Synthesis of higher carbon sugars from dihydroxyacetone and d-arabinose: An organocatalytic approach

Article abstract of DOI:10.1016/j.tetasy.2012.07.012

The reaction of 2,3:4,5-diacetone-d-arabinose with protected dihydroxyacetone catalyzed by l-proline afforded two diastereoisomeric octoses in a 7:1 ratio in 75% yield. The anti (3S,4S) configuration at the newly created stereogenic centers was assigned to the main isomer on the basis of the X-ray analysis. The same reaction when catalyzed with unnatural d-proline provided the same products in a 1:20 ratio.

Full text of DOI:10.1016/j.tetasy.2012.07.012

Tetrahedron: Asymmetry 23 (2012) 1213–1217
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Synthesis of higher carbon sugars from dihydroxyacetone and D-arabinose: an
organocatalytic approach
Maciej Cieplak a, Magdalena Ceborska b, Piotr Cmoch a, Sławomir Jarosz a,
⇑
a Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka, 44, 01-224 Warszawa, Poland
b Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka, 44, 01-224 Warszawa, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 9 July 2012
Accepted 27 July 2012
The reaction of 2,3:4,5-diacetone-
afforded two diastereoisomeric octoses in a 7:1 ratio in 75% yield. The anti (3S,4S) configuration at the
newly created stereogenic centers was assigned to the main isomer on the basis of the X-ray analysis.
D
-arabinose with protected dihydroxyacetone catalyzed by L-proline
The same reaction when catalyzed with unnatural
D
-proline provided the same products in a 1:20 ratio.
Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
eventual
first aldol
reaction
second aldol
reaction
Heptoses, octoses, and nonoses (L-glycero-D
-manno-heptose,1
O
Sug
Kdo,2 sialic acid3), commonly known as higher sugars, play an
important role in the biology of the living cells, and their synthesis
is well explored.4 The synthesis of higher sugars containing up to
10 carbon atoms in the chain is usually realized by elongation of
‘normal’ sugars by a small achiral unit (C1 to C3),5 or from the sim-
plest carbohydrate, glyceraldehyde.6
O
OH
O
organo
catalyst
Sug
Y
O
O
1
O
O
Y
3
2
Organocatalysis, which has emerged as an important tool in
stereoselective synthesis,7 may offer a useful alternative to the
‘classical’ synthesis of higher sugars. An aldol reaction of hydroxy-
or di-hydroxyacetone with aldehydes (chiral or achiral) could pro-
vide (poly)hydroxylated compounds with good selectivity. This
important topic, a subject of intensive research,8 was recently
reviewed.9
Figure 1. Planning of the reaction of sugar aldehydes.
2. Results and discussion
The reaction of 2,3:4,5-di-O-isopropylidene-
D
-arabinose 411
with 2, catalyzed with natural L-proline, afforded two stereoiso-
meric aldols 5 and 7 in good yield and with high (ca. 7:1) selectiv-
ity (Scheme 1).
We have decided to test the organocatalytic approach in the
reaction of di-hydroxyacetone with sugar aldehydes, which may
open up a route to higher carbon sugars. The successful first aldol
reaction of protected dihydroxyacetone 2 with a (poly)-hydroxyal-
dehyde should provide monoaldol 3 (as a mixture of diastereoiso-
mers), which could be used for the preparation of simple sugars;
we expected the preferential formation of the anti-adducts, since
anti-selectivity is usually observed in organocatalytic reactions of
ketone/aldehyde pairs (especially cyclic ketones).10 The eventual,
second aldol reaction (not necessarily in organocatalytic version)
could open up a route to higher carbon monosaccharides (Fig. 1).
Herein a model study on such an approach to the first step is
presented.
The anti-(3S,4S)-configuration of the main stereoisomer 5 was
assigned by X-ray analysis of its silylated derivative 6 (Fig. 2).
The best results were obtained in reaction performed at rela-
tively low temperatures with lithium bromide as the co-catalyst;
the results of the optimization of this process are shown in Table 1.
The reaction of
D
-arabinose 4 with ketone 2 catalyzed with
-pro-
unnatural -proline afforded the same products (as in case of
D
L
line) but this time, isomer 7 predominated; the ratio of 5 to 7 was
established as 1:20 (Scheme 1). This result strongly suggested that
aldol 7 should have the same relative configuration, that is the
opposite anti-arrangement.
It is known that when a reaction is catalyzed with unnatural D-
proline, it usually gives the product with the same relative, but
opposite absolute configuration as the one obtained with natural
proline. For example, the reaction of protected hydroxyacetone 8
⇑
Corresponding author. Fax: +48 22 632 66 81.
E-mail addresses: sljar@icho.edu.pl, slawomir.jarosz@icho.edu.pl (S. Jarosz).
with aldehyde 9 catalyzed with L-proline affords the syn-adduct
0957-4166/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetasy.2012.07.012

1214
M. Cieplak et al. / Tetrahedron: Asymmetry 23 (2012) 1213–1217
R-O
O
O
O
O
OH
(R)
(R)
O
O
(S)O
8
O
(S)O
(S)
1
HO
NCbz
+
O
O
O
O
O
O
O
4
8
9
5. R = H; 6 R = TBS
+
(S)-proline
(R)-proline
+
proline,
O
OH
O
58%
O
69%
OH
LiBr, +4°C
O
O
O
OH
O
O
O
O
O
O
NCbz
7
NCb|
2
O
O
O
O
O
O
Ratio 5 : 7 for:
L-proline: 7:1 (75% overall); D-proline: 1:20 (55%)
10
11
(R)-proline syn/anti = 5:1
Scheme 1. Preparation of aldols 5 and 7.
(S)-proline syn/anti = 20:1
Scheme 2. Reaction of 8 with 9 catalyzed with
L- and D-proline.
(
)
S
O
O
H
O
O
O
+
O
O
O
O
12
2
(R)-proline
DMF, rt
O
OH
(R)
(
)
S
O
H
O
1
4
3
(R)
O
O
O
O
O
13 (60%)
Figure 2. Configuration of the main stereoisomer 5 by X-ray analysis of its silylated
derivative 6.
Scheme 3. Synthesis of higher sugar 13 by Barbas.
and spectroscopic correlations. The determination of the configu-
ration of aldol 7 was based on indirect methods, that is the assign-
ment of the relative configuration of the diols resulting from the
reduction of the carbonyl group.
The reduction of the main product obtained in the reaction cat-
alyzed by D-proline (presumably the second anti-aldol 7) afforded
two stereoisomeric diols with different configurations at the C-2
center. Coupling of the 2- and 4-OH groups as an acetal or prefer-
ably as a cyclic ester allowed us to determine the relative configu-
ration between all three new stereogenic centers at the C2, C3, and
C4 positions; we connected these groups as cyclic carbonates
(structures A and B).
Table 1
Optimization of the organocatalytic aldol reaction between aldehyde 4 and ketone 2
(0.5 equiv of L-proline, 1.7 equiv additive, 4 °C)a
Solvent
Additive
Yield (%)
5:7
1
2
3
4
5
6
DMSO
DMSO
DMSO
DMSO
THF
—
27
30
47
75
—
2:1
1:1.1
5:1
7:1
—
PPTS
ZnCl2
LiBr
LiBr
LiBr
DMF
30
4.2:1
a
Small amounts (2–3%) of the product(s) with the same molecular mass (by MS)
were obtained in entries 1 and 6, which suggested the alternative syn-isomer(s).
The aldol 7 has the expected anti-configuration, then two cyclic
carbonates: 16 (=A) and 17 (=B) should be obtained (Scheme 4).
However, we have to consider the possibility that aldol 7 had
the syn-configuration (i.e., 7a or 7b; Fig. 3). Conversion of these
hypothetical products into cyclic carbonates would afford 18a
and 19a (from 7a) or 18b and 19b (from 7b).
10, while the application of unnatural
site syn-adduct 11 (Scheme 2).12
D-proline provides the oppo-
This assumption was also supported by the result of Barbas,13
who reported that the reaction of ketone 2 with ‘diacetonogalac-
tose aldehyde’ 12 [with the same, as in 4, (S)-configuration at the
All pairs of the stereoisomers should be readily distinguishable
by the results of the NOE measurements.
a-position with respect to the carbonyl group] when catalyzed
by -proline, exclusively afforded one stereoisomeric anti-adduct
13 with the (3R,4R)-configuration at the newly created stereogenic
centers (Scheme 3).
This assumption that aldol 7 also has the anti-arrangement of
the substituents at the C3, and C4 centers, was verified by chemical
D
First of all, identification of the structure was needed, which
was achieved by analysis of different 1D and 2D NMR experiments.
The 1H and 13C NMR assignment of the signals, based on the afore-
mentioned results for the two stereoisomeric carbonates (struc-
tures A and B) is shown in Table 2.

M. Cieplak et al. / Tetrahedron: Asymmetry 23 (2012) 1213–1217
1215
OH
Me2C
O
OH
OH
O
1
OH
2
OH
2
3.9%
O
3
NaBH4
H
4
4
4
2
R
O
H
R
R
2
3
3
3
2
O
O
O
O
1
O
O
+
H
O
O
O
O
3
3.8%
4
14
H
Me2C
15
4
H
5.2%
O
R
H
triphosgene, Et3N
O
R
17
16
O
Figure 4. Observed noe values for carbonates 16 and 17.
O
O
O
O
O
O
5
7
7
3
3
5
1
1
4
2
4
6
8
2
6
8
O
O
+
H
O
O
O
O
O
O
O
O
O
H
H
2
1
4
H
Me2C
O
1
O
2
O
4
3
O
3
(A) =16
Scheme 4. Synthesis of carbonates 16 and 17 derived from 7.
O
(B) = 17
O
R
H
O
O
H
O
Me2C
R
18a
19a
Me2C
O
1
H
O
O
O
OH
O
O
2 R
O
O
1
3
3
O
O
O
O
3
4
O
2
O
4
R
O
O
O
O
2
+
+
H
Me2C
2
4
R
H
O
O
3
4
H
R
R
R
O
H
7a
H
18b
19b
O
O
18a
19a
Figure 5. The (possible) pairs of stereoisomeric carbonates derived from (eventual)
syn-aldols.
O
O
O
OH
O
2
O
4
3
H4 = 3.9% was seen (Fig. 4). These results unambiguously proved
4
R
2
the structure of aldol 7.
3
O
O
R
In the reaction of D-arabino-aldehyde 4 with protected acetone
O
7b
O
2, only the anti-aldols were formed. Moreover, we have demon-
strated, that is possible to obtain the aldol with the required
anti-configuration at the newly created stereogenic centers, by
simply changing the organocatalyst from natural proline to its
unnatural enantiomer.
18a
19a
Figure 3. Stereosiomeric carbonates derived from (possible, hypothetic) syn-
adducts 7a and 7b.
We also checked the stability of the aldols and found that they
were configurationally stable. Treatment of aldol 5 with L-proline
Table 2
in the presence of the additive did not induce any changes,
although ‘scrambling’ of the products might be expected because
of the reversibility of the aldol reaction. Treatment of aldol 7 under
the same conditions also had no influence on the structure of the
product with compound 7 remaining unchanged.
This result may open up the possibility of applying the isolated
pure aldols 5 or 7 in the next aldol reaction without any scrambling
at the new stereogenic centers created in the first step.
Assignment of the 1H and 13C NMR chemical shifts for A and B obtained after
reduction of aldol 7
Atom number
Structure A d 1H/13C (ppm)
Structure B d 1H/13C (ppm)
1
2
3
4
5
6
7
8
3.32; 3.54/60.9
3.47/69.5
3.29; 3.68/61.5
4.22/70.3
4.11/65.1
3.63/63.6
4.51/79.9
4.71/78.5
4.25/78.4
3.72/81.0
4.38/75.9
4.27/77.2
3.87/77.7
3.86/77.7
3. Experimental
3.1. General
3.89; 3.93/68.1
3.87; 3.94/68.3
In order to establish the configuration and to identify which two
of the possible structures 16/17, 18a/18b, or 19a/19b could be as-
signed to structures A and B, 1D selective NOESY experiments were
employed; in both cases, the signals of protons H2/H3/H4 were
irradiated.
In the NOE spectrum of one of the carbonates derived from the
main diol obtained by reduction of 7 (or eventually 7a or 7b) no
interaction between H2–H4 was noted, which excluded structures
17, 18b, and 19a (which should show significant NOE effects see
for example 17 in Fig. 4). Two other observed important NOE’s:
H2–H3: 5.2%, H3–H4: 3.8% strongly suggested compound 16, since
in the remaining derivatives, the 18a and 19b interaction H2-H3
should be negligible (see Fig. 5)
The NMR spectra of all compounds were measured in CDCl3
solutions using the following spectrometers: Varian-NMR-
vnmrs500 (at temperature 298 K) equipped with a 500 MHz
PFG Auto XDB (1H–19F/15N–31P 5 mm) probehead, and Varian-
NMR-vnmrs600 (at temperature 298 K) equipped with
a
600 MHz PFG Auto XID (1H/15N–31P 5 mm) indirect probehead.
For carbonates 16 and 17, deuterated benzene was seen to have
the best 1H NMR signal separation needed for the determination
of the configuration. Standard experimental conditions and stan-
dard Varian programs were used. To assign the structures under
consideration, the following 1D and 2D experiments were em-
ployed: the 1D selective NOESY, 1D selective TOCSY, COSY,
1H–13C gradient selected HSQC and HMBC optimized for 1J(C–
H) = 130 Hz and nJ(C–H) = 8 Hz, respectively. The relative config-
In the NOE spectrum of the second carbonate (obtained from
the minor isomeric diol), only one interaction between H2 and

1216
M. Cieplak et al. / Tetrahedron: Asymmetry 23 (2012) 1213–1217
urations of the protons were determined based on 1H selective
NOESY experiments using standard Varian (ChemPack 4.1) se-
quence. The 1H and 13C NMR chemical shifts are given relative
to the TMS signal at 0.0 ppm. The concentration of all solutions
used for measurements was about 20-30 mg of compounds in
0.6 cm3 of solvent.
Mass spectra were recorded with an ESI/MS Mariner (PerSeptive
Biosystem) mass spectrometer. Optical rotations were measured
with a Digital Jasco polarimeter DIP-360 (k = 589 nm) for solutions
in CHCl3 (c = 1) at room temperature. Column chromatography was
performed on silica gel (Merck, 70-230 or 230–400 mesh). Organic
solutions were dried over anhydrous magnesium sulfate. THF was
distilled from potassium prior to use. Organocatalytic aldol reac-
tions were performed under an argon atmosphere.
ture was stirred at room temperature for 2 days. Next, it was
quenched with sat. NH4Cl (5 mL) and partitioned between AcOEt
(20 mL) and water (20 mL). The organic layer was separated and
the aqueous phase extracted with AcOEt (3 ꢀ 5 mL). The combined
organic solutions were washed with water (2 ꢀ 5 mL) and brine
(5 mL), dried, concentrated, and the product was purified by col-
umn chromatography (hexane–ethyl acetate, 9:1 to 4:1) to afford
6 (568 mg, 1.2 mmol, 43%) as a colorless oil, which crystallized in
the refrigerator after 3 days. Unreacted 5 was again subjected to
silylation under the same conditions. Overall yield of 6 was 51%
(615 mg, 1.3 mmol).
½
a rDt
ꢁ
¼ ꢂ93:1 (c 1, CHCl3); 1H NMR
(600 MHz, CDCl3) d: 4.41 (s, H-3), 4.31–4.27 (m, 2H, H-1, H-7),
4.19 (dd, J6,7 = 4.2 Hz, J5,6 = 5.9 Hz, H-6), 4.17 (dd, J4,3 = 1.6 Hz,
J4,5 = 8.9 Hz, H-4), 4.1 (dd, H-5), 4.05 (dd, J7,8 = 6.6 Hz,
J8,8 = 7.8 Hz, H-8), 3.93 (t, J7,8 = J4,5 = 7.8 Hz H-80), 3.87 (d,
0
J1,1 = 15.6 Hz, H-10), 1.49-1.28 (6s, CMe2), 0.89 (s, SiMe2-tert-Bu),
0
3.1.1. Reaction of 2,3:4,5-di-O-isopropylidene-D-arabinose 4
with protected dihydroxyacetone 2
0.15, 0.14 (2s, SiMe2-tert-Bu); 13C NMR d: 205.9 (C-2), 110.5,
109.3, 100.5 (3 ꢀ CMe2), 79.7 (C-6), 77.5 (C-3), 77.3 (C-5), 76.2
(C-7), 75 (C-4), 67 (C-1), 64.9 (C-8), 27.6, 27.1, 26.3, 25.8, 25.3,
24.7, 23.2 (6 ꢀ CMe2 + SiMe2-tert-Bu), -4.2, -4.4 (2 ꢀ SiMe2-tert-
Bu). ESI-MS: m/z Calcd for: C23H42O8SiNa: 497.25412. Found:
497.25455. Anal. Calcd for: C23H42O8Si + ½H2O: C, 57.12; H, 8.96.
Found: C, 57.50; H, 8.97.
3.1.1.1. Reaction with
L-proline.
To a solution of (S)-proline
(1.7 g, 14 mmol) and LiBr (4.3 g, 49 mmol) in dry DMSO (30 mL),
2,3:4,5-di-O-isopropylidene-
D-arabinose 4 (6.68 g, 29 mmol) and
2,2-dimethyldioxane-5-one
2 (13.4 g, 100 mmol) were added,
and the mixture was kept in a refrigerator at 4 °C for 4 days. Next,
it was quenched with sat. NH4Cl (5 mL) and partitioned between
ethyl acetate (30 mL) and water (10 mL). The organic layer was
separated and the aqueous phase extracted with diethyl ether
(3 ꢀ 10 mL). The combined organic solutions were washed with
water (2 ꢀ 10 mL) and brine (10 mL), dried, concentrated, and
the products were isolated by column chromatography (hexane–
ethyl acetate, 9:1 to 4:1) to provide isomer 5 (6.9 g, 19.2 mmol,
66%) and 7 (0.98 g, 2.7 mmol, 9.3%) as colorless oils.
3.2. Crystallographic data for 6
CCDC 886500 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
Colorless
crystal
of
approximate dimensions 0.20 ꢀ 0.14 ꢀ 0.09 was used. Diffraction
3.1.1.2. Reaction with
D
-proline.
This reaction was per-
data were collected at 100K using Bruker Kappa CCD diffractom-
formed analogously as that shown above starting from 1.2 g
(5.2 mmol) of arabinose 4 and 2.0 g (15 mmol) of ketone 2 to afford
5 (41 mg, 0.11 mmol, 2.2%) and 7 (997 mg, 2.8 mmol, 53%).
eter with graphite a monochromated Mo Ka radiation. Structure
was solved by direct methods (SHELXS-97) and refined on F2 by
full-matrix least-squares method (SHELXL-97). Non-hydrogen
atoms were refined with anisotropic thermal displacement
parameters. All hydrogen atoms were placed in geometric posi-
tions and treated as riding with C–H = 0.95 Å and O–H = 0.84 Å.
3.1.2. 1,3:5,6:7,8-Tri-O-isopropylidene-D-glycero-D-talo-oct-2-
ulose 5
½
a rDt
ꢁ
¼ ꢂ74:3 (c 1, CHCl3); 1H NMR (500 MHz, CDCl3) d: 4.53 (m,
Formula:
C23H42O8Si, orthorhombic, space group P212121,
0
H-3), 4.33 (dd, J1,3 = 1.5 Hz, J1,1 = 16 Hz, H-1), 4.21–4.17 (m, 2H, H-
a = 7.2309 (1) Å, b = 14.4666 (3) Å, c = 24.3601 (5) Å,
8, H-7), 4.13 (dd, J3,4 = 2.4 Hz, J4,5 = 8.3 Hz, H-4), 4.09–4.05 (m, 1H,
V = 2548.23 (8) Å3, Z = 4, R1 = 0.03 [I > 2
rI)], wR2 = 0.07 for all
H-6), 4.01 (dd, J7,8 = 5.1 Hz, J8,8 = 8.7 Hz, H-80), 3.93 (dd,
0
data.
0
0
J1 ,3 = 0.5 Hz, H-10), 3.75 (dd, J5,6 = 7.3 Hz, H-5), 2.17 (s, OH), 1.51-
1.3 (6s, CMe2); 13C NMR d: 206.9 (C-2), 110.3, 109.7, 100.5
(3 ꢀ CMe2), 81.3 (C-5), 79.4 (C-7), 76.7 (C-3), 76.3 (C-6), 73.1 (C-
4), 67.9 (C-8), 67 (C-1), 26.8, 26.4, 26.3, 25.2, 24.8, 23.2 (6 ꢀ CMe2).
ESI-MS: m/z = 383.2 [M+Na]+. Anal. Calcd for: C17H28O8 + ½H2O: C,
55.27; H, 7.91. Found: C, 55.31; H, 7.88.
3.3. Determination of the configuration of the adduct 7
To solution of ketone (96 mg, 0.27 mmol) in ether
a
7
(35 mL), sodium borohydride (45 mg) was added, and the mix-
ture was stirred for 5 days at room temperature. Water was then
added (5 mL), and the mixture was stirred for 30 min at rt, after
which the layers were separated, and the aqueous one extracted
with ether (2 ꢀ 10 mL). The combined organic solutions were
washed with water (2 ꢀ 10 mL) and brine (10 mL), dried, concen-
trated, and a ca 1:1 mixture of stereoisomeric products 14/15
(by NMR) was isolated as a colorless oil (85.2 mg, 0.24 mmol,
88.8%).
3.1.3. 1,3:5,6:7,8-Tri-O-isopropylidene-D-glycero-D-gulo-oct-2-
ulose 7
½
a rDt
ꢁ
¼ þ99:6 (c 1, CHCl3); 1H NMR (600 MHz, CDCl3) d: 4.42 (dd,
0
J1,3 = 1.5 Hz, J3,4 = 8.4 Hz H-3), 4.30 (dd, J1,1 = 17.4 Hz, H-1), 4.19
(dd, J4,5 = 2.1 Hz, J5,6 = 7.7 Hz, H-5), 4.14–4.11 (m, 2H, H-8, H-6),
4.08-4.05 (m, 2H, H-1‘, H-7), 4,02 (dd, H-4), 3.99 (dd,
J7,8 = 4.5 Hz, J8,8 = 7.5 Hz Hz, H-80), 2.19 (s, OH), 1.48-1.34 (6s,
CMe2); 13C NMR d: 211.6 (C-2), 109.7, 109.2, 101.4 (3 ꢀ CMe2),
78.4 (C-5), 77.3 (C-7), 75.8 (C-6), 72.9 (C-3), 68.4 (C-4), 67.8 (C-
8), 66.6 (C-1), 27.1, 26.7, 26.6, 25.4, 23.6, 23.4 (6 ꢀ CMe2). ESI-
MS: m/z = 383.2 [M+Na]+. Anal. Calcd for: C17H28O8 + H2O: C,
53.96; H, 7.99. Found: C, 54.24; H, 7.91.
This inseparable mixture of diols 14/15 (70 mg, 0.19 mmol) was
dissolved in dry CH2Cl2 (1.5 mL) and cooled to ꢂ78 °C. Pyridine
(0.08 mL), Et3N (0012 mL), molecular sieves 4 Å, and triphosgene
(290 mg, 0.97 mmol) were added, and the reaction mixture was
stirred for 40 min at ꢂ78 °C, quenched with aq. NH4Cl, and parti-
tioned between ethyl acetate (5 mL) and water (1 mL). The organic
layer was separated, washed with aq CuSO4 (3 mL), water
(2 ꢀ 3 mL), and brine (3 mL), and the products were isolated by
column chromatography (hexane–ethyl acetate 7:1 to 4:1) to af-
ford 16 (32 mg, 0.082 mmol, 43%) and 17 (19 mg, 0.049 mmol,
26%) as colorless oils.
0
0
3.1.4. 4-O-(tert-Butyl-dimethylsilyl)-1,3:5,6:7,8-tri-O-isopropyli-
dene-D-glycero-D-talo-oct-2-ulose 6
Alcohol 5 (1.01 g, 2.8 mmol) was dissolved in dry DMF (10 mL)
to which TBDMS-Cl (850 mg, 5.6 mmol) was added and the mix-

M. Cieplak et al. / Tetrahedron: Asymmetry 23 (2012) 1213–1217
1217
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3.3.1. 1,3:5,6:7,8-Tri-O-isopropylidene-2,4-O-carbonate-
erythro- -galacto-octitol 16
D-
½
a rDt
ꢁ
¼L þ25:2 (c 1, CHCl3); 1H NMR (600 MHz, C6H6) d: 4.71 (s, H-
4), 4.26 (t, J5,6 = J6,7 = 8.3 Hz, H-6), 4.22 (m, H-2), 3.94 (dd,
J7,8 = 5.6 Hz, J8,8 = 7.3 Hz, H-8), 3,88 - 3,85 (m, 2H, H-7, H-80),
0
37.1 (d, H-5), 3.67 (dd, J1,2 = 1.9 Hz, H-1), 3.63 (m, H-3), 3.29 (dd,
J1 ,2 = 1.8 Hz, J1,1 = 13.3 Hz, H-10), 1.40-0.96 (6s, CMe2); 13C NMR
d: 147 (–CO–), 111.4, 110.3, 98.9 (3 ꢀ CMe2), 81 (C-5), 78.5 (C-4),
77.7 (C-7), 77.7 (C-6), 70.3 (C-2), 68.2 (C-8), 63.6 (C-3), 61.5 (C-
1), 29.1, 27.4, 26.6, 26.3, 23.4, 18.4 (6 ꢀ CMe2). Anal. Calcd for:
0
0
C18H28O9: C, 55.66; H, 7.27. Found: C, 55.40; H, 7.23.
3.3.2. 2,4-Di-O-carbonate-1,3:5,6:7,8-Tri-O-isopropylidene-
erythro- -talo-octitol 17
D-
½
a rDt
ꢁ
¼L þ24:3 (c 1, CHCl3); 1H NMR (600 MHz, C6H6) d: 4.52 (dd,
J4,5 = 0.7 Hz, J4,3 = 9.2 Hz H-4), 4.37 (t, J5,6 = J6,7 = 8.2 Hz, H-6), 4.24
8. (a) Majewski, M.; Niewczas, I. Eur. J. Org. Chem. 2009, 33–37; (b) Majewski, M.;
Niewczas, I.; Palyam, N. Tetrahedron Lett. 2007, 48, 9195–9198; (c) Suri, J.;
Mitsumori, S.; Albertshofer, K.; Tanaka, F.; Barbas, C. F. J. Org. Chem. 2006, 71,
3822–3828; (d) Grondal, Ch.; Enders, D. Tetrahedron 2006, 62, 329–337; (e)
Majewski, M.; Niewczas, I.; Palyam, N. Synlett 2006, 2387–2390; (f) Enders, D.;
Voith, M.; Lenzen, A. Angew. Chem., Int. Ed. 2005, 44, 1304–1325; (g) Grondal,
Ch.; Enders, D. Angew. Chem., Int. Ed. 2005, 44, 1210–1212; (h) Suri, J.;
Ramachary, D.; Barbas, C. F. Org. Lett. 2005, 7, 1383–1385; (i) Majewski, M.;
Nowak, P. J. Org. Chem. 2000, 65, 5152–5160; (j) Majewski, M.; Nowak, P.
Synlett 1999, 9, 1447–1449; (k) Ohara, T.; Adibekian, A.; Esposito, D.;
Stallforthab, P.; Seeberger, P. H. Chem. Commun. 2010, 46, 4106–4108; (l)
Burroughs, L.; Clarke, P. A.; Forintos, H.; Gilks, J. A. R.; Hayes, Ch. J.; Vale, M. E.;
Wade, W.; Zbytniewski, M. Org. Biomol. Chem. 2012, 10, 1565–1570.
9. Mlynarski, J.; Gut, B. Chem. Soc. Rev. 2012, 41, 587–596.
(dd, H-5), 4.11 (t, J3,4 = J4,5 = 9.2 Hz, H-3), 3.93–3.88 (m, 3H, H-7,
H-8, H-80), 3.54 (dd, J1,2 = 5.3 Hz, J1,1 = 10.6 Hz, H-1), 3.46 (m, 1H,
0
H-2), 3.32 (t, J1 ,2 = J1,1 = 10.6 Hz,, H-10), 1.54–1.05 (6s, CMe2); 13C
NMR d: 146.8 (–CO–), 110.3, 109.7, 100.1 (3 ꢀ CMe2), 79.5 (C-4),
78 (C-5), 77.3 (C-7), 75.5 (C-6), 69.1 (C-2), 67.7 (C-8), 64.8 (C-3),
60.56 (C-1), 28.4, 27.2, 26.4, 26.2, 24.9, 18.4 (6 ꢀ CMe2). Anal. Calcd
for: C18H28O9 + 1½H2O: C, 52.04; H, 7.52. Found: C, 52.05; H, 7.25.
0
0
Acknowledgement
This work was financed by the Ministry of Science and Higher
Education, Grant No. N N204 092635.
10. Pihko, P. M.; Majander, I.; Erkkiloa, A. Top. Curr. Chem. 2010, 291, 29–75.
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1972, 27, 227–299; (b) Zinner, H.; Wittenburg, E.; Rembarz, G. Chem. Ber. 1959,
92, 1614–1617; (c) Jarosz, S.; Zamojski, A. J. Carbohydr. Chem. 1993, 12, 1223–
1228.
References
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2006, 71, 3822–3828.
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