4878
L. Zhou et al. / Tetrahedron Letters 49 (2008) 4876–4878
Table 2 (continued)
In summary, a new efficient and selective method for deprotec-
Entry
3
Product
t (h)
Yieldb (%)
81g
tion of aromatic benzyl ethers using NaHSO4SiO2 in thiophene or
anisole has been developed. This strategy features various func-
tional group tolerance, high yields, mild conditions, and easy work-
up. Therefore, it provides an alternative way for deprotection of
phenolic hydroxyls.
OBn
11
4k
3g
3k
COMe
Acknowledgements
a
Unless specified, see typical experimental procedure in Ref. 13.
Isolated yield.
Finely ground unsupported sodium hydrogen sulfate as catalyst in a ratio of
b
c
We are grateful for financial support from National Natural
Science Foundation of China (0801031005), Chinese National
Programs for High Technology Research and Development
(0604071005 and 0704051005), and the New Drug Basic Research
Program of the Shanghai Institute of Materia Medica
(07G603B005).
11:10 with 3a (mol/mmol), and 92% 3a recovered.
d
Silica gel as catalyst in a ratio of 500:1 of with 3a (mg/mmol), and no reaction
observed.
e
CF3COOH as catalyst in a ratio of 2:1 with 3e (mmol/mmol), and 91% 3e
recovered.
f
CF3COOH as catalyst in a ratio of 2:1 of it and 3g (mmol/mmol), and 85% 3g
recovered.
g
Anisole as solvent at 115 °C using a ratio of 300:1 of NaHSO4ÁSiO2 and 3 (mg/
mmol).
References and notes
h
Anisole as solvent at 115 °C using a ratio of 2:1 of CF3COOH and 3i (mmol/
mmol), and 92% 3i recovered.
Anisole as solvent at 115 °C using a ratio of 2:1 of CF3COOH and 3j (mmol/
mmol), and 92% 3j recovered.
´
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catalyzed hydrogenation cleavage of benzyl ethers in the presence
of nitro functionalities in substrates. Furthermore, the debenzyla-
tion process could be applied other substrates which bear different
functionalities such as COOMe, Br, OTs, and Me (entries 5–8). Gen-
erally, good to high yields were achieved. However, when the same
reaction conditions were employed for deprotection of carbonyl-
contained substrates, the reaction took place in low yield (5%, entry
9). We found that the use of anisole instead of thiophene led to sig-
nificant improving reaction yields (81–85%, entries 9–11). More-
over, comparison studies revealed that other acids as catalysts,
including finely ground sodium hydrogen sulfate, silica gel, or
CF3COOH, were not as efficient as NaHSO4ÁSiO2 (entries 1, 5, 7, 9,
and 10).
The reaction mechanism may involve initial protonation at the
oxygen atom of the aromatic benzyl ether followed by C–O cleav-
age to generate the corresponding benzylic cation along with the
desired phenol product. The use of cation scavenger such as thio-
phene and anisole can efficiently quench the cation and thus sig-
nificantly limiting the formation of side products. Moreover,
substrates containing electron-withdrawing substituents (Table
2, entries 1–7) afford the desired products in higher yields than
others bearing electron-donating groups (Table 1 and entry 8).
These data support the plausible reaction pathway.
12. Breton, G. W. J. Org. Chem. 1997, 62, 8952.
13. Typical procedure for debenzylation of aromatic benzyl ethers by NaHSO4ÁSiO2: 1-
(Benzyloxy)-4-nitrobenzene 3a (1 mmol, entry 1 in Table 2) was dissolved in
thiophene (3 mL) in a round-bottomed flask and NaHSO4ÁSiO2 (500 mg) was
added. The reaction system was equipped with reflux condenser and filled
with argon. The mixture was stirred under reflux for 5 h and then cooled to
room temperature, filtered, and evaporated to dryness. The residue was
purified by chromatography on silica gel to afford the product 4-nitrophenol 4a
(132 mg, 95% yield).