3104
S. Tani et al. / Tetrahedron Letters 48 (2007) 3103–3104
ods.3–15 A large-scale synthesis was also examined (entry
2) by using 50.1 g of the substrate, affording 43.6 g of the
corresponding product (87% yield).
Table 1. Synthesis of 4-O-benzyl derivatives from 4,6-O-benzylidene
acetalsa,f
CoCl2, BH3 THF
O
X
O
X
O
HO
BnO
The present study is the first example of facile, regio-
selective cleavage of 4,6-O-benzylidene acetals using
CoCl2/BH3ÆTHF. We believe this procedure will be of
great utility in the field of carbohydrate synthesis. Sim-
ilar experiments on reductive ring-opening in a variety
of other benzylidene acetal substrates with different pro-
tecting groups, and investigation of the mechanisms of
these reactions, are now in progress.
Ph
O
OR1
OR1
rt
OR2
OR2
Entry Substrate
Productb
Yieldc (%)
O
glc
OMe
HO
O
OMe
OR
O
Ph
O
OR
BnO
OR
OR
1
2
3
1: R = Bn
2: R = Ac
3: R = H
7: R = Bn
8: R = Ac
9: R = H
quant
91d
85d
Acknowledgments
O
SPh
OBn
O
SPh
OBn
O
HO
BnO
This work was partially supported by a ‘Science Fron-
tier project of Kanagawa University’ from the Ministry
of Education, Culture, Sports, Science and Technology,
Japan. The authors thank Professor Nakagawa for help-
ful discussions.
glc
Ph
Ph
Ph
O
O
O
4
5
6
quant
quant
85e
OBn
OBn
10
4
O
OMe
OBn
O
gal
OMe
OBn
HO
BnO
O
O
References and notes
OBn
OBn
1. Greene, T. W.; Wuts, P. G. M. Protective Groups in
Organic Synthesis, 3rd ed.; John Wiley and Sons: New
York, 1999.
2. Sato, K.; Igarashi, T.; Yanagisawa, Y.; Kawauchi, N.;
Hashimoto, H.; Yoshimura, J. Chem. Lett. 1988, 1699–
1702.
5
11
O
man
OMe
OBn
O
OMe
OBn
HO
BnO
OBn
OBn
´
´
´
3. Andras, L.; Ildiko, J.; Pal, N. Carbohydr. Res. 1975, 44,
1–11.
6
12
4. Mikami, T.; Asano, H.; Mitunobu, O. Chem. Lett. 1987,
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Commun. 1984, 3, 201–202.
a All reactions were carried out at room temperature using CoCl2
(3 equiv) and BH3ÆTHF (3 equiv).
b The NMR data of all products were identical with those reported
previously: 7 and 12, Ref. 14; 8, Ref. 15; 9, Ref. 16; 10, Ref. 17; 11,
Ref. 18.
c Isolated yield.
d The corresponding 4,6-di-OH derivatives were obtained as side
products in 5% (entry 2) and 12% (entry 3) yields, respectively.
e The corresponding 6-O-benzyl derivative was obtained in 10% yield.
f Three abbreviations are used: gluco- (glc), galacto- (gal), and manno-
(man).
9. Gelas, J. Adv. Carbohydr. Chem. Biochem. 1981, 39, 71–
156.
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1996, 231–233.
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2000, 11, 385–387.
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Hsu, C.-Y.; Hung, S.-C. Angew. Chem., Int. Ed. 2005, 44,
1665–1668.
in a form suitable for reuse. The filtered solution was
treated with aq NaBH4 (0.2 equiv) by stirring in a
two-phase condition, and the resulting black precipitate
was filtered off. The organic layer was washed with aq
NaHCO3 and water, dried with anhydrous MgSO4,
and evaporated to give the appropriate 4-O-benzyl
derivative with high selectivity. The product was purified
on a column of silica gel (EtOAc–hexane), if necessary.
The reaction results are summarized in Table 1. All sub-
strates gave the corresponding 4-O-benzyl derivatives in
good yields. In particular, the 2,3-di-O-benzyl deriva-
tives (entries 1, 4, and 5) gave the products quantita-
tively. Most of the yields obtained by this method
were better than those obtained by reported meth-
15. Sakagami, M.; Hamano, H. Tetrahedron Lett. 2000, 41,
5547–5551.
16. Haque, M. E.; Kikuchi, T.; Yoshimoto, K.; Tsuda, Y.
Chem. Pharm. Bull. 1985, 33, 2243–2255.
17. He, X.; Chan, T.-H. Synthesis 2006, 10, 1645–1651.
18. Takahashi, H.; Miyama, N.; Mitsuzuka, H.; Ikegami, S.
Synthesis 2004, 18, 2991–2994.