5146
J. Y. Baek et al. / Tetrahedron Letters 46 (2005) 5143–5147
In conclusion, we found that picolinate, prepared from
O
the corresponding alcohols using picolinoyl chloride, is
an efficient alcohol protecting group and is readily
cleaved by Zn(OAc)2Æ2H2O even in the presence of other
common alcohol protecting groups. Moreover, we dem-
onstrated that the picolinyl group at C-2 position can be
selectively cleaved to give methyl 4,6-O-benzylidene-3-
O-picolinyl-a-D-glucopyranoside 10a and a-D-galacto-
pyranoside 10b in good yields.
N
RO
2
Zn(OAc)2
ROH
MeOH
AcO
AcO
OAc
OAc
Zn
Zn
O
O
N
N
RO
MeO
A
B
MeOH
2
MeOPic
Acknowledgements
Scheme 2. Proposed deprotection mechanism.
This work was supported by a grant from the Korea Sci-
ence and Engineering Foundation through Center for
Bioactive Molecular Hybrids (CBMH).
OPic
OBn
OPic
OBn
OPic
3f
3g
a, 3 h
OH
2n
a, 6 h
OH
References and notes
a, 1.5 h
1. (a) Greene, T. W.; Wuts, P. G. M. Protective Groups in
Organic Synthesis, 3rd ed.; John Wiley and Sons: New
York, 1999; (b) Kocienski, P. J. Protective Groups, 3rd ed.;
Thieme: Stuttgart, 2003.
OH
OBn
4g (90%)
OBn
4f (94%)
1n (90%)
2. Recent examples for new alcohol protecting group: (a)
´
Barluenga, J.; Fan˜anas, F. J.; Sanz, R.; Marcos, C.;
Ignacio, J. M. Chem. Commun. 2005, 933; (b) Vatele, J.-M.
Scheme 3. Reaction time dependence of deprotection. Reagents and
conditions: (a) Zn(OAc)2Æ2H2O (1 equiv), CH2Cl2/MeOH (95/5), rt.
`
Tetrahedron Lett. 2005, 46, 2299; (c) Reddy, C. R.;
Chittiboyina, A. G.; Kache, R.; Jung, J.-C.; Watkins, E.
B.; Avery, M. A. Tetrahedron 2005, 61, 1289; (d) Ramesh,
R.; Bhat, R. G.; Chandrasekaran, S. J. Org. Chem. 2005,
70, 837; (e) Markovic, D.; Vogel, P. Org. Lett. 2004, 6,
2693; (f) Sharma, G. V. M.; Prasad, T. R.; Rakesh;
Srinivas, B. Synth. Commun. 2004, 35, 941; (g) Barma, D.
K.; Bandyopadhyay, A.; Capdevila, J. H.; Falck, J. R.
Org. Lett. 2003, 5, 4755; (h) Ali, I. A. I.; El Ashry, E. H.;
Schmidt, R. R. Eur. J. Org. Chem. 2003, 4121; (i)
Heldmann, D. K.; Stohrer, J.; Zauner, R. Synlett 2002,
1919; (j) Epling, G. A.; Provatas, A. A. Chem. Commun.
2002, 1036.
compared to the trans-positioned benzyloxy group in 3g.
This selective deprotection is highly desirable in carbo-
hydrate chemistry8 because a 1!2 linked disaccharides
are key subunits of numerous biologically potent oligo-
saccharides, antigens, antibiotics, glycoproteins, and
glycolipids.9 The synthesis of 2,3-dipicolinate 9a and
9b from methyl 4,6-O-benzylidene-a-D-glucopyranoside
8a and a-D-galactopyranoside 8b was carried out readily
with 2.5 equiv picolinoyl chloride in good yields
(Scheme 4). The regioselective cleavage of picolinate
group at the C-2 position of 9a and 9b has been achieved
using Zn(OAc)2Æ2H2O in THF/H2O (5/1 or 4/1)10 at low
temperature to afford 3-O-picolinyl protected methyl
4,6-O-benzylidene-a-D-glucopyranoside 10a and a-D-
galactopyranoside 10b in 82% and 65% yield, respec-
tively, because of the anchimeric assistance of cis-OMe
group at the C-1 position for zinc-chelation.
3. Sammakia, T.; Jacobs, J. S. Tetrahedron Lett. 1999, 40,
2685.
4. Typical procedure for deprotection of 2a: A solution of 2a
(48 mg, 0.20 mmol) and Zn(OAc)2Æ2H2O (44 mg,
0.20 mmol) in CH2Cl2 (1.9 mL) and MeOH (0.1 mL) was
stirred for 100 min at room temperature. The reaction
mixture was quenched with saturated aqueous NH4Cl
(1 mL) and diluted with CH2Cl2 (10 mL). The organic
layer was washed with 1 N aqueous HCl solution
(5 mL · 2) and brine to remove methyl picolinate, then it
was dried over MgSO4, and concentrated to give the pure
parent alcohol 1a (26 mg, 96%).
5. Corey, E. J.; Gras, J.-L.; Ulrich, P. Tetrahedron Lett. 1976,
809.
6. Leblanc, Y.; Fitzsimmons, B. J.; Adams, J.; Perez, F.;
Rokach, J. J. Org. Chem. 1986, 51, 789.
7. Matteson, D. S.; Man, H.-W.; Ho, O. C. J. Am. Chem.
Soc. 1996, 118, 4560.
8. (a) Wang, C.-C.; Lee, J.-C.; Luo, S.-Y.; Fan, H.-F.; Pai,
C.-L.; Yang, W.-C.; Lu, L.-D.; Hung, S.-C. Angew.
Chem., Int. Ed. 2002, 41, 2360; (b) Sridhar, P. R.;
Chandrasekaran, S. Org. Lett. 2002, 4, 4731; (c) Gridley,
J. J.; Hacking, A. J.; Osborn, H. M. I.; Spackman, D. G.
Tetrahedron 1998, 54, 14925.
9. (a) Burkhart, F.; Zhang, Z.; Wacowich-Sgarbi, S.; Wong,
C.-H. Angew. Chem., Int. Ed. 2001, 40, 1274; (b) Zhu, T.;
Boons, G.-J. Angew. Chem., Int. Ed. 1999, 38, 3495; (c)
Ph
O
Ph
O
Ph
O
O
O
O
O
a
b
c
O
O
HO
PicO
PicO
HO
PicO
HO
OMe
OMe
9a (85%)
OMe
8a
10a (82%)
Ph
Ph
Ph
O
O
O
O
O
O
a
O
O
O
HO
PicO
PicO
HO
HO
PicO
OMe
OMe
OMe
8b
10b (65%)
9b (87%)
Scheme 4. Selective deprotection of C-2 position in glucose and
galactose. Reagents and conditions: (a) picolinoyl chloride (2.5 equiv),
TEA (5 equiv), DMAP (0.4 equiv), CH2Cl2, rt, 3 h; (b) Zn(OAc)2Æ
2H2O (1 equiv), THF/H2O (5/1), ꢀ10 ꢁC, 5 h; (c) Zn(OAc)2Æ2H2O
(1 equiv), THF/H2O (4/1), ꢀ5 ꢁC, 4.5 h.