3148
F. Ding et al. / Tetrahedron Letters 51 (2010) 3146–3148
Houston, T. A.; Chervin, S. M.; Koreeda, M. ITE Lett. Batt. New Technol. Med. 2002,
Using the optimized reaction conditions, the scope of the Ferrier
3, 23.
azaglycosylation promoted by ZnCl2/Al2O3 was examined. The re-
sults are summarized in Table 2. Generally, the reactions provided
2,3-unsaturated pseudoglycals in high to excellent yields with
good anomeric selectivities. For example, sulfonamides 2a and 2f
bearing electron-donating groups gave the corresponding pseudo-
glycals 3a and 3f in excellent yields and selectivities (Table 2, en-
4. (a) Yadav, J. S.; Reddy, B. V. S.; Rao, C. V.; Chand, P. K.; Prasad, A. R. Synlett 2001,
1638; (b) Yadav, J. S.; Reddy, B. V. S. Synthesis 2002, 511; (c) Kawabata, H.;
Kubo, S.; Hayashi, M. Carbohydr. Res. 2001, 333, 153. and references cited
therein.
5. (a) De Clercq, E.; Aerschot, A. V.; Herdewijin, P.; Baba, M.; Pauwels, R.;
Balzarani, J. Nucleosides Nucleotides 1989, 8, 659; (b) Norbeck, D. W. Annu. Rep.
Med. Chem. 1990, 25, 149; (c)Nucleosides and Nucleotides as Antitumor and
Antiviral Agents; Chu, C. K., Baker, D. C., Eds.; Plenum: New York, 1993; (d)
Dwek, R. A. Chem. Rev. 1996, 96, 683; (e) Varki, A. Glycobiology 1993, 3, 97; (f)
Leutzinger, E. E.; Meguro, T.; Townsend, L. B.; Shuman, D. A.; Schweizer, M. P.;
Stewart, C. M.; Robins, R. K. J. Org. Chem. 1972, 37, 3695; (g) Herscovici, J.;
Montserret, R.; Antonakis, K. Carbohydr. Res. 1988, 176, 219; (h) Lee, K.; Choi, Y.;
Gumina, G.; Zhou, W.; Schinazi, R. F.; Chu, C. K. J. Med. Chem. 2002, 45, 1313.
6. Chandrasekhar, S.; Raji Reddy, Ch.; Chandrasekhar, G. Tetrahedron Lett. 2004,
45, 6481.
tries
1 and 6), while sulfonamides 2b–e bearing electron-
withdrawing groups provided lower yields of the desired products,
but typically with slightly higher selectivities (Table 2, entries 2–
5). In addition, the aromatic sulfonamide [benzenesulfonamide
(2g)] and methanesulfonamide (2h) (MsNH2) proved to be excel-
lent nucleophiles providing the corresponding products in high
yields and selectivities (Table 2, entries 7 and 8). Interestingly,
extension of this reaction to other nitrogen nucleophiles such as
benzamide 2i furnished the corresponding pseudoglycal 3i, in
moderate yield and selectivity (Table 2, entry 9). To our knowledge,
this is the first attempt using benzamide as a nucleophile in Ferrier
7. Colinas, P. A.; Bravo, R. D. Carbohydr. Res. 2007, 342, 2297.
8. (a) Lorpitthaya, R.; Xie, Z. H.; Kuo, J. L.; Liu, X. W. Chem. Eur. J. 2008, 14, 1561;
(b) Lorpitthaya, R.; Sophy, K. B.; Kuo, J. L.; Liu, X. W. Org. Biomol. Chem. 2009, 7,
1284; (c) Sudibya, H. G.; Ma, J.; Dong, X.; Ng, S.; Li, L.-J.; Liu, X.-W.; Chen, P.
Angew. Chem., Int. Ed. 2009, 48, 2723; (d) Lorpitthaya, R.; Xie, Z. H.; Sophy, K. B.;
Kuo, J. L.; Liu, X. W. Chem. Eur. J. 2010, 16, 588.
9. Gorityala, B. K.; Lorpitthaya, R.; Bai, Y.; Liu, X. W. Tetrahedron 2009, 65, 5844.
10. Sigma–Aldrich aluminium oxide, neutral, 150 mesh, STD grade was used for all
reactions. Alumina was freshly prepared by heating at 200 °C under vacuum for
5 h and flushed with nitrogen. Alumina (5.3 equiv) was combined with 1 equiv
of activated ZnCl2 (heated under vacuum at 160 °C for 2 h), and to this mixture
about 3 mL of dry THF or CH2Cl2 was added with stirring for 5 min. The solvent
was removed and the remaining solid was dried under vacuum.
glycosylation with tri-O-acetyl-D-glucal (1). This result encouraged
us to further exploit the Ferrier azaglycosylation with benzyl car-
bamate (CbzNH2), t-butyl carbamate (BocNH2) and trimethylsilyl
azide (TMSN3) as nucleophiles. Reaction of carbamates 2k and 2l
with glucal 1 furnished the corresponding pseudoglycals 3k and
3l, in good yields and selectivities (Table 2, entries 11 and 12).
These products can be easily transformed into the corresponding
amines by removal of the protecting group. Likewise, the glycosyl-
ation of glucal 1 with TMSN3 gave the corresponding glycosyl azide
in 92% yield (Table 2, entry 13). In contrast, reaction of benzyl-
11. Typical experimental procedure: To a stirred mixture of tri-O-acetyl-D-glucal (1)
(100 mg, 0.37 mmol) and nitrogen nucleophile 2 (1 equiv) in CH2Cl2 (0.2 mL)
was added 250 mg of ZnCl2/Al2O3 at ambient temperature. The mixture was
stirred for the appropriate amount of time (Table 2), and the extent of the
reaction was monitored by TLC analysis. The reaction mixture was filtered and
the solid residue was washed with CH2Cl2 (5 mL). The combined filtrate was
concentrated under vacuum to give the product which was purified by silica
gel column chromatography (EtOAc/hexane = 1:2). The products were
identified by IR, 1H and 13C NMR and mass spectroscopy. Spectroscopic data
amine 2j with tri-O-acetyl-D-glucal (1) was unsuccessful (Table 2,
entry 10).
for selected products (major anomers): 4,6-di-O-acetyl-2,3-dideoxy-a-D-
In summary, we have demonstrated a new protocol for the Fer-
rier azaglycosylation with various nitrogen nucleophiles under the
influence of ZnCl2/Al2O3. The main advantages of this method are
high anomeric selectivity and short reaction times. Low cost re-
agents and no aqueous work-up are required, and the catalyst
could be recycled (up to three times).
erythro-hex-2-enopyranosyl-20-nitrophenylsulfonamide (3c): 1H NMR (CDCl3,
400 MHz): d 8.16–8.23 (m, 1H), 7.85–7.88 (m, 1H), 7.69–7.77 (m, 2H), 6.49
(d, J = 10.0 Hz, 1H), 5.76–5.96 (m, 2H), 5.67 (d, J = 9.2 Hz, 1H), 5.27 (d, J = 9.2 Hz,
1H), 4.10 (q, J = 6.8 Hz, 1H), 3.70–3.73 (m, 1H), 3.10 (d, J = 12.0 Hz, 1H), 2.07 (s,
3H), 2.03 (s, 3H); 13C NMR (CDCl3, 100 MHz): d 170.4, 170.0, 135.2, 133.9,
133.2, 131.6, 131.1, 127.8, 126.0, 125.2, 125.1, 67.1, 64.1, 61.5, 20.9, 20.7; IR
(CHCl3) 3285, 1738, 1539, 1367, 1236, 1170, 1032, 742 cmꢁ1; HRMS (ESI) m/z
[M+H]+ calcd for C16H19N2O9S: 415.0811, found: 415.0816.
12. 4,6-Di-O-acetyl-2,3-dideoxy-a-D-erythro-hex-2-enopyranosyl-p-
chlorophenylsulfonamide (3d): 1H NMR (CDCl3, 300 MHz): d 7.88 (d, J = 6.9 Hz,
2H), 7.49 (d, J = 6.9 Hz, 2H), 5.94 (d, J = 6.9 Hz, 1H), 5.78–5.84 (m, 2H), 5.62 (d,
J = 7.8 Hz, 1H), 5.23 (dd, J = 8.7, 1.8 Hz, 1H), 3.93 (dd, J = 12.3, 3.6 Hz, 1H), 3.55–
3.63 (m, 2H), 2.04 (s, 3H), 2.01 (s, 3H); 13C NMR (CDCl3, 75 MHz): d 170.6,
170.1, 140.0, 139.4, 130.7, 129.3, 128.9, 128.7, 126.5, 67.2, 64.3, 61.9, 20.9,
20.7; IR (CHCl3): 3269, 1738, 1371, 1338, 1236, 1167, 1036, 756 cmꢁ1; HRMS
(ESI) m/z [M+H]+ calcd for C16H19ClNO7S: 404.0571, found: 404.0574.
Acknowledgements
Financial support from NTU (RG50/08) and the Ministry of Edu-
cation (MOE 2009-T2-1-030) Singapore is gratefully acknowledged.
References and notes
13. 4,6-Di-O-acetyl-2,3-dideoxy-a-D-erythro-hex-2-enopyranosyl-p-
fluorophenylsulfonamide (3e): 1H NMR (CDCl3, 300 MHz): d 7.93–7.98 (m, 2H),
7.17–7.23 (m, 2H), 5.94 (d, J = 8.4 Hz, 1H), 5.79–5.84 (m, 2H), 5.62 (d, J = 5.7 Hz,
1H), 5.24 (dd, J = 9.0, 2.1 Hz, 1H), 3.94 (dd, J = 12.9, 4.5 Hz, 1H), 3.54–3.60 (m,
2H), 2.03 (s, 3H), 2.01 (s, 3H); 13C NMR (CDCl3, 75 MHz): d 170.6, 170.0, 137.5,
130.6, 130.0, 129.9, 126.6, 116.4, 116.1, 67.1, 64.3, 61.9, 20.9, 20.7; IR (CHCl3):
3282, 1738, 1591, 1371, 1338, 1236, 1155, 1033, 754 cmꢁ1; HRMS (ESI) m/z
[M+H]+ calcd for C16H19FNO7S: 388.0866, found: 388.0869.
1. (a) Ferrier, R. J.; Prasad, N. J. Chem. Soc. 1969, C, 570; (b) Ferrier, R. J.; Zubkov, O.
A. Org. React. 2003, 62, 569. and references therein; (c) Ferrier, R. J. Top. Curr.
Chem. 2001, 215, 153.
2. (a) Descotes, G.; Martin, J. C. Carbohydr. Res. 1977, 56, 168; (b) Klaffke, W.;
Pudlo, P.; Springer, D.; Thiem, J. L. Ann. Chem. 1991, 6, 509; (c) Bhate, P.; Harton,
D.; Priebe, W. Carbohydr. Res. 1985, 144, 331; (d) Babu, B. S.; Balsubramanian, K.
K. Tetrahedron Lett. 2000, 41, 1271; (e) Das, S. K.; Reddy, K. A.; Roy, J. Synlett
2003, 1607; (f) Takhi, M.; Rahman, A.; Schmidt, R. R. Tetrahedron Lett. 2001, 42,
4053; (g) Masson, C.; Soto, J.; Besodes, M. Synlett 2000, 1281; (h) Yadav, J. S.;
Reddy, B. V. S.; Chandraiah, L.; Reddy, K. S. Carbohydr. Res. 2001, 332, 221; (i)
Swamy, N. R.; Venkateswarlu, A. Synthesis 2002, 598; (j) Bettadaiah, B. K.;
Srinivas, P. Tetrahedron Lett. 2003, 44, 7257; (k) Yadav, J. S.; Reddy, B. V.; Reddy,
J. S. J. Chem. Soc., Perkin Trans. 1 2002, 2390; (l) Yadav, J. S.; Reddy, B. V.; Murthy,
C. V.; Kumar, G. M. Synlett 2000, 1450; (m) Smitha, G.; Reddy, S. C. Synthesis
2004, 834; (n) Gorityala, B. K.; Cai, S.; Lorpitthaya, R.; Ma, J.; Pasunooti, K. K.;
Liu, X. W. Tetrahedron Lett. 2009, 50, 676; (o) Zhang, G.; Liu, Q.; Shi, L.; Wang, J.
Tetrahedron 2008, 64, 339; (p) Yadav, J. S.; Reddy, B. V. S.; Geetha, V. Synth.
Commun. 2003, 33, 717; (q) Rafiee, E.; Tangestaninejad, S.; Habibi, M. H.;
Mirkhani, V. Bioorg. Med. Chem. Lett. 2004, 14, 3611; (r) Nagaraj, P.; Ramesh, N.
G. Tetrahedron Lett. 2009, 50, 3970; (s) Watanabe, Y.; Itoh, T.; Sakakibara, T.
Carbohydr. Res. 2009, 344, 516; (t) Gorityala, B. K.; Cai, S.; Ma, J.; Pasunooti, K.
K.; Liu, X. W. Bioorg. Med. Chem. Lett. 2009, 19, 3093.
14. 4,6-Di-O-acetyl-2,3-dideoxy-a-D-erythro-hex-2-enopyranosyl-p-
methoxyphenylsulfonamide (3f): 1H NMR (CDCl3, 300 MHz): d 7.86 (d, J = 9.0 Hz,
2H), 6.97 (d, J = 9.0 Hz, 2H), 5.92 (d, J = 10.2 Hz, 1H), 5.68–5.82 (m, 2H), 5.59 (d,
J = 7.5 Hz, 1H), 5.26 (dd, J = 8.7, 1.5 Hz, 1H), 3.90 (dd, J = 10.2, 3.0 Hz, 1H), 3.87
(s, 3H), 3.50–3.58 (m, 2H), 2.03 (s, 3H), 2.01 (s, 3H); 13C NMR (CDCl3, 75 MHz):
d 170.8, 170.2, 163.1, 133.1, 130.6, 129.6, 128.7, 126.8, 114.2, 66.8, 64.4, 62.0,
55.8, 21.0, 20.8; IR (CHCl3): 3420, 1647, 1238, 1165, 1034, 721 cmꢁ1; HRMS
(ESI) m/z [M+Na]+ calcd for C17H21NO8SNa: 422.0886, found: 422.0888.
15. 4,6-Di-O-acetyl-2,3-dideoxy-a-D
-erythro-hex-2-enopyranosyl-benzamide (3i): 1H
NMR (CDCl3, 400 MHz): d 7.73 (d, J = 7.6 Hz, 2H), 7.45–7.48 (m, 1H), 7.36–7.40
(m, 2H), 6.51 (d, J = 10.0 Hz, 1H), 6.17 (d, J = 9.6 Hz, 1H), 5.83–5.93 (m, 2H), 5.26
(d, J = 9.6 Hz, 1H), 4.11–4.22 (m, 2H), 3.91–3.94 (m, 1H), 2.03 (s, 3H), 2.02 (s,
3H); 13C NMR (CDCl3, 100 MHz): d 170.9, 170.3, 166.7, 133.4, 132.2, 129.8,
129.6, 128.7, 127.2, 75.5, 74.3, 64.6, 63.1, 21.0, 20.9; IR (CHCl3): 3406, 1741,
;
1526, 1237, 1041 cmꢁ1 HRMS (ESI) m/z [M+H]+ calcd for C17H20NO6:
334.1291, found: 334.1286.
3. (a) Kahne, D.; Walker, S.; Cheng, Y.; Engen, D. V. J. Am. Chem. Soc. 1989, 111,
6881; (b) Bolitt, V.; Chaguir, B.; Sinou, D. Tetrahedron Lett. 1992, 33, 2481; (c)