Synthesis of azepane and nojirimycin iminosugars: the Sharpless asymmetric epoxidation of d-glucose-derived allyl alcohol and highly regioselective epoxide ring opening using sodium azide

Article abstract of DOI:10.1016/j.tetasy.2010.01.007

The Sharpless asymmetric epoxidation of d-glucose-derived allyl alcohol 4 afforded α- and β-epoxides 5a and 5b in high stereoselectivity. The epoxide ring opening in 5a/5b was studied with different nucleophilic azido reagents, under various reaction cond

Full text of DOI:10.1016/j.tetasy.2010.01.007

Tetrahedron: Asymmetry 21 (2010) 163–170
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Synthesis of azepane and nojirimycin iminosugars: the Sharpless
asymmetric epoxidation of D-glucose-derived allyl alcohol and highly
regioselective epoxide ring opening using sodium azide
Vrushali H. Jadhav a, Omprakash P. Bande a, Vedavati G. Puranik b, Dilip D. Dhavale a,
*
a Department of Chemistry, Garware Research Centre, University of Pune, Pune 411 007, India
b Centre for Material Characterization, National Chemical Laboratory, Pune 411 008, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 27 October 2009
Accepted 18 January 2010
The Sharpless asymmetric epoxidation of D-glucose-derived allyl alcohol 4 afforded a- and b-epoxides 5a
and 5b in high stereoselectivity. The epoxide ring opening in 5a/5b was studied with different nucleo-
philic azido reagents, under various reaction conditions, and was found to be highly regioselective to give
the preferential formation of 6-azido diol 6a/6b over 5-azido-diol 7a/7b. The 6-azido diol 6a/6b and 5-
azido diol 7a/7b thus obtained were converted to the corresponding seven- and six-membered iminosug-
ar, namely, azepane 1a/1b and 1-deoxy-nojirimycin 2a/2b.
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
Epoxides of type A (R1 = alkyl, aryl; Fig. 1) play a vital role in
synthetic sequences due to their capability to undergo nucleophilic
ring opening either at C-3 or at C-2 giving access to 3-substituted
or 2-substituted diols, respectively.1 In the case of azido nucleo-
philic reagents, namely, TMSN3–Et2AlF,2 TMSN3/Ti(O-i-Pr)4,3 Ti(O-
OH
1
attack C-2
attack C-3
O
2
HO
R1
3
O
N3
1
H
HO
2-azidodiol
N3
6
i-Pr)2(N3)2,4 Bu3SnN3,5 Et2AlN3 and NaN3 supported on calcium
R1
2
3
H
zeolite,7 epoxide ring opening of 2,3-epoxy alcohols takes place
at the C-3 position to give 3-azido diol. On the other hand, a few
examples pertaining to the C-2 selective epoxide ring opening by
azide to give 2-azido diol using NaN3–(CH3O)3B8 or NaN3–
PhB(OH)29 are known. In addition, when R1 is sterically demanding
in 2,3-epoxy alcohols, the favoured attack of the azido nucleophile
is at the C-2 position leading to the formation of 2-azido diol.10 For
A
1
2
HO
R1
3
OH
3-azidodiol
OMe
O
OBn
O
R1
H
O
H
=
example, in the case of 2,3-epoxy alcohol A (R1 =
and -ribose), wherein the C-3 position is sterically crowded due to
D
-glyceraldehyde
O
O
O
O
D
the sugar ring, the C-2 ring-opening product gives 2-azido diol as
the major product. In view of this observation, we studied the reg-
Figure 1. Nucleophilic ring opening of epoxides.
ioselective ring opening of 2,3-epoxy alcohol A (R1 =
D
-gluco-fura-
nose) with different azido nucleophiles under
a
variety of
reaction conditions that afforded the highly preferential formation
of the C-2 ring-opening product 6-azido diol and the C-3 ring-
opening product, namely, 5-azido diol formed as the minor prod-
uct. The 6- and 5-azido diols, with the sugar appendage thus
obtained, were converted into polyhydroxylated azepane 1a/1b
and 1-deoxy-nojirimycin 2a/2b analogues (Fig. 2), respectively.
R3
R4
R1
R2
H
H
N
R1
R2
N
OH
HO
OH
HO
OH
OH
2a R1 = CH2OH, R2 = H
2b R1 = H, R2 = CH2OH
1a R1 = OH, R2 = H, R3 = H, R4 = CH2OH
1b R1 = H, R2 = OH, R3 = CH2OH, R4 = H
* Corresponding author. Tel.: +91 (020) 25691727; fax: +91(020) 25691728.
E-mail address: ddd@chem.unipune.ernet.in (D.D. Dhavale).
Figure 2. Azepanes and piperidine iminosugars.
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.01.007

164
V. H. Jadhav et al. / Tetrahedron: Asymmetry 21 (2010) 163–170
Nitrogen-incorporated polyhydroxylated carbocyclic ring sys-
2. Result and discussion
tems,11 commonly known as azasugars or iminosugars, are of great
importance as they often exhibit significant glycosidase inhibitory
activity. In recent years, attention has been increasingly focused on
the structure-activity relationship of iminosugars, particularly in
seven-membered azepanes12 and six-membered piperidine imino-
sugars,13 due to their promising glycosidase inhibitory activity in
the treatment of various diseases such as diabetes,14 cancer15
and viral infections, including AIDS.16 In addition, azepanes are
DNA minor groove-binding ligands (MGBLs).17 The hydroxyl
groups in azepanes adopt different conformations due to the flex-
ibility of the seven-membered ring (compared to five- or six-mem-
bered ring) thereby increasing the probability of intramolecular
hydrogen bonding with the ring nitrogen, thus showing the ability
to point into the minor groove of DNA. The high water solubility,
which allows them to circumvent the problem of poor bioavailabil-
ity seen in many other MGBLs, is an additional advantage of these
compounds. Our efforts in the synthesis of azepane 1a/1b and
piperidine 2a/2b iminosugars are reported herein.
As shown in Scheme 2, the required (E)-ethyl-1,2-O-isopropyli-
dene-3-O-benzyl-5,6-dideoxy-
a-
D-xylo-5-eno-heptofuranuronate
3 was prepared from
D
-glucose in 55% overall yield as reported ear-
lier.18 The reduction of the ester group in 3 using DIBAL afforded
allyl alcohol 4 which upon treatment with m-CPBA in CH2Cl2 gave
a diastereomeric mixture of epoxides 5a and 5b in a ratio of 55:45
in 76% overall yield from 3. The appreciable difference in the Rf va-
lue allowed us to separate the mixture of diastereomers by column
chromatography. Fortunately, a-epoxide 5a was obtained as a col-
ourless solid and single crystal X-ray analysis19 (Fig. 3) established
the absolute configurations at the newly generated stereocentres
as (5S) and (6R) and therefore the b-epoxide 5b was given the
(5R,6S)-absolute configuration. The E-geometry of the starting
compound 3 was found to be retained in epoxide 5a/5b as evident
from the H-5/H-6 coupling constant of 2.5 Hz in both the com-
pounds.20 The diastereoselectivity in the formation of 5,6-epoxy
alcohol 5a/5b was improved by the Sharpless asymmetric
As shown in the retrosynthetic analysis (Scheme 1), azepane 1
and piperidine 2 iminosugars could be easily prepared by 1,2-ace-
tonide opening followed by the reductive aminocyclization of the
O
O
(a)
corresponding 6-aminoheptulose
A and 5-aminoheptulose B.
EtO
D-glucose
OBn
Intermediates A/B could be obtained by the reduction of the azide
functionality and selective amine protection of C/D. The nucleo-
philic azide ring opening of 2,3-epoxy alcohol E either at C-6 or
at C-5 would lead to the formation of C and/or D. The Sharpless
O
O
7
3
5
O
O
OBn
HO
HO
1
6
(b)
4
O
2
3
asymmetric epoxidation of the allylic alcohol F, obtained from D-
O
O
HO
(c)
(d)
glucose, will give 2,3-epoxy alcohol E. As per the precedence with
sugar-derived 2,3-epoxy alcohols, we anticipated that the nucleo-
philic ring opening in E will take place at the C-6 position to give
6-azido diol C, an intermediate to azepanes 1. However, if the
epoxide ring opening in E takes place at the more hindered carbon
atom C-5, the reaction will afford 5-azido diol D which could also
be used to produce piperidine iminosugars 2.
5a
OBn
or
+
O
O
O
O
OBn
4
O
O
5b
Scheme 2. Reagents and conditions: (a) Ref. 18; (b) DIBALH, THF, ꢀ78 °C, 2 h.; (c)
m-CPBA, dry CH2Cl2, 0 °C to rt, 12 h.; (d) Ti(O-i-Pr)4,
ꢀ20 °C, 24 h.
D/L-DET, t-BuOOH, CH2Cl2,
H
N
H
N
HO
HO
HO
HO
OH
OH
HO
OH
2
OH
1
OH
NHCbz
7
6
7
4
O
6
1
O
4
5
HO
5
OH
HO
HO
1
OH
NHCbz
O
OH
O
O
2 O
3
A
2O
3
B
N3
OH
O
O
OBn
HO
HO
OBn
OH
N3
O
O
O
O
D
C
O
7
O
OBn
4
O
1
HO
5
OBn
6
O
E 3
2 O
O
F
D-Glucose
Scheme 1. Retrosynthetic analysis.
Figure 3. ORTEP diagram of compound 5a.

V. H. Jadhav et al. / Tetrahedron: Asymmetry 21 (2010) 163–170
165
epoxidation. Thus, as shown in Table 1, the reaction of allyl alcohol
4 with Ti(O-i-Pr)4, t-BuOOH in the presence of
-(ꢀ)-diethyl
tartrate in dichloromethane at ꢀ20 °C afforded 5a and 5b in the
ratio of 92:08, while the use of -(+)-diethyl tartarate led to
stereoselectivity in the favour of 5b affording 5a/5b in a ratio
of 17:83. This result further corroborates the low sensitivity of
the Sharpless asymmetric epoxidation to the double asymmetric
induction effect.21
of triplet at the upfield region at d 3.62 and 3.83, compared to H-5
which appeared at d 3.96 and 3.98 as a doublet of doublets. The
appearance of H-6 as a doublet of triplets clearly indicated the
presence of the azido functionality at the C-6. Similarly, in the case
of 5-azido diols 7a and 7b, the corresponding H-5 appeared in the
upfield position as a doublet of doublets at d 3.84 and 3.60 as com-
pared to the H-6 proton which appeared in the downfield position
at d 3.96–3.88 as a multiplet in 7a, and at d 4.12 as a doublet of
triplets in 7b. The appearance of H-5 as a doublet of doublet indi-
cated the formation of a 5-azido diol.
D
L
Table 1
Asymmetric epoxidation of 4
It is known that the ring opening of the 2,3-epoxy alcohol A
(Fig. 1, R1 = aromatic, aliphatic), in the presence of a Lewis acid,
is favoured at C-3 leading to the formation of 3-azido diol. As a re-
sult of this observation and in order to alter the regioselectivity, we
studied the reaction of epoxy alcohol 5a/5b under various reaction
conditions using TMSN3, TMSN3/Ti(O-i-Pr)4, Ti(O-i-Pr)2(N3)2 and
NaN3/NH4Cl and results are given in Table 2 (entries 3–10).
In all the experiments, the highly preferred product is the 6-azi-
do diol 6 along with a minor amount of 5-azido diol 7 (attack at C-2
is preferred over C-3).22 The reaction of epoxide 5a/5b with NaN3
in acetone water at room temperature as well as at reflux did not
afford any product and the starting material was recovered in
quantitative yield (entries 11 and 12). The probable reason for
the observed regioselectivity in favour of the 6-azido diol could
be the presence of a bulky sugar substituent, which sterically hin-
ders the attack at the C-5 position. In addition, the presence of oxy-
gen and a sugar substituent exerts electron-withdrawing effect,
thus destabilizing the positive charge at the C-5 carbon and favour-
ing the attack at the C-6.
Entry Reagent
Ratioa
5a:5b
Yield
(%)
1
2
m-CPBA, CH2Cl2
Ti(O-i-Pr)4,
CH2Cl2
55:45
92:08
94
89
D
-(ꢀ)-diethyl tartrate, t-BuOOH,
3
Ti(O-i-Pr)4,
CH2Cl2
L
-(+)-diethyl tartrate, t-BuOOH,
17:83
86
Ratio determined by 1H NMR of the crude mixture.
a
In the next step, the regioselectivity of the epoxide ring opening
in 2,3-epoxy alcohol 5a/5b was examined with different nucleo-
philic azido reagents. For this purpose, -epoxide 5a was first trea-
a
ted with NaN3 in DMF at reflux for 6 h, which afforded 6-azido diol
6a and 5-azido diol 7a in the ratio of 92:08 (Scheme 3). Considering
the 2,3-epoxy alcohol 5 as 2,3-epoxy alcohol A (Fig. 1, R1 =
D-gluco-
furanose), it was observed that the attack at the less hindered C-2
position is preferred to that at the C-3 position. Similarly, when b-
epoxide 5b was reacted with NaN3 in DMF at reflux for 6 h, the ra-
tio of 6-azido diol 6b and 5-azido diol 7b was found to be 87:13
(Table 2, entries 1 and 2). The characterization of 6-azido diol 6a/
6b and 5-azido diol 7a/7b was based on the 1H NMR data, wherein
the coupling constant information and the assignment of the pro-
ton signals were made by the decoupling studies. In the case of 6-
azido diols 6a and 6b, the corresponding H-6 appeared as a doublet
2.1. Synthesis of azepane and nojirimycin iminosugars
The utility of azido diols 6 and 7 was demonstrated in the syn-
thesis of seven- and six-membered iminosugar (Scheme 4). Thus,
targeting towards the synthesis of azepane 1a/1b, the one-pot
reduction of the azide group and debenzylation of C-3 –OBn in 6-
azido alcohol 6a, using ammonium formate in the presence of
10% Pd/C, followed by reaction with benzyl chloroformate afforded
N-Cbz-protected 6-amino diol 8a. Treatment of 8a with TFA–water
gave hemiacetal, which on reductive aminocyclization using 10%
Pd/C in methanol afforded pentahydroxy azepane 1a as a sticky
N3
OH
7
O
O
6
(a)
(a)
4
1
HO
HO
HO
OBn
5
5a
5b
OBn
OH
O
O
N3
O
2
O
3
O
O
gum {observed ½a D25
ꢁ
¼ ꢀ5:2 (c 3.0, MeOH), lit.,23
½
a 2D5
ꢁ
¼ ꢀ4:8 (c
7a
6a
3.35, MeOH)}. A similar sequence of reactions was repeated with
N3
OH
6-azido diol 6b which afforded pentahydroxyazepane 1b as a semi-
solid {observed ½a D25
ꢁ
¼ þ14:7 (c 1.25, MeOH), lit.,23
½
a 2D5
ꢁ
¼ þ15:9 (c
O
O
HO
OBn
OBn
1.26, MeOH)}. The spectroscopic and analytical data of 1a/1b were
N3
O
OH
found to be in agreement with those reported.
O
The 5-azido diol 7 was found to be a precursor to piperidine
iminosugars 2. Thus, reduction of the azide functionality and deb-
enzylation in 7a using ammonium formate in the presence of 10%
7b
6b
Scheme 3. Reagents and condition: (a) NaN3, DMF, reflux, 6 h.
Table 2
Regioselective opening of the epoxides 5a/5b with azide nucleophile
No.
Substrate
Azide (equiv)
Solvent
Temp. (°C)
Time (h)
Product
Ratioa
Yield (%)
1
2
3
4
5
6
7
8
9
5a
5b
5a
5b
5°
5b
5°
5b
5a
5b
5a
5b
NaN3 (6)
NaN3 (6)
TMSN3 (1.5)
TMSN3 (1.5)
TMSN3(2),Ti(O-i-Pr)4 (1.0)
TMSN3(2), Ti(O-i-Pr)4 (1.0)
Ti(O-i-Pr)2(N3)2 (1.5)
Ti(O-i-Pr)2(N3)2 (1.5)
NaN3 (5), NH4Cl (2.2)
NaN3 (5), NH4Cl (2.2)
NaN3 (6)
DMF
DMF
Benzene
Benzene
Benzene
Benzene
Benzene
Benzene
MeOH–H2O
MeOH–H2O
Acetone–H2O
Acetone–H2O
153
153
80
80
80
80
80
80
65
65
25
25
6
6
1.5
1.5
2
6a and 7a
6b and 7b
6a and 7a
6b and 7b
6a and 7a
6b and 7b
6a and 7a
6b and 7b
6a and 7a
6b and 7b
No reaction
No reaction
92:08
87:13
90:10
88:12
95:05
90:10
96:04
92:08
88:12
85:15
96
94
92
90
97
92
96
95
91
91
2
1.5
1.5
12
12
12
12
10
11
12
NaN3 (6)
a
Ratio determined by 1H NMR.

166
V. H. Jadhav et al. / Tetrahedron: Asymmetry 21 (2010) 163–170
and 13C (75 MHz) NMR spectra were recorded with Varian Mercury
OH
300 using CDCl3 or D2O as the solvent. Chemical shifts were re-
ported in d unit (ppm) with reference to TMS as an internal stan-
dard and J values are given in hertz. Elemental analyses were
carried out with Thermo Flash Elemental Analyzer 1112. Optical
rotations were measured using Bellingham Stanley-ADP 220 digi-
tal polarimeter with sodium light (589.3 nm) at 25 °C. Thin layer
chromatography was performed on pre-coated plates (0.25 mm,
Silica Gel 60 F254). Visualization was made by absorption of UV
light or by thermal development after spraying with 3.5% solution
of 2,4-dinitrophenylhydrazine in ethanol–H2SO4 and with basic
aqueous potassium permanganate solution. Column chromatogra-
phy was carried out with silica gel (100–200 mesh). The reactions
were carried out in oven-dried glassware under a dry N2 atmo-
sphere. Distilled hexane and EtOAc were used for column chroma-
tography. After quenching of the reaction with water, reaction
work-up involved washing of the combined organic layer with
water, brine, drying over anhydrous Na2SO4 and evaporation of
the solvent at reduced pressure.
O
(a)
(a)
(c)
(c)
HO
HO
OH
1a
1b
6a
NHCbz
OH
O
O
O
O
8a
O
OH
6b
7a
NHCbz
8b
NHCbz
NHCbz
O
HO
O
HO
(c)
(c)
OH
(b)
(a)
(a)
OH
2a
2b
OH
OH
O
O
O
O
9a
10a
NHCbz
NHCbz
O
OH
HO
O
OH
HO
(b)
O
O
7b
O
O
10b
4.2. 3-O-Benzyl-5,6-dideoxy-1,2-O-isopropylidene-a-D-xylo-
9b
hept-5-eno-1,4-furanose 4
Scheme 4. Reagents and conditions: (a) (i) HCOONH4, 10% Pd/C, MeOH, 80 °C, 1 h;
(ii) CbzCl, MeOH/H2O (9:1), 0–25 °C, 18 h; (b) (i) NaIO4, acetone–water, 0 °C to rt,
2 h; (ii) NaBH4, MeOH–H2O, 0 °C to rt, 30 min;(c) (i) TFA–H2O, 0–25 °C, 2.5 h, 10%
Pd/C, MeOH–HCl, 80 psi, 24 h.
To a solution of 3 (4 g, 11.49 mmol) in THF (30 mL), di-isobutyl
aluminium hydride (1 M in THF) (17.2 mL, 17.23 mmol) was added
at ꢀ78 °C. The reaction mixture was stirred for 2 h and the reaction
was quenched by adding saturated NH4Cl. After completion of the
reaction, the reaction mixture was filtered through Celite. The
filtrate was dried over Na2SO4 and purified by column chromatog-
raphy (n-hexane/ethyl acetate = 8:2) to give alcohol 4 as a thick
liquid (3.26 g, 93%); Rf = 0.5 (n-hexane/ethyl acetate = 6:4);
Pd/C followed by reaction with benzyl chloroformate gave N-Cbz-
protected 5-amino alcohol 9a. Oxidative cleavage of diol 9a using
sodium metaperiodate gave
tion with sodium borohydride afforded N-Cbz-protected 5-amino-
-glucofuranose 10a. Compound 10a was reacted with TFA–water
a-amino aldehyde which upon reduc-
½
a 2D5
ꢁ
¼ ꢀ61:4 (c 0.01,CHCl3); IR (neat) 3441, 1649 cmꢀ1
;
1H NMR
D
(300 MHz, CDCl3) d 1.32 (s, 3H, CH3), 1.49 (s, 3H, CH3), 1.84 (br s,
1H, exchangeable with D2O), 3.80 (d, J = 3.0 Hz, 1H, H-3), 4.20 (br
d, J = 4.8 Hz, 2H, –CH2OH), 4.49 (d, J = 12.0 Hz, 1H, –OCH2Ph),
4.55–4.70 (m, 3H, H-2/H-4/–OCH2Ph), 5.80–6.06 (m, 3H, H-1/H-
5/H-6), 7.10–7.40 (m, 5H, ArH); 13C NMR (75 MHz, CDCl3) d 26.2
(CH3), 26.7 (CH3), 62.7 (C-7), 72.1 (–OCH2Ph), 80.5, 82.7, 83.2 (C-
2/C-3/C-4), 104.6 (C-1), 111.4 (O–C–O), 124.6, 127.5, 128.0,
128.3, 134.1, 137.2 (C-5/C-6/Ar-C’s). Anal. Calcd for C17H22O5: C,
66.65; H, 7.24. Found: C, 66.80; H, 7.10.
to cleave the 1,2-acetonide functionality, and the product thus ob-
tained was subjected to hydrogenation using 10% Pd/C in metha-
nol–HCl (9:1) to give 1-deoxy-nojirimycin 1a as a hydrochloride
salt. The specific rotation value and the spectroscopic data of the
natural 1-deoxy-D-nojirimycin hydrochloride 1a were found to be
in agreement with those reported {observed ½a D25
¼ þ47:0 (c
ꢁ
0.12, H2O), lit.,24
½
a 2D5
ꢁ
¼ þ47:1 (c 0.17, H2O)}. A similar sequence
of reactions was repeated with 7b which afforded 5-amino-
furanose 9b to give 1-deoxy- -ido-nojirimycin 1b as a thick liquid
{[ D = +8.5 (c 0.5, MeOH)}. The
D = +7.9 (c 0.25, MeOH), [lit.25
L-ido-
L
a]
[a]
4.3. 3-O-Benzyl-5,6-anhydro-1,2-O-isopropylidene-
-ido-hepto-1,4-furanose 5a
a-D-glycero-
spectroscopic and analytical data of compound 2b were found to
L
be in good agreement with those reported earlier.26
To a solution of Ti(O-i-Pr)4 (1.39 mL, 4.90 mmol) in CH2Cl2
(20 mL) at ꢀ20 °C was added -(ꢀ)-DET (1.0 mL, 4.90 mmol). After
3. Conclusion
D
stirring for 10 min, compound 4 (1.5 g, 4.90 mmol) was dissolved
in 20 mL of CH2Cl2 and added. After stirring for 20 min at ꢀ20 °C
t-BuOOH (0.52 M in toluene, 5.1 mL, 9.80 mmol) was added and
the reaction mixture was stirred for 24 h. Later the reaction was
quenched by the addition of saturated aq Na2SO4 and Et2O and
the reaction mixture was extracted with DCM. The extract was
dried over anhydrous Na2SO4, and purified by column chromatog-
raphy to afford 5a as a white crystalline solid (1.40 g, 89%); Rf = 0.3
In conclusion, the Sharpless asymmetric epoxidation of D-glu-
cose-derived allyl alcohol 4 gave epoxides 5a and 5b with high ste-
reoselectivity. The regioselective opening of the epoxides 5a and
5b gave 6-azido diol 6a/6b as the major product, which was con-
verted to the azepane iminosugar 1a/1b; while the minor product
5-azido diol 7a/7b was scaled up and used in the synthesis of
piperidine iminosugar 2a/2b. Work is currently in progress to alter
the regioselectivity at C-5 position leading to the formation of 5-
azido diol 7 with high regioselectivity product and to determine
its utility in the synthesis of iminosugars.
(n-hexane/ethyl acetate = 7:3);
½
a 2D5
ꢁ
¼ ꢀ51:8 (c 0.005, CHCl3);
mp = 105 °C; IR (KBr) 3502, 1454, 1375, 1217, 1082 cmꢀ1
;
1H
NMR (300 MHz, CDCl3) d 1.33 (s, 3H, CH3), 1.46 (s, 3H, CH3), 3.02
(dt, J = 4.2 and 2.7 Hz, 1H, H-6), 3.33 (dd, J = 5.7 and 2.4 Hz, 1H,
H-5), 3.61 (dd, J = 12.6 and 4.2 Hz, 1H, H-7a), 3.88 (dd, J = 12.6
and 2.4 Hz, 1H, H-7b), 3.90–4.00 (m, 2H, H-4/H-3), 4.49 (d,
J = 12.0 Hz, 1H, –OCH2Ph), 4.64 (d, J = 3.6 Hz, 1H, H-2), 4.73 (d,
J = 12.0 Hz, 1H, –OCH2Ph), 5.99 (d, J = 3.6 Hz, 1H, H-1), 7.23 (s,
5H, ArH); 13C NMR (75 MHz, CDCl3) d 26.4 (CH3), 26.8 (CH3),
53.5, 54.6, 61.0 (C-5/C-6/C-7), 71.8 (–OCH2Ph), 80.9, 82.3, 82.5
(C-2/C-3/C-4), 105.3 (C-1), 111.9 (O–C–O), 127.7 (s), 128.1, 128.5
4. Experimental section
4.1. General methods
Melting points were recorded with a Thomas Hoover Capillary
melting point apparatus and are uncorrected. IR spectra were re-
corded with Shimadzu FTIR-8400 as a thin film or in Nujol mull
or using KBr pellets and are expressed in cmꢀ1 1H (300 MHz)
.

V. H. Jadhav et al. / Tetrahedron: Asymmetry 21 (2010) 163–170
167
(s), 137.0 (Ar-C’s). Anal. Calcd for C17H22O6: C, 63.34; H, 6.88.
Found: C, 63.44; H, 6.48.
63.5, 70.5, 72.2 (C-5/C-6/C-7/OCH2Ph), 77.8, 82.0, 84.2 (C-2/C-3/C-
4), 104.8 (C-1), 112.2 (O–C–O), 127.9, 128.5, 128.7, 136.0 (Ar-C’s).
Anal. Calcd for C17H23N3O6: C, 55.88; H, 6.34. Found: C, 55.70; H,
6.50. Further elution gave compound 7a as a thick liquid (0.10 g,
4.3.1. Crystal data of 5a
Single crystals of the compound were grown by the slow evap-
oration of the solution mixture of hexane and ethyl acetate. Col-
ourless needle of approximately 0.42 ꢂ 0.20 ꢂ 0.17 mm was used
for data collection on Bruker SMART APEX CCD diffractometer using
7.4%); Rf = 0.36 (n-hexane/ethyl acetate = 7:3); ½a D25
¼ ꢀ71:0 (c
ꢁ
0.0012, CHCl3); IR (neat) 3475, 2106 cmꢀ1 1H NMR (300 MHz,
;
CDCl3) d 1.33 (s, 3H, CH3), 1.46 (s, 3H, CH3), 1.90–2.70 (broad, 2H,
exchangeable with D2O), 3.49 (dd, J = 12.6 and 5.4 Hz, 1H, H-7a),
3.58 (dd, J = 12.6 and 2.1 Hz, 1H, H-7b), 3.84 (dd, J = 8.7 and 2.1 Hz,
1H, H-5), 3.88–3.96 (m, 1H, H-6), 4.13 (d, J = 3.6 Hz, 1H, H-3), 4.43
(dd, J = 3.6 and 2.1 Hz 1H, H-4), 4.52 (d, J = 12.0 Hz, 1H, –OCH2Ph),
4.65 (d, J = 3.9 Hz, 1H, H-2), 4.75 (d, J = 12.0 Hz, 1H, –OCH2Ph), 6.00
(d, J = 3.9 Hz, 1H, H-1), 7.23 (m, 5H, ArH); 13C NMR (75 MHz, CDCl3)
d 26.3 (CH3), 26.8 (CH3), 53.9, 70.5, 70.8, 71.7 (C-5/C-6/C-7/OCH2Ph),
72.0, 82.1, 84.3 (C-2/C-3/C-4), 104.6 (C-1), 111.9 (O–C–O), 127.7 (s),
128.3, 128.6 (s), 136.1 (Ar-C’s). Anal. Calcd for C17H23N3O6: C, 55.88;
H, 6.34. Found: C, 55.68; H, 6.52.
Mo Ka radiation with fine focus tube with 50 kV and 30 mA. Crys-
tal to detector distance 6.05 cm, 512 ꢂ 512 pixels/frame, hemi-
sphere data acquisition. Total scans = 3, total frames = 1271,
oscillation/frame ꢀ0.3°, exposure/frame = 10.0 s/frame, maximum
detector swing angle = –30.0°, beam centre = (260.2, 252.5), in
plane spot width = 1.24, SAINT integration, h range = 1.78–25.00°,
completeness to h of 25.0° is 99.9%. SADABS correction applied,
C17H22O6, M = 322.35. Crystals belong to Orthorhombic, space
group P212121, a = 13.235(1), b = 5.482(4), c = 22.743(2) Å,
V = 1650.1(12) Å3, Z = 4, Dc = 1.298 g/cc,
T = 293(2) K, 8312 reflections measured, 2906 unique [I > 2
l
(MoK
a
) = 0.098 mmꢀ1
(I)], R
,
r
4.6. 6-Azido-3-O-benzyl-6-deoxy-1,2-O-isopropylidene-
a-D-
value 0.0342, wR2 = 0.0811. All the data were corrected for
Lorentzian, polarization and absorption effects. SHELX-97 (Shel-
xTL)27 was used for structure solution and full matrix least squares
refinement on F2. Hydrogen atoms were included in the refinement
as per the riding model. Ellipsoids are drawn at 50% probability.
glycero- -gluco-hepto-1,4-furanose 6b and 5-azido-3-O-benzyl-
5-deoxy-1,2-O-isopropylidene-b-L-glycero-L-ido-hepto-1,4-
furanose 7b
D
Reaction of 5b (1.2 g, 3.72 mmol) with NaN3 (1.45 g,
22.36 mmol) as described for 6a/7a gave 6b (1.10 g, 80.9%) as a
4.4. 3-O-Benzyl-5,6-anhydro-1,2-O-isopropylidene-b-
-gluco-hepto-1,4-furanose 5b
L-glycero-
thick liquid; Rf = 0.35 (n-hexane/ethyl acetate = 7:3);
½
a 2D5
ꢁ
¼
D
ꢀ28:7 (c 0.018, CHCl3); IR (neat) 3446, 2106 cmꢀ1
;
1H NMR
(300 MHz, CDCl3) d 1.33 (s, 3H, CH3), 1.49 (s, 3H, CH3), 2.40–2.70
(br s, 2H, exchangeable with D2O), 3.48 (m, 2H, H-7), 3.83 (dt,
J = 6.0 and 3.9 Hz, 1H, H-6), 3.98 (dd, J = 7.8 and 6.0 Hz, 1H, H-5),
4.10 (d, J = 3.6 Hz, 1H, H-3), 4.19 (dd, J = 7.8 and 3.6 Hz, 1H, H-4),
4.50 (d, J = 11.7 Hz, 1H, –OCH2Ph), 4.60 (d, J = 3.6 Hz, 1H, H-2),
4.72 (d, J = 11.7 Hz, 1H, –OCH2Ph), 5.94 (d, J = 3.6 Hz, 1H, H-1),
7.32 (m, 5H, ArH); 13C NMR (75 MHz, CDCl3) d 26.3 (CH3), 26.9
(CH3), 62.2, 64.4, 70.1, 72.1 (C-5/C-6/C-7/OCH2Ph), 78.7, 81.7,
81.9 (C-2/C-3/C-4), 105.1 (C-1), 112.0 (O–C–O), 128.0 (s), 128.4,
128.7 (s), 136.5 (Ar-C’s). Anal. Calcd for C17H23N3O6: C, 55.88; H,
6.34. Found: C, 55.60; H, 6.40 and further elution gave compound
7b (0.165 g, 12.2%) as a thick liquid; Rf = 0.35 (n-hexane/ethyl ace-
Reaction of 4 (1.5 g, 4.90 mmol) with Ti(O-i-Pr)4 (1.39 mL,
4.90 mmol), -(+)-DET (1.0 mL, 4.90 mmol), t-BuOOH (0.52 M in
L
toluene, 5.1 mL, 9.80 mmol) as described for 5a gave 5b as a thick
liquid (1.35 g, 86%); Rf = 0.31 (n-hexane/ethyl acetate = 7:3);
½
a 2D5
ꢁ
¼ ꢀ44:9 (c 0.08, CHCl3); IR (neat) 3400, 1454, 1377, 1215,
1163, 1024 cmꢀ1 1H NMR (300 MHz, CDCl3) d 1.32 (s, 3H, CH3),
;
1.46 (s, 3H, CH3), 3.26 (dt, J = 4.5 and 2.4 Hz, 1H, H-6), 3.33 (dd,
J = 6.6 and 2.4 Hz, 1H, H-5), 3.67 (dd, J = 12.6 and 4.2, 1H, H-7a),
3.92–4.02 (m, 2H, H4/H-7b), 4.07 (d, J = 3 Hz, 1H, H-3), 4.62 (d,
J = 12.3 Hz, 1H, –OCH2Ph), 4.63 (d, J = 3.9 Hz, 1H, H-2), 4.72 (d,
J = 12.3 Hz, 1H, –OCH2Ph), 5.93 (d, J = 3.9 Hz, 1H, H-1), 7.30 (s,
5H, ArH); 13C NMR (75 MHz, CDCl3) d 26.3 (CH3), 26.9 (CH3),
51.9, 57.8, 61.3 (C-5/C-6/C-7), 72.3 (–OCH2Ph), 80.2, 81.9, 82.5
(C-2/C-3/C-4), 105.2 (C-1), 111.9 (O–C–O), 127.5, 127.9 (s), 128.5
(s), 137.1 (Ar-C’s). Anal. Calcd for C17H22O6: C, 63.34; H, 6.88.
Found: C, 63.52; H, 6.71.
tate = 7:3); ½a 2D5
ꢁ
¼ þ32 (c 0.001, CHCl3); IR (neat) 3465, 2106 cmꢀ1
;
1H NMR (300 MHz, CDCl3) d 1.25 (s, 3H), 1.33 (s, 3H), 2.70–3.00 (br
s, exchangeable with D2O), 3.60 (dd, J = 7.8 and 4.8 Hz, 1H, H-5),
3.90 (m, 2H, H-7), 4.12 (dt, J = 4.8 and 3.0 Hz, 1H, H-6), 4.14 (d,
J = 3.0 Hz, 1H, H-3), 4.23 (dd, J = 7.8 and 3.0 Hz, 1H, H-4), 4.51 (d,
J = 11.4 Hz, 1H, –OCH2Ph), 4.62 (d, J = 3.3 Hz, 1H, H-2), 4.74 (d,
J = 11.4 Hz, 1H, –OCH2Ph), 5.93 (d, J = 3.3 Hz, 1H, H-1), 7.30–7.35
(m, 5H, Ar-H); 13C NMR (75 MHz, CDCl3) d 26.3 (CH3), 27.0 (CH3),
52.9, 62.0, 71.0, 73.0 (C-5/C-6/C-7/OCH2Ph), 77.0, 79.0, 81.9 (C-2/
C-3/C-4), 105.2 (C-1), 112.0 (O–C–O), 127.8, 128.2, 128.7, 137.1
(Ar-C’s). Anal. Calcd for C17H23N3O6: C, 55.88; H, 6.34. Found: C,
55.70; H, 6.50.
4.5. 6-Azido-3-O-benzyl-6-deoxy-1,2-O-isopropylidene-b-
L-
glycero- -ido-hepto-1,4-furanose 6a and 5-azido-3-O-benzyl-5-
L
deoxy-1,2-O-isopropylidene-a-D-glycero-D-gluco-hepto-1,4-
furanose 7a
Compound 5a (1.2 g, 3.72 mmol) was dissolved in a 10 mL DMF
solution. To this solution, sodium azide (1.45 g, 22.36 mmol) was
added and then the reaction mixture was refluxed for 6 h. After com-
pletion of the reaction, the reaction was quenched by adding water.
Next, DMF was removed in vacuo and then the aqueous phase was
extracted with ethyl acetate for three times (3 ꢂ 30 mL). Purification
was carried out by column chromatography (n-hexane/ethyl ace-
tate = 8:2) to afford 6a (1.20 g, 88.2%) as a thick liquid; Rf = 0.35
4.7. 6-Benzyloxycarbonylamino-6-deoxy-1,2-O-isopropylidene-
b-L
-glycero-
L-ido-hepto-1,4-furanose 8a
A solution of compound 6a (0.35 g, 0.95 mmol) in dry methanol
(15 mL) in the presence of 10% Pd/C (0.2 g) and ammonium for-
mate (0.41 g, 6.5 mmol) was refluxed for 1 h. The reaction mixture
was filtered through Celite and the residue was washed with meth-
anol. Now to this amine in methanol–water (20 mL, 8:1), benzyl
chloroformate (0.18 mL, 1.15 mmol) was added along with sodium
bicarbonate (0.23 g, 2.68 mmol) at 0 °C and stirred for 18 h. Meth-
anol was evaporated under reduced pressure and the residue was
extracted with ethyl acetate (3 ꢂ 20 mL). Usual work-up and puri-
fication by column chromatography (n-hexane/ethyl acetate = 4:6)
afforded 8a as a white solid (0.32 g, 92%). Mp = 119–121 °C;
(n-hexane/ethyl acetate = 7:3); ½a D25
¼ ꢀ35:1 (c 0.07, CHCl3); IR
ꢁ
(neat) 3446, 2106 cmꢀ1 1H NMR (300 MHz, CDCl3) d 1.35 (s, 3H,
;
CH3), 1.52 (s, 3H, CH3), 3.62 (dt, J = 7.8 and 4.5 Hz, 1H, H-6), 3.85
(dd, J = 12.0 and 4.8 Hz, 1H, H-7a), 3.90–4.10 (m, 2H, H-5, H-7b),
4.14 (d, J = 3.6 Hz, 1H, H-3), 4.33 (dd, J = 3.6 and 2.1 Hz, 1H, H-4),
4.52 (d, J = 11.6 Hz, 1H, –OCH2Ph), 4.66 (d, J = 3.9 Hz, 1H, H-2), 4.77
(d, J = 11.6 Hz, 1H, –OCH2Ph), 6.02 (d, J = 3.9 Hz, 1H, H-1), 7.25 (m,
5H, ArH); 13C NMR (75 MHz, CDCl3) d 26.4 (CH3), 26.9 (CH3), 62.5,

168
V. H. Jadhav et al. / Tetrahedron: Asymmetry 21 (2010) 163–170
Rf = 0.45 (hexane/ethyl acetate = 2:8); ½a D25
ꢁ
¼ ꢀ10:6 (c 0.56, CHCl3);
1H NMR (300 MHz,
and 3.2 Hz, 1H, H-6), 4.07 (t, J = 7.3 Hz, 1H, H-5), 4.22 (d,
IR (KBr) 3200–3600 (broad band), 1711 cmꢀ1
;
J = 2.6 Hz, 1H, H-3), 4.34 (dd, J = 7.3 and 2.6 Hz, 1H, H-4), 4.55 (d,
J = 3.8 Hz, 1H, H-2), 5.12 (s, 2H, N-Cbz), 5.91 (d, J = 3.8 Hz, 1H, H-
1), 7.23–7.45 (m, 5H, Ar-H); 13C NMR (75 MHz, CDCl3) d 26.4
(CH3), 27.0 (CH3), 53.5 (C-5), 64.6 (NCOOCH2Ph), 67.6 (C-7), 73.3
(C-6), 76.3, 81.1, 87.0 (C-2/C-3/C-4), 105.3(C-1), 112.6 (OCO),
128.7, 128.8, 128.9, 129.4, 129.5, 138.3 (Ar-C), 159.0 (NCOOCH2Ph).
Anal. Cald. for C18H25NO8: C, 56.39; H, 6.57. Found: C, 56.22; H,
6.28.
CDCl3 + D2O) d 1.30 (s, 3H, CH3), 1.46 (s, 3H, CH3), 3.72 (dd,
J = 11.4 and 4.5 Hz, 1H, H-7a), 3.77–3.79 (m, 1H, H-6), 3.98 (dd,
J = 11.7 and 2.7 Hz, 1H, H-7b), 4.19–4.24 (m, 2H, H4/H5), 4.30 (d,
J = 2.0 Hz, 1H, H-3), 4.53 (d, J = 3.9 Hz, 1H, H-2), 5.11 (ABq,
J = 11.0 Hz, 2H, –NCbz), 5.98 (d, J = 3.9 Hz, 1H, H-1), 7.32 (m, 5H,
ArH); 13C NMR (75 MHz, CDCl3) d 26.3 (CH3), 26.9 (CH3), 53.9,
61.8, 67.2, 72.1 (C-5/C-6/C-7/NCOOCH2), 76.0, 79.6, 85.2 (C-2/C-
3/C-4), 104.8 (C-1), 111.9 (O–C–O), 128.0 (s), 128.2, 128.4 (s),
135.8 (Ar-C’s), 156.8 (NCOOCH2Ph). Anal. Calcd for C18H25NO8: C,
56.57; H, 6.18. Found: C, 56.48; H, 6.25.
4.11. 5-Benzyloxycarbonylamino-5-deoxy-1,2-O-isopropylidene-
a-D-gluco-1,4-furanose 10a
4.8. 6-Benzyloxycarbonylamino-6-deoxy-1,2-O-isopropylidene-
To a cooled solution of compound 9a (0.1 g, 0.27 mmol) in ace-
a
-
D
-glycero-
D
-gluco-hepto-furanose 8b
tone–water (10 mL, 5:1) was added sodium metaperiodate
(0.086 g, 0.40 mmol). After stirring the reaction mixture for 1.5 h,
ethylene glycol (1 mL) was added and the reaction mixture was
concentrated and the residue was extracted with dichloromethane
(2 ꢂ 30 mL). Work-up and column purification (n-hexane/ethyl
acetate = 5:5) afforded an aldehyde, which was directly subjected
to reduction using NaBH4 (0.012 g, 0.32 mmol) in MeOH–H2O
(10 mL, 4:1) for 30 min and the reaction was quenched by adding
saturated NH4Cl. The reaction mixture was extracted with ethyl
acetate (1 ꢂ 30 mL). Usual work-up and purification by column
chromatography (n-hexane/ethyl acetate = 5:5) gave 10a (0.077 g,
89%) as a white solid: Rf = 0.4 (n-hexane/ethyl acetate = 1:9);
The reaction of 6b (0.35 g, 0.95 mmol) with ammonium formate
(0.41 g, 6.5 mmol), 10% Pd/C (0.2 g) followed by benzyl chlorofor-
mate (0.18 mL, 1.15 mmol), sodium bicarbonate (0.23 g,
2.68 mmol) as described for 8a gave 8b as a white solid (0.29 g,
88%). Rf = 0.41 (ethyl acetate); ½a D25
¼ þ11:7 (c 0.51, CHCl3); mp
ꢁ
135–137 °C; IR (KBr) 3200–3600 (broad band), 1687, 1560, 1456,
1375 cmꢀ1 1H NMR (300 MHz, CDCl3 + D2O) d 1.30 (s, 3H), 1.44
;
(s, 3H), 3.72 (dd, J = 12.3 and 4.8 Hz, 1H, H-7a), 3.92–3.99 (m, 2H,
H-6/H7b), 4.01 (dd, J = 8.1 and 3.9 Hz, 1H, H-5), 4.16 (dd, J = 8.1
and 2.4 Hz, 1H, H-4), 4.39 (d, J = 2.4 Hz, 1H, H-3), 4.51 (d,
J = 3.6 Hz, 1H, H-2), 5.10 (s, 2H, –NCbz), 5.92 (d, J = 3.6 Hz, 1H, H-
1), 7.24–7.34 (m, 5H, ArH); 13C NMR (75 MHz, CDCl3) d 26.3
(CH3), 27.0 (CH3), 53.4, 61.6, 70.8, 72.6 (C-5/C-6/C-7/NCOOCH2),
77.2, 79.3, 82.0 (C-2/C-3/C-4), 105.2 (C-1), 112.1 (O–C–O), 127.8
(s), 128.0, 128.5 (s), 137.1 (Ar-C’s), 162.3 (NCOOCH2Ph). Anal. Calcd
for C18H25NO8: C, 56.39; H, 6.57. Found: C, 56.48; H, 6.74.
½
a 2D5
ꢁ
¼ ꢀ4:2 (c 0.045, CHCl3); mp = 144–146 °C; IR (KBr) 3350,
1689 cmꢀ1 1H NMR (300 MHz, CDCl3) d 1.30 (s, 3H, CH3), 1.50 (s,
;
3H, CH3), 2.40–3.40 (broad, 2H, exchangeable with D2O), 3.90–
4.10 (m, 3H, CH2OH, H-4), 4.14 (d, J = 3.6 Hz, 1H, H-3), 4.28 (d,
J = 2.4 Hz, 1H, H-5), 4.50 (d, J = 3.6 Hz, 1H, H-2), 5.07 (s, 2H), 5.40
(broad, 2H, exchangeable with D2O), 5.94 (d, J = 3.6 Hz, 1H, H-1),
7.32 (s, 5H, ArH); 13C NMR (75 MHz, CDCl3) d 26.2 (CH3), 26.8
(CH3), 43.4, 61.0, 66.9 (C-5/C-6/N-COOCH2Ph), 76.6, 78.7, 85.5 (C-
2/C-3/C-4), 104.7 (C-1), 111.7 (O–C–O), 127.9 (s), 128.1 (s), 128.4
(s), 136.1 (Ar-C’s), 157.0 (NCOOCH2Ph). Anal. Calcd for
C17H23NO7: C, 57.78; H, 6.56. Found: C, 57.45; H, 6.20.
4.9. 5-Benzyloxycarbonylamino-5-deoxy-1,2-O-isopropylidene-
a-
D-glycero-
D-gluco-hepto-1,4-furanose 9a
A solution of compound 7a (0.1 g, 0.27 mmol) with ammonium
formate (0.10 g, 1.64 mmol), 10% Pd/C (0.05 g) followed by CbzCl
(0.05 mL, 0.32 mmol), sodium bicarbonate (0.06 g, 0.76 mmol) as
described for 8a gave 9a (0.092 g, 90%) as a white solid. Rf = 0.5
4.12. 5-Benzyloxycarbonylamino-5-deoxy-1,2-O-isopropylidene-
b-L-ido-1,4-furanose 10b
(n-hexane/ethyl acetate = 2:8);
½
a 2D5
ꢁ
¼ ꢀ9:1 (c 0.005, CHCl3);
mp = 143°C; IR (KBr) 3442, 3350, 1689, 1500, 1250 cmꢀ1
;
1H
Reaction of 9b (0.15 g, 0.40 mmol) with sodium metaperiodate
NMR (300 MHz, CDCl3) d 1.32 (s, 3H, CH3), 1.49 (s, 3H, CH3),
1.50–2.20 (brd, 3H, exchangeable with D2O), 3.35–3.70 (m, 2H,
H-5, H-6), 3.86 (br s, 2H, –CH2OH), 4.25 (br d, J = 3.5 Hz, 1H, H-
4), 4.32 (d, J = 3.5 Hz, 1H, H-3), 4.55 (d, J = 3.3 Hz, 1H, H-2), 5.11
(s, 2H, –NCOOCH2Ph), 5.29 (br s, 1H, exchangeable with D2O),
5.97 (d, J = 3.3 Hz, 1H, H-1), 7.23 (s, 5H, ArH); 13C NMR (75 MHz,
CDCl3 + DMSO-d6) d 26.1 (CH3), 26.6 (CH3), 43.5, 66.6, 70.7 (s) (C-
5/C-6/C-7/-NCOOCH2), 76.0, 79.4, 85.1 (C-2/C-3/C-4), 104.2 (C-1),
111.1 (O–C–O), 127.7 (s), 128.1 (s), 135.9 (Ar-C’s), 157.7
(NCOOCH2Ph). Anal. Calcd for C18H25NO8: C, 56.39; H, 6.57. Found:
C, 56.66; H, 6.33.
(0.13 g, 0.60 mmol) followed by NaBH4 (0.018 g, 0.48 mmol) gave
10b (0.11 g, 87%) as a white solid; Rf = 0.34 (30% ethyl acetate/n-
hexane); ½a 2D5
ꢁ
¼ þ13:3 (c 0.15, CHCl3); mp = 97–99 °C; IR (KBr)
3502 (broad), 2904, 1676, 1253 cmꢀ1
;
1H NMR (300 MHz, CDCl3)
d 1.32 (s, 3H, CH3), 1.49 (s, 3H, CH3), 3.58–3.74 (m, 3H, H-6, H-5),
4.15 (d, J = 1.9 Hz, 1H, H-3), 4.62 (d, J = 3.5 Hz, 1H, H-2), 4.86 (dd,
J = 9.0 and 1.9 Hz, 1H, H-4), 5.16 (ABq, J = 12.6 Hz, 2H, N-
COOCH2Ph), 5.99 (d, J = 3.5 Hz, 1H, H-1), 7.20–7.30 (m, 5H, Ar-H);
13C NMR (75 MHz, CDCl3) d (75 MHz, CDCl3) 26.3, 26.7 (CH3),
53.7 (C-5), 63.3 (N-COOCH2Ph), 67.4 (C-6), 77.7, 81.6, 81.9 (C-2/C-
3/C-4), 104.5 (C-1), 111.7 (O–C–O), 127.7, 127.9, 128.4, 136.1,
(Ar-C), 157.6 (N-COOCH2Ph). Anal. Calcd for C17H23NO7: C, 69.78;
H, 6.61; Found: C, 69.97; H, 6.49.
4.10. 5-Benzyloxycarbonylamino-5-deoxy-1,2-O-
isopropylidene-b-L-glycero-L-ido-hepto-1,4-furanose 9b
4.13. 1,6-Dideoxy-1,6-imino-
hydrochloride 1a
L-glycero-L-ido-heptitol
A solution of compound 7b (0.15 g, 0.41 mmol) with ammo-
nium formate (0.155 g, 2.5 mmol), 10% Pd/C (0.075 g), followed
by CbzCl (0.076 mL, 0.49 mmol), sodium bicarbonate (0.096 g,
1.15 mmol) as described for 8a gave 9b (0.14 g, 92%) as a white so-
A solution of 8a (0.10 g, 0.38 mmol) in TFA–H2O (3 mL, 2:1) was
stirred at 25 °C for 2.5 h. Trifluoroacetic acid was co-evaporated
with benzene to furnish a thick liquid. To a solution of the
above-mentioned product in methanolic hydrochloric acid (5 mL,
9:1) was added 10% Pd/C (0.05 g). The solution was hydrogenated
at 80 psi for 24 h. The catalyst was filtered through Celite and
washed with methanol. The filtrate was concentrated to get 1a
lid; Rf = 0.37 (ethyl acetate/n-hexane = 5:5); ½a D25
¼ ꢀ13:3 (c 0.15,
ꢁ
CHCl3); mp 132–135 °C; IR (KBr) 3523–3477 (broad), 3413, 1706,
1521, 1238 and 1083 cmꢀ1 1H NMR(300 MHz, CDCl3) d 1.23 (s,
;
3H,CH3), 1.42 (s, 3H, CH3), 3.59 (dd, J = 11.7 and 5.8 Hz, 1H, H-
7a), 3.65 (dd, J = 11.7 and 3.2 Hz, 1H, H-7b), 3.74 (ddd, J = 7.3, 5.8

V. H. Jadhav et al. / Tetrahedron: Asymmetry 21 (2010) 163–170
169
(h) Boruwa, J.; Borah, J. C.; Kalita, B.; Barua, N. C. Tetrahedron Lett. 2004, 45,
7355–7358; (i) Sabita, G.; Satheesh Babu, R.; RajKumar, M.; Yadav, J. S. Org. Lett.
2002, 4, 343–345.
as a sticky gum (0.073 g, 83%): Rf = 0.18 (chloroform/metha-
nol = 8:2); ½a 2D5
¼ ꢀ4:8 (c 3.35, MeOH); IR (neat) 3200–3600 (broad
ꢁ
band) cmꢀ1; 1H NMR (300 MHz, D2O) d 3.27–3.36 (m, 2H, H-1a/H-
6), 3.56–3.74 (m, 2H, H-1b, H-7a), 3.76–3.87 (m, 2H, H-7b/H-3),
3.88–3.96 (m, 1H, H-4), 3.98–4.16 (m, 2H, H-2/H-5); 13C NMR
(75 MHz, D2O) d 45.9 (C-1), 58.9, 60.5 (C-6/C-7), 67.5, 68.4, 75.1,
75.6 (C-2/C-3/C-4/C-5). Anal. Calcd for C7H16ClNO5: C, 36.61; H,
7.02. Found: C, 36.813; H, 7.20.
2. Maruoka, K.; Sano, H.; Yamamoto, H. Chem. Lett. 1985, 599–602.
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4.14. 1,6-Dideoxy-1,6-imino-D-glycero-D-gluco-heptitol
10. Behrens, C. H.; Sharpless, K. B. Aldrichim. Acta 1983, 16, 67–79.
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hydrochloride 1b
Reaction of 7a (0.10 g, 0.269 mmol) with TFA–H2O (3 mL, 2:1)
followed by hydrogenation with 10% Pd/C (0.05 g) in methanolic
HCl as described for 1a gave 1b as a semisolid. Rf = 0.20 (chloro-
form/methanol = 8:2); ½a D25
ꢁ
¼ þ15:9 (c 1.26, MeOH); IR (Nujol)
3200–3600 (broad band) cmꢀ1
;
1H NMR (300 MHz, D2O) d 3.19
(broad dd, J = 12.6, 7.2 Hz, 1H, H-1a), 3.26–3.35 (m, 1H, H-2),
3.38–3.48 (m, 1H, H-1b), 3.72 (dd, J = 12.4 and 6.0 Hz, 1H, H-7a)
3.80–3.92 (m, 4H, H-3/H-5/H-6/H-7b), 4.02 (brd, J = 7.2 Hz, 1H,
H-4); 13C NMR (75 MHz, D2O) d 45.3 (C-1), 59.7, 60.2 (C-6/C-7),
67.6, 70.5, 72.3, 75.1 (C-2/C-3/C-4/C-5). Anal. Calcd for
C7H16ClNO5: C, 36.61; H, 7.02. Found: C, 36.88; H, 7.25.
4.15. 1,5-Dideoxy-1,5-imino-D-glucitol hydrochloride 2a
Reaction of 10a (0.05 g, 0.22 mmol) with TFA–H2O (3 mL, 2:1)
followed by hydrogenation with 10% Pd/C (0.025 g) in methanolic
HCl as described for 1a gave white solid of 2a (0.034 g, 80.3%):
Rf = 0.25 (chloroform/methanol = 1:1);
½
a 2D5
ꢁ
¼ þ47:0 (c 0.12,
H2O); mp = 201–203°C; IR (KBr) 3200–3600 (broad band) cmꢀ1
;
1H NMR (300 MHz, D2O) d 3.02 (t, J = 12.2 Hz, 1H), 3.25 (ddd,
J = 9.5, 5.2 and 3.1 Hz, 1H), 3.57 (dd, J = 5.1 and 12.2 Hz, 1H), 3.59
(t, J = 9.5 Hz, 1H), 3.65 (t, J = 9.5 Hz, 1H), 3.85 (ddd, J = 12.2, 9.5
and 5.1 Hz, 1H), 3.95 (dd, J = 11.7 and 5.1 Hz, 1H), 4.02 (dd,
J = 11.7 and 3.1 Hz, 1H); 13C NMR (75 MHz, D2O) d 46.0 (C-1),
57.8 (C-5), 60.1 (C-6), 67.1, 67.9, 76.3 (C-2/C-3/C-4). Anal. Calcd
for C6H14ClNO4: C, 36.10; H, 7.07. Found: C, 36.30; H, 7.27.
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4.16. 1,5-Dideoxy-1,5-imino-L-iditol 2b
Reaction of 10b (0.1 g, 0.43 mmol) in TFA–water (2:1, 3 mL) and
10% Pd/C (0.05 g) in methanol as described for 10a gave 2b (0.07 g,
81%) as
D = +7.9 (c 0.25, MeOH); IR (neat) 3200–3600 (broad band)
cmꢀ1 1H NMR (300 MHz, D2O) d 2.72 (dd, J = 13.1 and 7.3 Hz,
a thick liquid Rf = 0.20 (60% methanol–chloroform);
[a]
;
1H, H-1a), 2.91 (dd, J = 13.1 and 3.3 Hz, 1H, H-1e), 3.08–3.14 (m,
1H, H-5) 3.50–3.58 (m, 2H, H-6), 3.60–3.69 (m, 3H, H-2/H-3/H-
4); 13C NMR (75 MHz, D2O) 44.0 (C-1), 56.3 (C-5), 57.7 (C-6),
69.2, 69.8, 71.3 (C-2/C-3/C-4). Anal. Calcd for C6H13NO4: C, 44.16;
H, 8.03. Found: C, 44.23; H, 8.23.
Acknowledgements
V.H.J. is thankful to UGC, New Delhi, for the Senior Research Fel-
lowship and University seed money 2009, BCUD project, University
of Pune, Pune, for financial support.
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