A. Graziani et al. / Tetrahedron Letters 42 (2001) 3857–3860
3859
OBz
BzO
HO
O
N3
O
BzO
BzO
OMe
BzO
OMe
BzO
BzO
2d
4
i. MsCl, pyr., rt, 2h,
ii. NaN3, DMSO, 100 °C,
48 h, 40-60%
N3
OH
BzO
BzO
BzO
BzO
O
OMe
O
BzO
OMe
3
5
Scheme 2.
double bond of 2f with H2 and Pd/CaCO3 5% and then
oxidation the secondary OH group with hypervalent
iodine(III)/TEMPO reagent combination (Scheme 3).13
The analytical and spectroscopic data were completely
in agreement with the structure of 6.14
Acknowledgements
We acknowledge financial support from CNR,
MURST COFIN 1998 (New Methodologies and
Strategies for the Synthesis of Biologically Interesting
Compounds).
In terms of regioselectivity and efficiency, our mild
protocol is superior to the above reported conventional
methods, as it uses a tin-free reaction sequence which
makes it possible to extend the procedure to more
reactive carbohydrate derivatives, such as glycals. Gly-
cals are emerging as a major frontier area for organic
chemistry.15,16 In addition to their well-appreciated
roles in finding new biologically active compounds,
glycals are cast in a variety of interesting new reactions,
due to their easily manipulated nature.17
References
1. (a) Kociensky, P. J. Protecting Groups; Thieme: Stuttgart,
1994; (b) Greene, T. W.; Wuts, P. G. M. Protective
Groups in Organic Chemistry, 3rd ed.; John Wiley: New
York, 1999.
2. Hanessian, S. Preparative Carbohydrate Chemistry;
Marcel Dekker: New York, 1997.
3. Triphenylmethyl ethers: Baker, G. R. Methods Carbo-
The reaction mechanism should be explained in terms
of a previously unreported domino process, initiated by
the fluoride, which cleaves the TIPS protecting group
and generating a primary C-6 alkoxy anion, which in
turns gives rise to an intramolecular migration of the
benzoyl group from C-4 to the less crowded C-6 posi-
tion. Furthermore, all the results clearly showed that
the reaction is site-selective, since only the C-4 benzoyl
group was involved in the migration, probably due to a
more accessible six-membered transition state. A steric
hindrance due a cis-decaline like transition state should
explain the formation of 3 as a by-product (Table 1,
entry 3).
hydr. Chem. 1963, 2, 168.
4. Hanessian, S.; Lavalle´e, P. Can. J. Chem. 1975, 53, 2975.
5. Garegg, P. J. Pure Appl. Chem. 1984, 56, 845 and refer-
ences cited therein.
6. Auge´, C.; David, S.; Veyrie`res, A. J. Chem. Soc., Chem.
Commun. 1976, 375.
7. Nashed, M. A.; Anderson, L. Tetrahedron Lett. 1976,
3503.
8. Peri, F.; Cipolla, L.; Nicotra, F. Tetrahedron Lett. 2000,
41, 8587.
9. Hakamata, W.; Nishio, T.; Oku, T. Carbohydr. Res.
2000, 324, 107.
1
10. Compound 2a: H NMR (200 MHz, CDCl3): l 8.18–7.97
(fs, 6H, Ph-CꢀO); 7.68–7.30 (fs, 9H, Ph-CꢀO); 5.83 (t,
In conclusion, our method opens new possibilities for
further protecting group manipulations, and it repre-
sents a substantial advance, when compared with
described strategies for obtaining a single free 4-OH in
a pyranosidic ring. We hope this elegant protection
method will see many applications in general carbohy-
drate chemistry and even in natural product synthesis.
Works are in progress in this area.
J
3,2=J3,4=10 Hz, 1H, H3); 5.28 (dd, J2,1=4 Hz, J2,3=10
Hz, 1H, H2); 5.17 (d, J1,2=4 Hz, 1H, H1); 4.80 (dd,
6A,6B=16 Hz, J6A,5=4 Hz, 1H, H6A); 4.16 (dd, J6B,6A
16 Hz, J6B,5=2 Hz, 1H, H6B); 4.12 (m, 1H, H5); 3.90 (t,
4,3=J4,5=10 Hz, 1H, H4); 3.48 (s, 3H, OCH3). 13C
J
=
J
NMR (50.3 MHz, CDCl3): l 167.39, 167.02, 166.08
(CꢀO); 133.47, 133.38 (CquatPh-CꢀO); 129.98–128.48
(Ph); 97.21 (C1); 73.98, 71.53, 70.18, 69.80 (C2, C3, C4,
C5); 63.60 (C6); 55.53 (OCH3).
BzO
11. Compound 4: 13C NMR (50.3 MHz, CDCl3): l 166.58,
166.53, 166.25 (CꢀO); 133.70, 133.35, 133.20 (CquatPh-
CꢀO); 130.00–128.40 (Ph-CꢀO); 102.03 (C1); 75.66, 71.63,
69.60 (C2, C3, C5); 62.30 (C6); 61.03 (C4); 56.30 (OCH3).
12. Compound 5: 13C NMR (50.3 MHz, CDCl3): l 165.63,
165.55, 165.30 (CꢀO); 133.72, 133.30, 133.24 (CquatPh-
CꢀO); 130.02–128.28 (Ph-CꢀO); 102.41 (C1); 73.66, 71.63,
69.60, 68.86 (C2, C3, C4, C5); 57.32 (OCH3); 50.93 (C6).
BzO
i. H2, Pd/CaCO3 5%, rt,
15 h, 80%
HO
BzO
O
O
BzO
O
ii. TEMPO, PhI(OAc)2,
rt, 48h, 70%
2f
Scheme 3.
6