exo-Glycals from glycosyl cyanides. First generation of C-glycosylmethylene carbenes from 2,5- and 2,6-anhydroaldose tosylhydrazones

Article abstract of DOI:10.1039/b102963k

In a one-pot reaction acylated glycosyl cyanides were transformed with Raney nickel-sodium hypophosphite into 2,5- and 2,6-anhydroaldose tosylhydrazones, which gave exo-glycals under Bamford-Stevens conditions.

Full text of DOI:10.1039/b102963k

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exo-Glycals from glycosyl cyanides. First generation of
C-glycosylmethylene carbenes from 2,5- and
2,6-anhydroaldose tosylhydrazones
1
Marietta Tóth and László Somsák*
Department of Organic Chemistry, University of Debrecen, POB 20, H-4010, Debrecen,
Hungary. E-mail: somsak@tigris.klte.hu; Fax: ϩ36-52-435-836; Tel.: ϩ36-52-512-900/2348
Received (in Cambridge, UK) 3rd January 2001, Accepted 2nd April 2001
First published as an Advance Article on the web 18th April 2001
In a one-pot reaction acylated glycosyl cyanides were
transformed with Raney nickel–sodium hypophosphite
into 2,5- and 2,6-anhydroaldose tosylhydrazones, which
gave exo-glycals under Bamford–Stevens conditions.
exo-Glycals (2,5- or 2,6-anhydro-1-deoxy-hex- or -hept-1-
enitols) are useful carbohydrate derivatives exemplified by their
applications e.g. in syntheses1 and biological investigations.2
Several synthetic protocols are known for the preparation
of such compounds: olefination of sugar lactones by using
the Tebbe reagent,3 dimethyltitanocene,1a or the Wittig
methodology;4 hydrogen halide eliminations from C-glycosyl-
iodomethanes;5 other methods using glycosyl carbanions as
intermediates have been reviewed recently.6
Here we report a novel method for the preparation of
exo-glycals based on the generation of C-glycosylmethylene
carbenes by application of the aprotic Bamford–Stevens
reaction7 to tosylhydrazones of 2,5- and 2,6-anhydroaldose
derivatives followed by their spontaneous rearrangement
(Scheme 1). The reaction of acylated glycosyl cyanides8 (1)
with Raney nickel–sodium hypophosphite in the presence of
Scheme 1
1.2–1.7 eq. of tosylhydrazine9 in acetic acid–water–pyridine
solvent mixture proved to provide easy access to the previously
unknown 2,5- and 2,6-anhydroaldose tosylhydrazones
2
(Table 1). With the exception of 2e, one isomer was formed in
Table 1 Synthesis and selected data of 2,5- and 2,6-anhydroaldose tosylhydrazones 2 and exo-glycals 3
2
3
NMRa
NMRa
H-1 (J1,2
C-1
)
H-1, H-1Ј
C-1
1
Yield (%)
64
[α]D b (c)
H-2 (J2,3
)
NH
8.12
Yield (%)
72
[α]D b (c)
C-2
a
b
ϩ4
7.16
4.34 (9.5)
ϩ43
4.70, 4.96
153.3
(1.00)
(6.3)
144.1
(0.98)
97.3
87
ϩ6
(0.97)
7.00c
(6.7)
144.1
4.14c (9.8)
11.6c
82
ϩ74
4.51, 4.82
96.1
154.1
(1.45)
Lit.12 ϩ69
(1.00)
c
73
58
Ϫ35
(2.03)
7.04
(6.8)
144.3
3.89 (9.5)
9.07
86
74
Ϫ94
(0.94)
4.49, 4.69c
96.9
154.5
151.9
d
ϩ65
(1.01)
7.10c
(5.5)
144.0
4.87c (10.4)
11.48c
ϩ29
(1.08)
4.24, 4.80
95.7
e
Inseparable mixture (probably two diastereomers)
26d,e
ϩ24
(0.90)
4.44,
4.67
87.1
157.7
a For CDCl3 solutions unless otherwise stated (δ/ppm, J/Hz). b Measured in CHCl3 at room temperature. [α]D Values are given in 10Ϫ1 deg cm2 gϪ1
c For DMSO-d6 solutions. d Overall yield for the two steps. e For deprotonation 2 eq. of NaH was used.
.
942
J. Chem. Soc., Perkin Trans. 1, 2001, 942–943
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b102963k

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these transformations. These compounds are new represent-
atives of the rather sparsely populated class of 2,5- and 2,6-
anhydroaldimine derivatives.10
due was purified by column chromatography (eluent : gradient
of ethyl acetate–hexane 1 : 2 to 1 : 1) to give exo-glycals 3a–e.
The tosylhydrazone salt formation and thermolysis were
performed in one operation as suggested in the literature:7a
a solution of 2 in 1,4-dioxane was added dropwise to boiling
1,4-dioxane containing 10 eq. of sodium hydride. exo-Glycals 3
were isolated by column chromatography. The reactions were
rather clean and highly selective in so far as no products of
1,2-C or 1,2-O shifts could be detected in the mixtures. This
was the case even with the furanoid derivative 2e, in contrast
to the ring enlargement observed with tetrahydrofuran-2-yl-
methylenes.11
In summary, we have described a new route to exo-glycals
from readily available glycosyl cyanides via 2,5- and 2,6-
anhydroaldose tosylhydrazones. This method can be a useful
alternative to the known procedures, especially for the prepar-
ation of acyl-protected derivatives.
Acknowledgements
This work was supported by the Hungarian Scientific Research
Fund (Grant: OTKA T 32124).
Notes and references
1 See as leading references: (a) C. R. Johnson and B. A. Johns, Synlett,
1997, 1406; (b) T. Vidal, A. Haudrechy and Y. Langlois, Tetrahedron
Lett., 1999, 40, 5677; (c) A. D. Campbell, D. E. Paterson,
T. M. Raynham and R. J. K. Taylor, Chem. Commun., 1999, 1599;
(d) I. P. Smoliakova, Curr. Org. Chem., 2000, 4, 589.
2 Leading references: G. Legler, Adv. Carbohydr. Chem. Biochem.,
1990, 48, 319; M. H. D. Postema, C-Glycoside Synthesis, CRC Press,
Boca Raton, 1995, pp. 353–355.
3 C. S. Wilcox, G. W. Long and H. Suh, Tetrahedron Lett., 1984, 25,
395; T. V. RajanBabu and G. S. Reddy, J. Org. Chem., 1986, 51,
5458.
4 Y. Lakhrissi, C. Taillefumier, M. Lakhrissi and Y. Chapleur,
Tetrahedron: Asymmetry, 2000, 11, 417.
Experimental
General procedure for the synthesis of 2,5- and 2,6-anhydro-
aldose tosylhydrazones (2)
5 M. Brockhaus and J. Lehmann, Carbohydr. Res., 1977, 53, 21;
J. Lehmann and B. Schwesinger, Carbohydr. Res., 1982, 107, 43;
O. R. Martin and F. Xie, Carbohydr. Res., 1994, 264, 141; R. D.
Guthrie, I. D. Jenkins, J. J. Watters, M. W. Wright and R. Yamasaki,
Aust. J. Chem., 1982, 35, 2169.
Raney nickel (1.5 g, from an aqueous suspension, Merck) was
added at room temperature to a vigorously stirred solution of
pyridine (5.7 mL), acetic acid (3.4 mL), and water (3.4 mL).
Then sodium hypophosphite (0.74 g, 8.4 mmol), tosylhydrazine
(0.22–0.32 g, 1.2–1.7 mmol), and the corresponding glycosyl
cyanide 1 (1 mmol) were added to the mixture. When the
reaction was complete (TLC, eluent: ethyl acetate–hexane 1 : 1)
the insoluble materials were filtered off with suction, and
washed with dichloromethane (10 mL). The organic layer of
the filtrate was separated, washed sequentially with water (3 mL),
10% aqueous hydrogen chloride solution (2 × 3 mL), cold,
saturated sodium hydrogen carbonate solution (2 × 3 mL) and
water (3 mL), and then dried on anhydrous magnesium sulfate.
The solution was concentrated under reduced pressure, and
traces of pyridine were removed by repeated co-evaporations
with toluene. The residue was purified by column chrom-
atography (eluent : ethyl acetate–hexane 1 : 1 or 1 : 2) to give
syrupy 2a–d.
6 L. Somsák, Chem. Rev., 2001, 101, 81.
7 (a) K.-P. Zeller and H. Gugel, in Methoden der organischen Chemie
(Houben-Weyl), Vol. E19b, ed. M. Regitz, Thieme, Stuttgart, 1989,
pp. 225–243; (b) K. Maruoka and H. Yamamoto, in Comprehensive
Organic Synthesis, Vol. 6, ed. B. M. Trost and I. Fleming, Pergamon,
Oxford, 1991, pp. 776–779.
8 Z. Györgydeák and I. Pelyvás, Monosaccharide Sugars—Chemical
Synthesis by Chain Elongation, Degradation and Epimerization,
Academic Press, San Diego, 1998, pp. 316–331.
9 This method is a modification of a protocol used for the preparation
of 2,5- and 2,6-anhydroaldoses from glycosyl cyanides in the
presence of 1,2-dianilinoethane: H. P. Albrecht, D. B. Repke and
J. G. Moffatt, J. Org. Chem., 1973, 38, 1836; H.-M. Dettinger,
G. Kurz and J. Lehmann, Carbohydr. Res., 1979, 74, 301.
10 Leading references for 2,5- and 2,6-anhydroaldoximes: S. Kim,
I. Y. Lee, J.-Y. Yoon and D. H. Oh, J. Am. Chem. Soc., 1996, 118,
5138; D.-P. Pham-Huu, M. Petrusová, J. N. BeMiller and L. Petrus,
Synlett, 1998, 1319; D.-P. Pham-Huu, M. Petrusová, J. N. BeMiller
ˇ
ˇ
ˇ
and L. Petrusˇ, J. Carbohydr. Chem., 2000, 19, 93; for nitrones
of 2,5- and 2,6-anhydroaldoses: A. Dondoni, F. Junquera,
F. L. Merchán, P. Merino, M.-C. Scherrmann and T. Tejero, J. Org.
Chem., 1997, 62, 5484; for silyl nitronates of 2,6-anhydroaldoses:
O. R. Martin, F. E. Khamis and S. P. Rao, Tetrahedron Lett., 1989,
30, 6143.
General method for the synthesis of exo-glycals (3)
Sodium hydride (0.24 g, 10 mmol) was added to dry 1,4-
dioxane (25 mL). The suspension was stirred and heated to
reflux, and then a solution of a tosylhydrazone 2 (1 mmol)
in dry 1,4-dioxane (25 mL) was added dropwise. When the
reaction was complete (TLC, eluent: ethyl acetate–hexane 1 : 1),
the mixture was cooled and the insoluble material filtered off.
The solvent was removed under reduced pressure, and the resi-
11 S. Kim, J.-Y. Yoon and C. M. Cho, Chem. Commun., 1996, 909;
S. Kim and J.-Y. Yoon, Synthesis, 2000, 1622.
12 H. Fritz, J. Lehmann and P. Schlesselmann, Carbohydr. Res., 1983,
113, 71.
J. Chem. Soc., Perkin Trans. 1, 2001, 942–943
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