Chemistry Letters Vol.34, No.4 (2005)
595
The p-nitrobenzyl group has been so far introduced to hydroxy
functions by using p-nitrobenzylbromide-Ag2O, p-nitrobenzyl-
bromide-AgOTf-2,4,6-collidine, or p-nitobenzyl triflate or by
Nishizawa’s method. The hydroxy group of 3 was conveniently
p-nitrobenzylated by the present method in a comparable yield
(Entry 6). p-Bromobenzylation of 3 by the present method did
not give good yield, because of debromination under the reduc-
ing condition of Et3SiH (Entry 7). This PBB (p-bromobenzyl)
ethers of 7 should be converted to the more labile, substituted
p-arylbenzyl ethers via a Pd-catalyzed Suzuki–Miyaura coupling
without using phosphine ligands and be subsequently removed
by acids or oxidants.9
p-Methoxybenzyl group was completely cleaved under the
present reaction conditions. We previously reported that p-acy-
laminobenzyl group was much more stable to Lewis acids than
p-methoxybenzyl group but was cleaved by DDQ in a compara-
ble rate.4d,10 p-Acylaminobenzyl group, however, also smoothly
cleaved with TMSCl–Et3SiH. In other words, a combination of
TMSCl–Et3SiH is useful for selective cleavage of p-methoxy-
benzyl and p-acylaminobenzyl groups.11
lanes: M. B. Sassaman, K. Kotian, G. K. S. Prakash, and
G. A. Olah, J. Org. Chem., 52, 4314 (1987). d) Reductive
benzylation via O-tetrahydropyranyl ether: T. Suzuki, K.
Ohashi, and T. Oriyama, Synthesis, 1999, 1561. e) Bismuth
trichloride catalyzed efficient reductive etherification of car-
bonyl compounds with alcohols: M. Wada, S. Nagayama, K.
Mizutani, R. Hiroi, and N. Miyoshi, Chem. Lett., 2002, 248.
Reductive N-benzylation has also reported. a) S.-C. Shim,
K.-T. Huh, S.-S. Oh, and D.-H. Oh, Bull. Korean Chem.
Soc., 7, 484 (1986). b) R. B. C. Pillai, Indian J. Chem. Sect.
B, 35B, 487 (1996).
5
6
7
K. Fukase, Y. Fukase, M. Oikawa, W.-C. Liu, Y. Suda, and
S. Kusumoto, Tetrahedron, 54, 4033 (1998).
A typical procedure for reductive benzylation was as fol-
lows: To a solution of methyl 2,3,4-O-tribenzyl-ꢀ–D-
glucopyranoside (3, 232 mg, 0.5 mmol) in CH2Cl2 (2.0
mL) was added chlorotrimethylsilane (0.63 mL, 5.0 mmol)
and benzaldehyde (0.05 mL, 0.5 mmol) and triethylsilane
(0.16 mL, 1.0 mmol). The mixture stirred at room tempera-
ture for 3 h, and evaporated under reduced pressure. The res-
idue was submitted to flash chromatography (silica gel, elu-
ent: CHCl3/MeOH, 10:1, v/v), to give a pure colorless prod-
uct 5. Yield 224 mg (81%). 5: 1H NMR (CDCl3) ꢁ 3.37
(3H, s, OCH3), 3.55 (1H, dd, J ¼ 9:5, 3.6 Hz, H-2), 3.59–
3.65 (2H, m, H-4 and H-5), 3.69–3.75 (2H, m, H-6), 3.97
(1H, dd, J ¼ 9:5, 9.2 Hz, H-3), 4.45–4.98 (8H, m, PhCH2-
x4), 4.61 (1H, d, J ¼ 3:6 Hz, H-1), 7.11–7.37 (20H, m,
PhCH2- x4). 6: 1H NMR (CDCl3) ꢁ 3.37 (3H, s, OCH3),
3.55 (1H, dd, J ¼ 9:5, 3.6 Hz, H-2), 3.60–3.64 (2H, m, H-4
and H-5), 3.69–3.75 (2H, m, H-6), 3.97 (1H, dd, J ¼ 9:5,
9.2 Hz, H-3), 4.45–4.98 (8H, m, PhCH2- x4), 4.62 (1H, d,
J ¼ 3:6 Hz, H-1), 7.12–7.37 (20H, m, PhCH2- x3), 7.63
(2H, d, J ¼ 9:0 Hz, NO2PhCH2–), 8.27 (2H, d, J ¼ 9:0 Hz,
In conclusion, we have developed a new convenient method
for the preparation of ethers from carbonyl compounds and non-
protected alcohols under non-basic and non-metal conditions.
TMSCl works as both an acid catalyst and dehydrating agent.
Although excess TMSCl was required for the foregoing reac-
tions, TMSCl could be readily removed by simple evaporation.
The present work was financially supported in part by ‘‘Re-
search for the Future’’ Program No. 97L00502 from the Japan
Society for the Promotion of Science, by Special Coordination
Funds of the Science and Technology Agency of the Japanese
Government, and by Grants-in-Aid for Scientific Research
No. 09044086 and No. 12640571 from the Ministry of Educa-
tion, Culture, Sports, Science and Technology, Japan.
1
NO2PhCH2–). 7: H NMR (CDCl3) ꢁ 3.35 (3H, s, OCH3),
3.54 (1H, dd, J ¼ 9:5, 3.6 Hz, H-2), 3.59–3.64 (2H, m, H-4
and H-5), 3.69–3.74 (2H, m, H-6), 3.97 (1H, dd, J ¼ 9:5,
9.2 Hz, H-3), 4.44–4.98 (8H, m, PhCH2- x4), 4.61 (1H, d,
J ¼ 3:6 Hz, H-1), 7.12–7.37 (20H, m, PhCH2- x3), 7.25
(2H, d, J ¼ 9:0 Hz, BrPhCH2–), 7.51 (2H, d, J ¼ 9:0 Hz,
BrPhCH2–).
a) K. Fukase, H. Tanaka, S. Torii, and S. Kusumoto, Tetra-
hedron Lett., 31, 389 (1990). b) K. Fukase, T. Matsumoto,
N. Ito, T. Yoshimura, S. Kotani, and S. Kusumoto, Bull.
Chem. Soc. Jpn., 65, 2643 (1992). c) K. Fukase, T.
Yoshimura, S. Kotani, and S. Kusumoto, Bull. Chem. Soc.
Jpn., 67, 473 (1994).
References and Notes
1
2
M. A. Brook and T.-H. Chan, Synthesis, 1983, 201.
T.-H. Chan, M. A. Brook, and T. Chaly, Synthesis, 1983,
203. Esterification was basically effected by using 2.2 equiv.
of TMSCl and alcohols as solvents at room temperature or
under reflux in THF. We found that esterification of N-fluo-
renylmethyloxycarbonyl (Fmoc) amino acids also proceeded
smoothly in CH2Cl2 at room temperature by using 2 equiv. of
alcohols and 5 equiv. of TMSCl against carboxylic acids to
give the desired esters quantitatively.
8
9
3
4
M. Izumi, K. Fukase, and S. Kusumoto, Biosci. Biotechnol.
Biochem., 66, 211 (2002).
X.-Y. Liu and P. H. Seeberger, Chem. Commun., 2004, 1708.
a) S. Hatakeyama, H. Mori, K. Kitano, H. Yamada, and M.
Nishizawa, Tetrahedron Lett., 35, 4367 (1994). b) Trityl
perchlorate promoted reduction of carbonyl compounds with
triethylsilane: J. Kato, N. Iwasawa, and T. Mukaiyama,
Chem. Lett., 1985, 743. c) Trimethylsilyl iodide catalyzed re-
ductive coupling of carbonyl compounds with trialkylsi-
10 K. Fukase, T. Yoshimura, M. Hashida, and S. Kusumoto,
Tetrahedron Lett., 32, 4019 (1991).
11 Reductive cleavage of 4-methoxybenzyl group with
.
Et3SiH-BF3 Et2O: Y. Morimoto, M. Iwahashi, K. Nishida,
Y. Hayashi, and H. Shirahama, Angew. Chem., Int. Ed. Engl.,
35, 904 (1996).
Published on the web (Advance View) March 19, 2005; DOI 10.1246/cl.2005.594