3,3'-Dideoxytrehaloses via dimerisation of 2-hydroxyglycal esters

Article abstract of DOI:10.1016/S0008-6215(99)00109-3

The susceptibility of 2-hydroxyglycal esters i.e., 2,3,4,6-tetra-O-acetyl-1,5-anhydro-D-arabino-hex-1-enitol and its D-lyxo analog towards dimerization to 2,3-unsaturated α,α-trehaloses is described, smoothly occurring in moist dichloromethane or acetone solution in the presence of iodine or boron trifluoride. The reaction involves Ferrier ionization and addition of water at C-1 of the delocalized glycosyl oxocarbenium ion, followed by addition of the hex-2-enopyranose thus formed, with its 1-OH, onto the educt still present. Hydrogenation of the dimers thus formed, i.e., 2,4,6-tri-O-acetyl-3-deoxy-α-D-erythro-hex-2-enopyranosyl 2,4,6-tri-O-acetyl-3-deoxy-α-D-erythro-hex-2-enopyranoside and its D-threo/D-threo analog proceeds with high stereoselectivity to give the peracetylated 3,3'-dideoxy-α,α-trehaloses with D-ribo/D-ribo and D-lyxo/D-lyxo configuration. Copyright (C) 1999 Elsevier Science Ltd.

Full text of DOI:10.1016/S0008-6215(99)00109-3

www.elsevier.nl/locate/carres
Carbohydrate Research 319 (1999) 47–54
3,3%-Dideoxytrehaloses via dimerisation of
2-hydroxyglycal estersꢀ
Frieder W. Lichtenthaler *, Bernd Werner
Institut fu¨r Organische Chemie, Technische Uni6ersita¨t Darmstadt, Petersenstraße 22, D-64287 Darmstadt, Germany
Received 9 March 1999; accepted 27 April 1999
Abstract
The susceptibility of 2-hydroxyglycal esters i.e., 2,3,4,6-tetra-O-acetyl-1,5-anhydro-D-arabino-hex-1-enitol and its
D
-lyxo analog towards dimerization to 2,3-unsaturated a,a-trehaloses is described, smoothly occurring in moist
dichloromethane or acetone solution in the presence of iodine or boron trifluoride. The reaction involves Ferrier
ionization and addition of water at C-1 of the delocalized glycosyl oxocarbenium ion, followed by addition of the
hex-2-enopyranose thus formed, with its 1-OH, onto the educt still present. Hydrogenation of the dimers thus
formed, i.e., 2,4,6-tri-O-acetyl-3-deoxy-a-
enopyranoside and its -threo/ -threo analog proceeds with high stereoselectivity to give the peracetylated 3,3%-
-ribo/ -ribo and -lyxo/ -lyxo configuration. © 1999 Elsevier Science Ltd. All rights
D
-erythro-hex-2-enopyranosyl 2,4,6-tri-O-acetyl-3-deoxy-a-D-erythro-hex-2-
D
D
dideoxy-a,a-trehaloses with
reserved.
D
D
D
D
Keywords: 3,3%-Dideoxy-a,a-trehaloses; 2-Hydroxyglycal esters; Allylic rearrangement; Dihydropyrans
loxy-glucal esters 1 and 2 can be liberated by
1. Introduction
N-bromosuccinimide-induced methanolysis to
afford ulosyl bromides of type 3 [5] that
proved to be particularly efficient ‘indirect’
Aside from glycals, which have extensively
been exploited as precursors for a variety of
naturally occurring products [2], the 2-acy-
loxyglycals of type 1 and 2, although just as
accessible [3], have found considerably less
attention. In fact, their unique enolester-
masked carbonyl group at C-2 adds a struc-
tural function that considerably extends the
variability of their ensuing reactions [4], and,
hence, their utility as enantiopure building
blocks. Thus, the C-2 carbonyl group in the
b-
D
-mannosyl donors [5,6]. Similar potential
-mannosaminyl donors [7] ap-
as ‘indirect’ b-
D
plies to the oximinoglycosulosyl bromides 5,
smoothly derived from 1 and 2 by a high-
yielding 3-step procedure involving hydroxy-
laminolysis (“4 [8]), benzoylation, and
photobromination [9,10]. Other important hy-
droxyglycal ester transformations involve
Lewis acid-induced allylic rearrangements to
3-deoxy-hex-2-enopyranoses by intra- or inter-
molecular addition at the anomeric center of
an acetoxy group (1“6 [11]), of alkoxy
residues (1“7 [12]), or of an acylperoxy
group, which by fragmentation of the primary
adduct leads to pyranoid enollactones (“8
[13]) (Scheme 1).
D-glucose-derived 2-acetoxy- and 2-benzoy-
ꢀ Enantiopure building blocks from sugars, Part 25. For
Part 24, see Ref. [1].
* Corresponding author. Tel.: +49-6151-162-376; fax: +
49-6151-166-674.
E-mail address: fwlicht@sugar.oc.chemie.tu-darmstadt.de
(F.W. Lichtenthaler)
0008-6215/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(99)00109-3

48
F.W. Lichtenthaler, B. Werner / Carbohydrate Research 319 (1999) 47–54
Scheme 1.
Described herein is a useful addition to this
oses in which the a anomer 6 is the preponder-
ant product. When the solvents used are not
absolutely dry, or by the deliberate addition of
small amounts of water, the Ferrier rearrange-
ment is followed by further reactions, the re-
spective products then depending on the
multifaceted array of versatile building blocks,
namely the Lewis acid-promoted allylic rear-
rangement of 2-acetoxyglucal triacetate 1 and
its galactose-derived 4-epimeric analog 16 and
subsequent dimerization to 2,3:2%,3%-unsatu-
rated trehalose-type dimers (10 and 18). This
reaction, which has its analogy in the Lewis
acid-induced dimerization of tri-O-acetyl-1,5-
conditions used. Exposure of
1
in
dichloromethane solution to borotrifluoride
diethyl etherate in the presence of water
rapidly forms a mixture of three main compo-
nents, characterized as acetoxymethylfurfural
(13), the a,a dimer 10, and the bis-enone 14.
Their formation can be readily rationalized by
14 arising from 10 via hydrolytic cleavage of
the enolester and subsequent elimination of
the 4-acetoxy group, whereas 13 is an ensuing
product of the intermediate hexenopyranose 9
(Scheme 2).
anhydro-2-deoxy-
D
-arabino-hex-1-enitol (tri-
O-acetyl-
D
-glucal) [14], opened up the way to
3,3%-dideoxy-a,a,-trehalose analogs that are of
interest as trehalase inhibitors.
2. Results and discussion
2,3,4,6-Tetra-O-acetyl-1,5-anhydro- -ara-
D
Evaluation of various other catalyst/solvent
combinations, e.g., zinc chloride/dichloro-
methane, N-iodosuccinimide or iodine/ace-
tonitrile, eventually led to iodine/acetone in
the presence of water as the most suitable
conditions for the conversion 1“10:
bino-hex-1-enitol (1) in boiling acetic acid
[11a] or cold acetic anhydride in the presence
of zinc chloride [11b], or in benzene with
catalytic amounts of boron trifluoride etherate
[11c], undergoes Ferrier rearrangement to an
anomeric mixture of 3-deoxyhex-2-enopyran-

F.W. Lichtenthaler, B. Werner / Carbohydrate Research 319 (1999) 47–54
49
Scheme 2.
dichloromethane containing water, however,
the conversion was readily achieved to yield
the reaction is rapid (30 min, 0 °C) and allows
the isolation of 10 in 58% yield. Saturation of
the two enolester double bonds was readily
effected only when hydrogenation was per-
formed over 5% rhodium on carbon in ethyl
acetate, providing the 3,3%-dideoxy-trehalose
in the form of its peracetate 11 (75% isol.
yield), or in its free form 12 following stan-
dard O-deacetylation. Over Pd, Pd/C and Pt/
(53%) the nicely crystalline
D
-threo/ -threo
D
dimer 18; it was hydrogenated with remark-
able stereoselectivity (84% isol. yield) to the
equally crystalline
D
-lyxo/ -lyxo-3-3%-dideoxy
D
trehalose hexaacetate 20 (Scheme 3).
It is interesting to note that the coupling of
the a- -hexenopyranose intermediate 17 with
D
unreacted 16, i.e., 16+17“18, cannot be in-
tercepted by other reagents, e.g., by m-
chloroperbenzoic acid to form the enollactone
20. Only when the BF3-mediated peroxidation
of 16 was effected under strictly anhydrous
conditions requiring the removal of water
from the commercially available MCPBA, a
high yield (90%) of the enollactone could be
obtained—obviously via fragmentation of the
1-peroxyacyl-hexenopyranose intermediate 19
[13].
C
catalysts, the hydrogenation of 10
proceeded sluggishly and stereochemically
non-uniformly, whereas the use of rhodium on
carbon catalyst and educt in a 1:1 ratio led to
some reductive deacetoxylation as evidenced
by the isolation of 8% of the 2,3:3%-trideoxy
derivative 15.
This simple 3-step sequence for the conver-
sion of 1 into a 3,3%-dideoxy-a,a-trehalose, i.e.,
1“10“11“12, appears to be generally ap-
plicable, since the respective
tol derivative 16 was also readily converted
into the -threo/ -threo-trehalose analog 18.
Interestingly, the 2-acetoxy- -galactal 16 was
considerably less reactive than its -glucal
D
-lyxo-hex-1-eni-
Although configurational assignments could
1
D
D
readily be inferred from H and 13C NMR
D
data, the high crystallinity of the
D
-galactal-
D
derived dimer 18 invited structural verification
by X-ray crystallography. As depicted in Fig.
1, the molecular geometry of 18 clearly unveils
the two O-linked dihydropyrane rings to be in
counterpart—a reactivity difference that has
previously been observed [15] in the acid-in-
duced Ferrier rearrangement to the hex-2-
enopyranose tetraacetate (4-epimer of 6).
Thus, exposure of 16 to iodine in aqueous
acetone had no effect; under somewhat more
forcing conditions, i.e., boron trifluoride in
a
OH5 halfchair conformation, in which the
ring oxygen is slightly more above the plane
formed by carbons 1–4 than C-5 is below
,
(0.36 vs. 0.32 A). The bond lengths and bond

50
F.W. Lichtenthaler, B. Werner / Carbohydrate Research 319 (1999) 47–54
Scheme 3.
angles are within the expected ranges [16], the
dihedral angles in the two pyranoid rings dif-
fer only slightly from each other (cf. Table 1,
forms A and B, respectively), and, moreover
are in very close agreement to those found for
tion of 2,3,4,6-tetra-O-acetyl-1,5-anhydro- -
D
arabino-hex-1-enitol (1, 3.96 g, 12 mmol) [3e]
in dry acetone (8 mL) was cooled (0 °C),
iodine (3.05 g, 12 mmol) and water (0.12 mL,
8 mmol) was added, and the mixture
the a- -threo-hex-2-enopyranose analogs 22
D
[17] and 23 [18]. The C-4–C-5–O-5–C-1 dihe-
dral angles are uniformly in the 64° range,
O
evidence for an essentially identical H5 con-
formation of 18, 22 and 23.
3. Experimental
General methods.—1H (300 MHz) and 13C
(75 MHz) NMR spectra were recorded at
25 °C with a Bruker AC 300 spectrometer.
Chemical shifts (l) are given in ppm relative
to the signal for internal Me4Si (CDCl3).
Column chromatography was performed on
Kieselgel 60 (E. Merck, 230 mesh) and frac-
tions were monitored by TLC on Kieselgel 60
F254 (E. Merck) by detection with UV light
and then charring with H2SO4. Optical rota-
tions were measured for solutions in CHCl3 at
20 °C with a Perkin–Elmer 241 polarimeter,
using a 10 cm/1 mL cell.
Fig. 1. Perspective drawing of the molecular structure of 2,4,6-
tri-O-acetyl-3-deoxy-a-D-threo-hex-2-enopyranosyl 2,4,6-tri-
2,4,6-Tri-O-acetyl-3-deoxy-h-
2-enopyranosyl 2,4,6-tri-O-acetyl-3-deoxy-h-
-erythro-hex-2-enopyranoside (10).—A solu-
D-erythro-hex-
O-acetyl-3-deoxy-a-D-threo-hex-2-enopyranoside (17), reveal-
ing a OH5 halfchair conformation for each of the pyranoid
D
rings.

F.W. Lichtenthaler, B. Werner / Carbohydrate Research 319 (1999) 47–54
51
Table 1
Selected torsion angles (°) for 18, and the monomeric analogs methyl 4,6-di-O-acetyl-2,3-dideoxy-a-
(22) [17] and 1,4,6-tri-O-acetyl-2-(N,N-diacetylamido)-2,3-dideoxy-a-
D
-threo-hex-2-enopyranoside
D
-threo-hex-2-enopyranose (23) [18]
Dihedral angels
18
A
B
22 a
23 b
Pyranoid ring
O-5–C-1–C-2–C-3
C-1–C-2–C-3–C-4
C-2–C-3–C-4–C-5
C-3–C-4–C-5–O-5
C-4–C-5–O-5–C-1
C-5–O-5–C-1–C-2
+12.2
+3.6
+12.8
−44.4
+64.4
−46.1
+14.4
+1.9
+12.1
−42.3
+62.6
−46.5
+13.2
+1.2
+14.8
−46.6
+64.9
−46.8
+14.4
+6.4
+7.1
−40.5
+64.1
−49.3
Glycosidic linkage
O-5–C-1–O-1–C-1%
+74.5
+76.5
+67.0
+76.8
Substituent angles
C-2–C-3–C-4–O-4
O-4–C-4–C-5–C-6
O-4–C-4–C-5–O-5
−107.8
−41.3
+76.0
−108.6
−38.7
+79.6
−102.4
−53.2
+68.7
−113.0
−39.5
+80.8
Cremer–Pople puckering parameters [20]
Q
0.466
52.4
0.444
51.0
0.466
51.3
0.475
55.1
[
b
328.1
331.9
326.0
336.0
Conformation
OH5
OH5
OH5
OH5(“OE)
a Dihedral angles not given in Ref. [17] and the Cremer–Pople parameters were calculated by S. Immel from the original
coordinates (REFC THHXPY).
b Cremer–Pople parameters were calculated by S. Immel from the original coordinates (REFC AAXTHP).
was stirred at 0 °C for 30 min. The reaction
was quenched with satd. Na2S2O3/satd.
NaHCO3 solution (3:1, 40 mL), extracted with
CH2Cl2, followed by consecutive washing of
the organic phase with water (30 mL), satd.
NaHCO3 (2×20 mL) and water (30 mL),
drying (MgSO4), and evaporation to dryness.
Purification of the syrupy residue by elution
from a silica gel column (3×30 cm) with 4:1
toluene–EtOAc afforded, after removal of the
solvents in vacuo, 1.95 g (58%) of 10 as a
colorless syrup; Rf 0.45 in 1:1 toluene–EtOAc;
[h]2D0+64.6° (c 1.1, CHCl3); 1H NMR
(CDCl3): l 5.83 (d, 1 H, H-3), 5.47 (ddd, 1 H,
H-4), 5.42 (bs, 1 H, H-1), 4.26 (dd, 1 H,
H-6b), 4.13 (m, 2 H, H-5, H-6a), 2.18, 2.10,
2.09 (three 3 H-s, AcCH3), J1,4ꢀ0.7, J3,4 2.0,
J4,5 9.5, J5,6a ꢀ2.6, J5,6b 12.0 Hz. 13C NMR
(CDCl3): l 170.6 (3 AcCO), 169.9, 167.8,
145.6 (C-2), 115.8 (C-3), 89.4 (C-1), 67.5 (C-
5), 65.3 (C-4), 62.5 (C-6), 20.8, 20.8, 20.6 (3
CH3); FD MS: m/z 581 [M+ +Na]. Anal.
Calcd for C24H30O15 (558.5): C, 51.60; H, 5.41.
Found: C, 51.41; H, 5.32.
When performing the reaction of 1 in
CH2Cl2 (990 mg in 20 mL) with BF3·Et2O (0.6
mL) in the presence of water (0.1 mL) by
stirring at ambient temperature for 1 h, an
approximate 2:1:1 mixture of dienone 14, a,a
dimer 10, and furfural 13 (Rf 0.6, 0.45 and 0.4,
resp., in 1:1 toluene–EtOAc), which, on
workup as described above, could be sepa-
rated on a silica gel column by elution with
4:1 toluene–EtOAc. The product eluted first
was secured as a colorless oil (55 mg, 11 %)
and proved to be 5-acetoxymethyl-2-
1
furanaldehyde (13) by identity of its H NMR
data with that of an authentic sample (from
Sigma–Aldrich Chemie). The fraction closely
1
following was rich in 10 (TLC, H NMR).
The dienone 14, eluted last, gave upon evapo-
ration of the appropriate fraction, 125 mg (23
1
%) of a colorless syrup; H NMR (300 MHz,
CDCl3): l 6.98 (dd, 1 H, H-4), 6.18 (dd, 1 H,

52
F.W. Lichtenthaler, B. Werner / Carbohydrate Research 319 (1999) 47–54
H-3), 5.28 (s, 1 H, H-1), 4.83 (ddd, 1 H, H-5),
4.39 and 4.28 (two 1 H-dd, two H-6), 2.10 (s,
3 H, AcCH3), J3,4 10.7, J3,5 2.4, J4,5 1.7, J5,6a
4.5, J5,6b 5.1, J6,6 11.8 Hz; FD MS : m/z+377
[M+Na+].
J1,250.5, J4,5 10.0, J5,6 2.1 and 6.1, J6,6 11.7
Hz; (b) ribo part: l 5.24 (d, 1 H, H-1), 4.96
(ddd, 1 H, H-2), 4.86 (ddd, 1 H, H-4), 4.24
and 4.10 (two 1 H-dd, two H-6), 3.89 (ddd, 1
H, H-5), 2.32 (ddd, 1 H, H-3b), 2.05 (10 H-m,
H-3a, 3 AcCH3); J1,2 3.5, J2,3a 4.7, J2,3b 12.4,
J3a,4 4.9, J3b,4 10.8, J4,5 10.1, J5,6a 2.4, J5,6b 5.2,
J6,6 11.8 Hz; FD MS: m/z 505 [MH+], 504
[M+].
Hexa-O-acetyl-3,3%-dideoxy-h,h-trehalose
(2,4,6-Tri-O-acetyl-3-deoxy-h-
D
-ribo-hexopy-
-ribo-
ranosyl 2,4,6-tri-O-acetyl-3-deoxy-h-
D
hexopyranoside) (11).—A solution of erythro-
disaccharide 10 (340 mg, 0.6 mmol) in EtOAc
(10 mL) was hydrogenated over 100 mg of 5
% rhodium on charcoal at ambient tempera-
ture for 20 h. The solution was then filtered
over Celite and the residue was washed with
EtOAc (80 mL), followed by removal of the
solvent in vacuo. The resulting syrup was
subjected to purification on a silica gel column
(2×30 cm) with 9:1 CH2Cl2–EtOAc. The elu-
ates carrying 11 (Rf 0.38 in 1:1 toluene–
EtOAc) were collected and evaporated to
dryness, 260 mg (75 %) of a colorless syrup of
3,3%-Dideoxy-h,h-trehalose (3-deoxy-h-
D
-
ribo-hexopyranosyl 3-deoxy-h- -ribo-hexo-
D
pyranoside) (12).—To a solution of hexaac-
etate 11 (170 mg, 0.3 mmol) in MeOH (5 mL)
was added 0.33 mL of N methanolic MeONa
and the mixture was kept at ambient tempera-
ture for 1 h, then quenched with AcOH (1
mL), and evaporated to dryness. Purification
of the residue by elution from a silica gel
column (1.5×20 cm) with 2:1 CHCl3–MeOH
gave, after evaporation of the appropriate
fraction, 83 mg (86 %) of 12 as a chromato-
graphically uniform solid; Rf 0.34 in 2:1
CHCl3–MeOH; [h]2D0 +161° (c 1.3, MeOH);
1H NMR (300 MHz, MeOH-d4): l 5.08 (d, 1
H, H-1), 3.8–3.5 (unresolved m, 5 H, H-2,
H-4, H-5, and two H-6), 2.09 (m, 1 H, H-3b),
1.94 (m, 1 H, H-3a), J1,2 3.4 Hz; 13C NMR
(75.5 MHz, MeOH-d4): l 92.7 (C-1), 70.4
(C-5), 67.4 (C-2), 65.3 (C-4), 61.8 (C-6), 35.3
(C-3); FD MS: m/z 333 [M+ +Na], 310
[M+], 293 [M+ –OH]. Anal. Calcd for
C12H22O9 (310.3): C, 46.45; H, 7.15. Found: C,
46.35; H, 7.03.
1
[h]2D0+132 (c 1, CHCl3); H NMR (300 MHz,
CDCl3): l 5.22 (d, 1 H, H-1), 4.96 (ddd, 1 H,
H-2), 4.83 (ddd, 1 H, H-4), 4.20 and 4.08 (two
1 H-dd, two H-6), 3.98 (ddd, 1 H, H-5), 2.36
(ddd, 1 H, H-3e), 2.08 (6 H, 3 AcCH3) and
2.07 (3 H), 2.05 (m, 1 H, H-3a); J1,2 3.4, J2,3a
12.3, J2,3e 4.6, J3a,4 10.8, J3e1,43 4.8, J4,5 10.5, J5,6a
2.1, J5,6b 5.9, J6,6 12.1 Hz; C NMR (CDCl3):
l 170.8 (3 CꢀO), 169.6, 169.6, 90.9 (C-1), 68.6
(C-5), 67.4 (C-2), 65.9 (C-4), 62.3 (C-6), 28.9
(C-3), 20.9 (3 CH3), 20.7, 20.7; FD MS: m/z
563 [MH+], 562 [M+], 273 [tri-O-acetyl-3-
deoxyglycosyl+]. Anal. Calcd for C24H34O15
(562.5): C, 51.24; H, 6.09. Found: C, 51.09; H,
6.02.
2,4,6-Tri-O-acetyl-3-deoxy-h-
2-enopyranosyl 2,4,6-tri-O-acetyl-3-deoxy-h-
-threo-hex-2-enopyranoside (18).—A sol-
ution of 2,3,4,6-tetra-O-acetyl-1,5-anhydro-
D
-threo-hex-
D
4,6-Di-O-acetyl-2,3-dideoxy-h-
D
-erythro-
D-
hexopyranosyl 2,4,6-tri-O-acetyl-3-deoxy-h-
D
-
lyxo-hex-1-enitol (16, 660 mg, 2 mmol)
[3e,15,19] in CH2Cl2 (10 mL) was stirred with
BF3·Et2O (803 mL, 20 mmol) for about 5 min
at room temperature. Water (360 mL, 20
mmol) was then added, followed by stirring
for another 5 min and quenching the reaction
by pouring into satd aq NaHCO3 (20 mL).
The mixture was diluted with CH2Cl2 (50
mL), and the organic phase was separated,
dried (MgSO4), evaporated to dryness, and the
syrupy residue was purified by elution from a
silica gel column (1.5×25 cm) with 9:1
CH2Cl2–EtOAc. Removal of the solvents gave
a syrup, which crystallized from t-BuOMe/n-
pentane: 290 mg (53%) of 18 as colorless
prisms; mp 156.0–156.5 °C; [h]2D0 −194.8° (c
ribo-hexopyranoside (15).—When using larger
amounts of catalyst in the hydrogenation of
10 as described above, e.g., a 1:1 ratio in mg,
a minor product was detectable in the reaction
mixture (Rf 0.43 in 1:1 toluene–EtOAc) which
could be eluted separately from a column and
was obtained as a colorless syrup (28 mg, 8
%), which proved to be the 4-deoxygenation
1
product 15; [h]2D0+114° (c 1.3, CHCl3); H
NMR (300 MHz, CDCl3): (a) erythro part: l
5.16 (broadened s, 1 H, H-1), 4.73 (ddd, 1 H,
H-4), 4.20 and 4.06 (1 H-dd each, two H-6),
3.95 (ddd, 1 H, H-5), 2.06–1.90 (7 H-m, 2
AcCH3, H-3b), 1.83 (3 H-m, two H-2, H-3a),

F.W. Lichtenthaler, B. Werner / Carbohydrate Research 319 (1999) 47–54
53
1
1.0, CHCl3); H NMR (300 MHz, CDCl3): l
1 H, H-3b), 2.16 (m, 1 H, H-3a), 2.11, 2.10,
13
6.06 (d, 1 H, H-3), 5.53 (s, 1 H, H-1), 5.31
(ddd, 1 H, H-4), 4.39–4.32 (m, 2 H, H-5,
H-6b), 4.22 (ddd, 1 H, H-6a), 2.24 (3 s, 3 H
each, 3 AcCH3), 2.14, 2.12; J3,4 6.1, J4,5 2.2,
J4,6a ꢀ1.0, J5,6a 3.6, J6a,b 9.8 Hz; 13C NMR
(75.5 MHz, CDCl3): l 170.4, 170.1, 167.7 (3
AcCO), 148.6 (C-2), 112.4 (C-3), 88.6 (C-1),
67.0 (C-5), 64.0 (C-4), 62.2 (C-6), 20.8 (3
AcCH3), 20.7, 20.6; FI MS: m/z 558 [M+].
Anal. Calcd for C24H30O15 (558.49): C 51.60;
H 5.41. Found: C 51.58; H 5.35.
2.05 (three 3 H-s, 3 AcCH3); J1,2 B0.5 Hz; C
NMR (CDCl3): l 170.6, 170.3, 169.9 (3
AcCO), 91.6 (C-1), 67.5 (C-5), 66.0 (C-2), 64.8
(C-4), 63.0 (C-6), 26.7 (C-3), 21.0, 21.0, 20.6 (3
AcCH3); FD MS: m/z 562 [M+ –H]. Anal.
Calcd for C24H34O15 (562.5): C, 51.24; H, 6.09.
Found: C, 51.19; H, 6.15.
2,4,6-Tri-O-acetyl-3-deoxy- -threo-hex-2-
D
enono-1,5-lactone [(5R,6R)-3,5-bis(acetoxy)-
6-acetoxymethyl-5,6-dihydro-2H-pyran-2-one]
(20).—A solution of 1.0 g (3 mmol) of 16 [15]
in CH2Cl2 (10 mL) was stirred for 20 min at
ambient temperature, then cooled to −20 °C
and followed by the addition of BF3·Et2O (267
mL, 2.2 mmol) and of a solution of anhydrous,
85 % m-chloroperbenzoic acid1 in CH2Cl2
(600 mg, 3.5 mmol, in 6 mL). After vigorous
stirring for 15 min at −20 °C, the mixture
was quenched by pouring into satd. NaHCO3
solution (15 mL) containing 10–20 mg of
Na2S2O3 (i.e., without prior warming to ambi-
ent temperature). The organic phase is re-
moved, and the aqueous layer is extracted
with CH2Cl2 (2×15 mL), followed by concen-
tration of the combined organic phases in
vacuo to a syrup, which was purified by elu-
tion from a silica gel column (2×25 cm) with
2:1 toluene–EtOAc. Removal of the solvents
from the eluates with Rf 0.30 (TLC in 2:1
toluene–EtOAc) gave 786 mg (90 %) of
enelactone 20 as a colorless syrup; [h]D20
−151.5° (c 1, CHCl3); lit. [22] : [h]2D5 −150° (c
The crystal of 18, subjected to X-ray analy-
sis, had the dimensions 0.55×0.375×0.175
mm, was monoclinic, space group P21 with
a=7.859 (4), b=22.401 (7), and c=8.092 (4)
3
,
,
A, h=k=90°, i=108.16 (4)°, V=1353.1 A ,
Z=2, T=298 K, v(Mo Ka)=0.11 mm−1
,
and Dc=1.37 g cm−3. A total of 2444 reflec-
tions were collected on a Enraf–Nonius
CAD4 diffractometer, equipped with
a
graphite-monochromated Mo Ka (u=0.71093
,
A) radiation using 1928 independent reflec-
tions to refine the complete structure, i.e.,
R(F) 0.0357 for 1860 reflections with I]2|I,
wR(F2), and 0.0961 for all 1928 reflections
(w=1/(|2(F20)+(0.0725)2+0.248P); P=(F02
−2F2c)/3. All non-hydrogen atoms were
refined anisotropically. Hydrogen atoms on
the molecule were considered in calculated
positions with the 1.2×Ueq value of the corre-
sponding atom. Data reduction was done by a
Stoe-REDU4 program, structural resolution
and refinement by SHELXS-86 and SHELXL-93
[21]. For atomic coordinates and further de-
tails, see Section 4.
1
0.5, CHCl3); H NMR (CDCl3): l 6.64 (d, 1
H, H-3), 5.44 (dd, 1 H, H-4), 4.93 (dt, 1 H,
H-5), 4.36 (d, 2 H, 7-H2), 2.20 (three 3 H-s, 3
AcCH3), 2.04, 2.03, J4,5 6.4, J5,6 2.6, J6,7 6.3
Hz; 13C NMR (CDCl3): l 170.5, 169.8, 168.1
2,4,6-Tri-O-acetyl-3-deoxy-h-
opyranosyl 2,4,6-tri-O-acetyl-3-deoxy-h-
lyxo-hexopyranoside (21).—In hydro-
D
-lyxo-hex-
D
-
a
genation vessel, rhodium on carbon (5 %, 30
mg) was added to an EtOAc solution of threo/
threo-disaccharide 18 (140 mg, 0.25 mmol, in
15 mL), and the mixture was hydrogenated
over H2 for 16 h. Subsequent filtration
through Kieselgur, thorough washing with
EtOAc and removal of the solvent in vacuo
left a syrup which crystallized from 2-
propanol: 120 mg (84 %) of 20 as colorless,
waddy needles; mp 201 °C; [h] +48.9° (c 1,
1 The m-chloroperbenzoic acid used was the commercially
available anhydrous 85% grade, i.e., containing 15% m-
chlorobenzoic acid. Since the overall reaction requires the
BF3-induced generation of an allylcarboxonium ion interme-
diate subsequently undergoing peroxidation, conditions have
to be strictly anhydrous (e.g., dry CH2Cl2 as the solvent) in
order to prevent hydrolysis of the Lewis acid. By conse-
quence, it is essential that lower grade MCPBA (e.g., 55%
with 30–35% of water and 10–15% 3-chlorobenzoic acid) is
freed from water before use. This is readily effected by
dissolving 55% MCPBA in CH2Cl2 (5 g in 100 mL of freshly
distilled solvent to exclude the presence of small amounts of
HCl), separating the aqueous layer, drying of the organic
phase (Na2SO4), and removal of the solvent in vacuo (bath
temp. below 35 °C) to yield a fluffy solid that can directly be
used.
1
CHCl3); H NMR (CDCl3): l 5.21 (bs, 1 H,
H-1), 4.90 (bs, 1 H, H-4), 4.75 (bs, 1 H, H-2),
4.26–4.13 (m, 3 H, H-5, two 6-H), 2.38 (brm,

54
F.W. Lichtenthaler, B. Werner / Carbohydrate Research 319 (1999) 47–54
[7] (a) F.W. Lichtenthaler, E. Kaji, S. Weprek, J. Org.
Chem., 50 (1985) 3505–3515. (b) E. Kaji, F.W. Lich-
tenthaler, T. Nishino, Y. Yamane, S. Zen, Bull. Chem.
Soc. Jpn., 61 (1988) 1291–1297. (c) E. Kaji, F.W.
Lichtenthaler, Y. Osa, K. Takahashi, S. Zen, Chem.
Lett., (1992) 707–710; Bull. Chem. Soc. Jpn., 68 (1995)
2401–2408. (d) E. Kaji, Y. Osa, K. Takahashi, M.
Hirooka, S. Zen, F.W. Lichtenthaler, Bull. Chem. Soc.
Jpn., 67 (1994) 1130–1140.
(3 AcCO), 157.6 (C-1), 141.7 (C-2), 124.6
(C-3), 76.2 (C-5), 63.0 (C-4), 61.3 (C-6), 20.6,
20.4, 20.3 (3 AcCH3); FI MS: m/z=287
[MH+], 286 [M+]. Anal. Calcd for C12H14O8
(286.2): C, 50.37; H, 4.91. Found: C, 50.33;
H, 4.96.
[8] (a) F.W. Lichtenthaler, E.S.H. El Ashry, V.H. Go¨ckel,
Tetrahedron Lett., 21 (1980) 1429–1432. (b) P. Jarglis,
F.W. Lichtenthaler, Tetrahedron Lett., 21 (1980) 1425–
1428; Angew. Chem., 94 (1982) 140–141; Angew. Chem.,
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(1982) 175–183.
[9] F.W. Lichtenthaler, P. Jarglis, W. Hempe, Liebigs Ann.
Chem., (1983) 1959–1972.
[10] Reviews: (a) E. Kaji, F.W. Lichtenthaler, Trends Gly-
cosci. Glycotechnol., 5 (1993) 121–142; (b) F. Barresi, O.
Hindsgaul, in S.H. Khan, R.A. O’Neill (Eds.), Modern
Methods in Carbohydrate Synthesis, Harwood, Amster-
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R.J. Ferrier, N. Prasad, G.H. Sankey, J. Chem. Soc. C,
(1968) 974–977.
4. Supplementary material
Tables of atomic coordinates, bond lengths
and bond angles have been deposited with the
Cambridge Crystallographic Data Centre as
supplementary publication no. CCDC-121452.
Copies of this data can be obtained, free of
charge, from CCDC, 12 Union Road, Cam-
bridge, CB2 1EZ, UK (fax: +44-1223-336-
033 or e-mail: deposit@ccdc.cam.ac.uk).
Acknowledgements
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C, (1969) 587–591. (b) S. Hanessian, P.C. Tyler, Y.
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The authors are indebted to the Fonds der
Chemischen Industrie for financial support
and to Mrs S. Foro and Professor Dr H.J.
Lindner for determining the X-ray structure of
18.
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