Synthesis of 6-deoxyheptose derivatives via cyclic sulfates and oxetanes

Article abstract of DOI:10.1055/s-1998-2219

Two approaches for the chain elongation and synthesis of 6-deoxyheptose derivatives are described. The first one is based on the regioselective ring opening of 4,6-cyclic sulfate glycopyranoside derivatives at carbon 6 by cyanide ion. The second approach involves the ring expansion of 5,6-anhydro to 5,7-anhydro sugars and subsequent opening of the resulting oxetane, derivative using acetate ion as nucleophile.

Full text of DOI:10.1055/s-1998-2219

SYNTHESIS
Papers
1778
Synthesis of 6-Deoxyheptose Derivatives via Cyclic Sulfates and Oxetanes
Antonio Vargas-Berenguel,a* Francisco Santoyo-González,b* José A. Calvo-Asín,b Francisco G. Calvo-Flores,b
Juan M. Expósito-López,a Fernando Hernández-Mateo,b Joaquín Isac-García,b Juan J. Giménez Martíneza
a Área de Química Orgánica, Universidad de Almería, 04120 Almería, Spain
Fax: +34(950)215481; E-mail: avargas@ualm.es
b Instituto de Biotecnología, Facultad de Ciencias, Universidad de Granada, 18071 Granada, Spain
Fax: +34(958)243186; E-mail: fsantoyo@goliat.ugr.es
Received 29 May 1998
Abstract: Two approaches for the chain elongation and synthesis
of 6-deoxyheptose derivatives are described. The first one is based
on the regioselective ring opening of 4,6-cyclic sulfate glycopyra-
disaccharides.12 On the other hand, it is known that ox-
noside derivatives at carbon 6 by cyanide ion. The second
teresting applications in the synthesis of episulfide and
olefin derivatives, thiosugars10,11 and, as well, thio-linked
iranes undergo ring expansion when treated with dimeth-
ylsulfoxonium methylide affording oxetanes.13,14 Since
oxetanes are latent 1,3-diols, we can envisage a new meth-
od for the chain elongation at C-6 of hexoses, and hence,
for the synthesis of 6-deoxyheptoses, from 5,6-anhydro-
hexofuranose derivatives.
approach involves the ring expansion of 5,6-anhydro to 5,7-anhy-
dro sugars and subsequent opening of the resulting oxetane deriv-
ative using acetate ion as nucleophile.
Key words: chain elongation, 6-deoxyheptoses, cyclic sulfate,
oxetanes, oxiranes
Naturally occurring 6-deoxyheptoses have been found as
constituents of bacterial polysaccharides1 although little is
known about their biosynthesis and biological role. Most
of the reported synthetic approaches are based on chain
extension at the C-6 position of hexoses, e.g. via a nitrile,
a Wittig reaction, dithioacetals and organometallic re-
agents, among others.1 Cyclic sulfates of mono-
saccharides2,3 or 5,6-anhydroaldose4–6 derivatives have
been used in some of those approaches as precursors of 6-
deoxyheptoses. In this paper we wish to report further on
the applications of these two classes of compounds in the
synthesis of 6-deoxyheptose derivatives.
Cyclic sulfates of sugars with D-gluco, D-manno and D-
galacto configuration 1–6 were prepared in good to high
yields (Table 1) from the corresponding diols following a
synthetic route described earlier for 3 and 611,12 which was
based on the procedure by Gao and Sharpless.15 The reac-
tion of compounds 1–6 with lithium or sodium cyanide
was performed in DMF at room temperature for 4–
40 hours giving rise to the lithium or sodium sulfate deriv-
atives 7–12 in good yields (Table 2, entries 1–7). As ex-
pected, the nucleophilic ring opening of the 4,6-cyclic sul-
fates 1–5 occurred regioselectively at the less sterically
hindered 6-position and the reaction conditions were com-
patible with ester protection of the hydroxyl groups at C-
2,3. However, the reaction of the less reactive 3,4-cyclic
sulfate 6 with lithium or sodium cyanide failed to give the
corresponding nitrile derivative and instead, the 2,3-anhy-
The use of cyclic sulfates as an active form of diols to-
wards nucleophilic attack provides an efficient and versa-
tile method in synthesis.7–9 We have investigated the reac-
tivity of cyclic sulfates of sugars and discovered some in-

SYNTHESIS
December 1998
1779
Table 1. Cyclic Sulfates 1, 2, 4 and 5 Prepared
Prod-
ucta
Yield
(%)
mp (°C)
[a]D25
(c, MeOH)
IR (KBr)
1H NMR (300 MHz, CDCl3/TMS)
δ, J (Hz)
13C NMR (75 MHz,
CDCl3/TMS)
ν (cm–1)
δ
1
2
4
92
90
85
155–156
+ 110 (1)
+ 32 (1)
+ 58 (1)
1749, 1205
2.09, 2.10 (2s, 6 H, 2 CH3CO), 3.45 (s, 3 H, 20.6 (2 CH3CO), 56.2
CH3O), 4.27 (ddd, 1 H, J = 5.3, 10.5, 10.5, H–5), (CH3O), 60.6, 67.1,
4.55 (dd, 1 H, J = 5.3, 10.5, H–6), 4.62 (dd, 1 H, 70.8 (C–2, 3, 5), 72.1
J = 10.5, H–4), 4.65 (t, 1 H, J = 10.5, H–6'), 4.83 (C–6), 81.4 (C–4),
(dd, 1 H, J = 3.6, 9.9, H–2), 5.03 (d, 1 H, J = 3.6, 97.7 (C–1), 169.3,
H–1), 5.61 (t, 1 H, J = 9.9, H–3)
170.1 (C=O)
135–140
102–103
1749, 1245, 2.06, 2.16 (2s, 6 H, 2 CH3CO), 3.44 (s, 3 H, 20.6, 20.7 (2 CH3CO),
1208
CH3O), 4.24 (ddd, 1 H, J = 5.0, 10.5, 10.2, H–5), 56.0 (CH3O), 61.9,
4.55 (dd, 1 H, J = 5.0, 10.6, H–6), 4.71 (d, 1 H, J 66.8, 69.4 (C–2, 3, 5),
= 1.6, H–1), 4.72 (dd, 1 H, J = 10.7, H–6'), 4.94 72.1 (C–6), 79.5 (C–
(t, 1 H, J = 10.2, H–4), 5.43 (dd, 1 H, J = 1.6, 3.5, 4), 99.8 (C–1), 169.4,
H–2), 5.43 (dd, 1 H, J = 3.6, 10.4, H–3)
170.5 (C=O)
1727, 1636, 3.33 (s, 3 H, CH3O), 3.81 (dd, 1 H, J = 2.0, 3.2, 55.5 (CH3O), 62.1 (C–
1412, 1202
H–2), 3.94 (dd, 1 H, J = 3.2, 10.0, H–3), 4.05 (dt, 5), 72.2 (C–6), 73.2,
1 H, J = 4.9, 10.5, H–5), 4.48 (dd, 1 H, J = 4.9, 73.9 (2 PhC), 75.3,
10.5, H–6), 4.58 (d, 1 H, J = 12.0, PhCH), 4.64 (d, 75.6 (C–2, 3), 83.1
1 H, J = 12.0, PhCH), 4.67 (d, 1 H, J = 2.0, H–1), (C–4), 100.6 (C–1),
4.69 (t, 1 H, J = 10.5, H–6'), 4.73 (d, 1 H, J = 12.0, 127.6–137.5 (2 C6H5)
PhCH'), 4.79 (d, 1 H, J = 12.0, PhCH'), 5.13 (t, 1
H, J = 10.0, H–4), 7.30–7.40 (m, 10 H, 2 C6H5)
5
54
148–152
+ 68 (0.3)
1728, 1630, 3.39 (s, 3 H, CH3O), 3.89, 4.02 (2 dd, 2 H, J = 3.4, 56.1 (CH3O), 60.0 (C–
1397, 1196
10.0, H–2, 3), 4.53 (dd, 1 H, J = 1.5, 12.1, H–6), 5), 72.7 (C–6), 73.6,
4.66 (d, 1 H, J = 12.1, PhCH), 4.67–4.69 (m, 2 H, 74.6 (C–2, 3), 74.2,
H–4, 5), 4.73 (d, 1 H, J = 12.0, PhCH), 4.80 (d, 1 74.4 (PhC), 82.0 (C–
H, J = 12.0, PhCH'), 4.81 (dd, 1 H, J = 1.5, 12.1, 4), 99.2 (C–1), 127.7–
H–6'), 4.89 (d, 1 H, J = 12.1, PhCH'), 5.10 (d, 1 138.0 (2 C6H5)
H, J = 3.4, H–1), 7.29–7.35 (m, 10 H, 2 C6H5)
a Satisfactory microanalyses obtained: C ± 0.47, H ± 0.25.
dro salt 12 was obtained. Presumably, in these conditions
the reaction proceeded by initial cyanolysis of the acetyl
group at the O-2 and subsequent ring opening of the cyclic
sulfate by internal nucleophilic attack of the resulting
alkoxide at carbon 3.
methoxymethyl ether. Thus, reaction of 13, 14 and 17
with dimethoxymethane/P2O5 in dichloromethane afford-
ed the 4-O-methoxymethyl derivatives 15, 16 and 18 in
good yields after chromatographic purification (Table 2,
entries 11–13). For the two step reduction of the 6-C-cy-
ano derivatives, compounds 15, 16 and 18 were treated
with DIBAH, followed by acid hydrolysis and subsequent
treatment with sodium borohydride yielding the expected
6-deoxyheptopyranoside derivatives 19–21 (Table 3).
Spectroscopic data of compounds 7–21 are given in Table
4.
In order to synthesize 6-deoxyheptose derivatives we sub-
jected the 2,3-di-O-benzyl sulfates 9–11 to acidic hydro-
lysis obtaining the methyl 2,3-di-O-benzyl-6-deoxy-α-D-
heptopyranosylurononitriles 13, 14, 17, respectively, in
78–89.5% yields (Table 2, entries 8–10). It is noteworthy
that, analogous to epoxides,8,11 the opening of the cyclic
sulfate ring followed by hydrolysis of the sulfate salt gave
compounds having a free hydroxy group at C-4. This hy-
droxy group may serve as a glycosyl acceptor, may allow
an inversion of the configuration16 or may be orthogonally
protected. At this stage, having obtained a nitrile group on
the carbon 6, conversion of the nitrile function into a hy-
droxymethyl group can be undertaken following the pro-
cedure reported by Aspinall et al.,16 namely, diisobutyl-
aluminium hydride (DIBAH) reduction, hydrolysis of the
resulting imine and further reduction with sodium boro-
hydride. When compound 13 was treated with an excess
of DIBAH no change was observed according to TLC.
Then, the hydroxy group at C-4 was protected as its
To develop the second approach, we selected the 5,6-an-
hydro-D-gluco (25a), D-manno (25b), L-ido (26a), and L-
gulo-furanose (26b) derivatives as starting materials.
Compounds 25a,b were synthesized from 3-O-ben-
zyl-1,2-O-isopropylidene-α-D-glucofuranoside (22a) and
methyl 2,3-O-isopropylidene-α-D-mannofuranoside (22b),
respectively. Thus, reaction of furanoside derivatives
22a,b17,18 with 2-naphthalenesulfonyl chloride generated
23a (62%), and 23b + 24b (47 and 15%), respectively.
The 6-O-(2-naphthalenesulfonyl)furanosides 23a,b could
be converted to the epoxides derivatives 25a,b by treat-
ment with sodium methoxide in methanol. The products
25a,b were isolated in 67 and 73% yields after column

SYNTHESIS
Papers
1780
Table 2. Preparation of Compounds 7–18
Entry Substrate
(mmol)
Reagent
Solvent
Time
(h)
Solvent for
Chromatography
Prod- Yield mp (°C)
[α]D25 (c, solvent)
uct
(%)
1
2
3
4
5
6
7
8
1 (0.59)
2 (0.59)
3 (1.62)
4 (0.47)
5 (0.32)
6 (0.50)
6 (1.00)
9 (1.17)
NaCN (1.5 equiv)
NaCN (1.5 equiv)
LiCNa (2.0 equiv)
LiCNa (5.1 equiv)
LiCNa (3.2 equiv)
NaCN (2.5 equiv)
LiCNa (1.1 equiv)
H2SO4 (100 µL)
DMF
DMF
acetone
acetone
acetone
DMF
DMF
THF/H2O
(30:0.7 mL)
THF/H2O
(15:0.2 mL)
THF/H2O
(20:0.1 mL)
4
4
MeOH/CHCl3 (1:6)
MeOH/CHCl3 (1:6)
MeOH/CHCl3 (1:5)
MeOH/CHCl3 (1:5) 10
MeOH/CHCl3 (1:5) 11
MeOH/CHCl3 (1:5) 12
MeOH/CHCl3 (1:5) 12
7
8
9
95
79
98
94
93
78
99
89
166–168
161–163
129 (dec.) + 79 (1, MeOH)
133 (dec.) + 55 (0.5, MeOH)
126 (dec.) + 112 (0.25, MeOH)
syrup
syrup
111–112
+ 90 (1, MeOH)
+ 38 (1, MeOH)
26
40
45.5
24
20
+ 32 (1, MeOH)
+ 32 (1, MeOH)
+ 118 (0.25, MeOH)
1.25 Et2O/hexane (2:1)
13
14
17
15
16
18
9
10
11
12
13
10 (0.44)
11 (0.30)
13 (1.74)
14 (3.57)
17 (1.42)
H2SO4 (40 µL)
H2SO4 (25 µL)
3.5b
Et2O/hexane (7:3)
84
78
87
86
56
100–101
syrup
– 8 (0.25, CHCl3)
+ 52 (0.75, CHCl3)
+ 96 (0.25, CHCl3)
+ 142 (0.25, CHCl3)
+ 46 (0.25, CHCl3)
0.75 Et2O/hexane (7:3)
(MeO)2CH2 (25 mL) 25 mL
P2O5 (3.8 g)
(MeO)2CH2 (50 mL) 50 mL
P2O5 (8.2 g)
(MeO)2CH2 (40 mL) 40 mL
P2O5 (5.7 g)
2.3
1.5
1.5
Et2O/hexane (2:3)
Et2O/hexane (1:3)
Et2O/hexane (2:3)
67–69
syrup
syrup
a 0.5 M solution of LiCN in DMF.
b The reaction is complete upon heating at 40°C.
chromatography, respectively. Similar treatment using the This reagent was prepared in situ from trimethysulfox-
6-chloro-6-deoxy derivative 24b gave the corresponding onium iodide and potassium tert-butoxide in tert-butyl al-
5,6-anhydro compound 25b in 72% yield (Table 5, entries cohol. Thus, epoxides 25a,b and 26a,b were allowed to
1–5). The remaining 5,6-anhydro derivatives 26a,b were react in the presence of trimethysulfoxonium methylide
prepared as described.17,18
for 6–20 hours at 50ºC, furnishing oxetanes 27a,b and
28a,b in 54–93% yields (see Table 5, entries 6–9). The
Having the 5,6-anhydro furanosides in hand, we tested the reactions proceeded with excellent regioselectivity,
key ring expansion reaction using dimethylsulfoxonium wherein the methylene insertion into the bond between the
methylide as nucleophilic methylene transfer reagent. oxirane oxygen and the primary carbon 6 took place.

SYNTHESIS
December 1998
1781
Table 3. Reduction of Compounds 15, 16 and 18
Substrate
(mmol)
DIBAH Toluene Time
NaBH4 MeOH Time Solvent for
Product Yield mp (°C) [α]D25
(mL)
(mL)
(h)
(g)
(mL)
(h)
Chromatography
(%)
(c, CHCl3)
15 (0.12)
16 (3.08)
18 (0.21)
0.26a
10b
7
20
5
1.5
0.75
0.95
0.03
1.65
0.11
5
35
12
1.5
0.5
1.65
Et2O/hexane (4:1) 19
Et2O/hexane (3:1) 20
40
59
25
56
syrup
syrup
+ 101 (0.25)
+ 88 (0.45)
+ 34 (0.20)
0.7b
Et2O
21
a 1 M in THF.
b 1 M in hexane.
Table 4. Spectroscopic Data for Compounds 7–21
Prod-
ucta
IR (KBr)
1H NMR (300 MHz, solvent/TMS)
δ, J (Hz)
13C NMR (75 MHz, solvent/TMS)
δ
ν (cm–1)
7
8
9
2261, 1749
DMSO-d6: 1.92, 2.00 (2s, 6 H, 2 CH3CO), 2.81 (dd, 1 H, J = 8.2, 17.2, H– DMSO-d6: 20.1 (C–6), 20.5, 20.8 (2
6), 3.06 (dd, 1 H, J = 3.4, 17.2, H–6'), 3.34 (s, 3 H, CH3O), 3.71 (m, 1 H, CH3CO), 54.8 (CH3O), 66.4, 69.2,
H–5), 4.00 (t, 1 H, J = 9.6, H–4), 4.73 (dd, 1 H, J = 3.3, 10.7, H–2), 4.90 (d, 70.0, 74.5 (C–2, 3, 4, 5), 96.0 (C–1),
1 H, J = 3.3, H–1), 5.18 (t, 1 H, J = 10.1, H–3)
118.1 (CN), 169.5, 169.7 (2 C=O)
1748, 1255
DMSO-d6: 1.92, 2.14 (2 s, 6 H, 2 CH3CO), 2.83 (dd, 1 H, J = 5.3, 17.2, H– DMSO-d6: 20.4 (C–6), 20.6, 20.7 (2
6), 3.09 (dd, 1 H, J = 3.4, 17.2, H–6'), 3.37 (s, 3 H, CH3O), 3.73 (ddd, 1 H, CH3CO), 54.6 (CH3O), 67.3, 68.2,
J = 3.4, 5.3, 9.7, H–5), 4.18 (t, 1 H, J = 9.7, H–4), 4.74 (d, 1 H, J = 1.7, H– 69.3, 71.9 (C–2, 3, 4, 5), 97.5 (C–1),
2), 4.97 (dd, 1 H, J = 3.6, 1.7, H–2), 5.07 (dd, 1 H, J = 9.6, 3.6, H–3)
118.1 (CN), 169.6 (2 C=O)
2254, 1654, DMSO-d6: 2.88 (dd, 1 H, J = 7.5, 16.6, H–6), 3.19 (br d, 1 H, J = 16.6, H– DMSO-d6: 20.3 (C–6), 54.6 (CH3O),
1260, 1025
6'), 3.32 (s, 3 H, CH3O), 3.40 (dd, 1 H, J = 2.0, 9.7, H–2), 3.65–3.70 (m, 1 66.3 (C–5), 71.8, 73.8 (2 PhCH2),
H, H–5), 3.65, 4.00 (2 t, 2 H, J = 9.7, H–3, 4), 4.56, 5.00 (2 d, 2 H, J = 10.9, 77.7, 78.2, 79.0 (C–2, 3, 4), 97.0 (C–
PhCH2), 4.82 (d, 1 H, J = 2.0, H–1), 4.62 (s, 2 H, PhCH2), 7.24–7.39 (m, 10 1), 118.4 (CN), 132.4–133.4 (2 C6H5)
H, 2 C6H5)
10
2270, 1653, DMSO-d6: 2.82 (dd, 1 H, J = 8.0, 17.2, H–6), 3.20 (dd, 1 H, J = 3.2, 17.2, DMSO-d6: 20.5 (C–6), 54.3 (CH3O),
1214, 1000
H–6'), 3.23 (s, 3 H, CH3O), 3.58–3.65 (m, 2 H, H–3,5), 3.70 (t, 1 H, J = 2.5, 71.7, 71.8 (2 PhCH2), 67.8, 74.9, 75.9,
H–2), 4.32 (dd, 1 H, J = 8.5, 9.4, H–4), 4.56, 4.82 (2 d, 2 H, J = 12.1, 76.6 (C–2, 3, 4, 5), 98.4 (C–1), 118.5
PhCH2), 4.63 (s, 2 H, PhCH2), 4.75 (d, 1 H, J = 2.5, H–1), 7.23–7.29 (m, 10 (CN), 127.0–139.1 (2 C6H5)
H, 2 C6H5)
11b,c
2259, 1652, DMSO-d6: 2.81 (dd, 1 H, J = 3.9, 16.9, H–6), 2.88 (dd, 1 H, J = 11.0, 16.9, DMSO-d6: 20.2 (C–6), 55.6 (CH3O),
1256, 1036
H–6'), 3.49 (s, 3 H, CH3O), 3.63 (dd, 1 H, J = 3.5, 10.3, H–2), 3.75 (dd, 1 65.9 (C–5), 69.8 (PhCH2), 71.6 (C–4),
H, J = 3.0, 10.3, H–3), 3.95 (m, 1 H, H–5), 4.45, 4.58 (2 d, 2 H, J = 11.8, 72.6 (PhCH2), 74.8 (C–2), 75.6 (C–3),
PhCH2), 4.67, 4.87 (2 d, 2 H, J = 11.8, PhCH2), 4.69 (d, 1 H, J = 3.0, H–4), 97.7 (C–1), 118.9 (CN), 127.0–139.2
4.82 (d, 1 H, J = 3.5, H–1), 7.30 – 7.50 (m, 10 H, 2 C6H5)
(2 C6H5)
12
13
1735, 1244d
DMSO-d6: 1.98 (s, 3 H, CH3CO), 3.28 (s, 3 H, CH3O), 3.40 (dd, 1 H, J = DMSO-d6: 20.6 (CH3CO), 50.2, 50.4
3.1, 3.7, H–2), 3.45 (dd, 1 H, J = 2.2, 3.8, H–3), 3.80 (ddd, 1 H, J = 2.0, 3.2, (C–2, 3), 54.2 (CH3O), 64.2 (C–6),
8.2, H–5), 4.00 (dd, 1 H, J = 8.2, 10.0, H–6), 4.07 (dd, 1 H, J = 3.2, 12.0, 65.1, 67.4 (C–4, 5), 93.9 (C–1), 170.1
H–6'), 4.32 (br t, 1 H, J = 2.0, H–4), 4.95 (d, 1 H, J = 3.1, H–1)
(C=O)
3466, 2252, CDCl3: 2.10 (d, 1 H, J = 0.8, OH), 2.57 (dd, 1 H, J = 7.1, 16.8, H–6), 2.77 CDCl3: 20.8 (C–6), 55.5 (CH3O), 66.7
1497, 1053d
(dd, 1 H, J = 3.3, 16.8, H–6'), 3.35 (br t, 1 H, J = 9.2, H–4), 3.43 (s, 3 H, (C–5), 72.5 (C–4), 73.3, 75.4 (2
CH3O), 3.56 (dd, 1 H, J = 3.6, 9.6, H–2), 3.74–3.80 (m, 2 H, H–3,5), 4.65 PhCH2), 79.7, 80.7 (C–2, 3), 98.2 (C–
(d, 1 H, J = 3.6, H–1), 4.67, 4.72 (2 d, 2 H, J = 11.5, PhCH2), 4.78, 5.05 (2 1), 117.1 (CN), 127.0–139.1 (2 C6H5)
d, 2 H, J = 1.5, PhCH2), 7.35–7.40 (m, 10 H, 2 C6H5)
14b
15b
3474, 2259, CDCl3: 2.39 (d, 1 H, J = 1.9, OH), 2.61 (dd, 1 H, J = 8.5, 16.8, H–6), 2.89 CDCl3: 21.0 (C–6), 55.2 (CH3O), 68.3
1454, 1049
(dd, 1 H, J = 2.8, 16.8, H–6'), 3.40 (s, 3 H, CH3O), 3.64 (dd, 1 H, J = 3.0, (C–5), 69.3 (C–4), 71.5, 72.8 (2
9.0, H–3), 3.71–3.85 (m, 3 H, H–2, 4, 5), 4.39, 4.57 (d, 1 H, J = 11.6, PhCH2), 73.4 (C–2), 79.2 (C–3), 99.2
PhCH2), 4.62, 4.68 (2 d, 2 H, J = 12.2, PhCH2), 4.77 (d, 1 H, J = 1.6, H–1), (C–1), 127.8–137.8 (2 C6H5)
7.28–7.40 (m, 10 H, 2 C6H5)
2254, 1454, CDCl3: 2.60 (dd, 1 H, J = 7.8, 16.8, H–6), 2.83 (dd, 1 H, J = 3.3, 16.8, H– CDCl3: 20.9 (C-6), 55.5, 56.2 (2
1101, 1028d
6'), 3.33 (t, 1 H, J = 9.0, H–4), 3.36 (s, 3 H, CH3OCH2), 3.42 (s, 3 H, CH3O), CH3O), 66.1 (C–5), 73.4, 75.7 (2
3.51 (dd, 1 H, J = 3.6, 9.0, H–2), 3.81 (dq, 1 H, J = 3.3, 7.6, H–5), 3.87 (t, PhCH2), 79.1, 79.6, 80.9 (C–2, 3, 4),
1 H, J = 9.0, H–3), 4.56 (d, 1 H, J = 3.6, H–1), 4.59, 4.87 (2 d, 2 H, J = 6.5, 97.9 (C–1), 98.5 (MeOCH2), 117.2
MeOCH2), 4.63, 4.77 (2 d, 2 H, J = 12.2, PhCH2), 4.70, 4.96 (2 d, 2 H, J = (CN), 127.7–137.7 (2 C6H5)
10.9, PhCH2), 7.29–7.40 (m, 10 H, 2 C6H5)

SYNTHESIS
Papers
Table 4. (continued)
1782
Prod-
ucta
IR (KBr)
1H NMR (300 MHz, solvent/TMS)
δ, J (Hz)
13C NMR (75 MHz, solvent/TMS)
δ
ν (cm–1)
16b
2247, 1453, CDCl3: 2.67 (dd, 1 H, J = 3.7, 16.7, H–6), 2.96 (dd, 1 H, J = 1.6, 16.7, H– CDCl3: 21.1 (C–6), 55.1, 56.2 (2
1125, 1033d
6'), 3.40 (s, 6 H, 2 CH3O), 3.77–3.82 (m, 4 H, H–2, 3, 4, 5), 4.53, 4.59 (2 d, CH3O), 67.7 (C–5), 71.8, 72.8 (2
2 H, J = 11.7, PhCH2), 4.68, 4.95 (2 d, 2 H, J = 6.4, MeOCH2), 4.68, 4.73 PhCH2), 74.0, 76.6, 79.39 (C–2, 3, 4),
(2 d, 2 H, J = 12.7, PhCH2), 4.75 (d, 1 H, J = 1.0, H–1), 7.28–7.40 (m, 2 H, 98.4 (MeOCH2), 99.1 (C–1), 117.7
2 C6H5)
(CN), 127.5–138.0 (2 C6H5)
17
3479, 2253, CDCl3: 2.63 (dd, 1 H, J = 6.0, 16.7, H–6), 2.76 (dd, 1 H, J = 8.0, 16.7, H– CDCl3: 19.7 (C–6), 55.7 (CH3O),
1496, 1106d
6'), 3.41 (s, 3 H, CH3O), 3.79 (dd, 1 H, J = 3.6, 9.3, H–2 or H–3), 3.83–3.92 65.7, 68.3 (C–4, 5), 73.3, 73.6 (2
(m, 2 H, H–2 or 3, 4), 4.02 (m, 1 H, H–5), 4.64 (d, 1 H, J = 3.6, H–1), 4.65, PhCH2), 75.3, 77.1 (C–2, 3), 98.7 (C–
4.81 (2 d, 2 H, J = 12.1, PhCH2), 4.70, 4.83 (2 d, 2 H, J = 11.5, PhCH2), 1), 117.4 (CN), 128.0–138.5 (2 C6H5)
7.35–7.40 (m, 10 H, 2 C6H5)
18b,c
2253, 1496, CDCl3: 2.58 (dd, 1 H, J = 5.3, 16.7, H–6), 2.77 (dd, 1 H, J = 8.5, 16.7, H– CDCl3:
55.7
(CH3O),
56.4
1387, 1038d
6'), 3.41 (s, 3 H, CH3O), 3.44 (s, 3 H, CH3OH2), 3.90–3.92 (m, 2 H, H–2, (CH3OCH2), 66.2 (C–5), 73.4, 73.6 (2
3), 3.97 (br s, 1 H, H–4), 4.08 (dd, 1 H, J = 5.3, 8.5, H–4), 4.66, 4.86 (2d, 2 PhCH2), 74.0 (C–4), 75.7, 77.7 (C–2,
H, J = 12.0, PhCH2), 4.67 (d, 1 H, J = 2.9, H–1), 4.71, 5.00 (2d, 2 H, J = 3), 97.9 (MeOCH2), 98.7 (C–1), 117.3
6.8, MeOCH2), 4.72, 4.82 (2 d, 2 H, J = 11.5, PhCH2), 7.30–7.42 (m, 10 H, (CN), 127.6–138.0 (2 C6H5)
2 C6H5)
19
3381, 3297, CDCl3: 1.65–1.81 (m, 1 H, H–6), 2.01–2.18 (m, 1 H, H–6'), 3.26 (t, 1 H, J CDCl3: 30.7 (C–6), 55.1, 56.4 (2
1453, 1372, = 9.3, H–4), 3.36, 3.39 (2 s, 6 H, 2 CH3O), 3.48 (dd, 1 H, J = 3.6, 9.3, H– CH3O), 61.0 (C–7), 66.6 (C–5), 73.4,
1106, 1027
2), 3.75–3.81 (m, 1 H, H–5), 3.87 (t, 1 H, J = 9.3, H–3), 4.54 (d, 1 H, J = 75.7 (2 PhCH2), 80.0, 80.1, 81.4 (C–2,
3.6, H–1), 4.61, 4.93 (2 d, 2 H, J = 6.5, MeOCH2), 4.63, 4.77 (2 d, 2 H, J = 3, 4), 97.8 (C–1), 98.5 (MeOCH2),
12.0, PhCH2), 4.72, 4.96 (2 d, 2 H, J = 11.0, PhCH2), 7.29–7.4 (m, 10 H, 2 127.6–136.0 (2 C6H5)
C6H5)
20
3445, 1457, CDCl3: 1.81–2.00 (m, 1 H, H–6), 2.09–2.20 (m, 1 H, H–6'), 2.45 (s, 1 H, CDCl3: 33.8 (C–6), 54.9, 56.4 (2
1369, 1278, OH), 3.32, 3.37 (2 s, 6 H, 2 CH3O), 3.70–3.85 (m, 6 H, H–2, 3, 4, 5, 7, 7'), CH3O), 60.8 (C–7), 70.9 (C-5), 71.9,
1119, 1035d
4.51, 4.57 (2 d, 2 H, J = 11.7, PhCH2), 4.65, 4.71 (2 d, 2 H, J = 12.4, 72.9 (2 PhCH2), 74.4, 76.3, 80.0 (C–2,
PhCH2), 4.67, 4.95 (2 d, 2 H, J = 6.3, MeOCH2), 7.29–7.40 (m, 10 H, 2 3, 4), 98.5 (MeOCH2), 99.1 (C–1),
C6H5)
127.5–134.0 (2 C6H5)
21b,c
3448, 1454, CDCl3: 1.70–1.80 (m, 1 H, H–6), 1.95–2.10 (m, 1 H, H–6'), 3.38–3.41 (2 s, CDCl3: 33.3 (C–6), 55.4, 56.4 (2
1358, 1260, 6 H, 2 CH3O), 3.75–3.83 (m, 2 H, H–7, 7'), 3.90–3.93 (m, 2 H, H–2, 3), 3.96 CH3O), 60.7 (C–7), 69.0 (C–5), 73.2,
1090, 1032d
(dd, 1 H, J = 1.6, 3.3, H–4), 4.02 (br d, 1 H, J = 3.6, H–5), 4.65, 4.84 (2 d, 73.7 (2 PhCH2), 75.5 (C–4), 76.3, 78.4
2 H, J = 12.0, PhCH2), 4.66 (d, 1 H, J = 2.7, H–1), 4.69, 5.03 (2 d, 2 H, J = (C–2, 3), 97.9 (MeOCH2), 98.8 (C–1),
6.8, MeOCH2), 4.71, 4.79 (2 d, 2 H, J = 11.5, PhCH2), 7.28–7.40 (m, 10 H, 127.6–138.4 (2 C6H5)
2 C6H5)
a Satisfactory microanalyses obtained: C ± 0.4, H ± 0.2.
b Assignments based on 2 D homonuclear (cosy) correlation spectra.
c Assignments based on 2 D heteronuclear (C–H) spectra.
d Film
Ring opening of the oxetanes 27a,b and 28a,b was carried ido-heptofuranoses 31a and 32a, and 6-deoxy-α-D-manno-
out at 140°C in acetic anhydride and using sodium acetate and β-L-gulo-heptofuranosides 31b and 32b. Compounds
as nucleophile. As expected, the nucleophilic attack hap- 31b and 32b were previously synthesized by Zamojski and
pened in a regiospecific fashion to the less hindered pri- cowokers19,20 using acetyliron complex derivatives.
mary position leading to the 5,7-di-O-acetyl-6-deoxyhep-
In summary, the results described in this paper show two
tofuranose derivatives 29a,b and 30a,b. While the hepto-
efficient approaches for the chain elongation of monosac-
furanoses 29a and 30a were isolated in 90 and 80% yields,
charides which are very useful for the synthesis of 6-deoxy-
respectively, after column chromatography, the 5,7-di-O-
heptose derivatives. The first one involves the use of 4,6-
acetyl-6-deoxy-2,3-O-isopropylidene derivatives 29b and
cyclic sulfate glycopyranoside derivatives as intermedi-
30b needed longer reaction times (20–24 h vs 5–6 h) and
ates. These compounds allow a highly regioselective ring
were isolated in 46 and 45% yields, respectively (Table 5,
opening at carbon 6 by cyanide ion as nucleophile. The
entries 10–13).
second approach involves the regioselective ring expan-
Finally, Zemplén de-O-acetylation of compounds 29a, 30a, sion of 5,6-anhydro to 5,7-anhydro sugars and subsequent
29b and 30b using sodium methoxide in methanol gave 1,2- regioselective opening of the resulting oxetane deriva-
isopropyliden-3-O-benzyl-6-deoxy-α-D-gluco- and β-L- tives using acetate as nucleophile.

SYNTHESIS
December 1998
1783
Table 5. Compounds 23–32 Prepared
Entry
Prod-
ucta
Yield
(%)
mp (°C)
[α]D25
(c = 1,
CHCl3)
IR (film)
1H NMR (300 MHz, CDCl3/TMS)
δ, J (Hz)
13C NMR (75 MHz,
CDCl3/TMS)
δ
ν (cm–1)
1
23a
23b
62
47
syrup
–27
3510, 1354, 1.29, 1.43 [2 s, 6 H, (CH3)2C], 2.84 (br s, 1 26.3, 26.8 [(CH3)2C],
1244, 1217, H, OH), 4.05–4.23 (m, 4 H, H–3, 4, 5, 6), 72.4 72.7 (C–6,
1179, 1113, 4.33 (dd, 1 H, J = 2.5, 10.0, H–6), 4.57 (d, 1 PhCH2), 67.4, 79.3,
1078, 1029, H, J = 3.7, H–2), 4.53, 4.66 (2 d, 2 H, J = 81.6, 82.1 (C–2, 3, 4,
967
11.6, PhCH2), 5.85 (d, 1 H, J = 3.7, H–1), 5), 105.2 (C–1), 112.0
7.20–8.00 (several m, 11 Harom), 8.44 (s, 1 (Me2C), 126.6–137.1
Harom
)
(Ph, C10H7)
2
104–105
+ 38.5
3380, 1457, 1.28, 1.39 [2 s, 6 H (CH3)2C], 2.73 (d, 1 H, 24.6, 25.9 [(CH3)2C],
1355, 1178, J = 8.0, OH), 3.23 (s, 3 H, CH3O), 3.91 (d, 1 54.7 (CH3O), 71.9 (C-
1092b
H, J = 3.7, 7.9, H–4), 4.16 (m, 1 H, H–5), 6), 68.2, 78.2, 79.7,
4.26 (dd, 1 H, J = 5.7, 10.0, H–6), 4.28 (dd, 84.7, (C–2, 3, 4, 5),
1 H, J = 3.0, 10.0, H–6'), 4.54 (d, 1 H, J = 107.1 (C–1), 112.9
5.9, H–2), 4.78 (dd, 1 H, J = 3.8, 5.9, H–3), (Me2C), 122.6–135.4,
4.85 (s, 1 H, H–1), 7.62–7.73 (m, 2 Harom), (C10H7)
7.89–8.03 (m, 4 Harom), 8.53 (s, 1 Harom
)
3
4
24b
25a
15
67
syrup
syrup
+ 57
3461, 1374, 1.32, 1.46 [2 s, 6 H, (CH3)2C], 2.82 (d, 1 H, 24.7, 26.0 [(CH3)2C],
1090, 1030b
J = 6.2, OH), 3.30 (s, 3 H, CH3O), 3.75 (dd, 47.9 (C–6), 54.6
1 H, J = 5.8, 11.4, H–6), 3.86 (dd, 1 H, J = (CH3O), 69.4, 79.1,
3.3, 11.4, H–6'), 3.95 (d, 1 H, J = 3.7, 8.4, 79.7, 84.8 (C–2, 3, 4,
H–4), 4.16 (m, 1 H, H–5), 4.57 (d, 1 H, J = 5), 107.1 (C–1), 112.8
5.9, H–2), 4.84 (dd, 1 H, J = 3.7, 5.9, H–3), (Me2C)
4.89 (s, 1 H, H–1)
– 50
1315, 1290, 2.78 (dd, 1 H, J = 2.6, 5.2, H–6), 2.92 (dd, 1 26.3, 26.8 [(CH3)2C],
1251, 1216, H, J = 3.8, 5.2, H–6'), 3.30 (ddd, 1 H, J = 47.0 (C–6), 48.3 (C–5),
1164, 1118, 2.6, 3.8, 7.5, H–5), 3.75 (dd, 1 H, J = 3.2, 72.4, (PhCH2), 81.8,
1076, 1030, 7.2, H–4), 4.08 (d, 1 H, J = 3.7, H–3), 4.64 82.1, 82.7 (C–2, 3, 4),
948
(d, 1 H, J = 3.7, H–2), 4.66, 4.73 (2 dd, 2 H, 105.4 (C–1), 112.0
J = 11.9, PhCH2), 5.95 (d, 1 H, J = 3.7, H– (Me2C), 127.7–137.4
1), 7.30–7.40 (m, 5 H, C6H5)
(C6H5)
5
6
25bc
73
86
syrup
syrup
+ 57 (c = 1373, 1211, 1.34, 1.49 [2 s, 6 H, (CH3)2C], 2.79 (dd, 1 H, 24.8, 26.1 [(CH3)2C],
2)
1194, 1163, J = 2.6, 5.2, H–6), 2.92 (dd, 1 H, J = 3.9, 5.2, 46.3 (C–6), 49.0 (C–5),
1102, 1085, H–6'), 3.25 (s, 3 H, CH3O), 3.30 (m, 1 H, H– 54.9 (CH3O), 80.1,
1052, 1026, 5), 3.66 (dd, 1 H, J = 3.7, 5.9, H–4), 4.59 (d, 80.3, 85.1 (C–2, 3, 4),
990
1 H, J = 5.9, H–2), 4.83 (dd, 1 H, J = 3.7, 107.5 (C–1), 112.9
5.9, H–3), 4.92 (s, 1 H, H–1) (Me2C)
27ad
– 18
1452, 1215, 1.31, 1.49 [2 s, 6 H, (CH3)2C], 2.67–2.84 24.5 (C–6), 26.3, 26.9
1163, 1121, (m, 2 H, H–6, 6'), 3.98 (d, 1 H, J = 3.3, H– [(CH3)2C], 69.9 (C–7),
1075, 1028
3), 4.42–4.67 (m, 6 H, H–2, 4, 7, 7', PhCH2), 72.0 (PhCH2), 79.5,
5.03 (m, 1 H, H–5), 5.97 (d, 1 H, J = 3.8, H– 81.7, 82.5, 82.6 (C–2,
1), 7.27–7.33 (m, 5 H, C6H5)
3, 4, 5), 105 (C–1),
111.8 (Me2C), 127.4–
137.5 (C6H5)
7
8
27be
81
54
syrup
– 94
1269, 1210, 1.27, 1.41 [2 s, 6 H, (CH3)2C], 2.63–2.74 24.5 (C-6), 24.3, 25.7
1163, 110, (m, 1 H, H–6), 2.78–2.90 (m, 1 H, H–6'), [(CH3)2C], 54.7
1054, 1024, 3.37 (s, 3 H, CH3O), 4.18 (t, 1 H, J = 4.1, H– (CH3O), 70.0 (C-7),
981, 965
4), 4.56 (d, 1 H, J = 5.9, H–2), 4.61–4.71 (m, 79.5, 79.9, 81.7, 84.8
2 H, H–7,7'), 4.74 (dd, 1 H, J = 3.8, 5.9, H– (C-2, 3, 4, 5), 107.2 (C-
3), 4.99 (s, 1 H, H–1), 5.08–5.14 (m, 1 H, 1), 112.5 (Me2C)
H–5)
28af
97–98
– 66
1453, 1261, 1.33, 1.50 [2 s, 6 H, (CH3)2C], 2.37 (m, 1 H, 23.8 (C–6), 26.5, 27.0
1210, 1162, H–6), 2.62 (m, 1 H, H–6'), 3.98 (d, 1 H, J = [(CH3)2C], 68.8 (C–7),
1080, 1027, 3.9, H–3), 4.43–4.64 (m, 3 H, H–4, 7, 7'), 71.7 (PhCH2), 80.3,
974
4.38, 4.65 (2 d, 2 H, J =12.2, PhCH2), 4.62 81.8, 82.7, 83.5 (C–2,
(d, 1 H, J = 3.9, H–2), 5.04 (q, 1 H, J = 7.0, 3, 4, 5), 105.6 (C–1),
H–5), 6.02, (d, 1 H, J = 3.9, H–1), 7.28–7.30 112.0 (Me2C), 127.8–
(m, 5 H, C6H5)
137.2 (C6H5)

SYNTHESIS
Papers
Table 5. (continued)
1784
Entry
9
Prod-
ucta
Yield
(%)
mp (°C)
70–71
[α]D25
(c = 1,
CHCl3)
IR (film)
1H NMR (300 MHz, CDCl3/TMS)
δ, J (Hz)
13C NMR (75 MHz,
CDCl3/TMS)
δ
ν (cm–1)
28be
93
+ 41
1379, 1280, 1.19, 1.34 [2 s, 6 H, (CH3)2C], 2.43 (dddd, 1 24.2 (C–6), 24.7, 25.9
1250, 1234, H, J = 7.1, 7.3, 9.1, 11.4, H-6), 4.21 (dddd, [(CH3)2C], 54.6
1212, 1161, 1 H, J = 6.2, 8.0, 8.1, 11.4, H–6'), 4.48 (d, 1 (CH3O), 68.9 (C–7),
1096, 1080, H, J = 6.0, H–2), 4.49–4.55 (m, 1 H, H–7), 79.3, 80.7, 83.3, 84.8
1056, 1026, 4.59–4.67 (m, 1 H, H–7'), 4.68 (dd, 1 H, J = (C–2, 3, 4, 5), 107.4
979b
3.8, 5.9, H–3), 4.87 (s, 1 H, H–1), 4.96 (q, 1 (C–1), 112.6 (Me2C)
H, J = 7.7, H–5)
10
29ad
90
syrup
– 44
1741, 1494, 1.30, 1.47 [2 s, 6 H, (CH3)2C], 1.91, 1.99 21.0 (2 CH3CO), 26.2,
1234, 1163, (2s, 6 H, 2 CH3CO) 2.16–2.24 (m, 2 H, H– 26.8 [(CH2)2C], 30.4
1124, 1076, 6, 6'), 3.91 (d, 1 H, J = 3.3, H–3), 4.04–4.17 (C–6), 60.7 (C–7), 72.0
1029, 890
(m, 2 H, H–7,7'), 4.19 (dd, 1 H, J = 3.2, 7.7, (PhCH2), 68.1, 80.5,
H–4), 4.43, 4.60 (2 d, 2 H, J = 11.6, PhCH2), 81.0, 81.7, (C–2, 3, 4,
4.58 (d, 1 H, J = 3.7, H–2), 5.30 (dt, 1 H, J 5), 105.1 (C–1), 111.8
= 3.7, 7.6, H–5), 5.89 (d, 1 H, J = 3.7, H–1), (Me2C), 128.1–137.0
7.30–7.38 (m, 5 H, C6H5)
(C6H5), 169.8, 171.0 (2
C=O)
11
12
29bg
47
80
syrup
syrup
– 51
1742, 1371, 1.25, 1.40 [2 s, 6 H, (CH3)2C], 1.91–2.08 21.0, 21.1 (2 CH3CO),
1236, 1163, (m, 1 H, H–6), 2.01, 2.02 (2 s, 6 H, 2 24.9, 26.1 [(CH3)2C],
1089, 1051, CH3CO), 2.14–2.25 (m, 1 H, H–6), 3.32 (s, 30.6
(C–6),
54.7
1031, 988, 3 H, CH3O), 3.94 (dd, 1 H, J = 3.7, 7.5, H– (CH3O), 60.9 (C–7),
969
4), 4.13 (m, 2 H, H–7,7'), 4.49 (d, 1 H, J = 68.8, 79.6, 80.3, 84.7
5.9, H–2), 4.66 (dd, 1 H, J = 3.7, 5.9, H–3), (C–2, 3, 4, 5), 107.2
4.86 (s, 9 H, H–1), 5.22 (dt, 1 H, J = 3.7, 7.6, (C–1), 112.8 (Me2C)
H–5)
30ad
– 28
1741, 1372, 1.33–1.50 [2 s, 6 H, (CH3)2], 1.75–1.82 (m, 20.9, 21.2 (2 CH3CO),
1235, 1166, 2 H, H–6, 6'), 1.99, 2.03 (2 s, 6 H, 2 26.3, 26.8 [(CH3)2C],
1075, 1025, CH3CO), 3.92 (d, 1 H, J = 3.4, H–3), 4.05 (t, 29.6 (C–6), 60.2 (C–7),
890, 863
2 H, J = 6.0, H–7, 7'), 4.21 (dd, 1 H, J = 3.5, 71.7 (PhCH2), 69.0,
8.3, H–4), 4.43, 4.70 (2 d system, 2 H, J = 81.0, 81.8 (C–2, 3, 4,
11.7, PhCH2), 4.65 (d, 1 H, J = 3.9, H–2), 5), 105.1 (C–1), 111.7
5.43 (dt, 1 H, J = 3.7, 8.1, H–5), 5.95 (d, 1 (Me2C), 128.2–137.2
H, J = 3.9, H–1), 7.34 (br s, 5 H, C6H5)
(C6H5), 170.2, 171.4,
(2 C=O)
13
14
30bd
45
85
syrup
+ 40
1742, 1235, 1.28, 1.46 [2 s, 6 H, (CH3)2C], 1.88–2.20 21.0, 21.1 (2 CH3CO),
1163, 1099, (m, 2 H, H–6, 6'), 2.03, 2.07 (2 s, 6 H, 2 25.1, 26.2 [(CH3)2C]
1051, 1022, CH3CO), 3.29 (s, 3 H, CH3CO), 3.94 (dd, 1 29.8
(C–6),
54.6
988
H, J = 3.6, 8.5, H–4), 4.10–4.16 (m, 2 H, H– (CH3O), 60.5 (C–7),
7, 7'), 4.55 (d, 1 H, J = 5.9, H–2), 4.67 (dd, 69.6, 79.6, 80.6, 85.3
1 H, J = 3.6, 5.9, H–3), 4.89 (s, 1 H, H–1), (C–2, 3, 4, 5), 106.9
5.39 (dt, 1 H, J = 3.4, 8.4, H–5)
(C–1), 113.0 (Me2C)
31a
61–62
– 40
3398, 1075b
1.32, 14.9 [2 s, 6 H, (CH3)2C], 1.66–1.78 26.3, 26.8 [(CH3)2C],
(m, 1 H, H–6), 1.87–1.97 (m, 1 H, H–6), 35.9 (C–6), 61.4 (C–7),
2.74, 3.02 (2 br s, 2 H, 2 OH), 3.85 (br s, 2 72.1 (PhCH2), 69.4,
H, H–7, 7'), 4.04 (dd, 1 H, J = 3.2, 7.7, H– 81.8, 82.1, 82.2 (C–2,
4), 4.10 (d, 1 H, J = 3.2, H–3), 4.13–4.17 (m, 3, 4, 5), 105.1 (C–1),
1 H, H–5), 4.63 (d, 1 H, J = 3.7, H–2), 4.56, 111.8 (Me2C), 128.0–
4.73 (2 d, 2 H, J = 11.8, PhCH2), 5.94 (d, 1 137.1 (C6H5)
H, J = 3.7, H–1), 7.36 (m, 5 H, C6H5)
15
31bh
62
93–94
+ 50
3413, 3334, 1.25, 1.34 [2 s, 6 H, (CH3)2C], 1.39–1.51 24.6, 25.9 [(CH3)2C],
1263, 1210, (dddd, 1 H, J = 5.5, 6.0, 9.1, 13.6, H–6'), 37.6 (C–6), 53.5
1191, 1120, 1.76–1.87 (dddd, 1 H, J = 2.7, 7.7, 7.7, 13.6, (CH3O), 57.4 (C–7),
1089, 1047, H–6), 3.19 (s, 3 H, CH3O), 3.52, 3.57 (m, 3 64.4 (C–5), 79.1, 82.1,
1026b
H, H–4, 7,7'), 3.77–3.85 (dddd, 1 H, J = 2.7, 84.1 (C–2, 3, 4), 106.3
6.5, 6.5, 9.1, H–5), 4.31 (t, 1 H, J = 5.2, OH– (C–1), 111.1 (Me2C)i
7), 4.46 (d, 1 H, J = 5.9, H–2), 4.59 (d, 1 H,
J = 6.5, OH–5), 4.71 (dd, 1 H, J = 3.3, 5.9,
H–3), 4.77 (s, 1 H, H–1)i

SYNTHESIS
December 1998
1785
Table 5. (continued)
Entry
Prod-
ucta
Yield
(%)
mp (°C)
75–76
[α]D25
(c = 1,
CHCl3)
IR (film)
1H NMR (300 MHz, CDCl3/TMS)
δ, J (Hz)
13C NMR (75 MHz,
CDCl3/TMS)
δ
ν (cm–1)
16
32a
76
– 50 (c = 3435, 1255, 1.49, 1.33 [2 s, 6 H, (CH3)2C], 1.52–1.60 26.3, 26.8 [(CH3)2C],
0.5)
1209, 1161, (m, 1 H, H–6), 1.70–1.80 (m, 1 H, H–6'), 34.8 (C–6), 60.8 (C–7),
1139, 1107, 3.26, 3.80 (2 br s, 2 H, 2 OH), 3.78 (m, 2 H, 71.9 (PhCH2), 69.7,
1027b
H–7, 7'), 3.97 (d, 1 H, J = 3.5, H–3), 4.06 82.2, 82.6 (C–2, 3, 4,
(dd, 1 H, J = 3.5, 5.6, H–4), 4.19 (m, 1 H, H– 5), 104.9 (C–1), 111.8
5), 4.45, 4.71 (2 d, 2 H, J = 11.8, PhCH2), (Me2C), 128.0–137.2
4.65 (d, 1 H, J = 3.8, H–2), 5.98 (d, 1 H, J = (C6H5)
3.8, H–1), 7.28–7.40 (br s, 5 H, C6H5)
17
32bj
80
56–57
+ 68
3430, 1211, 1.23, 1.33 [2 s, 6 H, (CH3)2C], 1.43–1.55 25.9, 24.5 [(CH3)2C]
1164, 1100, (m, 1 H, H–6), 1.63–1.73 (m, 1 H, H–6), 35.5 (C–6), 53.6
1093, 1052, 3.22 (s, 3 H, CH3O), 3.43–3.61 (m, 2 H, H– (CH3O), 57.6 (C–7),
1022, 987b
7, 7'), 3.65 (dd, 1 H, J = 3.2, 8.5, H–4), 66.5 (C–5), 79.2, 83.4,
3.72–3.80 (m, 1 H, H–5), 4.33 (t, 1 H, J = 84.4 (C–2, 3, 4), 106.0
5.2, OH–7), 4.47 (d, 1 H, J = 5.9, H–2), 4.62 (C–1), 111.2 (Me2C)i
(d, 1 H, J = 5.2, OH–5), 4.68 (dd, 1 H, J =
3.3, 5.9, H–3), 4.80 (s, 1 H, H–1)i
a Satisfactory microanalyses obtained: C ± 0.4, H ± 0.2.
b Recorded as KBr pellet.
c Similar treatment using 24b as starting material gave 25b (72%).
d Purified on silica gel using Et2O/hexane (1:1) as solvent.
e This compound was not stable on silica gel and the resulting product was spectroscopically pure.
f Crystallized from Et2O/hexane.
g Purified on silica gel using Et2O/hexane (4:1) as solvent.
h Lit.20 mp 94–95°C; Lit.20 [α]D + 58.8.
i Recorded in DMSO-d6
j Lit.19 mp 55–57°C; Lit.19 [α]D +67.5 (c = 1.4, CHCl3).
TLC was performed on Merck Silica Gel 60 F254 aluminium sheets
with detection by charring with H2SO4, and by UV light when appli-
cable. Flash and column chromatography was performed on silica gel
Scharlau (230–400 mesh, ASTM) and Merck (70–230 mesh, ASTM).
Melting points were measured on a Büchi melting point apparatus and
a Reichter hotplate microscope and are uncorrected. Elemental anal-
yses were carried out with Perkin-Elmer 240C instrument. Optical ro-
tations were recorded on a Perkin-Elmer 141 polarimeter at r.t. IR
Hydrolysis of the Lithium Sulfates 9–11; General Procedure:
To a solution of compound 9–11 in THF/H2O was added concd
H2SO4. The reaction mixture was stirred until no sulfate remained
(TLC), then diluted with Et2O, washed with aq satd NaHCO3 solution
and H2O, dried (MgSO4), and concentrated. The product was purified
by flash cromatography on silica gel (see Table 2, entries 8–10 for
reaction conditions and yields and Table 4 for physical and spectro-
scopic data).
1
spectra were recorded on a Perkin-Elmer 983G. H and 13C NMR
spectra were recorded on a Bruker AM 300, and 400 MHz spectrom-
eter. Chemical shifts are given in ppm and referenced to internal TMS
(δH, δC 0.00). J values are given in Hz.
Methoxymethylation of Compounds 13, 14 and 17; General Pro-
cedure:
To a vigorously stirred solution of compound 13, 14 and 17 in CH2Cl2
and dimethoxymethane at r.t. was added portionwise P2O5 until com-
pletion of the reaction. The solid residue was removed by decantation
and washed with CH2Cl2. The combined CH2Cl2 solutions were
washed with aq satd NaHCO3 solution and H2O, dried (K2CO3), con-
centrated, and the product was purified by flash chromatography on
silica gel (see Table 2, entries 11–13 for reaction conditions and
yields and Table 4 for physical and spectroscopic data).
Cyclic sulfates 1, 2, 4 and 5 were prepared from methyl 2,3-di-O-
acetyl-α-D-glucopyranoside,21 methyl 2,3-di-O-acetyl-α-D-man-
nopyranoside (prepared from methyl 2,3-di-O-acetyl-4,6-O-ben-
zylidene-α-D-mannopyranoside22), methyl 2,3-di-O-benzyl-α-D-
mannopyranoside,23 and methyl 2,3-di-O-benzyl-α-D-galactopyra-
noside,24 respectively, following the procedure of Gao and
Sharpless15 (seeTable 1 for yields and physical data).
Reduction of the Nitriles 15, 16 and 18; General Procedure:
To a solution of compounds 15, 16 and 18 in anhyd toluene at 0°C
was added DIBAH (1 M in hexane or THF). The reaction mixture was
stirred until no nitrile remained (TLC). Then MeOH and aq 2 M HCl
were added, the mixture was stirred for 45 min and filtered. The aque-
ous layer in the filtrate was extracted with Et2O, and the combined
organic layers were washed with 2 M HCl, aq satd NaHCO3 solution
and H2O, dried, and concentrated. NaBH4 was added to the crude
product in MeOH, and the solution was stirred at r.t. for 0.5–1.5 h.
Processing of the mixture by treatment with acetone to destroy the
excess of hydride and evaporation with several portions of added
Preparation of Compounds 7–12 by Reaction of Lithium or Sodi-
um Cyanide with Cyclic Sulfate Sugars; General Procedure:
To a solution of the cyclic sulfate 1–6 in anhyd DMF (2 mL) or
anhyd acetone (20 mL) was added LiCN or NaCN. The resulting
solution or suspension was then stirred at r.t. until no cyclic sulfate
remained (TLC). The solution was then concentrated, and the prod-
uct was purified by flash cromatography on silica gel (see Table 2,
entries 1–7 for reaction conditions and yields and Table 4 for phys-
ical data).

SYNTHESIS
Papers
1786
MeOH gave a residue that was diluted with Et2O and then washed
successively with aq 2 M HCl, satd NaHCO3 solution and H2O, dried
(MgSO4) and concentrated to give a product that was purified by flash
cromatography on silica gel (see Table 3 for reaction conditions and
Table 4 for physical and spectroscopic data).
0.18 mmol) was kept at r.t. for 1 h, deionized with Amberlite IR-120
(H+) (2 g) and the solvent evaporated. The residue was purified on
silica gel using EtOAc as solvent (see Table 5, entries 14–17).
This work was supported by two grants (PB92-1207 and PB96-1505)
from the Dirección General de Enseñanza Superior (M.E.C.) of
Spain.
Reaction of Furanosides 22a,b with 2-Naphthalenesulfonyl Chlo-
ride; General Procedure:
To a stirred solution of 22a,b17,18 (15 mmol) in pyridine (15 mL) was
slowly added 2-naphthalenesulfonyl chloride (2.7 equiv for 22a, and
1.4 equiv for 22b) at 0°C. After 20–24 h at r.t., H2O (50 mL) was
added and the mixture extracted with CHCl3 (100 mL). The organic
layer was washed successively with 5% aq HCl (2 × 75 mL), aq satd
NaHCO3 solution (100 mL) and H2O (50 mL). Then the organic so-
lution was dried (MgSO4), concentrated and the resulting residue was
chromatographed on silica gel (Et2O/hexane 3:1 for 23a, and EtOAc/
hexane 1:1 for 23b) (see Table 5, entries 1 and 2).
(1) Pakulski, Z.; Zamojski, A. Pol. J. Chem. 1995, 69, 509.
(2) van der Klein, P. A. M.; Boons, G. J. P. H.; Veeneman, G. H.;
van der Marel, G. A.; van Boom, J. H. Tetrahedron Lett. 1989,
30, 5477.
(3) van der Klein, P. A. M.; van Boom, J. H. Carbohydr. Res. 1992,
224, 193.
(4) Sepulchre, A. M.; Lukacs, G.; Vass, G.; Gero, S. D.Bull. Soc.
Chim. Fr. 1972, 4000.
(5) Achab, S.; Das, B. C. J. Chem. Soc., Chem. Commun. 1983,
391.
5,6-Anhydro Compounds 25a,b; General Procedure:
To a solution of compounds 23a,b (7.5 mmol) in anhyd MeOH/
CHCl3 (2:1, 30 mL) was added a solution of sodium (2.3 equiv for
23a, and 4.1 equiv for 23b) in MeOH (15 mL). The reaction mixture
was stirred at r.t. for 2 h. An aq 20% solution of NH4Cl (75 mL) was
added, the MeOH was evaporated, and the residue extracted with
EtOAc (2 × 100 mL). The organic layer was dried (MgSO4), concen-
trated and the crude product was purified by column chromatography
(Et2O/hexane 1:1 for 23a, and Et2O/hexane 1:3 for 23b) (Table 5,
entries 4 and 5). Similar treatment using the 6-deoxy-6-chloro deriv-
ative 24b as starting material gave 25b (72%).
(6) Achab, S.; Das, B. C. J. Chem. Soc., Perkin Trans. 1 1990,
2863.
(7) Lohray, B. B. Synthesis 1992, 1035.
(8) van der Klein, P. A. M.; Filemon, W.; Veeneman, G. H.; van der
Marel, G. A.; van Boom, J. H. J.Carbohydr.Chem. 1992, 11,
837.
(9) (a) Burgess, K.; Li, W. Tetrahedron Lett. 1995, 36, 2725.
(b) Schmidt, R. R.; Klotz, W. Synthesis 1996, 687.
(c) Hendrix, M.; Alper, P. B.; Priestley, E. S.; Wong, C. H. An-
gew. Chem. ,Int.Ed. Engl. 1997, 36, 95; Angew. Chem. 1997,
109, 119.
Synthesis of Oxetanes 27a,b and 28a,b; General Procedure:
To a stirred solution of trimethylsulfoxonium iodide (4.1 mmol) in t-
BuOH (8 mL) was added KOBu-t (4.1 mmol) at 50°C. After 30 min,
oxirane 25a,b and 26a,b17,18 (1.37 mmol) in t-BuOH (8 mL) was add-
ed, and the stirring was continued at the same temperature until TLC
(Et2O/hexane, 2:1) showed complete disappearance of the starting
material (6–20 h). The solvent was carefully evaporated under re-
duced pressure and H2O (50 mL) was added to the residual suspen-
sion. The mixture was extracted with Et2O (2 × 50 mL), and the com-
bined organic solutions were dried (MgSO4) and concentrated. Crude
27a was purified by a short column chromatography (Et2O/hexane,
1:1). Compounds 28a crystallized from Et2O/hexane. Compounds
27b and 28b were not stable upon treatment with silica gel and were
used directly in the next step as they showed to be spectroscopically
pure (see Table 5, entries 6–9).
(10) Santoyo-González, F.; Calvo-Flores, F. G.; García-Mendoza,
P.; Hernández -Mateo, F.; Isac-García, J.; Pérez- Álvarez, M.
D. J. Chem. Soc.,Chem.Commun. 1995, 461.
(11) Calvo-Flores, F. G.; García-Mendoza, P.; Hernández-Mateo, F.;
Isac-García, J.; Santoyo-González, F. J. Org. Chem. 1997, 62,
3944.
(12) Calvo-Asín, J. A.; Calvo-Flores, F. G.; Expósito-López, J.;
Hernández-Mateo, F.; García-López, J. J.; Isac-García, J.; San-
toyo-González, F.; Vargas-Berenguel, A. J. Chem. Soc. Perkin
Trans. 1 1997, 1079.
(13) Okuma, K.; Tanaka, Y.; Kaji, S.; Ohta, H. J. Org. Chem. 1983,
48, 5133.
(14) Fitton, A. O.; Hill, J.; Jane, D. E.; Millar, R. Synthesis 1987,
1140.
(15) Gao, Y.; Sharpless, K. B. J. Am. Chem. Soc. 1988, 110, 7538.
(16) Aspinall, G. O.; McDonald, A. G.; Sood, R. K. Can. J. Chem.
1994, 72, 247.
(17) Whistler, R. L.; Lake, W. C. Methods Carbohydr. Chem. 1972,
6, 286.
6-Deoxyheptoses 29a,b and 30a,b by Ring Opening of Oxetanes
27a,b and 28a,b; General Procedure:
A mixture of 27a,b or 28a,b (6.5 mmol) and anhyd NaOAc (6 g) in
Ac2O (25 mL) and AcOH (2 mL) was heated at 140°C until TLC
(Et2O/hexane 2:1 for 27a and 28a; Et2O/hexane 4:1 for 27b and 28b)
showed complete disappearance of the starting material (7–48 h). Af-
ter cooling, the mixture was dissolved in CH2Cl2 (150 mL) and
washed successively with aq satd NaHCO3 solution (3 × 150 mL) and
H2O (100 mL). The organic layer was dried (Na2SO4) and the solvent
removed under reduced pressure giving a crude product that was pu-
rified by column chromatography (Et2O/hexane 1:1 for 29a and 30a
and Et2O/hexane 4:1 for 29b and 30b) (see Table 5, entries 10–13).
(18) Yuasa, H.; Izukawa, Y.; Hashimoto, H. J. Carbohydr. Chem.
1989, 8, 753.
(19) Pakuslski, Z., Zamojski, A. Tetrahedron, 1995, 51, 871.
(20) Krajewski, J. W., Gluzinski, P., Pakulski, Z., Zamojski, A.,
Mishnev, A., Kemme, A. Carbohydr. Res., 1994, 252, 97.
(21) Hull, D. M. C.; Orchard, P. F.; Owen, L. N. Carbohydr. Res.,
1977, 57, 51.
(22) Horton, D.; Luetzow, A.E. Carbohydr. Res., 1968, 7, 101.
(23) Winnik, F. M.; Brisson, J.-R.; Carver, J. P.; Krepinsky; J.J. Car-
bohydr. Res. 1982, 103, 15.
Zemplén De-O-acetylation of 29a,b and 30a,b; General Procedure:
A solution of the corresponding acetyl derivative 29a,b or 30a,b
(1 mmol) in anhyd MeOH (30 mL) containing NaOMe (10 mg,
(24) Schneider, J.; Lee, Y. C.; Flowers, H. M. Carbohydr. Res. 1974,
36, 159.