1104
LETTER
A Simple and Regioselective Carbon-Oxygen Bond Cleavage Using
Niobium(V)
R
egioselective
h
Carbon-Oxy
i
genB
g
ondCleavage
e
UsingNio
r
bium(V
u
)
Arai,* Yukinori Sudo, Atsushi Nishida*
Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
Received 2 December 2003
87% together with 3 (8%) even at –78 °C (entry 5).12
These results suggest that acceleration of the reaction
depends strongly on the stability of a carbocation inter-
mediate and indicate the rate determining step would be
Abstract: A simple and convenient method for the differentiation
of alkoxy groups on aromatic rings is described. Niobium(V) is
found to possess a strong Lewis acid property to transform alkyl
arylethers smoothly to the corresponding phenols in high yields.
The excellent regioselectivity was also observed in dialkoxy C–O bond cleavage.
benzene derivatives under mild conditions.
Table 1 Selective Mono Dealkylation of 1
Key words: dealkylation, Friedel–Crafts acylation, niobium
NbCl5 (1.1 equiv)
OH
OR
OH
OH
OR
OR
+
Since niobium(III) has been reported as an efficient reduc-
tant to produce 1,2-dianion from alkynes by Pedersen1
and Utimoto and co-workers,2 independently, the devel-
opment of its utility in organic synthesis have been attrac-
tive area. On the other hand, high valence niobium acts as
a Lewis acid and its application to carbon-carbon bond
forming reactions has been investigated.3–9 We are also in-
terested in the character of its strong acidity and of its de-
velopment and utilization in organic synthesis. In this
article, we report our recent results concerning regioselec-
tive carbon-oxygen bond cleavage of alkyl arylethers and
regioselective Friedel–Crafts acylation promoted by
niobium(V).
3
2
Entry
R
Conditions
Yield
2 (%)
3 (%)
1
2
3
4
5
1a: R = Me
1a: R = Me
1b: R = Et
1b: R = Et
1c: R = Bn
DCE,a reflux,
3.5 h
2a: >99
Trace
Toluene, reflux,
3.5 h
2a: 99
1
DCE, reflux,
0.5 h
2b: 91
Trace
Since Nb(V) has been known to possess strong oxophilic-
ity to promote Lewis acid-mediated reactions such as
Diels–Alder reaction,3 allylation of aldehydes4 and imi-
nes,5 dealkylative acylation,6 sulfur transfer7 and others,8,9
we have planned to apply the utility of Nb(V) in deprotec-
tion of alkyl group of aryl ethers. First of all, mono
demethylation of binaphthol-dimethylether 1a was ex-
amined in dichloroethane and we were pleased to find that
the reaction proceeded smoothly as a spot-to-spot and
gave the corresponding mono deprotected compound 2a10
in an excellent yield, which was a useful chiral inter-
mediate for elaboration of various chiral ligands (Table 1,
entry 1). Toluene was also useful to give the compound in
an excellent yield as a sole product (entry 2).11 The reac-
tion was quite selective to give the 2a, exclusively, even
though a 2 mol equivalent of NbCl5 was used. We assume
that the ligand exchange between chlorine and oxygen
affords niobium(V) aryloxide complex which does not
exhibit enough Lewis acidity due to bidentate ability of
2a. Diethyl ether 1b was also employed under milder con-
ditions to give 2b quantitatively (entries 3 and 4). Further-
more, dibenzyl ether 1c was quite reactive to give 2c in
CH2Cl2, reflux,
7 h
2b: quant.
0
8
Toluene, –78 °C, 2c: 87b
3 h
a DCE: 1,2-dichloroethane.
b NBCl5 (1.5 equiv) was employed.
In order to confirm these speculations, the mixture of 1a
and 1b (1:1) were reacted with NbCl5 (1.0 equiv) under
similar conditions (Scheme 1). As expected, 1b reacted
much faster than 1a to give 2b in 80% conversion and
1
94% of unreacted 1a was observed in H NMR analysis.
This result clearly shows high selectivity in differentiation
of the alkyl groups (Me vs. Et). Furthermore, no trace
amount of BINOL (3) was detected during the reaction in-
dicating poor reactivity of the possible intermediate, nio-
bium phenoxide(V), for further deprotection due to lack
of Lewis acid property.
We next investigated the effect of the Lewis base as an
additive (Scheme 2). The treatment of 1a with BINOL 3
(1 equiv) in the presence of NbCl5(V) (1 equiv) resulted in
the recovery of 1a in 91% with BINOL (100%) and in
only 5% of 2a was isolated. On the other hand, 2a and 3
were isolated in quantitative yield, respectively, in case of
SYNLETT 2004, No. 6, pp 1104–1106
0
6.
0
5.
2
0
0
4
Advanced online publication: 25.03.2004
DOI: 10.1055/s-2004-817766; Art ID: U26503ST
© Georg Thieme Verlag Stuttgart · New York