Anion Dependence of Lewis Acid Behavior in the Deprotection of PMB Ethers
FULL PAPER
noncoordinated nucleophile is also not needed by cerium lated yields (98%) by preparative TLC [hexane/ethyl acetate (7:3)
as eluent]. Data of the by-product isolated by preparative TLC:
chloride. Triflate anions, conversely from chloride and iod-
ide anions, can shift the cerium center from the alkoxide, so
1
,3-Dimethoxy-4-(4-methoxybenzyl)benzene (13): Yield 115 mg
it can be catalytically used, since it is not consumed during
the reaction course. Finally, it can be easily recovered from
the reaction mixture.[
1
(
0.45 mmol, 95% yield). H NMR ϭ 3.76 (s, 3 H, CH
3
O), 3.77 (s,
3
H, CH O), 3.78 (s, 3 H, CH O), 3.83 (s, 1 H, CH ), 6.48Ϫ7.20
3 3 2
4]
ϩ
(m, 7 H, Ar) ppm. MS: m/z ϭ 258 (100) [M ], 227 (50), 121 (33).
16 18 3
C H O
(258.3): calcd. C 74.42, H 6.98; found C 74.40, H 7.00.
Deprotection of 1-Butoxy-1-(4-methoxyphenyl)ethane (15)
Experimental Section
a) With Cerium Triflate: Nitromethane (3 mL), cerium() triflate
(
3 mg, 5 µmol) and 15 (100 mg, 0.5 mmol) were mixed into a
General Remarks: Deprotection runs were monitored by a GC-MS
HewlettϪPackard workstation, formed by a GC-HP 6890 (30-m
round-bottom flask equipped with a magnetic stirrer and heater.
The reaction mixture was heated at 60 °C for 1 h. A saturated aque-
HPS capillary column, 1 mL/min He as carrier gas) and by an HP
ous solution of NaHCO was then added and the mixture extracted
3
1
5
973 mass detector. H NMR spectra were recorded with a Bruker twice with diethyl ether. Butanol (76%) was determined by the
WM 300 spectrometer, in CDCl
ternal standard. Chemical shifts (δ) are given in ppm and coupling
constants (J) in Hz. Commercial products (Aldrich or Fluka) were
3
solutions with TMS as the in-
standard addition method. The GC-MS profile revealed only high
amounts of butanol. Only trace amounts of 4-vinylanisole were de-
tected (m/z ϭ 134, match 98% with Nist98 spectral library).
[11]
used without further purifications. PMB ethers
and cerium()
[
12]
3 2
b) With Cerium Chloride: CeCl ·7H O (280 mg, 0.75 mmol) was
added to a solution of 15 (100 mg, 0.5 mmol) in acetonitrile (5 mL)
and the resulting mixture was stirred at reflux temperature for 1 h
triflate
were prepared by conventional methods. 1-Butoxy-1-(4-
methoxyphenyl)ethane (15) was prepared in two classical steps:
LAH reduction of 4-methoxyacetophenone and substitution on 1-
bromobutane with sodium 1-(4-methoxyphenyl)ethoxide. Depro-
tected diols were prepared from monoprotected PMB alcohols by
standard procedures for introduction of THP Bn, TBDPS and Tr
(
no starting material remained as monitored by GC-MS) The reac-
tion mixture was diluted with Et O and treated with HCl (0.5 ,
mL). The organic layer was separated, and the aqueous layer was
2
5
[
13]
extracted with Et O. Butanol (67%) was determined by the stand-
groups. All isolated compounds gave satisfactory microanalyses.
2
ard addition method. 1,3-Bis(4-methoxyphenyl)-1-butene (16) was
General Procedure: Nitromethane (3 mL), cerium() triflate (3 mg,
separated by preparative TLC [hexane/ethyl acetate (7:3) as eluent].
5.1 µmol) and the protected alcohol (0.51 mmol) were mixed into
Yield 76 mg (0.283 mmol, 57%):
1
H NMR: δ ϭ 1.42 (d, J ϭ 7.1
a round-bottom flask equipped with a magnetic stirrer and heater.
The reaction mixture was heated at reflux or at 60 °C and moni-
tored by GC-MS. When the starting material had disappeared
Hz, 3 H, CH ), 3.77Ϫ3.80 (m, 1 H, CH), 3.79 (s, 3 H, CH O), 3.80
3
3
(s, 3 H, CH O), 6.21 (dd, J ϭ 6.4 and 16.0 Hz, 1 H, CHϭ), 6.33
3
(d, J ϭ 16.0 Hz, 1 H, CHϭ), 6.70Ϫ7.30 (m, 8 H, Ar) ppm. MS:
ϩ
18 20 2
3 ], 253 (100), 145 (57), 121 (22). C H O
(Table 1), a saturated aqueous solution of NaHCO was added and m/z (%) ϭ 268 (62) [M
the mixture extracted twice with diethyl ether. The alcohols were
identified by comparison with authentic samples. GC yields were
determined by the standard addition method, but some reaction
mixtures (menthol, octanol, cyclohexanol, phenol) were separated
by preparative TLC [hexane/ethyl acetate (7:3) as eluent] with com-
parable yields and in high purity (Ͼ 97%) by NMR spectroscopy.
Data of by-products obtained from these runs:
(268.4): calcd. C 80.60, H 7.46; found C 80.70, H 7.40.
[
1]
S. Kobayashi, K. Manabe, Acc. Chem. Res. 2002, 209Ϫ217.
[2]
G. Bartoli, E. Marcantoni, L. Sambri, Synlett 2003,
2
101Ϫ2116.
[3]
R. Dalpozzo, A. De Nino, L. Maiuolo, M. Nardi, A. Procopio,
R. Romeo, G. Bartoli, Tetrahedron Lett. 2003, 44, 5621Ϫ5624.
R. Dalpozzo, A. De Nino, L. Maiuolo, A. Procopio, A. Taga-
relli, G. Sindona, G. Bartoli, J. Org. Chem. 2002, 67,
9093Ϫ9095.
1
Bis(4-methoxyphenyl)methane (9): Average yield 77%. H NMR ϭ
3
.76 (s, 6 H, CH
3
O), 3.85 (s, 2 H, CH
2
), 6.68Ϫ7.20 (A
2
B
2
, 8 H, Ar)
[4]
ϩ
ppm. MS: m/z (%) ϭ 228 (100) [M] , 197 (71), 121 (28). C15
16 2
H O
(228.3): calcd. C 78.95, H 7.02; found C 79.00, H 7.00.
[
[
[
5]
6]
7]
G. Bartoli, G. Cupone, R. Dalpozzo, A. De Nino, L. Maiuolo,
A. Procopio, L. Sambri, A. Tagarelli, Tetrahedron Lett. 2002,
43, 5945Ϫ5947.
A. Cappa, E. Marcantoni, E. Torregiani, G. Bartoli, M. C.
Bellucci, M. Bosco, L. Sambri, J. Org. Chem. 1999, 64,
4
6
6
-[(4-Methoxyphenyl)methyl]phenol (14): Yield 72 mg (0.34 mmol,
1
5%). H NMR ϭ 3.82 (s, 3 H, CH
.65Ϫ7.15 (2A , 9 H, Ar ϩ OH) ppm. MS: m/z (%) ϭ 214 (100)
(214.3): calcd. C 78.50,
3 2
O), 3.84 (s, 2 H, CH ),
2
B
2
ϩ
[M] , 183 (38), 121 (28), 108 (41). C14
14 2
H O
5
696Ϫ5699.
H 6.55; found C 79.40, H 6.60.
In refluxing acetonitrile p-methoxybenzyl cleavage from oc-
tanol proceeds sluggishly (only 10% was removed after 13 h).
In nonpolar solvents such as THF or DCM, the reaction does
not work at all.
[
14]
OH,[15] BnO(CH OH,[16]
)
2 5
THPO(CH
TrO(CH OH,
by comparison with literature data.
2
)
5
OH,
TBDPSO(CH
2
)
5
[
17]
[18]
2
)
5
and 2-PMBO-cyclohexanone
were identified
[
[
8]
9]
[2]
Many proposed mechanisms reported in ref. invoke catalysis
of cerium chloride in the reaction of carbonϪoxygen cleavage
by intervention of water in the last mechanistic step.
Deprotection of Phenyl PMB Ether (10) in the Presence of 1,3-Di-
methoxybenzene (11): Nitromethane (3 mL), cerium() triflate
G. Bartoli, M. C. Bellucci, M. Bosco, R. Dalpozzo, A. De
Nino, L. Sambri, A. Tagarelli, Eur. J. Org. Chem. 2000,
(3 mg, 5 µmol), 10 (100 mg, 0.47 mmol) and 11 (65 mg, 0.47 mmol)
were mixed into a round-bottom flask equipped with a magnetic
stirrer and heater. The reaction mixture was heated at reflux for
99Ϫ104.
[10]
S. Kobayashi, S. Nagayama, T. Busujima, J. Am. Chem. Soc.
1998, 120, 8287Ϫ8288.
11]
3
0 min. A saturated aqueous solution of NaHCO
the mixture extracted twice with diethyl ether. The GC yield (Ͼ
9%) was determined by the standard addition method, and iso-
3
was added and
[
L. A. Paquette, Encyclopedia of Reagents for Organic Synthesis,
John Wiley & Sons, New York, 1995, pp. 3326Ϫ3329.
9
Eur. J. Org. Chem. 2004, 2176Ϫ2180
www.eurjoc.org
2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2179