Efficient one-step synthesis of 2-hydroxy and 2-aminoglycals from selenoglycosides

Article abstract of DOI:10.1016/S0040-4039(03)01216-4

2-Hydroxy and 2-aminoglycals are readily synthesised in one step from selenoglycosides by a Sharpless-type oxidation, which is then followed by spontaneous selenoxide elimination.

Full text of DOI:10.1016/S0040-4039(03)01216-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 5221–5223
Efficient one-step synthesis of 2-hydroxy and 2-aminoglycals
from selenoglycosides
David J. Chambers,a Graham R. Evansb and Antony J. Fairbanksa,*
aDyson Perrins Laboratory, Oxford University, South Parks Road, Oxford OX1 3QY, UK
bCelltech R & D, Granta Park, Great Abington, Cambridge CB1 6GS, UK
Received 2 May 2003; accepted 16 May 2003
Abstract—2-Hydroxy and 2-aminoglycals are readily synthesised in one step from selenoglycosides by a Sharpless-type oxidation,
which is then followed by spontaneous selenoxide elimination. © 2003 Elsevier Science Ltd. All rights reserved.
Glycals are extremely useful carbohydrate derivates,
which are not only versatile as glycosyl donors,1 or as
substrates for Ferrier type rearrangements,2,3 but find
extensive application for many other synthetic pur-
poses, particularly as chiral building blocks for the
synthesis of natural products.4 As part of ongoing
studies into the use of tandem Tebbe/Claisen methodol-
ogy for the synthesis of C-glycosides5 we sought easy
access to a wide variety of differentially protected gly-
cals, including 2-hydroxy and 2-amino substituted
materials. However, existing synthetic routes to 2-
hydroxy glycals typically rely on the elimination of
anomeric halides by treatment with base at high tem-
perature, and are not high yielding.
Moreover, mindful that although thioglycosides have
very recently been used for such a reaction sequence,10
an alternative oxidative/elimination sequence via
selenoxides would seem more appealing, since selenox-
ides undergo thermal elimination at considerably lower
temperature than sulfoxides.11 Indeed spontaneous
elimination of selenoxides under the reaction conditions
used for the oxidation step would obviate the need for
isolation of any intermediates and also eliminate the
possibility of over-oxidation, which can be problematic
in the case of sulfoxides.
To this end, suitable oxidation conditions were sought
in order to achieve the desired transformation in a
single step. Selenoglycoside 17 was studied as a model
compound and subjected to a variety of reaction condi-
tions. Unfortunately attempted oxidation by treatment
of 1 with either meta-chloroperbenzoic acid (MCPBA)
or periodate was not successful, and resulted either in
decomposition of the substrate, or in the formation of
multiple products (Scheme 1).
The synthesis of a,b-unsaturated carbonyl derivatives
by the introduction of selenium a- to the carbonyl
group, and subsequent oxidation to produce a selenox-
ide which then undergoes facile elimination, is well
documented.6 Since selenoglycosides, which themselves
find extensive use as glycosyl donors, are accessible in
one step from either the corresponding glycosyl
acetates7 or halides,8 it was considered that selenogly-
cosides would prove to be excellent substrates for the
introduction of 1,2-unsaturation into carbohydrate
derivatives via a similar reaction sequence.9 Thus, it
was envisaged that oxidation of a selenoglycoside
would produce an anomeric selenoxide which could
then undergo spontaneous in situ syn elimination to
yield the corresponding 2-hydroxy glycal (Fig. 1).
However, subjection of 1 to Sharpless-type oxidation
conditions,4,12 namely tert-butyl hydroperoxide and
titanium(IV) tetra-isopropoxide, in the presence of di-
isopropylethylamine as a base,13 resulted in the forma-
tion of the desired 2-hydroxy glycal product 214 in
Keywords: carbohydrates; glycals; selenoglycosides; oxidation; elimi-
nation; selenoxides.
* Corresponding author.
Figure 1.
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01216-4

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D. J. Chambers et al. / Tetrahedron Letters 44 (2003) 5221–5223
ucts indicating a potential limitation in that this
methodology does not currently seem to be compatible
with selenoglycosides that possess a free hydroxyl
group. However, the generality of the approach for use
with other fully protected selenoglycosides is clearly
demonstrated by successful reaction of the phthalamido
protected 2-amino sugars 3e and 3f.
Scheme 1. Reagents and conditions: (i) tBuOOH, EtNiPr2,
Ti(OiPr)4, CH2Cl2, 0°C to rt, quantitative.
In summary, we have developed suitable methodology
for the high yielding synthesis of a variety of protected
2-hydroxy and 2-amino glycals directly from selenogly-
cosides. Such methodology could be considered advan-
tageous to the alternative sulfoxide approach in that
neither isolation of intermediate oxidation products or
elevated temperatures are required, since formation of
the desired glycal occurs spontaneously subsequent to
oxidation. The use of these differentially protected gly-
cals for the synthesis of a variety of C-glycosides,
C-glycosyl amino acids and C- and O-oligosaccharides
is currently under investigation and the results will be
published in due course.
quantitative yield. Clearly under these reaction condi-
tions the intermediate selenoxide, which was not
observed by NMR or TLC, underwent spontaneous
elimination to produce the desired glycal product. To
test the generality of this process a selection of seleno-
glycosides 3a–g were synthesised and subjected to these
reaction conditions (Table 1). In the majority of cases
the desired glycal products 4a–c,e,f15 were produced in
extremely high yield.16 The exception was the attempted
reaction of the alcohol 3d which resulted in product
decomposition and the formation of many minor prod-
Table 1.

D. J. Chambers et al. / Tetrahedron Letters 44 (2003) 5221–5223
5223
Acknowledgements
synthesis of 2-hydroxy and 2-amino glycals that was
published during the course of this work, see: Liu, J.;
Huang, C.-H.; Wong, C.-H. Tetrahedron Lett. 2002, 43,
3447–3448.
We gratefully acknowledge financial support from the
EPSRC (Project Studentship to D.J.C.) and from
Celltech (CASE award to D.J.C). We also acknowledge
the use of the Chemical Database Service (CDS) at
Daresbury, UK.
11. (a) Jones, N.; Mundy, D.; Whitehouse, R. D. J. Chem.
Soc., Chem. Commun. 1970, 86–87; (b) Reich, H. J.;
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J. Org. Chem. 1978, 43, 1697–1705.
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Evans, G. R.; Moya, E.; Dowden, J. J. Org. Chem. 1992,
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13. Required to prevent side reactions caused by selenenic
acids and their disproportionation products.
14. Gent, P. A.; Gigg, R. J. Chem. Soc., Perkin Trans. 1
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