1552
M. Giordano, A. Iadonisi / Tetrahedron Letters 54 (2013) 1550–1552
Table 3
References and notes
Sequential regioselective O-benzylation/per-O-acetylation of saccharide sugars in a
reducing form
1. Greene, T. W.; Wuts, P. G. M. Greene Protective Groups in Organic Synthesis, 4th
ed.; Wiley: New York, 2006.
2. (a) David, S.; Hanessian, S. Tetrahedron 1985, 41, 643–663; (b) Grindley, T. B.
Adv. Carbohydr. Chem. Biochem. 1998, 53, 17–142; (c) Simas, A. B. C.; da Silva, A.
A. T.; dos Santos Filho, T. J.; Barroso, P. T. W. Tetrahedron Lett. 2009, 50, 2744–
2746.
3. (a) Osborn, H. M. I.; Brome, V. A.; Harwood, L. M.; Suthers, W. G. Carbohydr. Res.
2001, 332, 157–166; (b) Gridley, J. J.; Osborn, H. M. I.; Suthers, W. G.
Tetrahedron Lett. 1999, 40, 6991–6994.
4. Eby, R.; Webster, K. T.; Schuech, C. Carbohydr. Res. 1984, 129, 111–120.
5. Gangadharmath, U. B.; Demchenko, A. V. Synlett 2004, 12, 2191–2193.
6. (a) Chan, L.; Taylor, M. S. Org. Lett. 2011, 13, 3090–3093; (b) Lee, D.;
Williamson, C. L.; Chan, L.; Taylor, M. S. J. Am. Chem. Soc. 2012, 134, 8260–8267.
7. Malik, S.; Dixit, V. A.; Bharatam, P. V.; Kartha, K. P. R. Carbohydr. Res. 2010, 345,
559–564.
8. For examples on non-saccharide substrates: (a) Wu, H.; Bernard, D.; Chen, W.;
Strahan, G. D.; Deschamps, J. R.; Parrish, D. A.; Lewis, J. W.; MacKerrell, A. D., Jr.;
Coop, A. J. Org. Chem. 2005, 70, 1907–1910; (b) Li, J. H.; Oh, C. O. Eur. J. Org.
Chem. 2012, 5913–5917.
9. Yang, G. B.; Kong, F.-Z.; Zhou, S. H. Carbohydr. Res. 1991, 211, 179–181.
10. Sawada, Y.; Nanboku, N.; Yanase, E.; Nakatsuka, S.-I. Heterocycl. Commun. 2010,
16, 21–24.
11. For regioselective O-alkoxycarbonylations: Adinolfi, M.; Barone, G.;
Guariniello, L.; Iadonisi, A. Tetrahedron Lett. 2000, 41, 9305–9309.
12. For regioselective O-acetylation: Adinolfi, M.; Barone, G.; Iadonisi, A.;
Schiattarella, M. Tetrahedron Lett. 2003, 44, 4661–4663.
13. For regioselective O-benzhydrylation or tritylation: Adinolfi, M.; Barone, G.;
Iadonisi, A.; Schiattarella, M. Tetrahedron Lett. 2003, 44, 3733–3735.
14. For regioselective de-O-benzylation: Pastore, A.; Valerio, S.; Adinolfi, M.;
Iadonisi, A. Chem. Eur. J. 2011, 17, 5881–5889.
Entry
Reagent
Products and yield (conversion)a
BnO
OAc
O
AcO
AcO
1
Methyl D-manno pyranoside
13
OMe
51%
BnO
AcO
O
AcO
2
3
4
D-Glucose
14 AcO
OAc
36%
OBn
O
AcO
AcO
15
AcO
OAc
AcO
D-Galactose
O
OAc
OAc
OAc
16
BnO
15+16: 44%
BnO
AcO
O
AcO
N-Boc glucosamine
BocHN
17
OAc
54 (92 %)
15. Ghathirwa, J. W.; Maki, T. Tetrahedron 2012, 68, 370–375.
16. Exposure of 1 to 2 equiv of p-methoxybenzyl chloride and DIPEA at 90 °C (and
no additive) provided a ca. 3:1 mixture of inseparable 6-O- and 5-O-PMB
regioisomers (ca. 55% combined yield).
17. Sato, S.; Ito, Y.; Nukada, T.; Nakahara, Y.; Ogawa, T. Carbohydr. Res. 1987, 167,
197–210.
General conditions: TBAI (0.3 equiv), DIPEA and BnBr (2 equiv), 90 °C, 4 h; then
addition of further DIPEA and BnBr (2 equiv), 2 h (for entry 1) or 5 h (for entries 2–
4); then addition of DIPEA (4 equiv) and acetic anhydride (6 equiv), overnight at rt.
The conversion refers to the recovery of starting material in a per-O-acetylated
form.
a
18. Shen, X.; Wu, Y.-L.; Wu, Y. Helv. Chem. Acta 2000, 83, 943–953.
19. General procedure for regioselective benzylation: to a vessel containing the polyol
(1 mmol) and TBAI (111 mg, 0.3 mmol) were sequentially added DIPEA
(0.34 mL, 2 mmol) and benzyl bromide (0.24 mL, 2 mmol). The vessel was
placed on an oil bath at 90 °C. After 4 h a further aliquot of DIPEA and benzyl
bromide (2 equiv both) was added. The vessel was kept at 90 °C for the times
indicated in the tables, then the mixture was diluted with dichloromethane
and the organic phase washed with water. Aqueous phase was re-extracted
with dichloromethane and collected organic phases were dried and
concentrated in vacuo. The residue was purified by silica-gel flash
chromatography (eluent: hexane/ethyl acetate mixtures). General procedure
for regioselective benzylation and ‘in situ’ acetylation: upon completion of the
benzylation step (see procedure above described) the reaction vessel was
cooled to rt and then DIPEA (0.68 mL, 4 equiv) and acetic anhydride (0.60 mL,
6 equiv) were sequentially added. After 2–3 h (overnight stirring was
occasionally applied for convenience) the mixture was treated with
methanol at 0 °C and then submitted to the analogous extractive work-up
and purification procedures described above.
primary carbinols within a few hours.19 The protocol appears prac-
tically very convenient in that reactions can be performed without
any solvent and without resorting to inert atmosphere conditions.
In addition, unlike other reported procedures, the proposed proto-
col does not entail preliminary polyol activation via generation of
metal complexes, neither the use of excess amounts of expensive
silver salts.
Acknowledgment
NMR and MS facilities of CIMCF (‘Centro Interdipartimentale di
Metodologie Chimico-Fisiche dell’Università di Napoli’) are
acknowledged.
Supplementary data
Supplementary data associated with this article can be found, in