Cerium(III) Chloride, a Novel Reagent for Nonaqueous Selective Conversion of Doxolanes to Carbonyl Compounds

Full text of DOI:10.1021/jo970014w

J . Org. Chem. 1997, 62, 4183-4184
4183
Cer iu m (III) Ch lor id e, a Novel Rea gen t for
Sch em e 1
Sch em e 2
Non a qu eou s Selective Con ver sion of
Dioxola n es to Ca r bon yl Com p ou n d s
Enrico Marcantoni* and Francesco Nobili
Dipartimento di Scienze Chimiche, via S. Agostino 1,
I-62032 Camerino (MC), Italy
Giuseppe Bartoli,* Marcella Bosco, and Letizia Sambri
Dipartimento di Chimica Organica “A. Mangini”,
v. le Risorgimento 4, I-40136 Bologna, Italy
Received J anuary 2, 1997
In tr od u ction
The electrophilicity of the carbonyl group is a dominant
feature of its extensive chemistry. A major challenge in
a multistep synthesis is to shield a carbonyl from
nucleophilic attack until its electrophilic properties can
be exploited. For this reason, the protection and depro-
tection of the carbonyl functional group remain crucial
challenges to organic chemists. Experience shows that
the critical parameters are generally the stability and
the cleavage of the protecting group rather than its
introduction. As with most protecting groups, then,
many methods are available for the deprotection of
acetals and ketals. Generally, this transformation is
remains the most usual protecting group for the ketone
functionality, can be effectively realized under mild
conditions by cerium(III) chloride hydrate in acetonitrile
(Scheme 1).
Resu lts a n d Discu ssion
1
The 1,3-dioxolane 1a is transformed to cyclohexanone
at room temperature after 3 days by treatment with 1.5
carried out by acid-catalyzed aqueous hydrolysis. How-
ever, very often this method is incompatible with the
presence of some other functional group in the molecule
like, e.g., a protected hydroxyl group. To overcome the
problem, several nonacidic cleaving methods of acetals
molar equiv of CeCl
greatly improved by adding a catalytic amount (15 mol
) of sodium iodide, and the parent ketone is then
3
‚7H
2
O. The rate of this reaction is
%
2
obtained with good yield (entry 1, Table 1). However,
the same conditions are inoperant with dioxolane 1c,
where after 48 h at room temperature only 3% deprotec-
tion is observed. To obtain high yields of the correspond-
ing ketone (entry 3, Table 1), refluxing of the reaction
mixture for only a few hours is sufficient.
The deprotection of dioxolane 1a is studied in different
solvents such as acetonitrile, THF, and dichloromethane.
Acetonitrile turned out to be a suitable solvent for the
reaction. We have also investigated the possibility that
have been employed, such as wet silica gel or lithium
tetrafluoroborate in wet acetonitrile.3 A few nonaqueous
methods utilizing phosphorous triiodide and diphospho-
4
5
rous tetraiodide, iodotrimethylsilane, chlorotrimethyl-
6
silane-sodium iodide, chlorotrimethylsilane-samarium
trichloride,7 titanium(IV) chloride,8 and boron trifluo-
9
ride-iodide ion have also been reported for deprotection
of acetals to carbonyl compounds, although the first four
reagents failed to deprotect the dioxolane moiety. Many
of these procedures suffer from one or more drawbacks:
lack of selectivity, unsatisfactory yields, cost or toxicity
of the reagent, or necessity of anhydrous conditions.
These limitations prompted us to further investigate a
new reagent, which is able to carry out the selective
cleavage of acetals and ketals with good yields.
CeCl
3
2
‚7H O could function catalytically or, at least, in
less than stoichiometric amounts. But high yields of
deprotected carbonyl compounds are found only for
[CeCl
3
‚7H
2
O]/[substrate] ratios larger than 1.5.
The cleavage of 1,3-dioxolanes in conjugated enone
Recently, several synthetically useful organic reactions
systems is faster than in saturated dioxolanes (entry 2,
Table 1). Thus, selective deacetalization is possible using
cerium(III) chloride hydrate reagent (entry 9, Table 1).
Transformation of acetals to aldehydes is known to be
slower than that to ketones; therefore, chemoselective
using trivalent lanthanide salts have been reported,10 and
3
the use of CeCl in methanol is a well-known method for
1
1
the acetalization of aldehydes. Now we wish to describe
here that the deprotection of 1,3-dioxolanes, which
(
1) For general methods see: (a) Green, T. W. Protective Group in
(10) (a) Luche, J .-L. J . Am. Chem. Soc. 1978, 100, 2226. (b) Imamoto,
T.; Kusumoto, T.; Yokoyama, M. Tetrahedron Lett. 1983, 24, 5233. (c)
Namy, J . L.; Soupe, J .; Collins, J .; Kagan, H. B. J . Org. Chem. 1984,
49, 2045. (d) Imamoto, T.; Takiyama, N.; Nakamura, K. Hatajima, T.;
Kamiya, Y. J . Am. Chem. Soc. 1989, 111, 4392. (e) Bartoli, G.;
Marcantoni, E.; Petrini, M. Angew. Chem., Int. Ed. Engl. 1993, 32,
1061. (f) Bartoli, G.; Marcantoni, E.; Sambri, L.; Petrini, M. Tetrahe-
dron Lett. 1994, 35, 8453. (g) Bartoli, G.; Cimarelli, C.; Marcantoni,
E.; Palmieri, G.; Petrini, M. J . Chem. Soc., Chem. Commun. 1994, 715.
(h) Imamoto, T. Lanthanides in Organic Synthesis; Academic Press:
New York, 1994. (i) Bartoli, G.; Marcantoni, E.; Sambri, L.; Tamburini,
M. Angew. Chem., Int. Ed. Engl. 1995, 34, 2046. (j) Bartoli, G.;
Marcantoni, E.; Petrini, M.; Sambri, L. Chem. Eur. J . 1996, 2, 973.
(11) Luche, J .-L.; Gemal, A. L. J . Chem. Soc., Chem. Commun. 1978,
976.
Organic Synthesis; Wiley: New York, 1991. (b) Kocienski, P. J .
Protecting Groups; Thieme: New York, 1994.
(2) Huet, F.; Lechevalier, A.; Pellet, M.; Conia, J . M. Synthesis 1978,
6
3.
(
(
3) Lipshutz, B. H.; Harvey, D. F. Synth. Commun. 1982, 12, 267.
4) Denis, J . N.; Krief, A. Angew. Chem., Int. Ed. Engl. 1980, 19,
1
006.
(
977, 48, 4175.
(
5) J ung, M. E.; Andrew, W. A.; Ornstein, P. L. Tetrahedron Lett.
1
6) Olah, G. A.; Hussain, A.; Singh, B. P.; Malhotra, A. K. J . Org.
Chem. 1983, 48, 3667.
(
(
(
7) Ukaji, Y.; Konmoto, N.; Fujisawa, T. Chem. Lett. 1989, 1623.
8) Balme, G.; Gor e´ , J . J . Org. Chem. 1983, 48, 3336.
9) Mandal, A. K.; Shrotri, P. Y.; Ghogare, A. D. Synthesis, 1985,
2
21.
(12) Meskens, F. A. J . Synthesis 1981, 501.
S0022-3263(97)00014-5 CCC: $14.00 © 1997 American Chemical Society

4
184 J . Org. Chem., Vol. 62, No. 12, 1997
Notes
Ta ble 1. Clea va ge of 1,3-Dioxola n es by Cer iu m (III)
Ch lor id e Hyd r a te
8, Table 1). Other functional groups, such as nitro and
ester functions, are stable under our reaction conditions
(entries 3, 6, and 7, Table 1). Also, the examples of 1d
and 1e are representative for the chemoselectivity of the
8
reagent since the deprotection-dehydration process is
not observed by conditions that remove completely the
ethylene ketal group (entries 4, and 5, Table 1).
The mechanism for these transformations of 1,3-
dioxolanes to carbonyl compounds is unclear. Some
reaction mechanisms have been proposed13 for other
reactions of dioxolanes initiated by titanium tetrachlo-
ride, trimethylsilyl iodide, or boron trifluoride etherate,
which would require the formation of 2-iodoethanol as a
byproduct (eq 1, Scheme 2). However, these mechanisms
are not supported by our experimental data, since it was
not possible to detect the presence of a â-iodoalkanol in
the reaction mixture. On the other hand, in the case of
substrate 1m , the lack of hydrogens in the R-position to
the C-2 atom of the 1,3-dioxolane ring suggests that the
deprotection does not proceed exclusively by formation
of the enol intermediate (eq 2, Scheme 2). A reasonable
explanation may be that the combination14 of a Lewis
acid-like species that polarizes the dioxolane oxygen and
the presencs of water effects easily the deprotection (eq
3
1
, Scheme 2). Indeed, in the case of dioxolane 1l (entry
2, Table 1), we have isolated the 1,2-hexanediol from
the reaction mixture. On the other hand, the deprotec-
tion did not proceed by treatment of 1,3-dioxolanes with
anhydrous cerium(III) chloride in dry acetonitrile at
reflux temperature.
It is clear that the simplicity of this approach, the low
cost of reagents, the ease of use, and the high yields of
the cleavage products display the attractiveness of the
reagent system described here. Various aspects of the
process of deprotection using cerium(III) chloride are
currently under investigation in this laboratory.
Exp er im en ta l Section
Flash chromatography15 was performed on Merck silica gel
(0.040-0.063 mm).
The procedure used in the case of dioxolane 1e is given as an
example. To a stirred suspension of 1-hydroxy-5-phenylpentan-
-one ethylene acetal (1e; 0.11 g, 0.5 mmol) and sodium iodide
11.2 mg, 0.075 mmol) in acetonitrile (5 mL) was added
CeCl ‚7H O (0.28 g, 0.75 mmol), and the resulting mixture was
3
(
3
2
stirred for 15 h at room temperature. The reaction mixture was
diluted with ether and treated with 0.5 N HCl (10 mL). The
organic layer was separated, and the aqueous layer was ex-
tracted with ether (3 × 25 mL). The combined organic layers
were washed twice with aqueous saturated sodium bicarbonate
solution and saturated brine solution and dried over anhydrous
sodium sulfate. The extracts were then concentrated under
reduced pressure and the residue chromatographed on a silica
gel column (eluent: hexane-ethyl acetate, 7:3) to give 81 mg
(92%) of the corresponding hydroxy ketone as an oil.
The conditions for the other reactions were given in Table 1.
During the deprotection of dioxolanes, one can note the
formation of a precipitae, which is solubilized in aqueous solution
during the hydrolysis.
Ack n ow led gm en t . The authors wish to thank
MURST-Italy and CNR-Italy for the financial assistance.
a
Dioxolanes were prepared by conventional methods.12 All
b
J O970014W
products were identified by their IR, NMR, and GC/MS spectra.
c
Yields of products isolated by column chromatography. d rt )
(
13) (a) Sakurai, H.; Sasaki, H.; Hosomi, A. Tetrahedron Lett. 1981,
2, 745. (b) Nishiyama, H.; Itah, K. J . Org. Chem. 1982, 47, 2496.
14) Cotton, F. A.; Wilkinson, G. Advanced Inorganic Chemistry, 5th
ed.; Wiley: Toronto, 1988.
(15) Still, W. C.; Kahn, M.; Mitra, A. J . Org. Chem. 1978, 43, 2923.
room temperature.
2
(
deprotection of dioxolanes to ketones is achieved by
treatment with dioxolanes of ketones and aldehyde (entry