Efficient activation of armed glycosyl trichloroacetimidates with Sm(OTf)3 in the stereoselective glycosidation of saccharidic acceptors

Article abstract of DOI:10.1016/S0040-4039(00)01622-1

Catalytic amounts of Sm(OTf)₃ activate armed glycosyl trichloroacetimidates under very mild conditions. This reagent proved effective in promoting the glucosylation of saccharidic acceptors 2, 3, 4, and 5, possessing primary or secondary hydroxyls, with the model donor 1. The stereoselectivity of these glycosidations can be controlled by a suitable choice of solvent. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01622-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 9005–9008
Efficient activation of armed glycosyl trichloroacetimidates
with Sm(OTf)3 in the stereoselective glycosidation of
saccharidic acceptors
Matteo Adinolfi, Gaspare Barone, Luigi Guariniello and Alfonso Iadonisi*
Dipartimento di Chimica Organica e Biologica, Universita` degli Studi di Napoli Federico II, Via Mezzocannone 16,
I-80134 Napoli, Italy
Received 31 July 2000; revised 11 September 2000; accepted 20 September 2000
Abstract
Catalytic amounts of Sm(OTf)3 activate armed glycosyl trichloroacetimidates under very mild condi-
tions. This reagent proved effective in promoting the glucosylation of saccharidic acceptors 2, 3, 4, and
5, possessing primary or secondary hydroxyls, with the model donor 1. The stereoselectivity of these
glycosidations can be controlled by a suitable choice of solvent. © 2000 Elsevier Science Ltd. All rights
reserved.
Keywords: glycosidation; samarium and compounds.
Recently we have reported on the conversion of glycosyl trichloroacetimidates into iodo- and
iodobutyl-glycosides mediated by air oxidised samarium diiodide in THF.1 This peculiar
reactivity led us to anticipate the feasible activation of anomeric trichloroacetimidates in
ordinary glycosidation reactions2 by using different trivalent samarium species with a non-nucle-
ophilic counterion. Herein we describe our first results concerning the efficiency of Sm(OTf)3 in
promoting the smooth glycosidation of primary and secondary saccharidic hydroxyls under very
mild conditions. Very recently3 this salt was reported to promote glycosidation reactions using
‘armed’4 anomeric sulfones as glycosidation donors. These reactions required the use of
stoichiometric amounts of promoter, prolonged reaction times, and high temperatures to
provide high yields. For our investigations we chose perbenzylated glucosyl trichloroacetimidate
1 as a model donor, and saccharidic compounds 2, 3, 4 and 5 as model acceptors.
* Corresponding author. Fax: +39 0815521217; e-mail: iadonisi@unina.it
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01622-1

9006
Initially we examined the reactivity of the donor with acceptor 2, possessing a primary
alcoholic function, in a variety of solvent mixtures. In all cases (Table 1, entries 1–8)
glycosidation occurred smoothly (within one hour), at low temperature and in the presence of
catalytic amounts of the lanthanide salt (10% or less) to provide disaccharide 6 (anomeric
mixture). In all the reported reactions the promoter was added as a solution in the minor
cosolvent (THF, acetonitrile or dioxane). As expected,5 the use of acetonitrile afforded high
b-selectivity (entry 4), while in 4:1 diethyl ether/dioxane a-selectivity was observed (entry 8). A
predominance of the b anomer was nearly always observed in the other cases. The noteworthy
Table 1
Reaction of 1 with sugar acceptors promoted by Sm(OTf)3
Entry
Acceptor
Solvent
Temp./°C
Sm(OTf)3/% mol
Yielda/%
a:b ratiob
1
2
3
4
5
6
7
8
9
10
11
12
13
14
2
2
2
2
2
2
2
2
3
3
4
4
5
5
4:1 CH2Cl2/THF
THF
4:1 CH3CN/THF
CH3CN
4:1 toluene/THF
4:1 toluene/dioxane
4:1 Et2O/THF
4:1 Et2O/dioxane
CH3CN
4:1 Et2O/dioxane
CH3CN
4:1 Et2O/dioxane
CH3CN
−78
−78
−25
−25
−25
−25
−25
−15 to 0
−25
−15 to 0
−25
−15 to 0
−25
10
10c
10
2
2
2
2
2
2
2
75
57
81
88
80
73
76
83
47 (55)
51 (60)
58 (70)
61 (70)
77 (90)
69 (80)
1:1.5
1:2
1:3
1:10
1:2
1:1
1:1
3.5:1
1:2
9:1
1:4
2
2
2
2
3.5:1
1:5.5
4:1
4:1 Et2O/dioxane
−15 to 0
a Isolated yields. In parentheses: yields evaluated by NMR analysis of the crude reaction mixture. All disaccharides
1
were identified by H NMR spectroscopy.
1
b Determined by integration of the relevant H NMR signals.
c Commercial Sm(OTf)3 without previous dehydration (see text) was used.

9007
activating power of Sm(OTf)3 having been established, we examined the reactivity of 1 toward
the less nucleophilic acceptors 3 and 4.6 In these cases as well, coupling reactions occurred
smoothly (within 60–90 minutes) under very mild conditions affording disaccharides 7 and 8 in
satisfying yields (entries 9–12). On the basis of evidence gained in the synthesis of disaccharide
6, we modulated the glycosidation stereoselectivity through the choice of the solvent mixture
(compare entries 9 and 11 to entries 10 and 12, respectively). Interestingly, a sensible increase of
yield was observed in the synthesis of the 3-O-linked disaccharides utilising a 2-O-benzylated
rather than a 2-O-acetylated acceptor (compare entries 9, 10 to 13, 14, respectively).7
These results highlight the potential of Sm(OTf)3 in oligosaccharide synthesis. Although the
hygroscopic nature of this white solid requires a careful dehydration procedure (heating at
190°C under vacuum for one night)8 prior to its use, this reagent offers several advantages over
the traditional activators of glycosyl trichloroacetimidates (BF3·OEt2, TMSOTf, TfOH),2 since it
is chemically stable to prolonged storage under air, easy to handle and highly active under very
mild conditions.9 In a typical procedure for reactions in solvent mixtures, donor 1 (0.07 mmol)
and the acceptor (0.05 mmol) were dissolved in the major cosolvent (0.8 mL) (see Table 1) in the
,
presence of 4 A molecular sieves. The mixture was cooled to the reaction temperature and then
a solution of Sm(OTf)3 in the minor cosolvent (0.2 mL) was added dropwise (temperature and
promoter amounts as in Table 1). After 60–90 min the reaction is generally completed (TLC)
and the mixture is diluted with CHCl3 and washed with water. Concentration of the organic
phase affords a crude product, which is purified by silica gel PLC (eluent: 7:3 or 3:1
hexane–ethyl acetate). We are currently investigating the extension of this approach to
disarmed4 glycosyl donors and the application to solid phase oligosaccharides synthesis.10
Acknowledgements
Financial support by MURST (PRIN 1999–2000), CNR and Universita` di Napoli (Progetto
Giovani Ricercatori 2000) is acknowledged. NMR spectra were performed at the ‘‘Centro di
Metodologie Chimico-Fisiche dell’Universita` di Napoli’’.
References
1. Adinolfi, M.; Barone, G.; Iadonisi, R.; Lanzetta, R. Tetrahedron Lett. 1998, 39, 5605–5608.
2. Schmidt, R. R.; Kinzy, W. Adv. Carbohydr. Chem. Biochem. 1994, 50, 21–123.
3. Chang, G. X.; Lowary, T. L. Org. Lett. 2000, 2, 1505–1508. For applications of other lanthanide triflates in
glycosidations: Inanaga, J.; Yokoyama, Y.; Hanamoto, T. Chem. Commun. 1993, 1090–1091; Inanaga, J.;
Yokoyama, Y.; Hanamoto, T. Tetrahedron Lett. 1993, 34, 2791–2794; Mukaiyama, T.; Matsubara, K.; Hora, M.
Synthesis, 1994, 1368–1373; Sanders, W. J.; Kiessling, L. L. Tetrahedron Lett. 1994, 35, 7335–7338; Hosono, S.;
Kim, W.-S.; Sasai, H.; Shibasaki, M. J. Org. Chem. 1995, 60, 4–5.
4. Fraser-Reid, B.; Udodong, U. E.; Wu, Z.; Ottesson, H.; Merritt, J. R.; Rao, C. S.; Roberts, C.; Maden, R.
Synlett 1992, 927–942.
5. Schmidt, R. R.; Behrendt, M.; Toepfer, A. Synlett 1990, 694–696.
6. Compounds 3 and 4 were readily obtained (50 and 24% yields, respectively) by treatment of commercially
available methyl 4,6-O-benzylidene-a-
subsequent chromatographic separation.
7. Boons, G.-J.; Zhu, T. Synlett 1997, 809–811.
D-glucopyranoside with one equivalent of acetic anhydride in pyridine and
.

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8. Forsberg, J. H.; Spaziano, V. T.; Balasubramanian, T. M.; Liu, G. K.; Kinsley, S. A.; Duckworth, C. A.;
Poteruca, J. J.; Brown, P. S.; Miller, J. L. J. Org. Chem. 1987, 52, 1017–1021.
9. Armed glycosyl trichloroacetimidates can be activated under neutral conditions in concentrated solutions of
LiClO4 in organic solvents. However, under these conditions prolonged reaction times are required to achieve
good yields: Waldmann, H.; Bohm, G.; Schmid, U.; Rottele, H. Angew. Chem., Int. Ed. Engl. 1994, 33,
1944–1946; Bohm, G.; Waldmann, H. Tetrahedron Lett. 1995, 36, 3843–3846; Waldmann, H.; Schene, H. Chem.
Commun. 1998, 2759–2760.
10. In preliminary experiments we have also disclosed that benzyl trichloroacetimidates can be activated by Sm(OTf)3
under suitably adjusted reaction conditions.