Elimination reactions of glycosyl selenoxides

Article abstract of DOI:10.1016/j.tet.2004.07.005

Glycosyl selenoxides, generated in situ from selenoglycosides by a Sharpless-type oxidation, undergo facile syn elimination leading to 2-hydroxy and 2-amino glycals in high yield. Graphical abstract.

Full text of DOI:10.1016/j.tet.2004.07.005

Tetrahedron 60 (2004) 8411–8419
Elimination reactions of glycosyl selenoxides
David J. Chambers,a Graham R. Evansb and Antony J. Fairbanksa,
*
aChemistry Research Laboratory, Oxford University, Mansfield Road, Oxford OX1 3TA, UK
bCelltech R&D, Granta Park, Great Abington, Cambridge CB1 6GS, UK
Received 17 May 2004; revised 10 June 2004; accepted 1 July 2004
Available online 6 August 2004
Abstract—Glycosyl selenoxides, generated in situ from selenoglycosides by a Sharpless-type oxidation, undergo facile syn elimination
leading to 2-hydroxy and 2-amino glycals in high yield.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
oxides13 such a spontaneous elimination of a glycosyl
selenoxide would advantageously obviate the need for
isolation of any intermediates, and also eliminate the
possibility of over-oxidation, which can be problematic in
the case of glycosyl sulfoxides. Following a previous report
on the use of glycosyl selenoxides as glycosyl donors3 it was
also decided to investigate the potential fate of glycosyl
selenoxides if the 2-hydroxyl or 2-amino group was cis to
the anomeric selenium, since in this case syn elimination
would not be possible (Fig. 1). In this paper we provide full
details14 of the synthetic utility of 1,2-trans glycosyl
selenoxides which smoothly eliminate in situ to allow the
synthesis of 2-substituted glycals in very high yield, and we
also outline some preliminary investigations into the fate of
1,2-cis glycosyl selenoxides.
Glycosyl sulfoxides are extremely useful glycosyl donors,
and have found wide application in oligosaccharide
synthesis.1 The thermal elimination of glycosyl sulfoxides
has also recently been applied to the synthesis of 2-
substituted glycals.2 However, the chemistry of glycosyl
selenoxides has not yet been the focus of extensive
investigation.3 As part of ongoing studies into expanding
the synthetic utility of glycals4–6 as starting materials for the
synthesis of a variety of C-glycosides7 we sought easy
access to a wide range of 2-hydroxy and 2-amino substituted
materials. Since existing synthetic routes to 2-hydroxy
glycals are not particularly high yielding, attention turned to
the possible use of the presumably facile elimination8 of
glycosyl selenoxides as a means of accessing these
materials. Indeed the elimination of selenoxides had already
been applied, both for the introduction of unsaturation into
carbohydrates at positions other than at the anomeric
centre,9 and also for the synthesis of 2-deoxy furanoid
materials.10
2. Results and discussion
2.1. Synthesis of selenoglycosides
A variety of selenoglycoside substrates possessing various
protecting group patterns were synthesized in order to test
the general applicability of the proposed methodology. The
known selenoglycosides 1a,11 2a,11 3a,15 4a,15 5a,11 7a,11
9a,11 and 11a11 were all accessed following previously
published literature procedures. New selenoglycoside sub-
strates were synthesized as follows (Scheme 1). Diacetonide
6a was accessed directly from the known manno selenogly-
coside tetraacetate 916 by deacetylation with catalytic
methoxide and immediate reprotection by treatment with
dimethoxypropane and catalytic camphor sulphonic acid
(74% yield). A variety of 2-amino selenoglycoside sub-
strates were also synthesized. Thus, the phthalimido
protected glucosamine selenoglycoside 8a was synthesized
from the known alcohol 1411 by treatment with acetic
anhydride and pyridine (98% yield). In order to investigate
Glycosyl selenoxides should be available by oxidation of
selenoglycosides, which have themselves found extensive
use as glycosyl donors and are readily accessible in one-step
from either the corresponding glycosyl acetates11 or
halides.12 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 in
a single step (Fig. 1). Since selenoxides undergo thermal
elimination at considerably lower temperatures than sulf-
Keywords: Carbohydrates; Glycals; Selenoglycosides; Oxidation; Elimin-
ation; Selenoxides.
* Corresponding author. Tel.: C44-1865-275647; fax: C44-1865-
275674.; e-mail: antony.fairbanks@chem.ox.ac.uk
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.07.005

8412
D. J. Chambers et al. / Tetrahedron 60 (2004) 8411–8419
Figure 1.
whether free hydroxyl groups could be tolerated, the alcohol
10a, possessing a free 3-hydroxyl, was accessed by selective
benzylation of the known diol 1511 by treatment with benzyl
bromide under phase transfer conditions (66% yield). To
investigate the effect of variation of nitrogen protecting
group the N-acetylglucosamine derivative 12a was accessed
from the chloride 1617 by treatment with diphenyl
diselenide and sodium borohydride (62% yield). Finally,
in order to investigate potential reactivity of a 1,2-cis
selenoglycoside, the a-selenoglucoside 13a was synthesized
in two steps from tribenzyl glucal 17 as follows. Reaction
with dimethyldioxirane in acetone yielded the a-epoxy
glycal which was then reacted directly with selenophenol in
THF to yield the a-gluco selenoglycoside 1818 (87% yield).
Treatment of alcohol 18 with benzyl bromide and sodium
hydride in DMF then produced the fully benzylated
selenoglycoside 13a (95% yield).
2.2. Oxidation and elimination reactions
Suitable reaction conditions were sought in order to achieve
the desired oxidation and elimination reactions in a single
step. Selenoglycoside 1a was studied as a model compound
and subjected to a variety of reaction conditions. Attempted
oxidation of 1a with either metachloroperbenzoic acid
(MCPBA) or periodate was not successful, and resulted
either in decomposition of the substrate, or in the formation
of multiple products. However, subjecting 1a to Sharpless-
Scheme 1. (i) Na, MeOH; (ii) dimethoxypropane, camphor sulphonic acid, DMF, 60 8C, 240 mbar, 74% over two steps; (iii) Ac2O, pyridine, 98%; (iv) BnBr,
NaOH (aq), CH2Cl2, Bu4NHSO4, 66%; (v) PhSeSePh, NaBH4, EtOH, 62%; (vi) dimethyldioxirane in acetone, CH2Cl2, 0 8C; (vii) PhSeH, THF, 87% over two
steps; (viii) BnBr, NaH, DMF, 95%.

D. J. Chambers et al. / Tetrahedron 60 (2004) 8411–8419
Table 1. Oxidation/elimination of 1,2-trans selenoglycosides
8413
Substrate
Glycal
Yield (%)
(a)
(b)
Quant.
1a
2a
1b
2b
99
(c)
90
3a
4a
5a
3b
4b
5b
(d)
(e)
95
91
(f)
86
6a
7a
8a
9a
6b
7b
8b
2b
(g)
(h)
(i)
Quant.
96
93
type oxidation conditions,10,19 namely tert-butyl hydro-
peroxide and titanium tetra-isopropoxide, in the presence of
di-isopropylethylamine as a base,20 resulted in the for-
mation of the desired 2-hydroxy glycal product 1b21 in
quantitative yield. No intermediate selenoxide was observed
either by NMR or thin layer chromatography (TLC), and the
only isolated product was the desired glycal 1b (Table 1).
possessing acetate, benzyl, benzylidene, allyl and acetonide
protection of hydroxyl groups. The reaction was also
compatible with phthalimido protection of 2-amino seleno-
glycosides as demonstrated by the successful reaction of 7a
and 8a.
Investigation then turned to the use of substrates that
possessed free hydroxyl groups. Reaction of the alcohol
10a, in which the 3-hydroxyl is free, under the optimized
oxidation conditions outlined above, resulted in decompo-
sition and the formation of multiple products by TLC. Since
the desired glycal product of this reaction 10b is an allylic
alcohol, which itself may be oxidized under the reaction
conditions, the oxidation of selenoglycoside 11a, in which
To test the generality of this process the fully protected
selenoglycosides 2a–9a were all subjected to these reaction
conditions (Table 1). In all cases the desired glycal products
2b–8b were produced in extremely high yield. The reaction
worked equally well for the a-manno selenoglycosides 6a
and 9a, and was compatible with fully protected substrates

8414
D. J. Chambers et al. / Tetrahedron 60 (2004) 8411–8419
Scheme 4. (i) Ti(OiPr)4, ButOOH, iPr2EtN, CH2Cl2, 0 8C, 64%; (ii)
Ti(OiPr)4, ButOOH, iPr2EtN, MeOH (10 equiv), CH2Cl2, 0 8C, 35%.
of the elimination step decompose under the reaction
conditions. The synthesis of 10b outlined in Scheme 2
indicates that glycal products with free hydroxyl groups can
be synthesized from selenoglycosides simply by the use of
acetate protection/deprotection steps.
The only previous report in the literature on the chemistry of
glycosyl selenoxides indicated that a glycosyl selenoxide
had acted as an efficient glycosyl donor at low temperature.3
In order to investigate the relative rates of the possible
nucleophilic substitution versus elimination reactions the
selenoglycoside 2a was subjected to oxidation under the
standard conditions at 0 8C in the presence of 10 equiv of
methanol. Under these reaction conditions no methyl
glycoside was obtained, the only product being the expected
glycal 2b, which was isolated in quantitative yield.
(Scheme 3), indicating that at least at 0 8C elimination of
a 1,2-trans glycosyl selenoxide competes effectively over
any intermolecular nucleophilic substitution. However, the
possibility of the anomeric selenoxide acting as a leaving
group was confirmed by reaction of the N-acetyl protected
selenoglycoside 12a, which revealed competitive intramo-
lecular substitution. In this case an inseparable mixture of
the 2-amino glycal 12b and the oxazoline 20 were isolated
in 96% yield (ratio 2.2:1) (Scheme 3). This reaction also
indicates that the efficient synthesis of 2-amino glycals by
this route requires phthalimido or similar double protection
of nitrogen.
Scheme 2. (i) Ti(OiPr)4, ButOOH, iPr2EtN, CH2Cl2, 0 8C; (ii) Ac2O,
pyridine, 96%; (iii) Ti(OiPr)4, ButOOH, iPr2EtN, CH2Cl2, 0 8C, quantitat-
ive; (iv) NaOMe, MeOH, 99%.
the 4-hydroxyl was not protected, was also investigated.
Unfortunately again this reaction resulted in decomposition
and the formation of multiple products. To further
investigate why decomposition was being observed, diace-
tone galactose was subjected to the oxidation conditions as a
model alcohol. Unsurprisingly no reaction of the free
hydroxyl was observed and the starting material recovered.
In order to investigate if the reaction product was actually
stable to the reaction conditions the glycal 10b was
synthesized in three steps from 10a by acetylation to yield
acetate 19a (96% yield) which then smoothly underwent
oxidation/elimination to yield glycal 19b (quantitative) and
then finally deacetylation to yield 10b (99% yield,
Scheme 2). Subjection of hydroxy glycal 10b to the
oxidation/elimination reaction conditions immediately
resulted in decomposition. It can therefore be concluded
that this selenoglycoside oxidation/elimination pathway can
only be applied to fully protected substrates as the products
Finally the potential fate of a 1,2-cis glycosyl selenoxide
was investigated by oxidation of the a-selenoglucoside 13a.
Reaction under the standard conditions resulted in con-
sumption of starting material and the formation of two more
polar products as visualized by TLC.22 However, attempted
isolation of these products resulted in decomposition and the
only material that could be isolated from the reaction
mixture was the lactol 21 (Scheme 4). Moreover attempted
in situ glycosylation by performing the reaction in the
presence of 10 equiv of methanol also produced only lactol
21, no methyl glycoside being observed. This result
indicates that at least under these Sharpless-type oxidation
conditions that glycosyl selenoxides have little potential to
act as efficient and synthetically useful glycosyl donors.23
3. Summary and conclusion
Oxidation/elimination of 1,2-trans selenoglycosides using
Sharpless type reaction conditions allows the high yielding
synthesis of a wide variety of protected 2-hydroxy and 2-
amino glycals. This methodology is advantageous to the
alternative sulfoxide approach in that, neither isolation of
intermediate oxidation products nor elevated temperatures
are required, since formation of the desired glycal occurs
Scheme 3. (i) Ti(OiPr)4, ButOOH, iPr2EtN, MeOH (10 equiv), CH2Cl2,
0 8C, quant.; (ii) Ti(OiPr)4, ButOOH, iPr2EtN, CH2Cl2, 0 8C, 96%, ratio
12b:20, 2.2:1.

D. J. Chambers et al. / Tetrahedron 60 (2004) 8411–8419
8415
spontaneously subsequent to oxidation. However, this
4.3. 2,3,4,6-Tetra-O-benzyl-D-glucal 1b
methodology is not applicable to selenoglycoside substrates
possessing free hydroxyl groups. Moreover competitive
intramolecular substitution of acetyl protected 2-amino
glycosyl selenoxides results in substantial oxazoline
formation, indicating double protection of 2-amino sub-
stituents is required for efficient reaction. However,
intermolecular nucleophilic substitution under these con-
ditions is not an efficient process, even for 1,2-cis
selenoglycoside substrates, which cannot undergo 1,2-syn
elimination. In this latter case only lactol products were
observed.
Selenoglucoside 1a (184.0 mg, 0.27 mmol, Rf 0.55 (petrol/
ethyl acetate, 4:1)) was subjected to the general oxidation
conditions to afford glucal 1b (143.5 mg, quant., Rf 0.5) as a
white crystalline solid, mp 65–66 8C (methanol) [lit. 68.5–
69 8C];21 [a]2D1 K7.5 (c, 1.0 in CHCl3) [lit. [a]DK6.2];21 dH
0
(400 MHz, CDCl3) 3.71 (1H, dd, J5,6Z3.6 Hz, J6.6
Z
0
0
10.8 Hz, H-6), 3.80 (1H, dd, J5,6 Z5.8 Hz, J6,6 Z10.8 Hz,
H-60), 3.92 (1H, dd, J3,4Z4.9 Hz, J4,5Z6.5 Hz, H-4), 4.09–
4.13 (1H, m, H-5), 4.28 (1H, d, H-3), 4.50–4.78 (8H, m, 4!
PhCH2), 6.33 (1H, s, H-1), 7.25–7.39 (20H, m, 20!Ar-H).
4.4. 2,3,4,6-Tetra-O-acetyl-D-glucal 2b
4. Experimental
Selenoglucoside 2a (1.45 g, 2.98 mmol, Rf 0.3 (petrol/ethyl
acetate, 2:1)) was subjected to the general oxidation
conditions to afford glucal 2b (0.966 g, 98%, Rf 0.25) as a
white crystalline solid, mp 62–63 8C (ether/petrol) [lit. 61–
62 8C (ether/petrol)];24 [a]D22 K25 (c, 1.2 in CHCl3) [lit.
[a]2D2 K33 (c, 1.24 in CHCl3)];24 dH (400 MHz, CDCl3)
4.1. General methods
Melting points were recorded on a Kofler hot block and are
uncorrected. Proton nuclear magnetic resonance (dH)
spectra were recorded on a Bruker AV 400 (400 MHz)
spectrometer. Carbon nuclear magnetic resonance (dC)
spectra were recorded on a Bruker AV 400 (100.6 MHz)
spectrometer. Multiplicities were assigned using DEPT
sequence. All chemical shifts are quoted on the d-scale in
parts per million (ppm). Infrared spectra were recorded on a
Perkin–Elmer 150 Fourier Transform spectrophotometer.
Low-resolution mass spectra were recorded on a Micromass
Platform 1 using electrospray ionisation (ES), or on a Fisons
AutoSpec-oaTof using chemical ionisation (CI). High-
resolution mass spectra (electrospray) were performed on
a Waters 2790-Micromass LCT electrospray ionisation
mass spectrometer (ES), or (chemical ionisation) on a
Fisons AutoSpec-oaTof (CI). Optical rotations were
measured on a Perkin–Elmer 241 polarimeter with a path
length of 1 dm. Concentrations are given in g/100 ml.
Microanalyses were performed by the microanalytical
services of the Inorganic Chemistry Department, Oxford
University. TLC was carried out on Merck Kieselgel 0.22–
0.25 mm thickness glass-backed sheets, pre-coated with
60F254 silica. Plates were developed using 5% w/v
ammonium molybdate in 2 M sulfuric acid. Flash column
chromatography was carried out using Sorbsil C60 40/60
silica. Dichloromethane was distilled from calcium hydride.
Petrol refers to the fraction of light petroleum ether boiling
in the range 40–60 8C. All procedures were performed under
an atmosphere of argon.
2.06, 2.10, 2.10 (12H, 3!s, 4!CH3), 4.22 (1H, dd, J5,6
Z
0
0
3.2 Hz, J6,6 Z11.8 Hz, H-6), 4.35–4.45 (2H, m, H-5, H-6 ),
5.23 (1H, dd, J4,5Z5.5 Hz, J3,4Z4.5 Hz, H-4), 5.56 (1H, d,
J3,4Z4.5 Hz, H-3), 6.63 (1H, s, H-1).
Selenomannoside 9a (200.7 mg, 0.41 mmol, Rf 0.35 (petrol/
ethyl acetate, 2:1)) was subjected to the general oxidation
conditions to afford glucal 2b (126.2 mg, 93%, Rf 0.3)
identical to the material described above.
4.5. 2,4,6-Tri-O-acetyl-3-O-allyl-D-glucal 3b
Selenoglucoside 3a (132 mg, 0.27 mmol, Rf 0.25 (petrol/
ethyl acetate, 2:1)) was subjected to the general oxidation
conditions to afford glucal 3b (80.1 mg, 90%, Rf 0.3) as a
colourless oil; [a]D23 K23 (c, 1.0 in CHCl3); nmax (thin film)
1743 (s, C]O) cmK1; dH (400 MHz, CDCl3) 2.10, 2.12,
2.16 (9H, 3!s, 3!CH3), 4.09–4.13 (3H, m, H-3, OCH2-
0
CH]CH2), 4.22 (1H, dd, J5,6Z3.4 Hz, J6,6 Z12.0 Hz, H-
0
6), 4.35–4.38 (1H,0 m, H-5), 4.45 (1H, dd, J5,6 Z7.8 Hz,
0
J6,6 Z12.0 Hz, H-6 ), 5.17–5.20 (2H, m, H-4, C]CHEHZ),
5.28 (1H, daq, 3JZ17.3 Hz, JZ1.7 Hz, C]CHEHZ), 5.80–
5.88 (1H, m, CH]CH2), 6.60 (1H, s, H-1); dC (100.7 MHz,
CDCl3) 20.7, 20.8, 20.9 (3!q, 3!CH3), 61.3 (t, C-6), 67.4
(d, C-4), 70.2 (t, OCH2CH]CH2), 70.6 (d, C-3), 74.0 (d, C-
5), 117.6 (t, C]CH2), 129.3 (s, C-2), 134.0 (d, C]CH2),
137.4 (d, C-1), 169.6, 169.9, 170.6 (3!s, 3!C]O); m/z
(ESC) 351 (MCNaC, 100), 346 (MCNH4C, 15%).
(HRMS (ESC) calcd for C15H20O8Na (MCNaC)
351.1056. Found, 351.1055). (Found: C, 54.77; H, 6.30.
C15H20O8 requires C, 54.87; H, 6.14%.)
4.2. General experimental procedure for
oxidation/elimination of selenoglycosides
The selenoglycoside (1 equiv) and N,N-diisopropylethyla-
mine (1.7 equiv) were dissolved in anhydrous dichloro-
methane and the solution cooled to 0 8C. tert-Butyl
hydroperoxide (5.5 M solution in decane, 2.3 equiv) was
added drop-wise over a period of 5 min, and then titanium
(IV) isopropoxide (1.0 equiv) was added. The reaction
mixture was stirred under an atmosphere of argon for 2 h,
after which time TLC indicated complete conversion of
starting material to the product. The yellow solution was
concentrated in vacuo, and purified by flash column
chromatography.
4.6. 3-O-Acetyl-2,4,6-tri-O-benzyl-D-glucal 4b
Selenoglucoside 4a (9.69 g, 15.3 mmol, Rf 0.3 (petrol/ethyl
acetate, 4:1)) was subjected to the general oxidation
conditions to afford glucal 4b (6.92 g, 95%, Rf 0.3) as a
colourless oil; [a]D24 C22 (c, 1.0 in CHCl3); nmax (thin film)
1741 (s, C]O) cmK1; dH (400 MHz, CDCl3) 2.01 (3H, s,
0
CH3), 3.69 (1H, dd, J5,6Z4.3 Hz, J6,6 Z10.06 Hz, H-6), 3.78
0
0
(1H, dd, J5,6 Z5.4 Hz, J6,6 Z10.6 Hz, H-6 ), 3.97 (1H, dd,
J3,4Z4.9 Hz, J4,5Z6.6 Hz, H-4), 4.11–4.16 (1H, m, H-5),

8416
D. J. Chambers et al. / Tetrahedron 60 (2004) 8411–8419
4.56, 4.59 (2H, ABq, JZ11.8 Hz, PhCH2), 4.65, 4.77 (2H,
ABq, JZ11.4 Hz, PhCH2), 4.68, 4.72 (2H, 2!s, PhCH2),
5.49 (1H, d, J3,4Z4.9 Hz, H-3), 6.37 (1H, s, H-1), 7.28–7.39
(15H, m, 15!Ar-H); dC (100.7 MHz, CDCl3) 21.1 (q,
CH3), 67.6 (t, C-6), 68.6 (d, C-3), 71.5, 72.7, 73.5 (3!t, 3!
PhCH2), 73.5 (d, C-4), 76.1 (d, C-5), 127.4, 127.7, 127.8,
127.9, 128.0, 128.4 (6!d, 15!Ar-C), 130.2 (d, C-1),
135.4, 136.9, 137.7, 137.8 (4!s, 3!Ar-C, C-2), 170.6 (s,
C]O); m/z (ESC) 497 (MCNaC, 100), 492 (MCNHC4 ,
35%). (HRMS (ESC) calcd for C29H30O6Na (MCNaC)
497.1940. Found, 497.1931.)
m/z (CIC) 401 (12%, MCHC). (HRMS (CIC) calcd for
C18H25O850Se (MCHC) 401.0867. Found, 401.0864).
(Found: C, 54.16; H, 5.99. C18H24O5Se requires C, 54.14;
H, 6.06%.)
4.9. 2,3:4,6-O-Di-iso-propylidene-D-glucal 6b
Selenomannoside 6a (118.0 mg, 0.30 mmol, Rf 0.60 (petrol/
ethyl acetate, 4:1)) was subjected to the general oxidation
conditions to afford glucal 6b (61.8 mg, 86%, Rf 0.65) as a
pale yellow oil; [a]D25 C44 (c, 1.1 in CHCl3); nmax (thin film)
no significant peaks; dH (400 MHz, CDCl3) 1.46, 1.47, 1.49,
1.56 (12H, 4!s, 4!CH3), 3.60 (1H, dat, JZ5.6, 10.4,
4.7. 2,3-Di-O-benzyl-4,6-O-benzylidene-D-glucal 5b
10.4 Hz, H-5), 3.83–3.93 (2H, m, H-4, H-6), 4.01 (1H, dd,
0
0
0
J5,6 Z5.6 Hz, J6,6 Z11.1 Hz, H-6 ), 4.60 (1H, dd, J1,3
Z
Selenoglucoside 5a (106.8 mg, 0.18 mmol, Rf 0.4 (petrol/
ethyl acetate, 4:1)) was subjected to the general oxidation
conditions to afford glucal 5b (71.2 mg, 91%, Rf 0.4) as a
white crystalline solid, mp 121–123 8C (methanol); [a]D21
K30 (c, 1.1 in CHCl3) [lit. [a]D C9.3 (c, 1.5 in CHCl3)];25
dH (400 MHz, CDCl3) 3.79–3.85 (1H, m, H-5), 3.85–3.91
1.8 Hz, J3,4Z7.6 Hz, H-3), 6.22 (1H, d, J1,3Z1.8 Hz, H-1);
dC (100.7 MHz, CDCl3) 19.0, 25.3, 26.7, 28.9 (4!q, 4!
CH3), 62.0 (t, C-6), 67.3 (d, C-5), 71.1 (d, C-4), 73.6
(d, C-3), 99.6, 113.2, 134.1 (C-2, 2!(CH3)2C), 122.2
(d, C-1); m/z (CIC) 243 (MCHC, 100%). (HRMS (CIC)
calcd for C12H19O5 (MCHC) 243.1232. Found, 243.1235.)
(1H, m, H-6), 4.15 (1H, dd, J3,4Z7.3 Hz, J4,5Z9.9 Hz,
0
0
0
H-4), 4.42 (1H, dd, J5,6 Z4.4 Hz, J6,6 Z9.8 Hz, H-6 ), 4.56
(1H, d, J3,4Z7.3 Hz, H-3), 4.77, 4.80 (2H, ABq, JZ
11.5 Hz, PhCH2), 4.92, 4.96 (2H, ABq, JZ12.0 Hz,
PhCH2), 5.65 (1H, s, PhCHO2), 6.36 (1H, s, H-1), 7.31–7
58 (15H, m, 15!Ar-H).
4.10. 3,4,6-Tri-O-acetyl-2-phthalimido-D-glucal 7b
Selenoglucoside 7a (150 mg, 0.26 mmol, Rf 0.2 (petrol/
ethyl acetate, 1:1)) was subjected to the general oxidation
conditions to afford glucal 7b (120 mg, quant., Rf 0.15) as a
colourless oil; [a]D25 K26 (c, 1.1 in CHCl3) [lit. [a]D25 K15
(c, 0.2 in CHCl3)];26 dH (400 MHz, CDCl3) 1.92, 2.11, 2.14
0
4.8. Phenyl 2,3:4,6-O-di-iso-propylidene-1-seleno-a-D-
mannopyranoside 6a
(9H, 3!s, 3!CH3), 4.37 (1H, dd, J5,6Z3.5 Hz, J6,6
Z
Tetraacetate 916 (405.5 mg, 0.83 mmol) was dissolved in
methanol (15 ml), and sodium methoxide (4.5 mg,
0.083 mmol) was added. The reaction mixture was stirred
under an atmosphere of argon for 1 h, when TLC (ethyl
acetate) indicated complete consumption of starting
material (Rf 0.7) and formation of a single product (Rf
0.3). The mixture was concentrated in vacuo, and co-
evaporated with toluene (2!30 ml). The residue was taken
up in anhydrous DMF (10 ml). 2,2-Dimethoxypropane
(0.41 ml, 3.33 mmol) and camphor sulphonic acid (39 mg,
0.17 mmol) were added, and the reaction mixture was
stirred at 60 8C at reduced pressure (240 mbar) for 4 h. After
this time, TLC (petrol/ethyl acetate, 2:1) indicated con-
sumption of starting material (Rf 0) and formation of a major
product (Rf 0.7). The mixture was concentrated in vacuo,
and the residue taken up in ether (100 ml). The solution was
washed with water (2!75 ml) and brine (2!75 ml of a
saturated solution). The aqueous layers were extracted with
ether (75 ml) and the combined organic phases were dried
(MgSO4), filtered, and concentrated in vacuo. The residue
was purified by flash column chromatography (petrol/ethyl
acetate, 6:1) to give diacetonide 6a (246.0 mg, 74%) as a
white crystalline solid, mp 109–110 8C (ether/petrol); [a]D25
C188 (c, 1.0 in CHCl3); nmax (KBr disc) no significant
peaks; dH (400 MHz, CDCl3) 1.36, 1.46, 1.52, 1.56 (12H,
4!s, 4!CH3), 3.73–3.79 (2H, m, H-6, H-60), 3.86 (1H, dd,
J3,4Z8.0 Hz, J4,5Z10.2 Hz, H-4), 3.92–3.98 (1H, m, H-5),
4.22 (1H, dd, J2,3Z5.4 Hz, J3,4Z8.0 Hz, H-3), 4.47 (1H, d,
J2,3Z5.4 Hz, H-2), 6.07 (1H, s, H-1), 7.27–7.59 (5H, m, 5!
Ar-H); dC (100.7 MHz, CDCl3) 18.8, 26.4, 28.3, 29.0 (4!q,
4!CH3), 61.6 (t, C-6), 64.2 (d, C-5), 72.9 (d, C-4), 74.6 (d,
C-3), 77.2 (d, C-2), 81.1 (d, C-1), 99.8, 109.8 (2!s, 2!
O2C), 128.1, 129.2, 134.5 (3!d, 5!Ar-C), 128.4 (s, Ar-C);
0
0
11.8 Hz, H-6), 4.50 (1H, dd, J5,6 Z6.7 Hz, J6,6 Z11.8 Hz,
H-60), 4.53–4.57 (1H, m, H-5), 5.31 (1H, at, JZ4.4 Hz,
H-4), 5.59 (1H, d, J3,4Z4.0 Hz, H-3), 6.76 (1H, s, H-1),
7.71–7.88 (4H, m, 4!Ar-H).
4.11. Phenyl 3-O-acetyl-4,6-O-benzylidene-2-deoxy-2-
phthalimido-1-seleno-b-D-glucopyranoside 8a
Alcohol 14 (506 mg, 0.94 mmol) was dissolved in a mixture
of acetic anhydride (4 ml) and pyridine (4 ml) and stirred
under an atmosphere of argon. After 16 h, TLC (petrol/ethyl
acetate, 2:1) indicated the consumption of starting material
(Rf 0.3) and formation of a single product (Rf 0.4). The
reaction mixture was poured into water, and extracted with
DCM (6!25 ml). The combined organic layers were
washed with hydrochloric acid (2!75 ml of a 1 M solution)
and sodium bicarbonate (2!75 ml of a saturated solution),
dried (MgSO4), filtered and concentrated in vacuo. The
residue was purified by flash column chromatography
(petrol/ethyl acetate, 3:1) to give acetate 8a (535 mg,
98%) as a white crystalline solid, mp 100–102 8C (ethyl
acetate/petrol); [a]2D5 C1.9 (c, 1.1 in CHCl3); nmax (KBr
disc) 1743, 1710 (s, 2!C]O); dH (400 MHz, CDCl3) 1.87
(3H, s, CH3), 3.72–3.85 (3H, m, H-4, H-5, H-6), 4.39–4.46
(2H, m, H-2, H-60), 5.54 (1H, s, PhCHO2), 5.89 (1H, at, JZ
9.4 Hz, H-3), 6.00 (1H, d, J1,2Z10.9 Hz, H-1), 7.21–7.86
(14H, m, 14!Ar-H); dC (100.7 MHz, CDCl3) 20.6 (q,
CH3), 55.4 (d, C-2), 68.6 (t, C-6), 70.5 (d, C-3), 71.6
(d, C-4), 79.0, 79.4 (2!d, C-1, C-5), 101.6 (d, PhCHO2),
126.3, 128.3, 135.2, 136.8 (4!s, 4!Ar-C), 127.9, 128.2,
128.2, 128.5, 129.1, 129.2, 134.2, 135.2 (8!d, 14!Ar-C);
m/z (ESC) 602 (100, MCNaC), 597 (85, MCNH4C), 580
(25%, MCHC). (HRMS (ESC) calcd for C29H29O7N820Se

D. J. Chambers et al. / Tetrahedron 60 (2004) 8411–8419
8417
(MCNHC4 ) 597.1140. Found, 597.1136). (Found: C, 59.99;
4.14. 2-O-Benzyl-4,6-O-benzylidene-D-glucal 10b
H, 4.56; N, 2.32. C29H25O7NSe requires C, 60.21; H, 4.36;
N, 2.42%.)
Acetate 19b (1.12 g, 2.93 mmol) was dissolved in methanol
(50 ml). Sodium methoxide (16 mg, 0.293 mmol) was
added, and the mixture stirred under an atmosphere of
argon for 1 h. After this time, TLC (petrol/ethyl acetate, 4:1)
indicated formation of a single product (Rf 0.3) with no
remaining starting material (Rf 0.4). The reaction mixture
was concentrated in vacuo. The residue was taken up in
DCM (100 ml) washed with water (2!75 ml), dried
(MgSO4), filtered, and concentrated in vacuo. The residue
was purified by flash column chromatography (petrol/ethyl
acetate, 4:1) to afford alcohol 10b (986 mg, 99%) as a white
crystalline solid, mp 133–134 8C (ethyl acetate/petrol);
[a]2D2 C1.5 (c, 1.1 in CHCl3); nmax (KBr disc) 3498 (br, OH)
cmK1; dH (400 MHz, CDCl3) 3.77–3.86 (2H, m, H-5, H-6),
3.95 (1H, dd, J3,4Z7.4 Hz, J4,5Z9.9 Hz, H-4), 4.37–4.40
(1H, m, H-60), 4.62 (1H, d, J3,4Z7.4 Hz, H-3), 4.69, 4.77
(2H, ABq, JZ11.2 Hz, CH2Ph), 5.60 (1H, s, PhCHO2), 6.25
(1H, s, H-1), 7.35–7.54 (10H, m, 10!Ar-H); dC
(100.7 MHz, CDCl3) 67.8, 68.3 (2!d, C-3, C-5), 68.3 (t,
C-6), 71.3 (t, CH2Ph), 80.0 (d, C-4), 101.5 (d, PhCHO2),
126.3 (d, C-1), 127.7, 127.9, 128.3, 128.6, 129.2 (5!d,
10!Ar-C), 136.3, 126.9, 129.1 (3!s, 2!Ar-C, C-2); m/z
4.12. 3-O-Acetyl-4,6-O-benzylidene-2-deoxy-2-
phthalimido-D-glucal 8b
Selenoglucoside 8a (154 mg, 0.27 mmol, Rf 0.3 (petrol/
ethyl acetate, 2:1)) was subjected to the general oxidation
conditions to afford glucal 8b (107.2 mg, 96%, Rf 0.2) as a
white crystalline solid, mp 199–202 8C (ethyl acetate/
petrol); [a]D25 C8.6 (c, 1.1 in CHCl3); nmax (KBr disc)
1745, 1923 (s, C]O), 1664 (w, C]C) cmK1; dH
(400 MHz, CDCl3) 1.88 (3H, s, CH3), 3.94 (1H, at, JZ
10.1 Hz, H-6), 4.24–4.34 (2H, m,0H-4, H-5), 4.49 (1H, dd,
0
0
J5,6 Z4.8 Hz, J6,6 Z10.5 Hz, H-6 ), 5.60 (1H, s, PhCHO2),
5.97 (1H, d, J3,4Z6.6 Hz, H-3), 6.72 (1H, s, H-1), 7.27–7.50
(5H, m, 5!benzylidene Ar-H), 7.74–7.92 (4H, m, 4!
phthalimide A-H); dC (100.7 MHz, CDCl3) 20.6 (q, CH3),
68.0 (t, C-6), 68.3 (d, C-3), 69.7, 77.4 (2!d, C-4, C-5),
101.7 (d, PhCHO2), 107.2 (s, C-2), 123.7, 126.2, 128.3,
129.3, 134.4 (5!d, 9!Ar-C), 131.6, 136.6 (2!s, 3!Ar-
C), 167.7, 170.5 (2!s, 2!C]O), 149.1 (d, C-1); m/z
(ESC) 444 (MCNaC, 100), 439 (MCNH4C, 90%).
(HRMS (ESC) calcd for C23H23N2O7 (MCNHC4 )
439.1505. Found, 439.1518). (Found: C, 65.50; H, 4.51;
N, 3.31. C23H19NO7 requires: C, 65.56; H, 4.54; N, 3.32%.)
(ESC) 703 (2MCNaC, 100), 358 (MCNH4C, 20%);
(HRMS (ESC) calcd for C20H24O5N (MCNH4
)
C
358.1654. Found, 358.1663). (Found: C, 70.60; H, 5.95.
C20H20O5 requires C, 70.58; H, 5.92%.)
4.13. Phenyl 2-O-benzyl-4,6-O-benzylidene-1-seleno-b-
D-glucopyranoside 10a
4.15. Phenyl 3,4,6-tri-O-acetyl-2-N-acetylamino-2-
deoxy-1-seleno-b-D-glucopyranose 12a
Diol 15 (8.66 g, 21.3 mmol) was dissolved in a mixture of
DCM (150 ml) and sodium hydroxide (40 ml of a 5%
aqueous solution). Benzyl bromide (2.5 ml, 21 mmol) and
tetra-N-butylammonium hydrogen sulphate (1.44 g,
4.3 mmol) were added to the mixture, and the mixture
stirred at 40 8C for 8 h. After this time, TLC (petrol/ethyl
acetate, 4:1) indicated the consumption of starting material
(Rf 0) and the formation of a major product (Rf 0.2) and a
minor product (Rf 0.4). The reaction mixture was diluted
with DCM (150 ml), and washed with water (2!250 ml).
The organic layers were dried (MgSO4), filtered, and
concentrated in vacuo. The residue was purified by flash
column chromatography (petrol/ethyl acetate, 9:1/4:1) to
afford the undesired dibenzylated compound (Rf 0.4, 1.24 g,
10%) as a white crystalline solid, and the desired alcohol
10a (Rf 0.2), which was then further purified by recrystal-
lisation (ethyl acetate/petrol) to yield a white crystalline
solid (6.93 g, 66%), mp 120–122 8C; [a]2D1 K41 (c, 1.04 in
CHCl3); nmax (KBr disc) 3467 (br, OH) cmK1; dH
(400 MHz, CDCl3) 2.57 (1H, br s, OH), 3.42–3.68 (3H,
m, H-2, H-4, H-5), 3.77 (1H, at, JZ10.3 Hz, H-6), 3.91 (1H,
To a solution of diphenyldiselenide (2.35 g, 7.5 mmol) in
ethanol (75 ml) was added sodium borohydride (780 mg,
21 mmol) under an atmosphere of argon. Chloride 1617
(5.00 g, 13.7 mmol) was dissolved in chloroform (25 ml),
and the solution transferred to the reaction mixture via
cannula. The mixture was stirred for 2 h, when TLC (ethyl
acetate/petrol, 3:1) indicated complete consumption of
starting material (Rf 0.5) and formation of a major product
(Rf 0.3). The reaction mixture was diluted with DCM
(300 ml), and washed with sodium hydroxide (300 ml of a
1 M solution) and brine (300 ml). The solution was dried
(MgSO4), filtered, and concentrated in vacuo. The residue
was purified by flash column chromatography (petrol/ethyl
acetate, 1:2) to give acetate 12a (4.11 g, 62%) as a white
crystalline solid, mp 193–196 8C (ethyl acetate/petrol);
[a]2D5 K29 (c, 1.0 in CHCl3); nmax (KBr disc) 3298 (s, NH),
1758 (s, C]O), 1660 (s, C]O); dH (400 MHz, CDCl3)
1.98, 2.02, 2.03, 2.08 (12H, 4!s, 4!CH3), 3.65–3.69 (1H,
m, H-5), 4.10–4.16 (1H, m, H-2), 4.15–4.23 (2H, m, H-6,
H-60), 5.00 (1H, d, J1,2Z10.5 Hz, H-1), 5.05–5.17 (2H, m,
H-3, H-4), 5.56 (1H, d, JNH,2Z9.2 Hz, NH), 7.27–7.64 (5H,
m, 5!Ar-H); dH (100.7 MHz, CDCl3) 20.6, 20.6, 20.7 (3!
q, 3!C(O)CH3), 23.3 (q, NHCH3), 54.0 (d, C-2), 62.4 (t,
C-6), 68.3 (d, C-4), 73.6 (d, C-3), 76.9 (d, C-5), 82.7 (d,
C-1), 128.3, 129.0 (2!d, 5!Ar-C), 127.9 (s, Ar-C), 169.3,
170.0, 170.6, 171.1 (4!s, 4!C]O); m/z (ESC) 510 (MC
NaC, 100), 488 (MCHC, 20%). (HRMS (ESC) calcd for
C20H25NO8Na80Se (MCNaC) 510.0643. Found,
510.0664).
0
0
at, JZ8.6 Hz, H-3), 4.38 (1H, dd, J5,6 Z4.9 Hz, J6,6
Z
10.6 Hz, H-60), 4.82, 4.95 (2H, ABq, JZ10.3 Hz, CH2Ph),
4.90 (1H, s, H-1), 5.53 (1H, s, PhCHO2), 7.29–7.69 (15H,
m, 15!Ar-H); dC (100.7 MHz, CDCl3) 68.6 (t, C-6), 71.1
(d, C-5), 75.3 (t, CH2Ph), 75.6 (d, C-3), 80.3, 81.3 (2!d,
C-2, C-4), 83.3 (d, C-1), 101.8 (d, PhCHO2), 126.2, 128.0,
128.1, 128.2, 128.3, 128.3, 128.5, 129.1, 129.3, 134.6,
135.3, 136.9, 138.0 (10!d, 3!s, 18!Ar-C); m/z (CIC)
499 (8%, MCHC). (HRMS (CIC) calcd for C26H27O850Se
(MCHC) 499.1024. Found, 499.1022.)

8418
D. J. Chambers et al. / Tetrahedron 60 (2004) 8411–8419
4.16. 3,4,6-Tri-O-acetyl-2-N-acetylamino-2-deoxy-D-
glucal 12b and methyl (3,4,6-tri-O-acetyl-1,2-dideoxy-a-
D-glucopyrano)-[2,1-D]-D2-oxazolidine 20
4.18. Phenyl 3-O-acetyl-2-O-benzyl-4,6-O-benzylidene-1-
seleno-b-D-glucopyranoside 19a
Alcohol 10a (1.84 g, 3.70 mmol) was dissolved in a mixture
of acetic anhydride (20 ml) and pyridine (20 ml). The
reaction mixture was stirred for 16 h under an atmosphere of
argon. After this time, TLC (petrol/ethyl acetate, 4:1)
indicated complete consumption of starting material (Rf 0.3)
and formation of a single product (Rf 0.4). The reaction
mixture was poured into water, and extracted with DCM
(4!50 ml). The organic layers were washed with hydro-
chloric acid (50 ml of a 1 M solution), sodium bicarbonate
(50 ml of a saturated solution) and brine (50 ml of a
saturated solution), dried (MgSO4), filtered, and concen-
trated in vacuo. The residue was purified by flash column
chromatography (petrol/ethyl acetate, 6:1) to afford acetate
19a (1.92 g, 96%) as a white crystalline solid, mp 148–
149 8C (ethyl acetate/petrol); [a]2D1 K42 (c, 1.1 in CHCl3);
nmax (KBr disc) 1730 (s, C]O) cmK1; dH (400 MHz,
CDCl3) 1.97 (3H, s, CH3), 3.51–3.62 (3H, m, H-2, H-4,
Selenoglucoside 12a (161.6 mg, 0.33 mmol, Rf 0.4 (ethyl
acetate)) was subjected to the general oxidation conditions
to afford a 2.2:1 mixture (172.3 mg, 96%, Rf 0.3) of glucal
12b and oxazolidine 20 as a pale yellow oil; nmax (thin film)
1744, 1665 (2!s, amide I, amide II, N]C–O); dH
(400 MHz, CDCl3) data for 12b: 2.03–2.14 (12H, m, 4!
CH3), 4.11–4.28 (1H, m, H-6), 4.35–4.43 (2H, m, H-5,
H-60), 5.22 (1H, at, JZ4.7 Hz, H-4), 5.34 (1H, d, J3,4
Z
4.0 Hz, H-3), 6.94 (1H, s, NH), 7.41 (1H, s, H-1); data for
20: 2.03–2.14 (12H, m, 4!CH3), 3.60–3.65 (1H, m, H-3),
4.11–4.28 (2H, m, H-6, H-2), 4.35–4.43 (1H, m, H-60),
4.93–4.97 (1H, m, H-4), 5.28 (1H, at, JZ2.4 Hz, H-5), 5.99
(1H, d, J1,2Z7.5 Hz, H-1); dC (100.7 MHz, CDCl3) data for
12b: 21.1, 21.1, 21.3, 24.2 (4!q, 4!CH3), 61.6 (t, C-6),
67.5, 67.8 (2!d, C-3, C-4), 73.6 (d, C-5), 111.6 (s, C-2),
140.8 (d, C-1), 169.2, 170.0, 170.9, 171.0 (4!s, 4!C]O);
data for 20: 14.3, 21.1, 21.3, 24.2 (4!q, 4!CH3), 63.8 (t,
C-6), 65.4 (d, C-2), 67.9 (d, C-3), 68.8 (d, C-4), 70.8
(d, C-5), 99.8 (d, C-1), 167.1, 169.6, 170.9, 172.1 (4!s, 3!
C]O, C]N); m/z (ESC) 352 (MCNaC, 100%). (HRMS
(ESC) calcd for C14H19NO8Na (MCNaC) 352.1008.
Found, 352.1009.)
H-5), 3.78 (1H, at, JZ10.0 Hz, H-6), 4.39 (1H, dd, J5,6
Z
0
0
4.6 Hz, J6,6 Z10.5 Hz, H-6 ), 4.61, 4.88 (2H, ABq, JZ
10.9 Hz, PhCH2), 5.01 (1H, d, J1,2Z9.7 Hz, H-1), 5.38 (1H,
at, JZ9.1 Hz, H-3), 5.48 (1H, s, PhCHO2), 7.28–7.68 (15H,
m, 15!Ar-H); dC (100.7 MHz, CDCl3) 20.9 (q, CH3), 68.6
(t, C-6), 71.4, 78.6, 79.8 (3!d, C-2, C-4, C-5), 74.4 (d,
C-3), 75.0 (t, PhCH2), 83.6 (d, C-1), 101.3 (d, PhCHO2),
126.1, 128.0, 128.2, 128.2, 128.3, 128.5, 129.1, 129.2, 134.6
(9!d, 15!Ar-C), 136.9, 137.5 (2!s, 3!Ar-C), 169.7 (s,
C]O); m/z (ESC) 563 (100, MCNaC), 558 (75%, MC
NH4C). (HRMS (ESC) calcd for C28H32O6N80Se (MC
NH4C) 558.1395. Found, 558.1378). (Found: C, 62.20; H,
5.23. C28H28O6Se requires C, 62.34; H, 5.23%.)
4.17. Phenyl 2,3,4,6-tetra-O-benzyl-1-seleno-a-D-
glucopyranoside 13a
To a solution of selenoglucoside 1818 (1.01 g, 1.71 mmol) in
anhydrous DMF (20 ml) was added benzyl bromide
(0.30 ml, 2.56 mmol) and then sodium hydride (60% in
mineral oil, 82 mg, 2.05 mmol). The reaction mixture was
stirred under an atmosphere of nitrogen for 16 h, when TLC
(petrol/ethyl acetate, 4:1) indicated consumption of starting
material (Rf 0.2) and formation of a major product (Rf 0.4).
The reaction mixture was quenched with methanol (6 ml),
diluted with ether (100 ml) and washed with water (2!
75 ml) and brine (2!75 ml of a saturated solution). The
solution was dried (MgSO4), filtered, and concentrated in
vacuo. The residue was purified by flash column chroma-
tography (petrol/ethyl acetate, 6:1) to afford selenogluco-
side 13a (1.11 g, 95%) as a white crystalline solid, mp 71–
72 8C (ether/petrol); [a]2D0 C162 (c, 0.9 in CHCl3); nmax
(KBr disc) no significant peaks; dH (400 MHz, CDCl3) 3.56
4.19. 3-O-Acetyl-2-O-benzyl-4,6-O-benzylidene-D-glucal
19b
Acetate 19a (145 mg, 0.27 mmol, Rf 0.35 (petrol/ethyl
acetate, 4:1)) was subjected to the general oxidation
procedure to afford glucal 19b (106.3 mg, quant., Rf 0.4)
as a fluffy white crystalline solid, mp 125–127 8C
(methanol); [a]D22 K12 (c, 0.9 in CHCl3); nmax (KBr disc)
1745 (s, C]O) cmK1; dH (400 MHz, CDCl3) 2.14 (3H, s,
CH3), 3.82–3.92 (2H, m, H-5, H-6), 4.08 (1H, dd, J3,4
Z
7.9 Hz, J4,5Z9.8 Hz, H-4), 4.38–4.41 (1H, m, H-60), 4.63,
4.82 (2H, ABq, JZ11.6 Hz, PhCH2), 5.57 (1H, s, PhCHO2),
6.02 (1H, d, H-3), 6.34 (1H, s, H-1), 7.31–7.52 (10H, m,
10!Ar-H); dC (100.7 MHz, CDCl3) 21.1 (q, CH3), 68.0 (d,
C-3), 68.3 (t, C-6), 69.0 (d, C-5), 71.8 (d, PhCH2), 77.3 (d,
C-4), 101.3 (d, PhCHO2), 126.2, 127.3, 127.9, 128.3, 128.5,
129.2 (6!d, 10!Ar-C), 131.1 (d, C-1), 136.5, 136.7, 138.8
(3!s, 2!Ar-C, C-2), 170.7 (s, C]O); m/z (ESC) 405
(MCNaC, 60), 400 (MCNH4C, 95%); (HRMS (ESC)
calcd for C22H26NO6 (MCNH4C) 400.1760. Found
400.1767). (Found: C, 69.09; H, 5.82. C22H22O6 requires
C, 69.10; H, 5.80%.)
0
(1H, dd, J5,6Z1.8 Hz, J6,6 Z10.4 Hz, H-6), 3.71–3.80 (2H,
m, H-4, H-60), 3.84–3.88 (2H, m, H-2, H-3), 4.27 (1H, br dd,
JZ1.3, 10.1 Hz, H-5), 4.41, 4.59 (2H, ABq, JZ12.1 Hz,
PhCH2), 4.52 (1H, d, JZ10.9 Hz, PhCH), 4.67 (1H, d, JZ
11.7 Hz, PhCH), 4.79–4.88 (3H, m, 3!PhCH), 5.00 (1H, d,
JZ10.9 Hz, PhCH), 6.05 (1H, d, J1,2Z4.1 Hz, H-1), 7.17–
7.61 (25H, m, 25!Ar-H); dC (100.6 MHz, CDCl3) 68.3 (t,
C-6), 72.7 (d, C-5), 72.4, 73.3, 75.1, 75.8 (4!t, 4!PhCH2),
77.4 (d, C-4), 80.1, 83.2 (2!d, C-2, C-3), 85.8 (d, C-1),
127.4, 127.6, 127.6, 127.7, 127.9, 127.9, 127.9, 128.0,
128.2, 128.3, 128.4, 128.4, 128.9 (13!d, 25!Ar-C),
129.1, 137.6, 137.8, 138.2, 138.6 (5!s, 5!Ar-C); m/z
(ESC) 703 (MCNaC, 100%). (HRMS (ESC) calcd
for C40H44NO580Se (MCNH4C) 698.2385. Found,
698.2380.)
4.20. 2,3,4,6-Tetra-O-benzyl-D-glucopyranose 21
Selenoglucoside 13a (113 mg, 0.17 mmol) and diiso-
propylethylamine (0.05 ml, 0.28 mmol) were dissolved in
anhydrous DCM (6 ml) and the solution cooled to 0 8C. tert-
Butylhydroperoxide (5.5 M in decane, 0.15 ml, 0.73 mmol)

D. J. Chambers et al. / Tetrahedron 60 (2004) 8411–8419
8419
Commun. 1982, 701–703. (b) Heath, C. E.; Gillam, M. C.;
Callis, C. S.; Patto, R. R.; Abelt, C. J. Carbohydr. Res. 1998,
307, 371–373. (c) Yang, W.-B.; Yang, Y.-Y.; Gu, Y.-F.;
Wang, S.-H.; Chang, C.-C.; Lin, C.-H. J. Org. Chem. 2002, 67,
3773–3782.
was added drop-wise over 5 min, and then titanium(IV)
isopropoxide (0.05 ml, 0.17 mmol) was added. The reaction
mixture was stirred under an atmosphere of argon for 16 h,
when TLC (petrol/ethyl acetate, 4:1) indicated consumption
of starting material (Rf 0.5) and formation of two products
(Rf 0.1, 0.05). The yellow solution was concentrated in
vacuo, and purified by flash column chromatography
(petrol/ethyl acetate, 6:1/2:1) to afford lactol 21 (Rf 0.4,
57.6 mg, 64%) as a white crystalline solid; dH (400 MHz,
CDCl3)27 a anomer: 3.03 (1H, br s, OH), 3.52–3.73 (4H, m,
H-2, H-4, H-6, H-60), 3.98 (1H, at, JZ9.3 Hz, H-3), 4.03–
4.05 (1H, m, H-5), 4.13–4.98 (8H, m, 4!PhCH2), 5.24 (1H,
d, J1,2Z3.5 Hz, H-1), 7.12–7.53 (20H, m, 20!Ar-H); b
anomer: 3.03 (1H, br s, OH), 3.41 (1H, dd, JZ7.7, 8.9 Hz,
H-2), 3.52–3.73 (4H, m, H-3, H-4, H-6, H-60), 4.03–4.05
(1H, m, H-5), 4.13–4.98 (8H, m, 4!PhCH2), 4.69–4.74
(1H, m, H-1), 7.12–7.53 (20H, m, 20!Ar-H).
10. For a synthetic route to 2-deoxy furanoid glycals via
´
selenoxide elimination see Bravo, F.; Kassou, M.; Dıaz, Y.;
´
Castillon, S. Carbohydr. Res. 2001, 336, 83–97.
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14. For a preliminary communication see: Chambers, D. J.; Evans,
G. R.; Fairbanks, A. J. Tetrahedron Lett. 2003, 44, 5221–5223.
15. Ennis, S. C.; Cumpstey, I.; Fairbanks, A. J.; Butters, T. D.;
Mackeen, M.; Wormald, M. R. Tetrahedron 2002, 58,
9403–9411.
Acknowledgements
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.
16. Randall, K. D.; Johnston, B. D.; Brown, P. N.; Pinto, M. B.
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and their disproportionation products.
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22. These could possibly be the corresponding glycosyl selenoxide
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glycoside, might arise from an Se to O rearrangement to
produce a glycosyl selenenate which then hydrolyses.
However, we currently have no evidence to support this
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acid catalysed decomposition of the glycosyl selenoxide on
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