J . Org. Chem. 1998, 63, 9103-9104
9103
Ta ble 1
tempa (°C)
A Mild a n d High ly Selective Dep r otective
Meth od of P r en yl Eth er s Usin g Ytter biu m
compd
time (h)
yield (%)
Tr ifla te†
1
2
3
4
5
6
7
8
9
0.5
2
1
12
1
24
10
9
rt
rt
rt
rt
rt
rt
100
rt
rt
79
85
90
72
74
55
70
85
80
55
60
60
G. V. M. Sharma,* A. Ilangovan, and A. K. Mahalingam
Discovery Laboratory, Organic Chemistry Division III,
Indian Institute of Chemical Technology, Hyderabad 500
007, India
2
12
2
10
11
12
rt
rt
100
Received March 13, 1998
The correct choice of protecting groups1 is often decisive
for the realization of the overall operation of the total
synthesis of complex natural products. Hence, a wide
range of such groups are currently available for the
different functional groups. The proposed use of an
allylic protective group by Gigg2 has paved the way for
the related allyl groups3 such as crotyl,4 prenyl,5 meth-
allyl,6 etc. The crotyl and prenyl groups are readily
removed by base (t-BuOK, DMSO)7 with concomitant
isomerization of allylic protecting groups; hence, the
difference in rates does not appear to be sufficient to
allow good selectivities.4 Herein, we describe a highly
selective deprotection method for the prenyl protecting
group in preference over the allyl and crotyl groups, by
using Yb(OTf)3 as Lewis acid catalyst.
Rare earth triflates8 are versatile Lewis acids that have
been employed in a number of reactions both in organic
and aqueous media in catalytic quantities. Since the first
utilization of Yb(OTf)3 by Forsberg et al.,9 it has found a
wide utility in organic synthesis. In connection with our
studies on the synthesis of calanolides (anti HIV active
coumarins), we have observed a facile prenyl group
deprotection, under the influence of a catalytic amount
of Yb(OTf)3 as a Lewis acid catalyst (eq 1). This acid-
catalyzed deprenylation reaction has prompted us to
undertake a study of the deprotection of prenyl and other
relevant allyl groups.
12
a
rt ) room temperature.
To start a general study, p-methoxyphenol was con-
verted into prenyl, allyl, and crotyl ethers and these
ethers were subjected to deprotection reaction using a
catalytic (5 mol %) amount of Yb(OTf)3 in CH3NO2 as
solvent at room temperature. It was observed that only
prenyl ether underwent a facile deprotection in 30 min,
while both the allyl and crotyl ethers were unaffected
even after 24 h. This observation is of immense impor-
tance due to (a) mild reaction conditions, (b) use of
catalytic quantities (5 mol %) of acid reagent, and (c)
unlike the base (t-BuOK) catalyzed reaction the present
method using the acid, Yb(OTf)3, is highly selective
toward deprenylation.
Having established its high selectivity toward depre-
nylation, we prepared several prenyl ethers and subjected
them to deprenylation (Figure 1). Yb(OTf)3 smoothly
cleaved both the aromatic as well as aliphatic prenyl
ethers (1-6) in excellent yields. Similarly, the esters (7
and 8) also underwent smooth cleavage under the
standard reaction conditions. These mild and general
conditions were extended to carbohydrate-derived prenyl
ethers (9-11) having acid sensitive acetonide groups,
which gave the expected products. However, the excep-
tion for the generality was observed for the two sub-
strates (7 and 12), where the reaction had to be per-
formed at 100 °C instead of room temperature. All the
results are summarized in Table 1.
(1)
Thus this reagent can be considered as a general
deprenylating agent for aliphatic and aromatic as well
as carbohydrate prenyl ethers. The added advantage of
Yb(OTf)3 is that it is highly selective for the prenyl ethers,
while the other allylic groups such as crotyl and allyl are
untouched. On the basis of this observation we propose
that the coordination of Yb with ethereal oxygen (Figure
2), double bond migration, coordination of -OTf with the
carbocation, and finally loss of H+ from the methyl group
to -OR would lead to smooth deprotection. This model
also helps us in explaining the high selectivity observed
for the prenyl group over the allyl and crotyl groups by
the stability of the initially formed carbocation.
* To whom correspondence should be addressed.
† IICT communication no. 3999.
(1) (a) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis, 2nd ed.; J ohn Wiley and Sons: New York, 1991; pp 10-
142. (b) Schelhaas, M.; Waldmann, H. Angew. Chem., Int. Ed. Engl.
1996, 35, 2056-2083. (c) J arowicki, K.; Kocienski, P. Contemp. Org.
Synth. 1997, 454-492. (d) Guibe, F. Tetrahedron 1997, 53, 13509-
13556.
(2) Cunningham, J .; Gigg, R.; Warren, C. D. Tetrahedron Lett. 1964,
1191-1196.
(3) Gigg, R. ACS Symp. Ser. 1977, No. 39, 253; 1978, No. 77, 844.
(4) (a) Gigg, R.; Warren, C. D. J .Chem. Soc. 1968, 1903-1911. (b)
Gent, P. A.; Gigg, R.; Conant, R. J . Chem. Soc., Perkin Trans. I 1972,
1535-1542.
(5) Gigg, R. J . Chem. Soc., Perkin Trans. I 1980, 738-740.
(6) Gent, P. A.; Gigg, R.; Conant, R. J . Chem. Soc., Perkin Trans. I
1973, 1858-1863.
(7) (a) Hubert, A. J .; Reimligen. Synthesis 1968, 97. (b) Prosser, T.
J . Am. Chem. Soc. 1961, 83, 1701-1704. (c) Price, C. C.; Snyder, W.
H. J . Am. Chem. Soc. 1961, 83, 1773.
In conclusion, a mild, efficient, and highly selective
prenyl deprotection method has been developed using Yb-
(9) Forsberg, J . H.; Spaziano, V. T.; Balasubramanian, T. M.; Liu,
G. K.; Kinsley, S. A.; Duckworth, C. A.; Poteruca, J . J .; Brown, P. S.;
Miller, J . L. J . Org. Chem. 1987, 52, 1017-1021.
(10) Martin, O. R.; Rao, S. P.; El-Shenawy, H. A.; Kurz, K. G.; Cutler,
A. B. J . Org. Chem. 1988, 53, 3287-3292.
(8) (a) Marshman, R. W. Aldrichim. Acta 1995, 28, 77-84. (b)
Kobayashi, S. Synlett. 1994, 689-701.
(11) Chenera, B.; West, M. L.; Finkelstein, J . A.; Dreyer, G. B. J .
Org. Chem. 1993, 58, 5605-5606.
10.1021/jo9804846 CCC: $15.00 © 1998 American Chemical Society
Published on Web 11/01/1998
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