Novel 3-C-aminomethyl-hexofuranose-derived thioureas and their testing in asymmetric catalysis

Article abstract of DOI:10.1016/j.tetasy.2015.07.003

Abstract Both 1,2:5,6-di-O-isopropylidene- and 1,2:5,6-di-O-cyclohexylidene-α-d-glucofuranose-derived ketones provided the corresponding branched 3-C-nitromethyl-congeners in the Henry reaction with nitromethane anion. Reduction of the nitro moiety follow

Full text of DOI:10.1016/j.tetasy.2015.07.003

Tetrahedron: Asymmetry xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Novel 3-C-aminomethyl-hexofuranose-derived thioureas and their
testing in asymmetric catalysis
a
b
b
c
Maris Turks a, , Evija Rolava , Dmitrijs Stepanovs , Anatoly Mishnev , Dean Markovic
⇑
´
¯
a Faculty of Materials Science and Applied Chemistry, Institute of Technology of Organic Chemistry, Riga Technical University, P. Valdena Str. 3, Riga LV-1048, Latvia
b Latvian Institute of Organic Synthesis, 21 Aizkraukles Str, Riga LV-1006, Latvia
c Department of Chemistry, Josip Juraj Strossmayer University of Osijek, Cara Hadrijana 8/A, 31000 Osijek, Croatia
a r t i c l e i n f o
a b s t r a c t
Article history:
Both 1,2:5,6-di-O-isopropylidene- and 1,2:5,6-di-O-cyclohexylidene-a-D-glucofuranose-derived ketones
Received 8 June 2015
Accepted 9 July 2015
Available online xxxx
provided the corresponding branched 3-C-nitromethyl-congeners in the Henry reaction with nitro-
methane anion. Reduction of the nitro moiety followed by derivatization with iso(thio)cyanates gave
3-C-aminomethyl-hexofuranose-derived (thio)ureas. The relative configuration of the products in each
series was unambiguously established by X-ray analysis. The title products were shown to act as
organocatalysts in Friedel–Crafts alkylations of indoles with b-nitrostyrenes and in Michael additions
of nitromethane to trans-chalcones.
Ó 2015 Elsevier Ltd. All rights reserved.
1. Introduction
stituted equivalents14 among other transformations are success-
fully used in aza-Henry reactions, decarboxylative Mannich reac-
The structural motif of vicinal or b-amino alcohols is frequently
found in natural products and synthetic biologically active sub-
stances. More importantly for the synthetic community, they are
found to act as chiral catalysts, ligands for metal complexes, and
privileged structural components of chiral auxiliaries.1
Carbohydrate derived vicinal amino alcohols2 have also been used
as ligands in Reformatsky reactions3 and in Zn(OTf)2-mediated
additions of alkynes to aldehydes.4 The fine-tuning of the confor-
mational restriction and the relative configuration of the functional
groups in the monosaccharide ligand gave excellent ee’s for the lat-
ter transformation.
tions and Michael additions to nitrostyrene. The latter reaction
can be equally effectively catalyzed by carbohydrate-based thiour-
eas containing fragments of chiral diamines of linear type.15 The
design of the aforementioned catalysts most frequently exploits
the thiourea attachment via a glycosidic bond. There are only
few examples in which the cores of glucosamine and 4,6-
dideoxy-4,6-diamino-hexopyranose are used for thiourea
synthesis.16
Despite the fact that b-amino alcohol derived thiourea type cat-
alysts have shown promising results,17 there are only a few of their
counterparts in carbohydrate chemistry.16a It should also be noted
that the comparison of a number of pyranose-based and furanose-
based organocatalysts shows the predominance of the former.18 On
the other hand, furanose-like isohexides have proved to be versa-
tile scaffolds in asymmetric catalysis.19
Similarly, enantioselective additions of Et2Zn to aldehydes have
benefited from monosaccharide-based amino alcohols,5 including
xylo-furanose based structures.6
On the other hand, carbohydrate scaffolds have gained interest
in the field of organocatalysis.7 Thus, both furanose8 and pyranose9
derived prolinamides have shown excellent results in asymmetric
aldol reactions. Simple monosaccharide-based b-amino alcohols
also catalyze the latter transformation.10 Even more examples of
carbohydrate-derived catalysts can be found in the area of hydro-
gen-bond donor catalysis.11 These include ureas12 and thioureas.
The thiourea derivatives arising from the corresponding glycosidic
isothiocyanates and diaminocyclohexane13 or their N-monosub
2. Results and discussion
We have recently reported a user-friendly large scale synthesis
of isopropylidene-protected 3-C-aminomethyl-hexofuranoses via
their nitro congeners.20 Hence, we were interested in exploring
the organocatalytic applications of furanose-derived ureas and
thioureas 3 obtained from the branched b-amino alcohols of gen-
eral type 2 (Scheme 1).
The required starting materials, isopropylidene-protected vici-
nal amino alcohols 5 and 6 with allo- and gluco-configuration, were
⇑
Corresponding author. Tel.: +371 67089251; fax: +371 67615765.
E-mail address: maris_turks@ktf.rtu.lv (M. Turks).
http://dx.doi.org/10.1016/j.tetasy.2015.07.003
0957-4166/Ó 2015 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Turks, M.; et al. Tetrahedron: Asymmetry (2015), http://dx.doi.org/10.1016/j.tetasy.2015.07.003

2
M. Turks et al. / Tetrahedron: Asymmetry xxx (2015) xxx–xxx
NaClO,
TEMPO
NaBr
O
O
O
HO
HO
HO
O
O
O
O
MeNO2
O
O
O
O
O
O
X
NaOH,
MeOH
O
O
HO
O
X
OH OH
H2N
OH
7
1
2
8a (X=O) : 8b (X=OH) = 9:1
8a 8b
+
= 77%
O
O
O
O
O
O
O
O
O
O
O
HO
O2N
O
+
O
O
O2N
OH
O
X
NH OH
9
:
10
3
3:1
F3C
NH
9
10
= 84%
+
crystallization
Hex/EtOAc
Ac2O,
DMSO
CF3
O
9, 38%
O
Scheme 1. General structure of furanose-based urea (X = O) and thiourea (X = S) 3
derived from 3-C-aminometyl-hexofuranose 2.
O
O
NaOH
10, 47%
O
NO2
11, 59% (Z/E=5:1)
prepared from the corresponding ketone 421 as described earlier
(Scheme 2).20a
Scheme 3. Synthesis of cyclohexylidene-protected 3-C-nitromethyl-allofuranose 9
and 3-C-nitromethyl-glucofuranose 10.
O
O
H2N
O
O
O
O
O
OH
O
O
In order to unambiguously prove the relative configuration of
the obtained nitro alcohols 9 and 10 by X-ray analysis, we deriva-
tized them into the corresponding spiro-oxazolidinones. Thus,
nitro alcohols 9 and 10 were catalytically hydrogenated in the
presence of palladium catalyst (Scheme 4). Product 12 with an
allo-configuration was obtained as a white solid in 87% yield. It
was further transformed into phenylcarbamate 13 and then
cyclized into spirooxazolidinone 14. The latter provided crystals
suitable for single crystal X-ray analysis, which unambiguously
established its relative configuration (Fig. 1).25 In this way, the rel-
ative configuration of all cyclohexylidene-protected product
sequence 9 ? 12 ? 13 ? 14 and thus the diastereoselectivity of
Henry reaction 8a,b ? 9+10 was proved. The minor nitro alcohol
isomer 10 was transformed by hydrogenation and the addition of
TsOH into the amine tosylate salt 16 which provided an additional
option for purification via crystallization. The same approach as
described above gave a rise to spirooxazolidinone 18 in excellent
yield. It should be noted, that chiral oxazolidinones are well-estab-
lished chiral auxiliaries in asymmetric synthesis.26 Several types of
diastereoselective transformations have profited from oxazolidi-
nones which were derived from conformationally defined carbohy-
drate scaffolds.27 Carbohydrate–nitrogen heterocycle conjugates
with non-glycosidic spiranic junction are interesting in terms of
their biological activity.20a
Ref. [20a]
O
5
O
O
O
O
O
4
HO
O
H2N
6
Scheme 2. General synthetic approach toward isopropylidene-protected 3-C-
aminomethyl-allofuranose 5 and 3-C-aminomethyl-glucofuranose 6.
In order to check the influence of the steric bulk of the protect-
ing groups, a cyclohexylidene-protected version was also prepared.
Its synthesis followed a similar scheme to that used for obtaining 5
and 6 (Scheme 3). The unprotected HO-group of glucose derivative
722 was oxidized with bleach in the presence of TEMPO. The
obtained mixture of ketone 8a and its hydrate 8b was submitted
to a Henry reaction with nitromethane under basic conditions.23
A mixture of nitro alcohols 9 and 10 was obtained in 84% total
yield.24 The major allo-isomer 9 can be obtained diastereomerically
pure by direct crystallization in 38% isolated yield. The mother
liquor containing 9 and 10 after evaporation was submitted to a
Moffatt dehydration–rehydration sequence which provided pure
gluco-isomer 10 via the nitromethylene intermediate 11.20
Compound 14
Compound 23
Figure 1. X-ray structures of spiro-oxazolidinone 14 and thiourea 23.
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M. Turks et al. / Tetrahedron: Asymmetry xxx (2015) xxx–xxx
3
O
O
O
O
O
H2 40 atm,
Pd/C
O
PhOC(O)Cl,
O
O
O
O
NEt3
NaOH
BnEt3N+ Cl-
O
O
9
O
O
O
O
O
HN
O
H2N
OH
OH
NH
PhO
O
12
, 87%
13, 76%
14, 96%
O
O
O
O
H2 35 atm,
Pd/C
O
O
NaOH
O
O
O
O
O
10
O
HO
HO
BnEt3N+ Cl-
O
O
O
O
O
N
H
H2N
15
N
H
PhO
17, 93%
18, 89%
O
O
PhOC(O)Cl,
NEt3
TsOH
O
O
HO
O
TsO H3N
16, 60%
Scheme 4. Synthesis of cyclohexylidene-protected 3-C-aminomethyl-hexofuranoses 12 and 15 and their transformations into spiro-oxazolidinones 14 and 18 via carbamate
approach.
O
RO
3,5-(CF3)2-C6H3-NCX
O
O
O
O
O
RO
Next, all four available 3-C-aminomethyl-hexofuranoses 5, 6,
12, and the tosylate salt 16 were transformed into the planned
urea and thiourea derivatives 19–26 (Scheme 5). The 5,6-O-iso-
propylidene protecting groups in compounds 20 and 23 were
selectively cleaved to obtain compounds with additional hydrogen
bond donating structural motifs. The molecular structure of fura-
nose-derived thiourea catalyst 23 was unambiguously established
by X-ray analysis (Fig. 1).28
With two urea and six thiourea catalysts in hand, we evaluated
their activity in several organocatalytic transformations. We
started with the Friedel–Crafts alkylation of indole 2717a with b-
nitrostyrene 28 (Table 1).29 All of the prepared furanose-based urea
and thiourea derivatives were catalytically active and provided the
expected product 29 in good to excellent yields, but required rela-
tively long reaction times and gave poor enantiomeric excess. The
best ee for compound 29 (20%) was obtained with cyclohexyli-
dene-protected allo-furanose derivative 25 at ambient tempera-
ture. Chiral carboxylic and sulfonic acid additives decreased the
reaction time, but did not increase the ee. For example, either
stereoisomer of 10-camphorsulfonic acid as a sole substance cat-
alyzed the reaction equally fast, but gave a racemate (Table 1, entry
14).
F3
C
X
O
O
H2N
NH
OH
OH
NH
5
F3
C
19: X=O, R=CMe2, 75%
20: X=S, R=CMe2, 95%
H2SO4
21: X=S, R=H, 85%
O
RO
3,5-(CF3)2-C6H3-NCX
O
O
O
O
O
RO
HO
H2N
HO
O
O
F3
F3
C
C
X
NH
NH
6
22: X=O, R=CMe , 83%
23: X=S, R=CMe22, 97%
H2SO4
24: X=S, R=H, 96%
O
O
3,5-(CF3)2-C6H3-NCS
O
O
O
O
O
O
O
O
F3
F3
C
C
H2N
HN
OH
OH
12
N
H
S
25, 94%
The best combination of catalyst and additive was 25 and
(1R,3S)-(+)-camphoric acid which provided product 29 in 81% yield
and 20% ee (Table 1, entry 14). It is interesting to note that in all
cases, even in those with almost racemic product 29, a distinct
selectivity was observed: allo-furanose derived catalysts 19, 20,
21, and 25 gave predominantly (S)-29, but gluco-furanose derived
catalysts 22, 23, 24, and 26 gave predominantly (R)-29.
O
O
O
O
3,5-(CF3)2 -C6H3-NCS
NEt3
O
O
O
O
HO
HO
O
O
F3
F3
C
C
S
H3N
N
TsO
H
26, 55%
16
NH
On the other hand, the aforementioned urea and thiourea com-
pounds did not catalyze the classic Michael additions of acetone
and diethylmalonate into b-nitrostyrene, most probably due to
the absence of the additional basic functionality (e.g., amine) in
the structure of the catalysts. However, we found that nitro-
methane adds to trans-chalcone 30 in the presence of 1,2-O-iso-
propylidene protected allo-furanose derived thiourea 21
(Scheme 6). The reaction took place over 14 days and gave product
(S)-31 in 30% yield and 48% ee. For substrate 30, which does not
Scheme 5. Synthesis of 3-C-aminomethyl-hexofuranose-based urea and thiourea
organocatalysts.
O2N
O
O
MeNO2
21
Ph
Ph
Ph
Ph
-31
, 30%, 48% ee
(10 mol-%)
14 days
30
(S)
contain additional complexation sites17b and for
a standard
thiourea catalyst without enhanced N–H acidity,17e,17d this is a
reasonable achievement.
Scheme 6. Organocatalyzed Michael addition of nitromethane to trans-chalcone
30.
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4
M. Turks et al. / Tetrahedron: Asymmetry xxx (2015) xxx–xxx
noted. Commercial reagents were used without purification.
3. Conclusion
Solvents were distilled prior to use and, if required, dried over
standard drying agents (THF from metallic sodium, DMSO, DMF,
and Et3N form CaH2). Analytical thin layer chromatography (TLC)
was performed on Merck precoated analytical plates, 0.25 mm
thick, silica gel 60F254. Preparative flash chromatography was per-
In conclusion, we have developed a straightforward synthesis of
novel 3-C-aminomethyl-hexofuranose-based ureas and thioureas.
En route to this we have validated the nitromethane addition
chemistry on cyclohexylidene-protected glucofuranose. The
spirooxazolidinones derived from the latter might be useful as chi-
ral auxiliaries in the future. The selected model reactions of indole
alkylation and Michael addition of nitromethane have, in principle,
proved the potential of the title compounds as organocatalysts.
Further elaboration of the described molecular scaffolds might pro-
duce easy to access furanose-based organocatalysts.
formed on silica gel (60 Å, 40–63 lm, ROCC). Melting points were
recorded with a Fisher Digital Melting Point Analyzer Model 355
apparatus and are uncorrected. IR spectra were recorded as thin
films on KBr plates or in KBr with FT-IR Perkin Elmer Spectrum BX.
Optical rotations were measured at 25 °C on a Anton Paar MCP
500 polarimeter using
a sodium lamp as the light source
(589 nm). 1H and 13C NMR spectra were recorded on a Bruker
300 MHz and Varian 400 MHz spectrometers in CDCl3 or DMSO-
d6. The proton signals for residual non-deuterated solvents (d
7.26 for CDCl3 and d 2.50 for DMSO-d6) and carbon signals (d
77.1 for CDCl3 and d 39.5 for DMSO-d6) were used as internal ref-
erences for 1H NMR and 13C NMR spectra, respectively. Chemical
shift (d) values are reported in ppm and coupling constants J in
4. Experimental
4.1. General
All non-aqueous reactions were carried out under an inert
atmosphere of argon in oven-dried glassware unless otherwise
Table 1
Organocatalyzed alkylation of indole 27 + 28 ? 29a
Ph
NO2
organocat.
NO2
+
Ph
(additive)
N
H
N
H
27
Additive
28
29
Entry
1
Catalyst
React. time (h)
375
Yield of 29 (%)
ee (%), config.b
19
—
—
—
—
67
7 (S)
5 mol-%
2
22c
84
3
11 (R)
40 mol-%
20
3
4
5
160
624
240
94
48
41
12 (S)
7 (S)
5 (R)
21d
23e
100 mol-%
24
6
7
8
9
—
—
—
—
720
312
144
288
144
70
28
78
48
92
9 (R)
20 (S)
10 (S)
rac
25
25f
26
25
10
(+)-Di-O-benzoyl-
D-tartaric acid
7 (S)
15 mol-%
11
12
13
14
15
16
17
18
25
25
(ꢀ)-Di-O-benzoyl-
L
-tartaric acid
144
168
72
81
50
19
81
81
99
81
89
15 (S)
rac
15 mol-%
(1R)-(-)-10- Camphorsulfonic acid
15 mol-%g
25e
12 mol-%
—
(1R)-(-)-10- Camphorsulfonic acid
15 mol-%
rac
(1R)-(ꢀ)-10-Camphorsulfonic acid
168
168
144
144
144
rac
15 mol-%g
25
25
25
25
(1R,3S)-(+)-Camphoric acid
15 mol-%
20 (S)
9 (S)
15 (S)
15 (S)
(S)-(+)-a-Methoxyphenylacetic acid
15 mol-%g
Acetic acid
15 mol-%
Benzoic acid
15 mol-%
a
Reaction conditions: 20 mol-% catalyst in CH2Cl2 (1 M in substrates, 0.2 M in catalyst) at ambient temperature if not stated otherwise.
b
Enantiomeric ratio was determined by HPLC analysis of 29 using Chiralpak IA column (0.46 ꢁ 25 cm). Isocratic method: 5% iPrOH/Hex; 40 min; injection 5
ll (0.70 mg/mL
Hex + 30% iPrOH); flow rate 1 mL/min; detector wavelength 254 nm. The absolute configuration of the product was determined by comparing the specific rotation of 29 with
that of literature data.
c
CH2Cl2:toluene = 1:1, +4 °C.
CHCl3.
+5 °C.
+35 °C.
d
e
f
g
The enantiomer gave nearly equal result in terms of yield and ee.
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M. Turks et al. / Tetrahedron: Asymmetry xxx (2015) xxx–xxx
5
Hz. HRMS spectra (ESI+) were performed using a Q-TOF Micromass
and elemental analyses on a Carlo-Erba EA1108 analyzer. Yields
refer to chromatographically and spectroscopically homogeneous
materials.
20H, (Chx)2-C(1,2:5,6)); 13C NMR (CDCl3, 75 MHz) d: 114.1, 111.1,
103.3, 81.9, 79.4, 78.5, 77.1, 72.7, 67.8, 36.3, 36.1, 35.9, 34.6,
25.0, 24.8, 24.0, 23.9, 23.8, 23.5.
4.1.3. 3-Deoxy-3-C-nitromethylene-1,2:5,6-di-O-cyclohexylidene-
4.1.1. A 9:1 mixture of 1,2:5,6-di-O-cyclohexylidene-
a-
D-ribo-3-
a-D-ribo-hexofuranose 11
hexofuranose-3-ulose 8a and its hydrate 8b
Acetic anhydride (161 mL, 1.70 mol, 50 equiv) was added to a
In an open-mouth beaker equipped with mechanical stirrer, a
solution of NaBr (1.36 g, 13.0 mmol, 0.15 equiv) in water (6 mL)
stirred solution of a diastereomeric mixture of nitro sugars 9 and
10 (13.6 g, 34.0 mmol, 1 equiv) in dry DMSO (48.0 mL, 68.3 mmol,
20 equiv) at room temperature. The resulting reaction mixture was
stirred at ambient temperature for 48 h and the Ac2O was evapo-
rated (ꢂ120 mL, 50 °C, 8 mbar). The residual mixture was cooled
to 0 °C and poured with vigorous stirring into a cold acetate buffer
solution (32.0 g AcONa in 130 mL H2O adjusted to pH 6 with AcOH)
at ꢀ10 °C. The resulting mixture was further neutralized with solid
NaHCO3 (ꢂ30 g) to pH 6 followed by extraction with EtOAc
(3 ꢁ 30 mL). The combined organic layer was washed with brine
(6 ꢁ 30 mL), dried over anhydrous Na2SO4, filtered, and evapo-
rated. The purification of the crude product by column chromatog-
raphy on silica gel (150 g) (Hex/EtOAc (4%) provided product 11
(7.59 g, 59%) which consisted of isomers Z-11:E-11 in a 5:1 ratio
and unreacted starting material compound 10 (Hex/EtOAc 3%)
(4.30 g, 32% from starting material loading). The purification of
product 11 was carried out repeatedly by column chromatography
on silica gel (Hex/EtOAc 3%) to yield isomers (Z)-11:(E)-11 in a 25:1
ratio. Data for compound (Z)-11: Rf = 0.55 (EtOAc/Hex 1:6);
was added to a solution of 1,2:5,6-di-O-cyclohexylidene-
a-D-gluco-
furanose-3-ulose (30.0 g, 88.0 mmol, 1.0 equiv) in CH2Cl2
7
(200 mL), followed by TEMPO (0.220 g, 1.41 mmol, 0.016 equiv).
The resulting mixture was cooled to ꢀ10 °C (internal temperature)
and vigorously stirred, and an aqueous solution of NaClO
(ꢂ1.6 mol/L, pH 9.5 (pH-meter control; adjusted by NaHCO3),
330 mL, 0.528 mol, 6 equiv) was added dropwise in 45 min while
keeping the internal temperature in the range of ꢀ10 to 0 °C.
After addition of the bleach solution, the resulting reaction mixture
was stirred for 5 min. The organic layer was separated and washed
successively with a solution of KI (0.730 g, 4.40 mmol, 5.5 mol-%) in
0.5 M aqueous sulfuric acid (80 mL), a 10% aqueous solution of
Na2S2O3 (80 mL),
a saturated aqueous solution of NaHCO3
(200 mL), and brine (200 mL). After drying (Na2SO4), filtration and
evaporation under reduced pressure, the crude product (23.0 g,
77%) contained a mixture of ketone 8a and ketone hydrate 8b in a
ꢂ9:1 ratio. The NMR data and other characteristics of products 8a
fully corresponded to those reported earlier.22 Data for compound
8a: 1H NMR (300 MHz, CDCl3): d 6.15 (d, 1H, 3J = 4.5 Hz, H-C(1)),
4.41–4.31 (m, 3H, H-C(2), H-C(4), Ha-C(6)), 4.04–4.01 (m, 2H, H-
C(5), Hb-C(6)), 1.71–1.30 (m, 20H, (Chx)2-C(1,2:5,6)).
[a]
23 = +138 (c 0.48, CHCl3) (Z-11:E-11 = 25:1); IR (KBr): 2934,
D
2857, 1531, 1366, 1348, 1280, 1162, 1117, 1090, 1027. (Z-11:E-
11 = 25:1); 1H NMR (CDCl3, 300 MHz) d: 7.47 (t, 1H, 4J = 1.7 Hz,
H-C(30)), 5.90 (d, 1H, 3J = 4.1 Hz, H-C(1)), 5.80 (dt, 1H, 3J = 4.1,
4J = 1.7 Hz, H-C(2)), 4.73 (dt, 1H, 3J = 8.2, 4J = 1.9, Hz, H-C(4)), 4.13
(dd, 1H, 2J = 8.7 Hz, 3J = 5.8 Hz, Ha-C(6)), 4.04 (dd, 1H, 2J = 8.7 Hz,
3J = 4.3 Hz, Hb-C(6)), 4.00 (ddd, 1H, 3J = 8.2, 5.8, 4.3 Hz, H-C(5)),
1.70–1.32 (m, 20H, (Chx)2-C(1,2:5,6)); 13C NMR (CDCl3,
75.5 MHz) d: 149.7, 135.7, 114.2, 111.3, 104.6, 79.3, 78.0, 75.9,
67.2, 36.9, 36.6 (2C), 34.6, 25.0, 24.7, 24.1, 23.9, 23.8, 23.6.
HRMS: calcd [C19H27NO7+H+] 382.1860, found 382.1861.
4.1.2. A 3:1 mixture of (3R)-3-C-nitromethyl-1,2:5,6-di-O-cycloh-
exylidene-a-D-allofuranose 9 and (3S)-3-C-nitromethyl-1,2:5,6-
di-O-cyclohexylidene-
a-D
-glucofuranose 10
Nitromethane (23.0 mL, 0.410 mol, 6 equiv) was added to a
solution of NaOH (5.40 g, 0.135 mol, 2 equiv) in MeOH (100 mL)
at 0 °C and stirred for 10 min. The resulting mixture was added
to a solution of a 3:1 mixture of ketone 8a and ketone hydrate
8b (23.0 g, 0.068 mol, 1 equiv) in MeOH (60 mL) at 0–10 °C and
vigorously stirred for 30 min. The reaction mixture was stirred at
ambient temperature for 2.5 h and then poured into a saturated
aqueous solution of (NH4)2SO4 (150 mL) at 0 °C. The organic layer
was separated and, after evaporation under reduced pressure, the
residual mixture was dissolved in ethyl acetate (200 mL). The
water layer was extracted by EtOAc (60 mL). The combined organic
layer was washed with brine (150 mL), dried over anhydrous
Na2SO4, filtered, and evaporated under reduced pressure to afford
a mixture of compounds 9 and 10 in a ꢂ3:1 ratio (30.0 g). The
purification of the crude product by column chromatography on
silica gel (300 g) (Hex/EtOAc 8–15%) and crystallization yielded 9
(10.3 g, 38%, de >95%) as a white solid. The filtrate was evaporated
under reduced pressure to afford brown oil (12.3 g, 46%) which
consists of epimers 9 (50%) and 10 (50%). The total yield of the
major isomer 9 was 6.15 g, 61% and minor isomer 10 6.15 g, 23%.
This mixture of 9 and 10 was used in the next step without addi-
tional purification. NMR data and other physicochemical data of
the product 9 were consistent with those reported earlier.23 Data
4.1.4. (3S)-3-C-Nitromethyl-1,2:5,6-di-O-cyclohexylidene-a-D-
glucofuranose 10
An aqueous (30 mL) solution of NaOH (0.770 g, 19.0 mmol,
1.2 equiv) was added to a solution of nitro-ene derivative 11 (Z-
11:E-11 = 5:1) (6.14 g, 16.60 mmol, 1 equiv) in THF (20 mL) at
30 °C. The resulting mixture was stirred for 3 h at 30 °C and was
monitored by TLC. The reaction mixture was neutralized by satu-
rated aqueous (40 mL) solution of (NH4)2SO4 and stirred for
30 min until pH 6–7. After evaporation of THF, the residue was
dissolved in EtOAc (200 mL). The phases were separated and the
organic layer was washed with brine (5 ꢁ 30 mL), dried over anhy-
drous Na2SO4, filtered, and evaporated under reduced pressure.
The purification of the crude product by column chromatography
on silica gel (60 g) (Hex/EtOAc 5%) provided product 10 (2.99 g,
47%). NMR and other physicochemical data of the product 10 were
consistent with those reported earlier.
[a]
25 = +28.1 (c 0.77,
D
CHCl3); 1H NMR (CDCl3, 300 MHz) d: 5.94 (d, 1H, 3J = 3.7 Hz, H-
2
C(1)), 4.95 (d, AB syst., 1H, J = 14.8 Hz, Ha-C(30)), 4.76 (d, AB syst.,
2
1H, J = 14.8 Hz, Hb-C(30)), 4.59 (d, 1H, 3J = 3.7 Hz, H-C(2)), 4.39
for compound 9: [
a
]
23 = 48 (c 0.20, CHCl3); 1H NMR (CDCl3,
(ddd, 1H, 3J = 8.9, 6.3, 4.8 Hz, H-C(5)), 4.15 (dd, AB syst., 1H,
2J = 8.9 Hz, 3J = 6.3 Hz, Ha-C(6)), 3.99 (dd, AB syst., 1H, 2J = 8.9 Hz,
3J = 4.8 Hz, Hb-C(6)), 3.69 (d, 1H, 3J = 8.9 Hz, H-C(4)), 3.48 (br s,
1H, HO-C(3)), 1.81–1.32 (m, 20H, (Chx)2-C(1,2:5,6)); 13C
NMR (CDCl3, 75 MHz) d: 113.8, 110.5, 104.5, 85.0, 81.5, 79.8,
76.0, 71.5, 67.3, 36.6, 36.45, 35.8, 34.4, 25.0, 24.8, 24.1, 23.9,
23.7, 23.5.
D
300 MHz) d: 5.86 (d, 1H, 3J = 4.0 Hz, H-C(1)), 4.99 (d, AB syst., 1H,
2J = 12.1 Hz, Ha-C(30)), 4.87 (d, 1H, 3J = 4.0 Hz, H-C(2)), 4.49 (d, AB
2
syst., 1H, J = 12.1 Hz, Hb-C(30)), 4.13 (dd, AB syst., 1H, 2J = 8.1 Hz,
3J = 5.5 Hz, Ha-C(6)), 4.00 (ddd, 1H, 3J = 8.5, 5.5, 4.7 Hz, H-C(5)),
3.93 (dd, AB syst., 1H, 2J = 8.1 Hz, 3J = 4.7 Hz, Hb-C(6)), 3.86 (d,
1H, 3J = 8.5 Hz, H-C(4)), 3.28 (br s, 1H, HO-C(3)), 1.73–1.32 (m,
Please cite this article in press as: Turks, M.; et al. Tetrahedron: Asymmetry (2015), http://dx.doi.org/10.1016/j.tetasy.2015.07.003

6
M. Turks et al. / Tetrahedron: Asymmetry xxx (2015) xxx–xxx
4.1.5. (3R)-3-C-Aminomethyl-1,2:5,6-di-O-cyclohexylidene-
allofuranose 12
a
-
D
-
1235, 1169, 1133; 1H NMR (CDCl3, 300 MHz) d: 5.71 (d, 1H,
3J = 3.4 Hz, H-C(1)), 5.62 (br s, 1H, H-N-C(30)), 4.46 (d, 1H,
3J = 3.4 Hz, H-C(2)), 4.17–4.06 (m, 3H, H-C(4), H-C(5), Ha-C(6)),
3.97 (dd, AB syst., 1H, 2J = 8.3 Hz, 3J = 3.6 Hz, Hb-C(6)), 3.89 (d, AB
A solution of nitro alcohol 9 (10.7 g, 27.0 mmol, 1 equiv) in
EtOH (400 mL) was hydrogenated at 40 atm and 40 °C in the pres-
ence of 10% Pd/C (1.00 g) for 14 h. The resulting mixture was fil-
tered through Celite and washed by EtOH (200 mL). The filtrate
was evaporated to dryness under reduced pressure. The crude pro-
duct 12 (10.4 g) was purified by column chromatography
(EtOAc/EtOH (5%)) and recrystallized (Hex/EtOAc). Product 12
2
syst., 1H, J = 8.7 Hz, Ha-C(40)), 3.26 (d, AB syst., 1H, 2J = 8.7 Hz,
Hb-C(40)), 1.88–1.30 (m, 20H, (Chx)2-C(1,2:5,6)); 13C NMR (CDCl3,
75.5 MHz) d: 158.3, 115.2, 110.9, 102.7, 85.6, 83.6, 77.5, 73.5,
68.0, 44.3, 36.3 (2C), 36.0, 34.8, 25.1, 24.8, 23.9, 23.8 (2C), 23.6;
HRMS: calcd [C20H29NO7+H+] 396.2017; found 396.2014.
was obtained as
(CH2Cl2/EtOH 1:1, 1% NH3); [
a
white solid (8.56 g, 87%). Rf = 0.79
a
]
D
25 = +24 (c 0.38, CHCl3); mp = 92–
4.1.8. (1,2:5,6-Di-O-cyclohexylidene-a-D-glucofuranos-3-C-
yl)methylamonium tosylate 16
94 °C; IR (KBr): 3543, 2936, 2862, 1615, 1449, 1369, 1284, 1165,
1118, 1014; 1H NMR (CDCl3, 300 MHz) d: 5.75 (d, 1H, 3J = 4.0 Hz,
H-C(1)), 4.61 (d, 1H, 3J = 4.0 Hz, H-C(2)), 4.12–4.04 (m, 2H, H-
C(5), Ha-C(6)), 3.93–3.85 (m, 1H, Hb-C(6)), 3.80 (d, 1H, 3J = 8.3 Hz,
A solution of nitro alcohol 10 (7.08 g, 17.7 mmol, 1 equiv) in
ethanol (300 mL) was hydrogenated at 40 atm and 40 °C in the
presence of 10% Pd/C (0.700 g) for 24 h. The resulting mixture
was filtered through Celite and washed by EtOH (100 mL). The fil-
trate was evaporated to dryness under reduced pressure. A solu-
tion of p-TsOH (2.32 g, 1.31 mmol, 1 equiv) in EtOAc (50 mL) was
2
H-C(4)), 3.21 (d, AB syst., 1H, J = 13.0 Hz, Ha-C(30)), 2.67 (d, AB
2
syst., 1H, J = 13.0 Hz, Hb-C(30)), 2.54 (br s, 3H, H2N-C(30), HO-
C(3)), 1.82–1.32 (m, 20H, (Chx)2-C(1,2:5,6)); 13C NMR (CDCl3,
75.5 MHz) d: 113.2, 110.4, 103.2, 81.9, 80.1, 79.3, 72.8, 67.8, 42.6,
36.2 (2C), 36.0, 34.8, 25.1, 24.9, 24.1, 23.9 (2C), 23.5; HRMS: calcd
[C19H31NO6+H+] 370.0222; found 370.0222.
added to
a solution of crude product 15 (6.40 g) in EtOAc
(100 mL) at ꢀ10 °C. The resulting reaction mixture was stirred at
temperature ꢀ10 °C for 30 min and filtered. Product 16 was
obtained as a white solid (5.76 g, 60%). Rf = 0.7 (EtOAc/EtOH 4:1);
4.1.6. 3-C-(N-Phenyloxycarbonyl)aminomethyl-1,2:5,6-di-O-
[a]
23 = +1.7 (c 0.4, CHCl3); mp = 184–189 °C (decomp.); IR (KBr):
D
cyclohexylidene-
a
-
D
-allofuranose 13
3251, 3086, 2934, 2862, 2671, 1614, 1603, 1504, 1462, 1449,
1368, 1336, 1276; 1H NMR (DMSO-d6, 300 MHz) d: 7.80 (br s, 3H,
H3N-C(30)), 7.47 (d, 2H, 3J = 7.8 Hz, H-C(Ar)), 7.11 (d, 3J = 7.8 Hz,
H-C(Ar)), 6.11 (br s, 1H, HO-C(30)), 5.87 (d, 1H, 3J = 3.6 Hz, H-
C(1)), 4.43 (d, 1H, 3J = 3.6 Hz, H-C(2)), 4.20 (ddd, 1H, 3J = 8.3, 6.4,
5.4 Hz, H-C(5)), 4.04 (dd, AB syst., 1H, 2J = 8.4 Hz, 3J = 6.4 Hz, Ha-
C(6)), 3.81 (dd, AB syst., 1H, 2J = 8.4 Hz, 3J = 5.4 Hz, Hb-C(6)), 3.64
(d, 1H, 3J = 8.3 Hz, H-C(4)), 3.14 (d, AB syst., 2J = 12.8 Hz, 1H, Ha-
Triethylamine (2.56 mL, 18.4 mmol, 1.7 equiv) was added to a
stirred solution of 12 (4.00 g, 11.0 mmol, 1 equiv) in dry THF
(70 mL) under an argon atmosphere cooled to 0 °C. After 10 min,
phenyl chloroformate (2.15 mL, 16.5 mmol, 1.5 equiv) was added
dropwise at 0 °C. The resulting reaction mixture was stirred at
ambient temperature for 1.5 h, then it was evaporated to dryness
under reduced pressure, and redissolved in ethyl acetate (50 mL).
The organic layer was washed with a saturated aqueous solution
2
C(30)), 3.04 (d, AB syst., J = 12.8 Hz, 1H, Hb-C(30)), 2.28 (s, 3H,
of CuSO4 (2 ꢁ 15 mL) and
a
saturated aqueous solution of
H3C-C(Ar)), 1.66–1.30 (m, 20H, (Chx)2-C(1,2:5,6)); 13C NMR
(DMSO-d6, 75 MHz) d: 146.1, 138.1, 128.5, 126.0, 112.9, 109.8,
104.2, 83.8, 81.7, 79.3, 71.8, 66.9, 40.2, 36.6, 36.3, 35.9, 34.9,
25.0, 24.8, 24.1 (2C), 23.9, 23.6, 21.2; HRMS: calcd
[C26H39NO9S+H+] 370.2224; found 370.2223.
NaHCO3 (4 ꢁ 20 mL), dried over Na2SO4, and evaporated under
reduced pressure. Recrystallization of the crude product from hex-
ane/ethylacetate afforded the title compound 13 (4.02 g, 76%).
Rf = 0.43 (EtOAc/Hex 3:7); [a]
23 = +48 (c 0.65, CHCl3); mp = 129–
D
131 °C; IR (KBr): 3387, 2942, 2889, 2854, 1727, 1526, 1451,
1481, 1457, 1446, 1400; 1H NMR (CDCl3, 300 MHz) d: 7.36 (t, 2H,
3J = 7.8 Hz, H-C(Ar)), 7.20 (t, 1H, 3J = 7.0 Hz, H-C(Ar)), 7.14 (d, 2H,
3J = 7.8 Hz, H-C(Ar)), 5.80 (d, 1H, 3J = 4.0 Hz, H-C(1)), 5.71 (t, 1H,
3J = 5.8 Hz, H-N-C(30)), 4.39 (d, 1H, 3J = 4.0 Hz, H-C(2)), 4.18–4.08
(m, 2H, H-C(5), Ha-C(6)), 3.95–3.85 (m, 1H, Hb-C(6)), 3.78 (d, 1H,
4.1.9. 3-C-(N-Phenyloxycarbonyl)aminomethyl-1,2:5,6-di-O-
cyclohexylidene-a-D-glucofuranose 17
Triethylamine (1.94 mL, 14.0 mmol, 2.7 equiv) was added to a
stirred solution of 16 (2.80 g, 5.17 mmol, 1 equiv) in dry THF
(55 mL) under an argon atmosphere and the resulting mixture was
cooled to 0 °C. After 10 min, phenyl chloroformate (1.00 mL,
7.75 mmol, 1.5 equiv) was added dropwise at 0 °C. The resulting
reaction mixture was stirred at 0 °C for 10 min followed by 2.5 h at
ambient temperature, then it was evaporated to dryness under
reduced pressure, and redissolved in ethyl acetate (40 mL). The ethyl
acetate layer was washed with a saturated aqueous solution of
CuSO4 (2 ꢁ 15 mL), a saturated aqueous solution of NaHCO3
(2 ꢁ 20 mL), brine (3 ꢁ 30 mL) and dried over Na2SO4, and evapo-
rated under reduced pressure. Recrystallization of the crude product
from hexane/ethylacetate afforded the title compound 17 as a white
2
3J = 7.9 Hz, H-C(4)), 3.60 (d, AB syst., 1H, J = 11.6 Hz, Ha-C(30)),
2
3.54 (d, AB syst., 1H, J = 11.6 Hz, Hb-C(30)), 3.00 (s, 1H, HO-C(3)),
1.83–1.32 (m, 20H, (Chx)2-C(1,2:5,6)); 13C NMR (CDCl3,
75.5 MHz) d: 155.3, 150.9, 129.4, 125.5, 121.5, 113.5, 110.7,
103.3, 81.6, 80.1, 79.4, 72.8, 68.0, 42.4, 36.3, 36.1 (2C), 34.7, 25.1,
24.8, 24.1, 23.9, 23.8, 23.5; HRMS: calcd [C26H35NO8+Na+]
512.2255; found 512.2239.
4.1.7. (3R)-1,2:5,6-Di-O-cyclohexylidene-spiro(3-deoxy-a-D-
allofuranose-3,50-oxazolidin)-20-one 14
A solution of NaOH (0.810 g, 20.0 mmol, 2.1 equiv) in water
(23.0 mL) and benzyltrimethylammonium chloride (0.110 g,
solid (2.34 g, 93%). Rf = 0.60 (EtOAc/Hex 2:3); [a]
23 = +73 (c 0.17,
D
CHCl3); IR (KBr): 3402, 3351, 2934, 2863, 1740, 1494, 1370, 1270,
1211, 1164, 1121; 1H NMR (CDCl3, 300 MHz) d: 7.39 (t, 2H,
3J = 7.7 Hz, H-C(Ar)), 7.24 (t, 1H, 3J = 7.4 Hz, H-C(Ar)), 7.17 (d, 2H,
3J = 7.5 Hz, H-C(Ar)), 5.93 (t, 1H, 3J = 6.1 Hz, H-N-C(30)), 5.92 (d, 1H,
3J = 3.8 Hz, H-C(1)), 4.46 (d, 1H, 3J = 3.8 Hz, H-C(2)), 4.33 (ddd, 1H,
3J = 8.5, 6.2, 5.5 Hz, H-C(5)), 4.18 (dd, 1H, 2J = 8.7 Hz, 3J = 6.2 Hz,
Ha-C(6)), 4.00 (dd, 1H, 2J = 8.7 Hz, 3J = 5.5 Hz, Hb-C(6)), 3.84 (dd, AB
48.0 mmol, 5-mol %) was added to
a stirred solution of 13
(4.73 g, 9.66 mmol, 1 equiv) in CH2Cl2 (30 mL) at 0 °C. The resulting
biphasic reaction mixture was stirred at 0 °C for 10 min followed
by 3.5 h at ambient temperature. The phases were separated and
the aqueous residue was extracted with CH2Cl2 (4 ꢁ 25 mL). The
combined CH2Cl2 layer was extracted with aq 2 M NaOH solution
(2 ꢁ 20 mL) and with brine (5 ꢁ 10 mL). The resulting solution
was dried over Na2SO4, filtered, and evaporated under reduced
pressure to afford the title compound 14 (3.67 g, 96%). Rf = 0.18
3
syst., 1H, 2J = 14.7 Hz, J = 5.8 Hz, Ha-C(30)), 3.81 (d, 1H, 3J = 8.5 Hz,
3
H-C(4)), 3.65 (d, AB syst., 1H, 2J = 14.7 Hz, J = 7.0 Hz, Hb-C(30)),
3.34–3.14 (br s, 1H, HO-C(3)), 1.79–1.36 (m, 20H, (Chx)2-
C(1,2:5,6)); 13C NMR (CDCl3, 75.5 MHz) d: 156.7, 151.0, 129.4,
125.6, 121.5, 113.4, 110.5, 104.3, 86.0, 83.0, 82.2, 71.8, 67.6, 44.3,
(EtOAc/Tol 2:3); mp = 180–181 °C; [
(KBr): 3374, 2944, 2896, 2862, 1760, 1451, 1443, 1367, 1281,
a]
23 = +63 (c 0.37, CHCl3); IR
D
Please cite this article in press as: Turks, M.; et al. Tetrahedron: Asymmetry (2015), http://dx.doi.org/10.1016/j.tetasy.2015.07.003

M. Turks et al. / Tetrahedron: Asymmetry xxx (2015) xxx–xxx
7
36.7, 36.5, 36.0, 34.6, 25.1, 24.9, 24.1, 24.0, 23.7, 23.6; HRMS: calcd
[C26H35NO8+Na+] 512.2255; found 512.2239.
3J = 3.7 Hz, H-C(2)), 4.16 (q, 1H, 3J = 6.4 Hz H-C(5)), 3.98 (dd, AB syst.,
1H, 2J = 7.9 Hz, 3J = 6.4 Hz, Ha-C(6)), 3.90 (d, 1H, 3J = 6.4 Hz, H-C(4)),
3.80–3.72 (m, 1H, Ha-C(30)), 3.71 (dd, AB syst., 1H, 2J = 7.9 Hz,
3J = 6.4 Hz, Hb-C(6)), 3.58 (dd, AB syst., 1H, 2J = 13.8 Hz, 3J = 4.7 Hz,
Hb-C(30)), 1.50, 1.33, 1.26, 1.23 (4s, 12H, (H3C)2C-O-C(1,5)); 13C
NMR (DMSO-d6, 75.5 MHz) d: 181.2, 142.3, 130.7 (q, 2JC–F = 33 Hz),
4.1.10. (3S)-1,2:5,6-Di-O-cyclohexylidene-spiro(3-deoxy-a-D-
glucofuranose-3,50-oxazolidin)-20-one 18
A solution of NaOH (0.383 g, 9.58 mmol, 2.1 equiv) in water
(10 mL) and benzyltrimethylammonium chloride (0.052 g,
0.228 mmol, 5-mol %) was added to a stirred solution of 17
(2.23 g, 4.56 mmol, 1 equiv) in CH2Cl2 (15 mL) at 0 °C. The resulting
biphasic reaction mixture was stirred at 0 °C for 10 min followed
by 2 h at ambient temperature. The phases were separated and
the aqueous residue was extracted with CH2Cl2 (5 ꢁ 10 mL). The
combined organic layer was extracted with a solution of 2 M
NaOH (2 ꢁ 15 mL), with a saturated aqueous solution of NaCl
(5 ꢁ 25 mL) and dried over Na2SO4. The resulting solution was fil-
tered and evaporated under reduced pressure to afford the title
compound 18 (1.60 g, 89%). Rf = 0.45 (EtOAc/Tol 3:7);
1
123.7 (q, JC–F = 274 Hz), 122.0 (m), 116.7 (m), 112.1, 108.8, 103.5,
81.4, 80.7, 79.6, 73.3, 66.5, 46.1, 27.1, 26.8 (2C), 25.5; HRMS: calcd
[C22H26F6N2O6S+H+] 560.1489; found 560.1483.
4.1.13. (3R)-3-C-[(3,5-Bis(trifluoromethyl)phenylthioureido-
methyl]-1,2-O-isopropylidene-a-D-allofuranose 21
At first, 1 M H2SO4 (1.38 mL, 1.38 mmol, 0.2 equiv) was added
to a solution of thiourea 20 (3.87 g, 6.91 mmol, 1 equiv) in MeOH
(25 mL) and CH2Cl2 (50 mL), and stirred at 60 °C for 4 h. Next,
anhydrous NaHCO3 (0.29 g, 3.45 mmol, 0.5 equiv) was added to
the resulting reaction mixture at 0 °C followed by stirring 30 min
at ambient temperature. The reaction mixture was dried over
Na2SO4, filtered, and evaporated under reduced pressure.
Purification by column chromatography (EtOAc/Hex 70%) yielded
[a]
23 = +21.6 (c 0.52, CHCl3); IR (KBr): 3302, 2938, 2862, 1768,
D
1433, 1368, 1279, 1218, 1164, 1101, 1076, 1016; 1H NMR (CDCl3,
300 MHz) d: 5.92 (d, 1H, 3J = 3.6 Hz, H-C(1)), 5.26 (s, 1H, H-N-
C(30)), 4.54 (d, 1H, 3J = 3.6 Hz, H-C(2)), 4.36 (ddd, 1H, 3J = 8.5, 6.2,
5.3 Hz, H-C(5)), 4.15 (dd, AB syst. 1H, 2J = 8.7 Hz, 3J = 6.2 Hz, Ha-
C(6)), 3.98 (dd, AB syst., 1H, 2J = 8.7 Hz, 3J = 5.3 Hz, Hb-C(6)), 3.87
21 (3.07 g, 85%). Rf = 0.39 (EtOAc); [a]
20 = +54.3 (c 0.74, CHCl3); IR
D
(KBr): 3337, 3102, 2993, 2941, 2888, 1542, 1474, 1385, 1278,
1177, 1133; 1H NMR (DMSO-d6, 300 MHz) d: 10.47–10.35 (br s,
1H, H-N-C(Ar)), 8.35 (s, 2H, H-C(Ar)), 8.22–8.04 (br s, 1H, H-N-
C(30)), 7.74 (s, 1H, H-C(Ar)), 5.69 (d, 1H, 3J = 3.7 Hz, H-C(1)), 5.08–
4.98 (br s, 1H, HO-C(3)), 4.82 (d, 1H, 3J = 4.9 Hz, HO-C(5)), 4.59 (t,
1H, 3J = 5.8 Hz, HO-C(6)), 4.32 (d, 1H, 3J = 3.7 Hz, H-C(2)), 3.94
2
(d, 1H, AB syst., J = 8.9 Hz, Ha-C(40)), 3.79 (d, 1H, 3J = 8.5 Hz, H-
2
C(4)), 3.81 (d, 1H, AB syst., J = 8.9 Hz, Hb-C(40)), 1.73-1.34 (m,
20H, (Chx)2-C(1,2:5,6)); 13C NMR (CDCl3), 75.5 MHz) d: 159.9,
113.7, 110.4, 104.5, 88.1, 83.6, 81.6, 72.2, 67.5, 42.1, 36.6 (2C),
36.0, 34.4, 25.1, 24.8, 24.2, 23.9, 23.7, 23.6; HRMS: calcd
[C20H29NO7+H+] 396.2017; found 396.2014.
3
(dd, AB syst., 1H, 2J = 14.1 Hz, J = 5.7 Hz, Ha-C(30)), 3.83 (d, 1H,
3J = 7.4 Hz, H-C(4)), 3.72 (dd, AB syst., 1H, 2J = 14.1 Hz, 3J = 2.6 Hz,
Hb-C(30)), 3.67–3.53 (m, 2H, Ha-C(6), H-C(5)), 3.38 (dd, AB syst.,
1H, 2J = 11.1 Hz, 3J = 5.8 Hz, Hb-C(6)), 1.47, 1.25 (2s, 6H, (H3C)2C-
O-C(1)); 13C NMR (CD3OD, 75.5 MHz) d: 180.6, 140.3, 129.8 (q,
4.1.11. (3R)-3-C-[(3,5-Bis(trifluoromethyl)phenylureidomethyl]-
1,2:5,6-di-O-isopropylidene-a-D-allofuranose hemihydrate 19
1
3
Bis(3,5-trifluoromethyl)phenyl
isocyanate (0.041 mL,
2JC–F = 34 Hz), 121.8 (q, JC–F = 272 Hz), 120.8 (q, JC–F = 3 Hz),
115.1 (m), 111.78, 102.0, 79.6, 78.6, 77.5, 68.8, 62.3, 43.9, 23.9,
23.7; HRMS: calcd [C19H22F6N2O6S+H+] 521.1176; found 521.1172.
0.159 mmol, 1.15 equiv) was added to a solution of amino alcohol
5 (40.0 mg, 0.138 mmol, 1 equiv) in CH2Cl2 (1.5 mL). After stirring
at reflux at 40 °C for 4 h, the solvent was removed under reduced
pressure. Purification by column chromatography (EtOAc/Hex
25%) yielded 19 (76.0 mg, 75%). Rf = 0.39 (EtOAc/Hex 2:3);
4.1.14. (3S)-3-C-[(3,5-Bis(trifluoromethyl)phenylureidomethyl]-
1,2:5,6-di-O-isopropylidene-
a
-
D
-glucofuranose hydrate 22
isocyanate (0.101 mL,
[a]
25 = +26 (c 1.2, CHCl3); mp = 95–99 °C (Hex/EtOAc); IR (KBr):
D
Bis(3,5-trifluoromethyl)phenyl
3370, 2993, 2141, 1664, 1571, 1389, 1280, 1182, 1132; 1H NMR
(CDCl3, 300 MHz) d: 7.84 (s, 2H, H-C(Ar)), 7.59–7.39 (br s, 2H, H-
C(Ar), H-N-C(Ar)), 5.84 (d, 1H, 3J = 3.6 Hz, H-C(1)), 5.67 (dd, 1H,
3J = 5.6, 5.0, Hz, H-N-C(30)), 4.39 (d, 1H, 3J = 3.6 Hz, H-C(2)), 4.20–
4.12 (m, 2H, H-C(5)), Ha-C(6)), 3.99–3.92 (m, 1H, Hb-C(6)), 3.80
0.398 mmol, 1.15 equiv) was added to a solution of amino alcohol
6 (0.100 g, 0.346 mmol, 1 equiv) in CH2Cl2 (3 mL). After stirring at
reflux at 40 °C for 4 h, the solvent was removed under reduced
pressure. Purification by column chromatography (EtOAc/Hex
25%) yielded 22 (0.162 g, 83%). Rf = 0.48 (EtOAc/Hex 2:3);
3
(d, 1H, J = 8.2 Hz, H-C(4)), 3.68–3.53 (m, 2H, H-C(30)), 3.24–3.15
[a]
25 = +31 (c 0.5, CHCl3); mp = 93–98 °C (Hex/EtOAc); IR (KBr):
D
(br s, 1H, HO-C(3)), 1.75 (1H, 0.5H2O), 1.57, 1.45, (2s, 6H,
3359, 3123, 2992, 2941, 1673, 1573, 1475, 1388, 1280, 1181,
1133, 1074; 1H NMR (CDCl3, 300 MHz) d: 7.84 (s, 2H, H-C(Ar)),
7.51 (s, 1H, H-C(Ar)), 7.20–7.06 (br s, 1H, H-N-C(Ar)), 5.90 (d, 1H,
(H3C)2C-O-C(1)), 1.34 (1s, 6H, (H3C)2C-O-C(5)); 13C NMR (CDCl3,
2
1
75.5 MHz) d: 155.5, 140.5, 132.3 (q, JC–F = 34 Hz), 123.2 (q, JC–F
=
3
3
3
273 Hz), 118.7 (q, JC–F = 3.3 Hz), 116.1 (sept, JC–F = 3.8 Hz),
3J = 3.6 Hz, H-C(1)), 5.66 (dd, 1H, J = 6.6, 6.0, Hz, H-N-C(30)),
113.0, 110.1, 103.7, 81.3, 80.4, 79.9, 73.0, 68.1, 41.2, 26.8, 26.2
4.58–5.45 (br s, 1H, HO-C(3)), 4.42 (d, 1H, 3J = 3.6 Hz, H-C(2)),
4.39 (ddd, 1H, 3J = 8.2, 6.4, 4.9 Hz, H-C(5)), 4.15 (dd, AB syst., 1H,
2J = 8.9 Hz, 3J = 6.4 Hz, Ha-C(6)), 4.04 (dd, AB syst., 1H, 2J = 8.9 Hz,
3J = 4.9 Hz, Hb-C(6)), 3.90 (dd, AB syst., 1H, 2J = 14.9 Hz,
3J = 6.0 Hz, Ha-C(30)), 3.80 (d, 1H, 3J = 8.2 Hz, H-C(4)), 3.47 (dd, AB
(2C), 25.2; Elemental analysis: calcd
(553.17): C, 47.74; H, 4.92; N, 5.06; found C, 47.98; H, 4.80; N, 4.81.
C
22H26F6N2O7ꢃ0.5H2O
4.1.12. (3R)-3-C-[(3,5-Bis(trifluoromethyl) phenylthioureido-
3
methyl]-1,2:5,6-di-O-isopropylidene-
a
-
D
-allofuranose 20
(1.45 mL,
syst., 1H, 2J = 14.9 Hz, J = 6.6 Hz, Hb-C(30)), 1.81 (br s, 2H, H2O),
Bis(3,5-trifluoromethyl)phenyl isothiocyanate
1.53, 1.43, 1.35, 1.31 (4s, 12H, (H3C)2C-O-C(1,5)); 13C NMR
2
8.00 mmol, 1.15 equiv) was added to a solution of amino alcohol 5
(2.00 g, 7.00 mmol, 1 equiv) in CH2Cl2 (30 mL). After stirring at reflux
at 40 °C for 4 h, the solvent was removed under reduced pressure.
Purification by column chromatography (EtOAc/Hex 25%) yielded
(CDCl3, 75.5 MHz) d: 155.7, 0.2, 132.4 (q, JC–F = 34 Hz), 124.7 (q,
3
3
1JC–F = 274 Hz), 118.9 (q, JC–F = 4 Hz), 116.5 (sept, JC–F = 4 Hz),
113.0, 109.7, 104.7, 86.0, 82.9, 82.3, 72.6, 67.6, 43.6, 27.2, 26.9,
26.5, 25.2; Elemental analysis: calcd C22H26F6N2O7ꢃH2O (562.18):
C, 46.98; H, 5.02; N, 4.98; found C, 46.62; H, 4.90; N, 5.00.
20 (3.62 g, 94%). Rf = 0.48 (EtOAc/Hex 2:3); [a]
25 = +8 (c 1.0, CHCl3);
D
mp = 100–102 °C (Hex/EtOAc); IR (KBr): 3374, 3306, 2990, 2943,
2888, 1521, 1382, 1281, 1181, 1136, 1080; 1H NMR (DMSO-d6,
300 MHz) d: 10.53–10.40 (br s, 1H, H-N-C(Ar)), 8.33 (s, 2H, H-
C(Ar)), 8.07 (t, 1H, 3J = 4.7 Hz, H-N-C(30)), 7.75 (s, 1H, H-C(Ar)), 5.75
(d, 1H, 3J = 3.7 Hz, H-C(1)), 5.49 (s, 1H, HO-C(3)), 4.32 (d, 1H,
4.1.15. (3S)-3-C-[(3,5-Bis(trifluoromethyl)phenylthioureido-
methyl]-1,2:5,6-di-O-isopropylidene-
Bis(3,5-trifluoromethyl)phenyl isothiocyanate
0.199 mmol, 1.15 equiv) was added to a solution of amino alcohol
a
-D
-glucofuranose 23
(0.036 mL,
Please cite this article in press as: Turks, M.; et al. Tetrahedron: Asymmetry (2015), http://dx.doi.org/10.1016/j.tetasy.2015.07.003

8
M. Turks et al. / Tetrahedron: Asymmetry xxx (2015) xxx–xxx
6 (50.0 mg, 0.173 mmol, 1 equiv) in CH2Cl2 (2 mL). After stirring at
reflux at 40 °C for 4 h, the solvent was removed under reduced
pressure. Purification by column chromatography (EtOAc/Hex
20%) yielded 23 (94.0 mg, 97%). Rf = 0.58 (EtOAc/Hex 2:3);
23.8 (2C); HRMS: calcd [C28H34F6N2O6S+Na+] 663.1934; found
663.1925.
4.1.18. (3S)-3-C-[(3,5-Bis(trifluoromethyl)phenylthioureidome-
thyl]-1,2:5,6-di-O-cyclohexylidene-a-D-glucofuranose 26
[a
]
D
25 = ꢀ13.2 (c 1.0, CHCl3); mp = 85–90 °C (Hex/EtOAc); IR (KBr):
3304, 2991, 2940, 2894, 1623, 1542, 1472, 1378, 1280, 1180,
1138, 1071; 1H NMR (DMSO-d6, 80 °C, 300 MHz) d: 10.43–10.34
(br s, 1H, H-N-C(Ar)), 8.29 (s, 2H, H-C(Ar)), 7.97 (t, 1H, 3J = 4.8 Hz,
H-N-C(30)), 7.74 (s, 1H, H-C(Ar)), 5.86 (d, 1H, 3J = 3.6 Hz, H-C(1)),
5.75 (s, 1H, HO-C(3)), 4.38 (d, 1H, 3J = 3.6 Hz, H-C(2)), 4.27 (q, 1H,
3J = 6.3 Hz, H-C(5)), 4.01 (dd, AB syst., 1H, 2J = 8.3 Hz, 3J = 6.3 Hz,
Ha-C(6)), 3.95–3.82 (m, 3H, Hb-C(6), Ha-C(30), H-C(4)), 3.77 (dd,
At first, Et3N (0.103 mL, 0.738 mmol, 1 equiv) was added to a
solution of ammonium tosylate 16 (0.400 g, 0.738 mmol, 1 equiv)
in CH2Cl2 (5 mL). The resulting mixture was stirred for 10 min
and bis(3,5-trifluoromethyl)phenyl isothiocyanate (0.103 mL,
0.738 mmol, 1 equiv) was added. After stirring at reflux at 35 °C
for 6 h, the solvent was removed under reduced pressure. The resi-
due mixture was dissolved in ethyl acetate (30 mL), washed with
brine (5 ꢁ 20 mL), dried over anhydrous Na2SO4, filtered, and evap-
orated under reduced pressure. Purification by column chromatog-
raphy (EtOAc/Hex 8%) yielded 26 (0.260 g, 55%). Rf = 0.36
3
AB syst., 1H, 2J = 13.9 Hz, J = 4.8 Hz, Hb-C(30)), 1.47, 1.33, 1.30,
1.24 (4s, 12H, (H3C)2C-O-C(1,5)); 13C NMR (DMSO-d6), 75.5 MHz)
2
1
d: 181.4, 142.8, 131.2 (q, JC–F = 33 Hz), 124.1 (q, JC–F = 274 Hz),
3
122.3 (m), 116.8 (sept, JC–F = 4 Hz), 112.6, 109.1, 105.0, 86.3,
(EtOAc/Hex 1:3); [a]
20 = 4.0 (c 0.55, CHCl3); IR (KBr): 3294, 2941,
D
83.0, 80.6, 73.2, 67.1, 47.2, 27.8, 27.4, 27.3, 26.1; Elemental analy-
sis: calcd C22H26F 6N2O6S (560.14): C, 47.14; H, 4.68; N, 5.00; found
C, 47.07; H, 4.62; N, 4.84.
2864, 1542, 1466, 1377, 1279, 1181, 1137; 1H NMR (DMSO-d6,
300 MHz) d: 10.36 (s, 1H, H-N-C(Ar)), 8.31 (s, 2H, H-C(Ar)), 7.98–
7.92 (br s, 1H, H-N-C(30)), 7.74 (s, 1H, H-C(Ar)), 5.86 (d, 1H,
3J = 3.4 Hz, H-C(1)), 5.72 (s, 1H, HO-C(3)), 4.34 (d, 1H, 3J = 3.4 Hz,
H-C(2)), 4.26–4.14 (m, 1H, H-C(5)), 4.07–3.96 (m, 2H, Ha-C(30),
Ha-C(6)), 3.87–3.76 (m, 3H, Hb-C(30), H-C(4), Hb-C(6)), 1.69–1.21
(m, 20H, (Chx)2-C(1,2:5,6)); 13C NMR (DMSO-d6, 75.5 MHz) d:
181.0, 142.4, 130.8 (q, JC–F = 32 Hz), 123.8 (q, JC–F = 273 Hz),
121.8 (m), 116.5 (m), 112.7, 109.3, 104.2, 85.5, 82.7, 80.3, 72.3,
66.6, 46.9, 36.8, 36.4, 36.1, 35.0, 25.1, 24.8, 24.1, 24.0, 23.8, 23.7;
HRMS: calcd [C28H34F6N2O6S+Na+] 641.2115; found 641.2096.
4.1.16. (3S)-3-C-[(3,5-Bis(trifluoromethyl)phenylthioureidomet-
hyl]-1,2-O-isopropylidene-a-D-glucofuranose 24
At first, 1 M H2SO4 (1.38 mL, 1.38 mmol, 0.2 equiv) was added
to a solution of thiourea 23 (3.87 g, 6.91 mol, 1 equiv) in MeOH
(25 mL) and CH2Cl2 (70 mL) and stirred at 60 °C for 2.5 h. Next,
anhydrous NaHCO3 (0.29 g, 3.45 mmol, 0.5 equiv) was added to
the resulting reaction mixture at 0 °C followed by stirring 30 min
at ambient temperature. The reaction mixture was dried over
Na2SO4, filtered, and evaporated under reduced pressure.
Purification by column chromatography (EtOAc/Hex 50%) yielded
24 (3.45 g, 96%). Rf = 0.56 (EtOAc/Hex 3:2, 0.5% MeOH);
2
1
4.1.19. Catalytic enantioselective Friedel–Crafts alkylation of
indoles with trans-b-nitrostyrene
General procedure (reaction conditions and results are summa-
rize in Table 1): A mixture of indole 27, trans-b-nitrostyrene 28,
selected catalyst organocatalyst and additives were dissolved in a
selected solvent. The resulting reaction mixture was held at the
[a]
23 = +18 (c 0.35, CHCl3); IR (KBr): 3327, 2993, 2942, 2888,
D
1542, 1474, 1380, 1279, 1176, 1136, 1069; 1H NMR (DMSO-d6,
300 MHz) d: 10.40–10.29 (br s, 1H, H-N-C(Ar)), 8.32 (s, 2H, H-
C(Ar)), 8.18–8.12 (br s, 1H, H-N-C(30)), 7.72 (s, 1H, H-C(Ar)), 5.82
(d, 1H, 3J = 3.6 Hz, H-C(1)), 5.55–5.48 (br s, 1H, HO-C(3)), 4.89–
4.78 (br s, 1H, HO-C(5)), 4.52 (t, 1H, 3J = 5.6 Hz, HO-C(6)), 4.32 (d,
given temperature and controlled by GC–MS [a sample (10 ll)
was taken from the reaction mixture, diluted with CH2Cl2 (2 mL)
and analyzed by GC–MS]. Solvents were removed under reduced
pressure. Purification by column chromatography (EtOAc/Hex 3%)
yielded the product. The NMR data and other characteristics of pro-
duct 29 fully corresponded to those reported earlier.17c The
absolute configuration of the product was determined by
comparing the specific optical rotation with that of the literature
3
1H, J = 3.6 Hz, H-C(2)), 3.82–3.66 (m, 4H, H-C(30), H-C(4), H-
C(5)), 3.57 (ddd, AB syst., 1H, 2J = 11.2 Hz, 3J = 5.3 Hz, 3J = 2.5 Hz,
Ha-C(6)), 3.39 (dd, AB syst., 1H, 2J = 11.2 Hz, 3J = 5.6 Hz, Hb-C(6)),
1.42, 1.26 (2s, 6H, (H3C)2C-O-C(1)); 13C NMR (DMSO-d6,
2
1
75.5 MHz) d: 180.8, 142.4, 130.7 (q, JC–F = 34 Hz), 123.7 (q, JC–F
=
273 Hz), 121.6 (m), 116.3 (m), 111.9, 104.1, 85.7, 81.4, 80.6, 69.1,
64.0, 47.3, 27.4, 27.0; HRMS: calcd [C19H22F6N2O6S+H+] 520.1176;
found 521.1175.
data: [
a]
20 = ꢀ6.1 (c 1.0, CHCl3), 74% ee (R); [
a]
rDt = ꢀ8 (c 0.65,
D
CHCl3), 85% ee (R).30 The enantiomeric excess was determined by
HPLC analysis of 29 using Chiralpak IA column (0.46 ꢁ 25 cm) (iso-
i
cratic method: 5% PrOH/Hex; 40 min; Injection 5
l
l (0.70 mg/mL
4.1.17. (3R)-3-C-[(3,5-Bis(trifluoromethyl)phenylthioureidomet-
Hex + 30% iPrOH); Flow rate 1 mL/min; Detector wavelength
254 nm.): tR = 27.9 (S); tR = 25.0 (R).
hyl]-1,2:5,6-di-O-cyclohexylidene-a-D-allofuranose 25
Bis(3,5-trifluoromethyl)phenyl
isothiocyanate
(0.227 mL,
1H NMR (CDCl3, 300 MHz) d: 8.10 (br s, 1H, H-N(1)), 7.46 (d, 1H,
3J = 8.1 Hz, H-C(c)), 7.37–7.25 (m, 6H, H-C(e), H-C(g), H-C(4), H-
C(5), H-C(6), H-C(7)), 7.21 (td, 1H, 3J = 8.3 Hz, 4J = 0.9 Hz, H-C(d)),
7.09 (td, 1H, 3J = 8.1 Hz, 4J = 0.9 Hz, H-C(f)), 7.03 (d, 1H,
3J = 2.5 Hz, H-C(2)), 5.20 (dd, 1H, 3J = 7.7 Hz, 3J = 8.1 Hz, H-C(a)),
5.08 (dd, AB syst., 1H, 2J = 12.4 Hz, 3J = 7.5 Hz, Ha-C(b)), 4.95 (dd,
AB syst., 1H, 2J = 12.4 Hz, 3J = 8.3 Hz, Ha-C(b)); 13C NMR (CDCl3),
75 MHz) d: 139.2, 136.6, 129.0, 127.8, 127.6, 122.8, 121.7, 120.1,
119.0, 114.5, 111.4, 79.6, 41.6.
1.25 mmol, 1.15 equiv) was added to a solution of amino alcohol
12 (0.400 g, 1.08 mmol, 1 equiv) in CH2Cl2 (5 mL). After stirring
at reflux at 40 °C for 3 h, the solvent was removed under reduced
pressure. Purification by column chromatography (EtOAc/Hex 8%)
yielded 25 (0.653 g, 94%). Rf = 0.65 (EtOAc/Hex 7:12); [a]
23 = +6.4
D
(c 0.43, CHCl3); IR (KBr): 3523, 3356, 2940, 2864, 1624, 1541,
1473, 1451, 1384, 1280, 1145, 1015; 1H NMR (DMSO-d6,
300 MHz) d: 10.45 (s, 1H, H-N-C(Ar)), 8.33 (s, 2H, H-C(Ar)), 8.19–
8.05 (br s, 1H, H-N-C(30)), 7.76 (s, 1H, H-C(Ar)), 5.75 (d, 1H,
3J = 3.6 Hz, H-C(1)), 5.53–5.43 (br s, 1H, HO-C(3)), 4.30 (d, 1H,
3J = 3.6 Hz, H-C(2)), 4.16 (m, 1H, H-C(5)), 3.98 (m, 1H, Ha-C(6)),
4.1.20. Catalytic Michael 1,4-addition of nitromethane to trans-
chalcone: synthesis of (S)-3-nitro methyl-1,3-diphenyl-2-propen-
1-one (S)-31
3
3.88 (d, 1H, J = 6.1 Hz, H-C(4)), 3.81–3.57 (m, 3H, H-C(30), Hb-
C(6)), 1.78–1.17 (m, 20H, (Chx)2-C(1,2:5,6)); 13C NMR (DMSO-d6,
Nitromethane (46.0 lL, 0.85 mmol, 3.0 equiv) was added to a
2
1
75.5 MHz) d: 181.1, 142.3, 130.7 (q, JC–F = 33 Hz), 123.7 (q, JC–
F = 273 Hz), 122.0 (m), 116.7 (m), 112.6, 109.3, 103.1, 80.9, 80.7,
79.6, 72.9, 66.4, 46.0, 36.4, 36.0 (2C), 34.7, 25.1, 24.9, 24.0 (2C),
solution of 1,3-diphenyl-2-propen-1-one 30 (60 mg, 0.289 mmol,
1.0 equiv) and organocatalyst 21 (15 mg, 0.029 mmol, 0.1 equiv)
in toluene (0.2 mL). The reaction was controlled by GC–MS [a
Please cite this article in press as: Turks, M.; et al. Tetrahedron: Asymmetry (2015), http://dx.doi.org/10.1016/j.tetasy.2015.07.003

M. Turks et al. / Tetrahedron: Asymmetry xxx (2015) xxx–xxx
9
11. Auvil, T. J.; Schafer, A. G.; Mattson, A. E. Eur. J. Org. Chem. 2014, 2633–2646.
12. Becker, C.; Hoben, C.; Kunz, H. Adv. Synth. Catal. 2007, 349, 417–424.
sample (10 ll) was taken from the reaction mixture, diluted with
CH2Cl2 (2 mL) and analyzed by GC–MS]. After 14 days at 18 °C,
the solvent was removed under reduced pressure. Purification by
column chromatography (2% EtOAc/Hex) yielded product 31
(23 mg, 30%). The NMR data and other characteristics of product
31 corresponded fully to those reported earlier.31 The absolute
configuration of the product was determined by comparing the
specific rotation of 31 with that of the literature data:
13. (a) Liu, K.; Cui, H.-F.; Nie, J.; Dong, K.-Y.; Li, X.-J.; Ma, J.-A. Org. Lett. 2007, 9,
923–925; (b) Ma, H.; Liu, K.; Zhang, F.-G.; Zhu, C.-L.; Nie, J.; Ma, J.-A. J. Org.
Chem. 2010, 75, 1402–1409; (c) Lindhorst, T.; Kieburg, C. Synthesis 1995, 1228–
1230; (d) Li, X.-J.; Liu, K.; Ma, H.; Nie, J.; Ma, J.-A. Synlett 2008, 3242–3246; (e)
Wang, C.; Zhou, Z.; Tang, C. Org. Lett. 2008, 10, 1707–1710; (f) Gu, Q.; Gua, X.-
T.; Wu, X.-Y. Tetrahedron 2009, 65, 5265–5270.
14. Yuan, H.-N.; Wamg, S.; Nie, J.; Meng, N.; Yao, Q.; Ma, J.-A. Angew. Chem., Int. Ed.
2013, 52, 3869–3873.
15. (a) Lu, A.; Hu, K.; Wang, Y.; Song, H.; Zhou, Z.; Fang, J.; Tang, C. J. Org. Chem.
2012, 77, 6208–6214; (b) Pu, X.-W.; Peng, F.-Z.; Zhang, H.-B.; Shao, Z.-H.
Tetrahedron 2010, 66, 3655–3661; (c) Pu, X.; Li, P.; Peng, F.; Li, X.; Zhang, H.;
Shao, Z. Eur. J. Org. Chem. 2009, 4622–4626.
16. (a) Shen, C.; Shen, F.; Xia, H.; Zhang, P.; Chen, X. Tetrahedron: Asymmetry 2011,
22, 708–712; (b) Ágoston, K.; Fügedi, P. Carbohydr. Res. 2014, 389, 50–56.
17. (a) Herrera, R. P.; Sgarzani, V.; Bernardi, L.; Ricci, A. Angew. Chem., Int. Ed. 2005,
44, 6576–6579; (b) Sibi, M. P.; Itoh, K. J. Am. Chem. Soc. 2007, 129, 8064–8065;
(c) Jensen, K. H.; Sigman, M. S. Angew. Chem., Int. Ed. 2007, 46, 4748–4750; (d)
Ganesh, M.; Seidel, D. J. Am. Chem. Soc. 2008, 130, 16464–16465; (e) Robak, M.
T.; Trincado, M.; Ellman, J. A. J. Am. Chem. Soc. 2007, 129, 15110–15111.
18. For examples of few other furanose-derived organocatalysts, see: (a) Wang, L.;
Liu, J.; Miao, T.; Zhou, W.; Li, P.; Ren, K.; Zhang, X. Adv. Synth. Catal. 2010, 352,
2571–2578; (b) Wynands, L.; Delacroix, S.; Van Nhien, A. N. S.; Soriano, E.;
Marco-Contelles, J.; Postel, D. Tetrahedron 2013, 69, 4899–4907.
[
a
]
22 = ꢀ5.6 (c 0.43, CHCl3); Lit.: [
a
]
22 = ꢀ7.3 (c 1.05, CHCl3), 90%
D
D
ee, (S). The enantiomeric excess (48% ee) was determined by
HPLC analysis of 31 using Chiralpak IA column (0.46 ꢁ 25 cm)
(Isocratic method: 5% iPrOH/Hex; 40 min; Injection 30
ll
(1.00 mg/mL Hex + 30% iPrOH); Flow rate 1 mL/min; Detector
wavelength 254 nm.): tR = 15.0 (S); tR = 19.3 (R). 1H NMR (CDCl3,
3
300 MHz) d: 7.92 (d, 3H, J = 7.3 Hz, H-C(200), H-C(600)), 7.58 (t, 1H,
3J = 7.3 Hz, H-C(400)), 7.46 (t, 2H, J = 7.5 Hz, H-C(300), H-C(500)),
3
7.38–7.24 (m, 5H, H-C(Ar)), 4.84 (dd, AB syst., 1H, 2J = 12.4 Hz,
3J = 6.8 Hz, Ha-C(30)), 4.69 (dd, AB syst., 1H, 2J = 12.4 Hz,
3J = 7.9 Hz, Hb-C(30)), 4.23 (quintet, 1H, 3J = 7.2 Hz, H-C(3)), 3.53–
3.37 (m, 2H, H-C(2)).
19. (a) Kadraoui, M.; Maunoury, T.; Derriche, Z.; Guillarme, S.; Saluzzo, C. Eur. J.
Org. Chem. 2014. http://dx.doi.org/10.1002/ejoc.201402851; (b) Chen, L.-Y.;
Guillarme, S.; Saluzzo, C. ARKIVOC 2013, 227–244.
Acknowledgments
20. (a) Turks, M.; Rodins, V.; Rolava, E.; Ostrovskis, P.; Belyakov, S. Carbohydr. Res.
ˇ
2013, 375, 5–15; (b) Turks, M.; Veze, K.; Kiselovs, G.; Mackevica, J.; Luginßina, J.;
¯
´
Mishnev, A.; Markovic, D. Carbohydr. Res. 2014, 391, 82–88; (c) Luginßina, J.;
Rjabovs, V.; Belyakov, S.; Turks, M. Carbohydr. Res. 2012, 350, 86.
This work was financed by Riga Technical University Grant ZP-
2014/4. The authors thank JSC ‘Olainfarm’ for kind donation of
diacetone-a-D-glucose. E.R. thanks JSC ‘Olainfarm’ and the Latvian
ˇ
21. Ostrovskis, P.; Mackevica, J.; Kumpinßš, V.; López, Ó.; Turks, M.; Alternative, An
An Alternative, Large Scale Synthesis of 1,2:5,6-Di-O-isopropylidene-
a-D-
ribohex-3-ulofuranose In Carbohydrate Chemistry: Proven Synthetic Methods;
van der Marel, G., Codee, J., Eds.; CRC Press: Boca Raton, London, New York,
2014; Vol. 2, pp 275–281.
Academy of Sciences for scholarships. Mr. A. Kinens is acknowl-
¯
edged for HPLC analyses.
22. Spescha, M. Helv. Chim. Acta 1993, 76, 1832–1845.
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Please cite this article in press as: Turks, M.; et al. Tetrahedron: Asymmetry (2015), http://dx.doi.org/10.1016/j.tetasy.2015.07.003