2918
J . Org. Chem. 1996, 61, 2918-2919
involved treating 6 with 5 mol % PdCl2(CH3CN)2, 10 mol
A Desilyla tion a n d a On e-P ot
% PPh3, and 2-bromomesitylene (1.1 equiv) in DMF
con ta in in g 5 equ iv of w a ter 14 at 110 °C for 4 h.
Acetophenone was formed in 90% yield. Unfortunately,
we discovered the desilylation and the oxidation reactions
would not proceed in wet DMF and wet acetone, respec-
tively. Thus, neither solvent alone was suitable for the
other reaction.
Desilyla tion -Oxid a tion of Alip h a tic
ter t-Bu tyld im eth ylsilyl Eth er s Usin g
Ca ta lytic Qu a n tities of P d Cl2(CH3CN)2
Noel S. Wilson and Brian A. Keay*
Department of Chemistry, University of Calgary,
Calgary, Alberta T2N 1N4, Canada
After many attempts with different solvents, temper-
atures, and catalysts, we found that a stepwise desily-
lation-oxidation was possible. The silyl group in 2 was
first removed in wet acetone. After GC indicated no
starting material was remaining (6 h, 75 °C), the acetone
was removed on a rotoevaporator. DMF, 2-bromomesi-
tylene, PPh3, and K2CO3 were added, and the mixture
was heated to 120 °C for 5 h. Acetophenone (7) was
obtained in 80% yield. Although this procedure was
satisfactory, we felt that removal of the acetone was a
weak step in the above sequence. Finally, we found that
a mixture of acetone and DMF (1:1) containing 5 equiv
of water was an ideal combination for a stepwise desi-
lylation-oxidation reaction.15 Thus, treatment of com-
pound 2 with 5 mol % PdCl2(CH3CN)2 in acetone/DMF
(1:1) containing 5 equiv of water for 9 h at 120 °C
provided 6 (by GC). 2-Bromomesitylene (1.1 equiv), PPh3
(10 mol %), and K2CO3 were then added to the reaction
vessel, and the mixture was heated for 4 h to provide
acetophenone (7) in 94% yield. Unfortunately, the desi-
lylation-oxidation cannot be performed in the presence
of the mesityl bromide, PPh3, and K2CO3, since we found
that the desilylation reaction was inhibited in the pres-
ence of a variety of bases like K2CO3.
Received December 15, 1995
The tert-butyldimethylsilyl (TBDMS) protecting group1
for alcohols has become widely used by many chemists
due to the ease in which it can be attached to and
removed from alcohols.2 Although a large number of
reagents have been used to remove the TBDMS group,
only four methods have been reported in which a TBDMS
group is removed and the resulting alcohol oxidized in
one step.3-7 Most chemists use a two-step procedure,
wherein (1) the silyl ether is desilylated and (2) the
resulting alcohol is then oxidized.8 Since PdCl2(CH3CN)2
has been reported to desilylate aliphatic9 and phenolic10
silyl ethers and palladium acetate has been used with
2-bromomesitylene to oxidize primary and secondary
alcohols to aldehydes (or acids) and ketones,11,12 respec-
tively, we investigated whether the desilylation and
oxidation reactions could be combined into a one-pot
reaction using a Pd(II) catalyst. We report herein that
PdCl2(CH3CN)2 can be used catalytically to both desily-
late and oxidize TBDMS-protected primary and second-
ary alcohols to aldehydes and ketones, respectively. In
addition, the scope of the desilylation reaction of aliphatic
TBDMS ethers has been expanded.
The desilylation16 and desilylation-oxidation17 proce-
dures were not limited to the tert-butyldimethylsilyl
group or benzylic secondary alcohols. Trimethylsilyl
protected ethers (1) were successfully cleaved (alcohol,
95%) and oxidized (acetophenone, 89%), while triisoprop-
yl- (4), and tert-butyldiphenylsilyl ethers (5) were not
removed under the optimized desilylation or desilyla-
tion-oxidation conditions. The triethylsilyl moiety (3)
Optimized desilylation conditions involved heating 2
in acetone containing 5 equ iv of w a ter 13 in the presence
of 5 mol % PdCl2(CH3CN)2 for 6 h at 75 °C; compound 6
was formed in 90% yield. Optimized oxidation conditions
* To whom correspondence should be addressed. Phone: 403-220-
5354. Fax: 403-284-1372. E-mail: keay@acs.ucalgary.ca.
(1) Corey, E. J .; Venkateswarlu, A. J . Am. Chem. Soc. 1972, 94,
6190.
(2) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis, 2nd ed.; J ohn Wiley and Sons, Inc.: New York, 1991.
(13) Treatment of 2 according to the procedure reported by Lipshitz9
provided 6 in 40% yield. The yield improved to 90% upon the addition
of 5 equiv of water and increasing the temperature of the reaction to
75 °C. The best desilylation results were obtained with 5 equiv of water.
Alcohol 6 was formed in 79%and 75% yield when 0.6 and 1.0 equiv of
water was used, respectively (75 °C, 24 h). The byproduct from this
desilylation reaction is t-BuMe2SiOH by GC/MS.
(3) For
a review on oxidative deprotection of silyl ethers, see:
Muzart, J . Synthesis 1993, 11.
(4) Olah, G. A.; Gupta, B. G. B.; Fung, A. P. Synthesis 1980, 897.
(5) Liu, H.-J .; Han, I.-S. Synth. Commun. 1985, 15, 759.
(6) Cossio, F. P.; Aizpurua, J . M.; Palomo, C. Can. J . Chem. 1986,
64, 225.
(7) Piva, O.; Amougay, A.; Pete, J .-P. Tetrahedron Lett. 1991, 32,
3993.
(8) For examples of two-step desilylation-oxidation sequences,
see: (a) Sames, D.; Polt, R. J . Org. Chem. 1994, 59, 4596. (b) Angle, S.
R.; Frutos, R. P. J . Org. Chem. 1993, 58, 5135. (c) Wild, H. J . Org.
Chem. 1994, 59, 2748.
(9) Lipshutz, B. H.; Pollart, D.; Monforte, J .; Kotsuki, H. Tetrahedron
Lett. 1985, 26, 705.
(10) Wilson, N. S.; Keay, B. A. Tetrahedron Lett. 1996, 37, 153.
(11) (a) Tamaru, Y.; Yamada, Y.; Inoue, K.; Yamamoto, Y.; Yoshida,
Z.-I. J . Org. Chem. 1983, 48, 1286. (b) Tamaru, Y.; Inoue, K.; Yamada,
Y.; Yoshida, Z.-I. Tetrahedron Lett. 1981, 22, 1801. (c) Tamaru, Y.;
Yamamoto, Y.; Yamada, Y.; Yoshida, Z.-I. Tetrahedron Lett. 1979, 20,
1401. (d) Choudary, B. M.; Reddy, N. P.; Kantam, M. L.; J amil, Z.
Tetrahedron Lett. 1985, 26, 6257.
(14) Although Tamaru and co-workers11 emphasized that anhydrous
conditions were necessary for the oxidation, we felt at the time that if
the oxidation would proceed in wet DMF then the desilylation might
also be possible in wet DMF. To our delight, the oxidation of 6 to 7
proceeded smoothly in DMF containing 5 equiv of water.
(15) At this time, we do not understand why the mixed solvent
system works so well. For material on the use of and effects of mixed
solvents with other systems, see: (a) Ta-Shma, R.; Rappoport Z. Adv.
Phys. Org. Chem. 1992, 27, 239. (b) Watts, D. W. In Physical Chemistry
of Organic Solvent Systems; Covington, A. V., Dickinson, T., Eds.;
Plenum Press: New York, 1973; pp 715-716.
(16) Optimized desilylation procedure: To a solution of 2 (100 mg,
0.42 mmol) in reagent-grade acetone (2.1 mL) and water (38 µL, 5
equiv) was added PdCl2(CH3CN)2 (5.5 mg, 21 µmol). The reaction
mixture was refluxed (75 °C) for 6 h (followed by GC) and cooled to rt
and the acetone removed in vacuo to leave an oil. Purification by
distillation provided 1-phenyl-1-ethanol (90%).
(12) For other oxidations of alcohols involving palladium catalysts,
see: (a) Berzelus, J . J . Ann. 1828, 13, 435. (b) Lloyd, W. G. J . Org.
Chem. 1967, 32, 2816. (c) Blackburn, T. F.; Schwartz, J . J . Chem. Soc.,
Chem. Commun. 1977, 157. (d) Tsuji, J .; Takahashi, H.; Morikawa,
M. Tetrahedron Lett. 1965, 4387. (e) Nagashima, H.; Tsuji, J . Tetra-
hedron 1985, 41, 5645. (f) Baba, T.; Kameta, K.; Nishiyama, S.;
Tsuruya, S.; Masai, M. Bull. Chem. Soc. J pn. 1990, 63, 255. (g) Baba,
T.; Kameta, K.; Nishiyama, S.; Tsuruya, S.; Masai, M. J . Chem. Soc.,
Chem. Commun. 1989, 1072. (h) Benhaddou, R.; Czernecki, S.; Ville,
G.; Zegar, A. Organometallics 1988, 7, 2435. (i) Bellosta, V.; Benha-
ddou, R.; Czernecki, S. Synlett 1993, 861.
(17) Optimized desilylation-oxidation procedure: To a solution of
2 (60 mg, 0.25 mmol) in reagent-grade acetone (1.25 mL), DMF (1.25
mL), and water (23 µL, 5 equiv) was added PdCl2(CH3CN)2 (3.3 mg,
13 µmol). The reaction mixture was heated at 110 °C until GC (or TLC)
indicated the desilylation was complete (6 h). Triphenylphosphine (13.3
mg, 55 µmol), 2-bromomesitylene (39 µL, 0.27 mmol), and potassium
carbonate (39 mg, 0.28 mmol) were added, and the reaction was heated
at 110 °C for 4 h. The reaction mixture was cooled to rt, diluted with
ether (2 mL), and washed with saturated NaCl (2 × 4 mL). The ether
was dried (MgSO4) and removed in vacuo to leave an oil which was
distilled to provide acetophenone (94%).
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