Chemistry Letters 2001
425
the presence of 5 mol% of methanesulfonic acid (MsOH) or 10-
camphorsulfonic acid (CSA) in dichloromethane, 3 was obtained
in high yield though the reaction proceeded slowly (entries 7 and
8). On the other hand, the conventional p-methoxybenzylation of
1 with PMB trichloroacetimidate gave 3 in 77% yield.4
Encouraged by the above results, the p-methoxybenzylation
of several alcohols with 1 was tried (Table 2). When alcohols
bearing alkali-sensitive ester groups were treated with 1 in the
presense of Me3SiOTf (1.0–1.1 mol%) in dichloromethane, the
reactions proceeded smoothly and gave the corresponding PMB
ethers in high yields (entries 1–5). It is noted that secondary and
tertiary alcohols were p-methoxybenzylated without any diffi-
culties, which clearly indicated the merit of the present method
superior to the conventional ones. Furthermore, neither epimer-
ization at the α-position of ester carbonyl groups (entries 1, 3 and
5) nor elimination of β-hydroxy carbonyl compounds (entries 1,
2, 5 and 8) was observed during the p-methoxybenzylation.
Other alkali-sensitive groups such as acryloyloxy, halo or keto
groups were unaffected (entries 6–10), and alcohols bearing even
acid-sensitive protecting groups such as acetals or silyloxy group
gave the protected products in high yields (entries 11 and 12)
under the present conditions.
General procedure for the preparation of PMB ethers is as
follows: to a stirred solution of alcohol (0.5 mmol) and
PMBONPy (0.75 mmol) in dichloromethane (1.5 mL) under
argon atmosphere was added a solution of Me3SiOTf (0.5–1.4
mol%) in dichloromethane (0.1 mL) at 0 °C. The reaction was
allowed to warm up to room temperature and stirred for 5–30
min. After the completion of reaction (detected by TLC), it was
quenched with saturated aqueous sodium hydrogencarbonate
solution and the mixture was extracted with dichloromethane.
Organic layers were dried with anhydrous magnesium sulfate and
evaporated, and the residue was purified by preparative TLC or
silica-gel column chromatography to afford the corresponding
PMB ethers in high yields.
It is noted that a new reagent 1 which is moisture- and air-
resistant and easy to be handled is quite useful in the p-methoxy-
benzylation of various hydroxy groups even in the cases of alco-
hols bearing alkali- or acid-sensitive functional groups.
The present research is partially supported by Grant-in-Aids
for Scientific Research from the Ministry of Education, Science,
Sports and Culture, Japan.
References and Notes
1
a) O. Mitsunobu, “Comprehensive Organic Synthesis,” ed. by B.
M. Trost and I. Fleming, Pergamon Press, Oxford (1991), Vol. 6,
p. 22. b) “Protective groups in organic synthesis,” ed. by T. W.
Greene and P. G. M. Wuts, John Wiley & Sons, New York
(1999), p. 86.
2
3
O. J. Plante, S. L. Buchwald, and P. H. Seeberger, J. Am. Chem.
Soc., 122, 7148 (2000).
a) F. Cramer, K. Pawelzik, and H. J. Baldauf, Chem. Ber., 91,
1049 (1958). b) T. Iversen and D. R. Bundle, J. Chem. Soc.,
Chem. Commun., 1981, 1240. c) H.-P. Wessel, T. Iversen, and D.
R. Bundle, J. Chem. Soc., Perkin Trans. 1, 1985, 2247.
a) N. Nakajima, K. Horita, R. Abe, and O. Yonemitsu,
Tetrahedron Lett., 29, 4139 (1988). Recently, two stable p-
methoxybenzylating reagents were reported. b) 4-Methoxybenzyl
perfluoroimidate: N. Nakajima, M. Saito, and M. Ubukata,
Tetrahedron Lett., 39, 5565 (1998). c) 4-Methoxybenzyl-2-
pyridylthio carbonate: S. Hanessian and H. K. Huynh,
Tetrahedron Lett., 40, 671 (1999).
4
5
M. Nakano, J. Matsuo, and T. Mukaiyama, Chem. Lett., 2000,
1352.
6
7
T. Mukaiyama, T. Masui, and T. Izawa, Chem. Lett., 1976, 1177.
T. Yasukochi, K. Fukase, and S. Kusumoto, Tetrahedron Lett., 40,
6591 (1999).
8
9
P. Ballesteros, R. M. Claramunt, and J. Elguero, Tetrahedron, 43,
2557 (1987).
2-(4-Methoxybezyloxy)pyridine (PMBOPy) did not give satisfac-
tory results in the p-methoxybenzylation under the present condi-
tions. Further, it is noted that the agent 1 was prepared more easi-
ly compared to PMBOPy.
10 a) J. C. W. Chien, W.-M. Tsai, and M. D. Rausch, J. Am. Chem.
Soc., 113, 8570 (1991). b) Trityl tetrakis(pentafluorophenyl)-
borate has been used as a catalyst of the glycosylation because it is
easy to be handled. See: H. Uchiro and T. Mukaiyama, Chem.
Lett., 1996, 79.