Chemistry Letters 2000
1353
under an argon atmosphere. The mixture was stirred for 24 h at
room temperature and then filtered through silica gel. The eluent
was concentrated in vacuo, and the crude product was purified by
preparative TLC to afford benzyl 4-chlorobutyl ether (0.48
mmol, 96%).
Thus, it is noted that a new and convenient method for the
benzylation of alcohols with benzyl mesylate was developed by
using a catalytic amount of LiB(C6F5)4 in the coexistence of
LiOTf and MgO. Advantageously the present benzylation reac-
tion proceeded under almost neutral conditions to give the corre-
sponding benzyl ethers in good to excellent yields.
The present research is partially supported by Grant-in-Aids
for Scientific Research from the Ministry of Education, Science,
Sports and Culture.
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. Green and P. G. M. Wuts, John
Wiley & Sons, New York (1999), p. 76.
2
3
a) T. Iversen and D. R. Bundle, J. Chem. Soc., Chem.
Commun., 1981, 1240. b) H. Wessel, T. Iversen, and D. R.
Bundle, J. Chem. Soc., Perkin Trans. 1, 1985, 2247. c) U.
Widmer, Synthesis, 1987, 568.
K. Takai and C. H. Heathcock, J. Org. Chem., 50, 3247
(1985). Other practical application of Ag2O was reported.
A. Bouzide and G. Sauve, Tetrahedron Lett., 38, 5945
(1997).
Next, benzylation of several alcohols was further examined
(Table 2). Generally, it is difficult to prepare the corresponding
benzyl ethers from halohydrins under strongly alkaline condi-
tions because the conditions cause some side reactions such as
intermolecular or intramolecular etherification of halohydrins or
olefin formation by elimination of hydrogen halide. Our prelimi-
nary experiments on benzylation of 4-chloro-1-butanol under
several conditions of using NaH and BnBr in DMF, benzyl
trichloroacetimidate and triflic acid, or Ag2O and BnBr in DMF
had led to the corresponding benzylated products in rather low
yields. On the other hand, treatment of 4-chloro-1-butanol with
benzyl mesylate using the catalyst system described above (Table
1, entry 5) afforded a benzylated product in 96% yield (entry 1).
Benzylation of secondary and tertiary halohydrins gave the ben-
zylated products in good yields. In these cases, benzylation pro-
ceeded more slowly than that of primary alcohol (entries 2 and
3).8 Several other halohydrins also gave satisfactory results
under the present conditions (entries 4–8). Further, the ben-
zylation of alcohols possessing ester or ketone groups were
examined. It is known that alcoholysis or aldol condensation of
esters and also aldol condensation of ketones often take place
under strongly alkaline conditions. According to the present pro-
cedure, however, benzylation of alcohols possessing ester or
ketone groups gave the benzylated products in good to high
yields (entries 9 and 10).9
4
5
R. U. Lemieux and T. Kondo, Carbohydr. Res., 35, C4
(1974).
T. Mukaiyama, M. Nakano, W. Kikuchi, and J. Matsuo,
Chem. Lett., 2000, 1010. Recently, Lewis acidity of naked
lithium ion was evaluated. K. Fujiki, S. Ikeda, H.
Kobayashi, A. Mori, A. Nagira, J. Nie, T. Sonoda, and Y.
Yagupolskii, Chem. Lett., 2000, 62.
6
Benzyl mesylate was prepared by reported procedure and
purified by silica-gel chromatography. The mesylate was
stored at 4 °C for periods of up to a month. X. Creary and
T. L. Underiner, J. Org. Chem., 50, 2165 (1985). Lithium
tetrakis(pentafluorophenyl)borate was pretreated according
to reported procedure.5 Commercial lithium triflate and
magnesium oxide were used without pretreatment.
Recently, it was reported that lithium triflate worked an
effective promotor in Diels–Alder reaction. J. Augé, R.
Gil, S. Kalsey, and N. Lubin-Germain, Synlett, 2000, 877.
An efficient method for a disaccharide formation by using
a p-chlorobenzyl protected glycosyl-donor was reported.
T. Mukaiyama, K. Miyazaki, and H. Uchiro, Chem. Lett.,
1998, 635.
The secondary alcohol (5-chloro-2-pentanol) was obtained
by treatment of 5-chloro-2-pentanone with sodium borohy-
dride in ethanol. The tertiary alcohol (5-chloro-2-methyl-
2-pentanol) was obtained by treatment of 5-chloro-2-pen-
tanone with trimetylaluminum in dichloromethane.
Monobenzoyl 1,6-hexanediol was obtained by treating 1,6-
hexanediol with benzoyl chloride in pyridine and 5-
hydroxypentyl phenyl ketone was obtained by treating ε-
caprolactone with phenyl magnesium bromide in ether.
7
8
A typical experimental procedure6 is described for the reac-
tion of 4-chrloro-1-butanol with benzyl mesylate (Table 2, entry
1): to a mixture of LiB(C6F5)4 (0.05 mmol), LiOTf (0.50 mmol)
and MgO (0.80 mmol) was added a solution of 4-chloro-1-
butanol (0.50 mmol) and benzyl mesylate (0.60 mmol) in a mix-
ture of cyclohexane (1.30 mL) and dichloromethane (0.70 mL)
9