevier Science Ltd. All rights reserved.
Pyridinium poly(hydrogen fluoride) [PPHF, expressed
as Py(HF)x],1 comprising 30% pyridine and 70% HF by
weight, has been used as an HF-equivalent reagent in
substitution and addition reactions for various func-
tional groups.2,3 The reagent was also used for depro-
tection of tetraisopropyldisiloxanyl ethers4 as well as
other silyl ether derivatives.5 However, we found that
while the same disiloxanyl ether function in the inositol
derivative 1 was kept intact, PPHF [14 equiv. as x=ca.
9 in PPHF purchased from Aldrich™] selectively
cleaved the cyclohexylidene group in anhydrous CHCl3
to afford 1,2-diol 2.6 The result is also contradictory to
the fact that acetals7 and tetrahydropyranyl ethers8
have been reported to be tolerant toward PPHF. Since
the reaction conditions are nearly anhydrous9 and less
acidic than those of ordinary procedures for deprotec-
tion of acetals, the PPHF procedure might be promis-
ing for cleavage of acetals without decomposition of
other acid-sensitive groups in the same molecule. With
this expectation, we investigated the generality of the
procedure and here propose a new acetal cleavage
method using PPHF (Scheme 1).
As a typical example of an acyclic ketal, diethyl ketal of
4-phenyl-2-butanone 3 was cleaved quite smoothly by
the action of 0.5 molar equivalent of PPHF in aceto-
nitrile within 30 min at room temperature in a polypropyl-
ene vessel, giving the deprotected ketone in 96% yield
(Table 1). Anhydrous acetonitrile as a solvent gave the
best result in the reaction, while other solvents such as
anhydrous benzene, chloroform, and dichloromethane
were equally adequate. A limited amount of water (2
equiv.) in acetonitrile enhanced the reaction of 3 (rt, 10
min), resulting in the formation of the ketone in 90%.
Its cyclic ketal version 4 needed 21 equiv. of PPHF for
satisfactory conversion to the ketone. On the other
hand, diethyl and dimethyl acetals 6 and 7 derived from
dodecanal required a much larger quantity of PPHF to
obtain a high yield of the aldehyde. The reaction of a
benzylic acetal 5 proceeded faster than that of acetals 6
O
O
OH
OH
Py(HF)x
Si
O
O
Si
O
O
O
O
O
O
CHCl3
0 °C, 30 min then
r.t., 30 min
O
O
Si
Si
O
O
O(O)P(OBn)2
O(O)P(OBn)2
89%
1
2
Scheme 1.
Keywords: acetal; ketal; pyridinium poly(hydrogen fluoride); deprotection; inositol.
* Corresponding author. E-mail: wyutaka@dpc.ehime-u.ac.jp
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00808-5

4642
Y. Watanabe et al. / Tetrahedron Letters 42 (2001) 4641–4643
Table 1. Deacetalization using PPHFa
and 7, as monitored by TLC (almost completion within
1 h), to afford the benzaldehyde in excellent yield
though the reaction took longer. In the case of a cyclic
ethylene acetal of dodecanal, the reaction was sluggish,
even in a large amount of PPHF, to give unacceptable
results.
of the most reactive acyclic ketal 3 was examined in the
presence of other acetals.10 As shown in Table 2, com-
petition reactions with 8, MOM ether 9, and cyclic
ketals 10 showed almost complete selectivities. Coexis-
tence of docecanal acetal 7 and tetrahydropyranyl
ether8 of 3-phenylpropanol exhibited fairly good selec-
tivity, but dodecanal and 3-phenylpropanol were gener-
ated in about 20 and 30% yields, respectively, as
analyzed by NMR. In the latter case, some other
unidentified products were also obtained to a slight
extent.
The PPHF-aided cleavage reaction of acetals was
reversible, as longer reaction time decreased the yield of
dodecanal. In order to shift the equilibrium of the
reaction to the left, chloral or chloral hydrate was
additionally applied. Thus, 2.5 equiv. of these additives
permitted a decrease in the quantity of PPHF and a
smooth reaction to afford the aldehyde in excellent
yields, as shown in Table 1. The hydrate was slightly
more efficient than chloral.
The isopropylidene acetal in the inositol derivative 12
was efficiently cleaved with 40 equiv. of PPHF to afford
quite unstable diol 13 in 85% yield, suppressing the
migration and decomposition of the phosphate func-
tion, while employment of ordinary acetal exchange
procedures (MeOH–CF3CO2H and ethylene glycol–
Since the reactivity of acetals toward PPHF depended
markedly upon their structure type, selective cleavage
Table 2. Selective cleavage of 3 in the coexistence of other acetals
Py(HF)x
O
OEt
EtO
+
acetal
+
8 ~ 10
Ph
Ph
CH3CN
r.t.
(recovered)
3
8 ~ 10
11
Run
Coexistent
acetal
Py(HF)x,
equiv
Time,
min
Yield, %
8 ~ 10
11
98
90
O
1
2
8
9
0.5
7.0
20
15
99
OBn
O
Ph
BnO
OCH2OMe
100
O
O
OBn
BnO
3
10
0.5
20
93
99
OBn

Y. Watanabe et al. / Tetrahedron Letters 42 (2001) 4641–4643
4643
O
O
O
O
OClAc
OClAc
(FmO)2 P O
O
(FmO)2 P O
O
O
O
P O
OFm
P O
OFm
Py(HF)x
O
O
OH
OH
(FmO)
CH2Cl2
0 °C, 1 h
(FmO)
2P O
2P O
OClAc
OClAc
OClAc
OClAc
85%
12
13
(Fm: 9-fluorenylmethyl, ClAc: chloroacetyl)
Scheme 2.
TsOH) for the same purpose gave poorer results (45
and 60% yields, respectively, Scheme 2).
Alamo, E. M.d.; Bona, M.; Franco, S.; Merchan, F. L.;
Tejero, T.; Vieceli, O. Tetrahedron Lett. 2000, 41, 9239–
9243.
Judging from these results, the present procedure using
PPHF is concluded to provide an alternative method
for cleavage of acetals.11
8. Masamune, S.; Lu, L. D.-L.; Jackson, W. P.; Kaiho, T.;
Toyoda, T. J. Am. Chem. Soc. 1982, 104, 5523–5526.
9. Procedures for cleavage of acetals under nearly anhy-
drous conditions: (SnCl2·2H2O); Ford, K. L.; Roskamp,
E. J. Tetrahedron Lett. 1992, 33, 1135–1138. (Montmoril-
lonite K10™); Gautier, E. C. L.; Graham, A. E.;
McKilop, A.; Standen, S. P.; Taylor, R. J. K. Tetrahedron
Lett. 1997, 38, 1881–1884. (CuCl2·2H2O); Saravanan, P.;
Chandrasekhar, M.; Anand, R. V.; Singh, V. K. Tetra-
hedron Lett. 1998, 39, 3091–3092. (Magtrieve™); Ko,
K.-Y.; Park, S.-T. Tetrahedron Lett. 1999, 40, 6025–6027.
10. (a) Catelani, G.; D’Andrea, F.; Puccioni, L. Carbohyr.
Res. 2000, 324, 204–209; (b) Chiang, C.-C.; Chen, Y.-H.;
Hsieh, Y.-T.; Luh, T.-Y. J. Org. Chem. 2000, 65, 4694–
4697.
11. A typical experimental procedure: To a solution of 4-
phenyl-2-butanone diethyl ketal 3 (306 mg, 1.38 mmol) in
acetonitrile (1.5 ml) in a polypropylene vessel was added
PPHF (118 ml, 4.13 mmol) at room temperature and the
mixture was stirred at the same temperature for 15 min.
After addition of an adequate quantity of solid NaHCO3
(slightly exothermic) to neutralize briefly, the mixture was
stirred for about 5 minutes and transferred into a separa-
tory funnel using ethyl ether. The resultant organic layer
was treated successively with a saturated NaHCO3 solu-
tion, H2O, and a saturated NaCl solution, dried over
MgSO4, concentrated, and chromatographed on silica gel
(AcOEt/hexane, 1:4) to give the ketone 11 (173 mg, 85%
yield).
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