amounts; furthermore, this catalyst can be reused several times
without significant loss of activity. All cleavage reactions are
performed smoothly at rt and almost in neutral conditions,
the solution 0.1 M of Er(OTf)3 in water is only weakly acidic
(pH ca. 5.9). Moreover, the present method fulfils most of
the 12 Principles of Green Chemistry.14 In fact, erbium is not
toxic, it is used in true catalytic amounts at rt, and can be
recovered and reused after reaction without significant loss of
activity. Finally, the presented protocol permits the simultaneous
transformation of acid-labile protected substrates into base-
labile acetate derivatives in quantitative yields by using an easily-
recoverable non-toxic catalyst, and without further purification
steps, showing very versatile applicability and tangible improve-
ment with respect to the other existing methods.
by comparison of their EI-MS and 1H NMR spectral data
with those of authentic compounds and literature reported
data.15
Methyl 2,3,4,6-tetraacetyl-a-D-glucopyranoside (3b). 1H-
NMR (CDCl3): d = 1.57 (s, 3H, OAc); d = 1.75 (s, 3H, OAc);
d = 1.99 (s, 3H, OAc); d = 2.45 (s, 3H, OAc); d = 3.38 (s, 3H,
OMe); d = 3.95 (ddd, 1H, H5, JH5–H4 = 10.29; JH5–H6 = 4.50;
ꢀ
ꢀ
ꢀ
ꢀ
JH5–H6 = 2.20); d = 4.05 (dd, 1H, H6 , JH6 -H6 = 12.30; JH6 –H5
=
ꢀꢀ
2.20); d = 4.25 (dd, 1H, H6, JH6–H6 = 12.30; JH6–H5 = 4.50); d =
4.47 (dd, 1H, H2, JH2–H1 = 3.71; JH2–H3 = 10.02); d = 4.87 (d, 1H,
H1, JH1–H2 = 3.71); d = 5.43 (t, 1H, H3).
Anal. calcd for C15H22O10: C 49.72; H 6.08; found: C 49.70; H
6.07.
Methyl-4,6-O-benzylidene-2,3,-diacetyl-a-D-glucopyranoside
(3bꢀ). 1H-NMR (CDCl3): d = 1.80 (s, 3H, OAc); d = 2.o5 (s,
3H, OAc); d = 3.37 (s, 3H, OAc); d = 3.56 (t, 1H, H4); d = 3.73
Experimental
All reactants, catalyst and solvents are commercially available
and were used without purification, except methyl 2,3-anhydro-
4,6-O-benzyliden-a-D-mannopyranoside (1d) and methyl 2,3-
anhydro-4,6-O-benzyliden-a-D-allopyranoside (1e) which were
synthesized following reported procedures.15 1H- and 13C-NMR
spectra were recorded with a Brucker WM 300 instrument at
300 MHz and 75 MHz respectively. Samples were dissolved in
CDCl3. Chemical shifts are given in parts per million (ppm)
ꢀ
ꢀ
(1H, t, H6, JH6–H6 = JH6–H5 10.29); d = 3.90 (dt, 1H, H5, JH5–H6
=
ꢀ
ꢀ
4.80); d = 4.30 (dd, 1H, H6, JH6–H6 = 10.15; JH6 –H5 = 4.80); d =
4.55 (dd, 1H, H2 JH2–H3 = 9.74; JH2–H1 = 3.57); d = 4.85 (d, 1H,
H1); d = 5.45 (d, 1H, H7); d = 5.55 (t, 1H, H3); d = 7.25–7.45
(m, 3H, Ar); d = 7.80 (d, 2H, Ar).
Anal. calcd for C18H22O8: C 59.02; H 6.01; found: C 59.07; H
6.07.
from tetramethylsilane as internal standard for H- and 13C-
1
References
NMR. Coupling constants (J) are given in Hz. The reactions
have been monitored by TLC when possible or with a GC-MS
Shimadzu workstation, constituted by a GC 2010 (provided of
a 30 m-QUADREX 007–5MS capillary column, operating in
“splitless” mode, 1 ml min−1 flow of He as carrier gas) and a
2010 quadrupole mass-detector or by HPLC analysis [HP 1100,
Phenomenex Luna NH2, 250 × 4.6 mm, 5 lm, RI detector,
1.0 ml min−1, H2O, 50 ◦C].
1 (a) T. W. Greene, P. G. M. Wuts, Protective Groups in Organic
Synthesis, 3rd edn., John Wiley and Sons, New York, 1999; (b) P. J.
Kocienski, Protecting Groups, 1st edn, George Thieme Verlag,
Stuttgart, 1994; (c) P. J. Kocienski, J. Chem. Soc., Perkin Trans. 1,
2001, 2109–2135.
2 Preparative Carbohydrate Chemistry, ed. S. Hanessian, Marcel
Dekker Inc., New York, 1997, pp. 53–67.
3 (a) M. P. DeNinno, J. B. Etienne and K. C. Duplantier, Tetrahedron
Lett., 1995, 36, 669–672; (b) N. L. Pohl and L. L. Kiessling,
Tetrahedron Lett., 1997, 38, 6985–6988; (c) J. Lu and T.-H. Chan,
Tetrahedron Lett., 1998, 39, 355–358; (d) H. Kotsuki, Y. Ushio, N.
Yoshimura and M. Ochi, J. Org. Chem., 1987, 52, 2594–2596; (e) A.
Arasappan and B. Fraser-Reid, J. Org. Chem., 1996, 61, 2501–2506;
(f) C. W. Andrews, R. Rodebaugh and B. Fraser-Reid, J. Org. Chem.,
1996, 61, 5280–5289.
4 (a) L. Qiao and J. C. Vederas, J. Org. Chem., 1993, 58, 3480–3482;
(b) B. Mukhopadhyay and N. Roy, Carbohydr. Res., 2003, 338, 589–
596; (c) H. Tanaka, T. Amaya and T. Takahashi, Tetrahedron Lett.,
2003, 44, 3053–3057; (d) Y. Vera-Ayoso, P. Borrachero, Cabrera-
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37, 1015–1018; (g) P. Meresse, C. Monneret and E. Bertounesque,
Tetrahedron, 2004, 60, 2657–2671.
General procedure for benzylidene cleavage
Er(OTf)3 (50 lmol, 5 mol%) was added at rt to a magnetically
stirred solution of benzylidene derivative 1a–h (1.0 mmol) in
CH3CN (4.0 mL). The reaction course was followed by TLC or
HPLC analysis until disappearance of the starting material or
to invariance of starting material : product ratio. Crude reaction
mixture was poured into water and extracted with organic sol-
vent. This organic layer was dried over anhydrous Na2SO4 and
evaporated under reduced pressure. Unless otherwise specified,
all products were identified by comparison of their EI-MS and
1H NMR spectral data with those of authentic compounds and
literature reported data.14
Methyl 2,3-anhydro-a-D-mannopyranoside (2d). 1H-NMR
5 (a) T. W. Greene, P. G. M. Wuts, Protective Groups in Organic
Synthesis, 3rd edn, John Wiley and Sons, New York, 1999, pp. 217–
222; (b) P. J. Kocienski, Protecting Groups, 1st edn, George Thieme
Verlag, Stuttgart, 1994, pp. 96–102.
6 P. Meresse, C. Monneret and E. Bertounesque, Tetrahedron, 2004,
60, 2657–2671.
(CDCl3): d = 4.89 (s, 1H, H1); d = 3.86 (d, 1H, H4, JH4–H5
=
ꢀ
9.19); d = 3.78 (dd, 2H, H6, JH6–H6 = 3.98; JH6 = 3.43); d =
H
5
3.51 (m, 1H, H5); d = 3.46 (s, 3H, OMe); d = 3.32 (d, 1H, H2,
JH2–H3 = 3.70); d = 3.13 (d, 1H, H3, JH3–H2 = 3.70).
Anal. calcd for C7H12O5: C 47.73; H 6.82; found: C 47.70; H
6.87.
7 B. Mukhopadhyay and N. Roy, Carbohydr. Res., 2003, 338, 589–596.
8 M. Smith, D. H. Rammler, I. H. Goldberg and H. G. Khorana, J. Am.
Chem. Soc., 1962, 84, 430–440.
9 U. Ellervik, Tetrahedron Lett., 2003, 44, 2279–2281.
General procedure for simultaneous peracetylation
10 (a) G. Bartoli, G. Cupone, R. Dalpozzo, A. De Nino, L. Maiuolo,
E. Marcantoni and A. Procopio, SYNLETT, 2001, 12, 1897–1900;
(b) G. Bartoli, G. Cupone, R. Dalpozzo, A. De Nino, L. Maiuolo, A.
Procopio, L. Sambri and A. Tagarelli, Tetrahedron Lett., 2002, 43,
5945–5947; (c) R. Dalpozzo, A. De Nino, L. Maiuolo, A. Procopio,
A. Tagarelli, G. Sindona and G. Bartoli, J. Org. Chem., 2002, 67,
9093–9095; (d) R. Dalpozzo, A. De Nino, L. Maiuolo, A. Procopio,
M. Nardi, G. Bartoli and R. Romeo, Tetrahedron Lett., 2003, 44,
5621–5624; (e) G. Bartoli, M. Bosco, R. Dalpozzo, E. Marcantoni,
M. Massaccesi, S. Rivalsi and L. Sambri, SYNLETT, 2003, 1,
39–42; (f) R. Dalpozzo, A. De Nino, L. Maiuolo, M. Nardi, A.
Procopio and Tagarelli, Synthesis, 2004, 496–498; (g) A. Procopio,
R. Dalpozzo, A. De Nino, M. Nardi, G. Sindona and A. Tagarelli,
Er(OTf)3 (50 lmol, 5 mol%) was added at rt to a magnetically
stirred solution of benzylidene derivative 1a–h (1.0 mmol) in
acetic anhydride (1.0 mL). The reaction course was followed
by TLC or HPLC analysis until disappearance of the start-
ing material or to invariance of starting material : product
ratio. Crude reaction mixture was poured into water and
extracted with organic solvent. This organic layer was dried
over anhydrous Na2SO4 and evaporated under reduced pressure
giving the product pure enough without any other purification
steps. Unless otherwise specified, all products were identified
4 1 3 2
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 4 1 2 9 – 4 1 3 3