Phenylsulfonylethylidene (PSE) acetals as atypical carbohydrate- protective groups

Article abstract of DOI:10.1016/S0040-4039(00)00199-4

We introduce a new class of arylsulfonylated cyclic acetals derived from carbohydrate structures which are synthesized with high yields under basic conditions. Deprotection methods for such acetals are also investigated. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00199-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 2357–2360
Phenylsulfonylethylidene (PSE) acetals as atypical
carbohydrate-protective groups
Florence Chéry,a Patrick Rollin,a,∗ Ottorino De Lucchi b and Sergio Cossu b
aInstitut de Chimie Organique et Analytique, associé au CNRS, Université d’Orléans, B.P. 6759, F-45067 Orléans, France
bDipartimento di Chimica, Università Ca’ Foscari di Venezia, Dorsoduro 2137, I-30123 Venezia, Italy
Received 13 January 2000; accepted 27 January 2000
Abstract
We introduce a new class of arylsulfonylated cyclic acetals derived from carbohydrate structures which are
synthesized with high yields under basic conditions. Deprotection methods for such acetals are also investigated.
© 2000 Elsevier Science Ltd. All rights reserved.
Selective introduction–expulsion of protective groups still remains a major concern in carbohydrate
chemistry strategies.1,2 An impressive part of the chemistry of carbohydrates has dealt with cyclic
acetals (mainly 1,3-dioxolanes and 1,3-dioxanes). Besides being useful for selective protection of
monosaccharides, cyclic acetals can display a number of interesting reactions — this is particularly true
for benzylidene acetals which can undergo regiospecific oxidative3 and reductive4,5 openings. Hence,
studies of new cyclic acetals showing atypical properties remain an important topic because of the
uncommon synthetic features they can bring out. Within the frame of our continuous exploration of
thiofunctionalized sugars, we have started to investigate the preparation and the reactivity of arylsulfonyl
acetals as carbohydrate-protective groups.
1,2-Bis(phenylsulfonyl) alkenes — already known as powerful electrophilic partners for Diels–Alder
or Michael reactions — are well-suited reagents for this purpose.6 As an extension of recent literature
results,7 we have demonstrated that phenylsulfonylethylidene (PSE) acetals can be readily prepared from
unprotected glycosides under basic conditions (Fig. 1).
Following a double Michael addition pathway, either Z- or E-1,2-bis(phenylsulfonyl) ethylene8 reacted
at room temperature with diverse α- and β-diols in THF, using NaH as the base and Bu4NBr as the phase
transfer catalyst.9 Saccharidic polyols reacted similarly in DMF, using tBuOK as the base. In all cases,
the initial Michael addition of an alkoxide ion is followed by eliminative expulsion of a phenylsulfinate
ion. The resulting transient alkoxy vinyl sulfone then undergoes Michael addition of a second alkoxide
ion.
∗
Corresponding author. Tel: +33 (0) 2 38 41 73 70; fax: +33 (0) 2 38 49 45 79; e-mail: patrick.rollin@univ-orleans.fr (P.
Rollin)
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00199-4
tetl 16479

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Fig. 1. Synthesis of PSE acetals
Various diols and polyols derived from pyrano- and furano-sugars have been submitted with success
to the above reaction conditions10 (Figs. 2 and 3).
Fig. 2. Pyrano-sugar derived PSE acetals
As expected, β-diols gave, exclusively, the equatorially-configurated cyclic acetals in conformity
with the well-documented case of 4,6-O-benzylidene derivatives. In contrast, the diastereoselectivity of
dioxolane-type acetals is quite poor (Fig. 3; entries 9, 10 and 11).
A thorough examination of deprotection conditions for the PSE acetals have shown interesting results.
Classical hydrolysis or alcoholysis in acidic medium at 60–80°C — CH3COOH 80% or H2SO4 0.7 N
or BF3·Et2O/CH2Cl2/MeOH — proved totally ineffective: no degradation could be observed and the
starting material was entirely recovered. What is more, when PSE acetal 1 was submitted to 9:1 TFA:H2O
(60°C, 2 h), the benzyl groups were expelled, whereas the PSE acetal remained unaffected (Fig. 4).
The reluctance of PSE acetals to acid-catalyzed hydrolysis may be connected with the fact that both
acetalic oxygen atoms become harder (therefore more difficult to be protonated) because of the presence
of a sulfonyl group; this behaviour was previously observed in the case of other acetals bearing electron-
withdrawing groups.11
Nevertheless, PSE acetals can be readily deprotected under classical reductive conditions: for example,
treatment of 1 by LiAlH4 in Et2O (optionally in the presence of AlCl3) delivers the corresponding 4,6-
diol with 75–85% yield. In contrast, milder reducing systems such as NaBH3CN/TFA proved ineffective.

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Fig. 3. Furano-sugar derived PSE acetals
Fig. 4.
In summary, a new class of cyclic acetals have been synthesized under basic conditions, with
high yields and high regio- and stereoselectivity. These compounds present abnormal properties when
compared to classic benzylidene acetals: they resist acid hydrolysis and can be deprotected under
reductive conditions.
Further broad range exploration of the chemical behaviour of carbohydrate-derived PSE acetals is
currently being performed in our laboratory.
Acknowledgements
The authors would like to thank Dr. D. Craig (Imperial College, London) and Dr. A. Tatibouët (ICOA)
for helpful comments and discussions. MENRT is also acknowledged for financial support.
References
1. Haines, A. H. Adv. Carbohydr. Chem. Biochem. 1981, 39, 13–70.
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4. Garegg, P. J.; Hultberg, H. Carbohydr. Res. 1981, 93, C10–C12.
5. Umemura, K.; Matsuyama, H.; Kobayshi, M.; Kamigata, N. Bull. Chem. Soc. Japan 1989, 62, 3026–3029.
6. De Lucchi, O.; Lucchini, V.; Pasquato, L.; Modena, G. J. Org. Chem. 1984, 49, 596–604.
7. Cossu, S.; De Lucchi, O.; Fabris, F.; Ballini, R.; Bosica, G. Synthesis 1996, 12, 1481–1484.
8. De Lucchi, O.; Pasquato, L. In Encyclopedia of Reagents for Organic Synthesis; Paquette, L., Ed.; Wiley & Sons: New York,
1995; p. 547, and references cited therein.
9. In a typical procedure, 2 equivalents of NaH were added at 0°C to a THF solution of the diol; after 15 min, 1 equivalent of 1,2-
bis(phenylsulfonyl)ethylene and a few crystals of Bu4NBr were added. After 12 h stirring at room temperature, the mixture

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was treated with brine and extracted with AcOEt. The combined organic phases were dried over MgSO4, concentrated under
reduced pressure and the crude product was purified by silica gel column chromatography.
10. Fully satisfactory NMR and mass spectrometry data were obtained for all new compounds. Selected data for 1: 1H NMR δ
3.34 (s, 3H, OMe), 3.35 (dd, 1H, H-4, J4–5=9.6), 3.43 (dd, 1H, H-6b, J5–6b=10.1), 3.47 (dd, 1H, H-2), 3.48 (d, 2H, CH2SO2),
3.59 (ddd, 1H, H-5), 3.85 (dd, 1H, H-3, J2–3=J3–4=9.1), 4.00 (dd, 1H, H-6a, J5–6a=4.7, J6a–6b=10.1), 4.51 (d, 1H, H-1, J1–2=3.8),
4.64 and 4.81 (2d, AB system, 2H, Jgem=12.1, PhCH2O), 4.74 and 4.78 (2d, AB system, 2H, Jgem=11.2, PhCH2O), 4.98 (t,
1H, H-7, J=4.9), 7.29–7.61 (m, 13H, H-Ar), 7.89–7.93 (m, 2H, ortho-H-Ar PhSO2), 13C NMR δ 55.8 OMe, 60.3 CH2SO2,
62.0 C-5, 69.0 C-6, 74.2 PhCH2O, 75.2 PhCH2O, 78.5 C-3, 79.4 C-2, 82.3 C-4, 97.0 C-7, 99.5 C-1, 126.3–134.2, 15*CH,
138.4, 139.1, 140.2, 3*CIV Ph, MS (Ionspray®): [M+Na]+=563, [α]D=+23 (c 1, CHCl3).
11. Frank, M.; Miethchen, R. Carbohydr. Res. 1998, 313, 49–53.