A concise enantioselective synthesis of 1,4-dideoxy-1,4-imino-D-arabinitol using Co(III)(salen)-catalyzed hydrolytic kinetic resolution of a two-stereocentered anti-azido epoxide

Article abstract of DOI:10.1016/j.tetasy.2016.10.013

A concise enantioselective synthesis of 1,4-dideoxy-1,4-imino-D-arabinitol, (+)-DAB-1, has been described in good overall yield (18.1%) and with high enantiomeric purity (up to 98% ee) starting from a simple raw material, cis-2-butene-1,4-diol. The Co-catalyzed hydrolytic kinetic resolution of a two-stereocentered racemic azido epoxide followed by asymmetric dihydroxylation of the alkene and ‘one pot’ reductive cyclisation of the azido diol are key reactions in the synthetic sequence.

Full text of DOI:10.1016/j.tetasy.2016.10.013

Tetrahedron: Asymmetry xxx (2016) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
A concise enantioselective synthesis of 1,4-dideoxy-1,4-imino-D-
arabinitol using Co(III)(salen)-catalyzed hydrolytic kinetic resolution
of a two-stereocentered anti-azido epoxide
⇑
Rambabu N. Reddi, Pragati K. Prasad, Rupali G. Kalshetti, Arumugam Sudalai
Chemical Engineering & Process Development Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune, Maharashtra 411008, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A
concise enantioselective synthesis of 1,4-dideoxy-1,4-imino-D-arabinitol, (+)-DAB-1, has been
Received 19 October 2016
Accepted 26 October 2016
Available online xxxx
described in good overall yield (18.1%) and with high enantiomeric purity (up to 98% ee) starting from
a simple raw material, cis-2-butene-1,4-diol. The Co-catalyzed hydrolytic kinetic resolution of a two-
stereocentered racemic azido epoxide followed by asymmetric dihydroxylation of the alkene and ‘one
pot’ reductive cyclisation of the azido diol are key reactions in the synthetic sequence.
Ó 2016 Elsevier Ltd. All rights reserved.
1. Introduction
two-stereocentered hydrolytic kinetic resolution of racemic azido
epoxide 4 as the key reaction (Schemes 2 and 3).
Polyhydroxylated pyrrolidines and piperidines have inspired
the design of novel potential glycosyltransferase inhibitors.1,2 The
field of the therapeutic applications of such compounds seems
promisingly broad since they could be involved in the treatment
of fungal infections (chitin synthase inhibition), inflammatory pro-
OH
OH
HO
HO
HO
HO
N
N
cesses, xenotransplant rejection or tumor growth (a-1,3-fucosyl-
H
H
transferase inhibition), and glycosphingolipid storage disorders
(ceramide glucosyltransferase inhibition). 1,4-Dideoxy-1,4-imino-
DAB-1 1
LAB-1 ent-1
D
-arabinitol (DAB-1) 1 is one such naturally occurring pyrrolidine
Figure 1. Structure of both the enantiomers of 1,4-dideoxy-1,4-iminoarabinitol.
alkaloid found in Arachniodes standishii3 and Angylocalyx bou-
tiqueanus,4 which is a specific inhibitor of glycosidase and potential
inhibitor of HIV replication.5 The structural complexity (three con-
tiguous stereocenters) and biological importance of both DAB-1 1
and its antipode LAB-1 2 (Fig. 1) have attracted considerable inter-
est toward their synthesis. The reported methods of their synthe-
sis, however, largely rely upon chiral pool resources6 and
invariably involve multiple steps while asymmetric version involv-
ing enzymatic or kinetic resolution strategy is rather limited in
terms of its utility.7 Recently, we reported the Co-catalyzed hydro-
lytic kinetic resolution of racemic anti-azido epoxides with two
consecutive stereocenters to generate the corresponding diols
and epoxides with high enantiomeric purity (97–99% ee) in a single
step.8 As part of our research program aimed at developing the
enantioselective synthesis of biologically active molecules,9 we
herein report a concise synthesis of (+)-DAB-1 1 that utilizes a
2. Results and discussion
The retrosynthetic plan of 1,4-dideoxy-1,4-imino-D-arabinitol,
(+)-DAB-1 1, is shown in Scheme 1. We thus envisioned the pyrro-
lidine formation at the final stage of the synthesis by reductive
cyclization of azido diol 2. Azido diol 2 was in turn visualized from
diol 3 by a series of simple reaction sequences (oxidation, Wittig
reaction and dihydroxylation). The key intermediate diol 3 could
be readily obtained from racemic azido epoxide 4 by utilizing the
Co-catalyzed two-stereocentered hydrolytic kinetic resolution of
racemic azido epoxide. The formation of racemic azido epoxide 4
was planned from cis-2-butene-1,4-diol 5 by following standard
azido bromination and epoxidation reaction sequences.
The complete synthetic sequence for obtaining the key chiral
diol intermediate 3 via hydrolytic kinetic resolution commencing
from commercially available cis-2-butene-1,4-diol 5 is outlined in
Scheme 2. The azidobromination of 5 using N-bromosuccinimide
⇑
Corresponding author. Tel.: +91 20 25902547; fax: +91 20 25902676.
E-mail address: a.sudalai@ncl.res.in (A. Sudalai).
http://dx.doi.org/10.1016/j.tetasy.2016.10.013
0957-4166/Ó 2016 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Reddi, R. N.; et al. Tetrahedron: Asymmetry (2016), http://dx.doi.org/10.1016/j.tetasy.2016.10.013

2
R. N. Reddi et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
OH
was carried out to give azido alcohol 10 in 84% yield. Pyridinium
OBn
HO
chlorochromate mediated oxidation of alcohol 10 resulted in the
formation of the aldehyde, which was immediately subjected to
one carbon homologation to give olefin 11 in 81% yield over two
steps. The asymmetric dihydroxylation of alkene 11 using AD-
BnO
OH
HO
N
N3
OH
H
2
1
mix-a gave the corresponding diol 2 with high diastereoselectivity
OH
O
HO
(dr = 14:1; anti:syn), which was smoothly separated using flash
column chromatography.10 Finally, the primary hydroxyl group
of diol 2 was selectively protected as its tosylate using Bu2SnO
and tosyl chloride. The crude tosylate, without purification, was
then subjected to catalytic hydrogenation [10% Pd/C, H2 (1 atm)
MeOH] under strongly acidic conditions (6 M HCl) for 24 h, which
resulted in the reduction of the azide group to the amine, concomi-
tant nucleophilic displacement of the tosylate moiety by in situ
formed amine10 and global deprotection of benzyl groups, all
occurring in a ‘one pot’ operation to afford the target molecule
(+)-DAB-1 1 in 90% yield. The 1H and 13C NMR as well as other
spectroscopic data of 1 were in complete agreement with the val-
ues reported in the literature.10
BnO
BnO
N3
OH
N3
OH
( )-4
5
3
Scheme 1. Retrosynthetic plan for (+)-DAB-1 1.
O
Br
ii
i
HO
OH
HO
HO
iv
OH
N3
N3
7
6
5
OH
O
O
BnO
iii
BnO
BnO
3. Conclusion
N3
N3
OH
N3
In conclusion, an efficient and straightforward enantioselective
synthesis of (+)-DAB 1 1 with reasonably good overall yield (18.1%)
and high enantioselectivity (ee ꢁ99%) has been described. The ini-
tial Co-catalyzed hydrolytic kinetic resolution of the two-stereo-
centered racemic azido epoxide 4 for the induction of chirality
and the subsequent dihydroxylation constitute as the key reactions
for obtaining three contiguous stereocenters in the desired fashion.
We believe that the synthetic strategy described herein has signif-
icant potential for further extension to other stereoisomers and
related analogues of multi-functionalized pyrrolidine alkaloids
owing to the flexible synthesis of racemic azido epoxides with
different stereochemical combinations and with different
substituents.
( )-4
(+)-8 (2S,3S)
(-)-3 (2R,3R)
48% yield
50% yield
Scheme 2. Reagents and conditions: (i) NBS (1.1 equiv), NaN3 (2 equiv), CH3CN:
H2O (3:1), 0 °C, 4 h, 89%; (ii) NaOH powder, THF, 0 °C, 1 h, 84%; (iii) BnBr (1.1 equiv),
NaH (1.5 equiv), DMF, 0–25 °C, 92%; (iv) (S,S)-salen-cobalt(III)OAc (1 mol %), H2O
(0.5 equiv), 0 °C, 14 h.
(NBS) and sodium azide (NaN3) in CH3CN:H2O afforded azido diol
product 6 in 89% isolated yield. The azido diol 6 thus obtained
was readily transformed into racemic anti-azido epoxy alcohol 7
(84% yield) under basic conditions. The free-hydroxyl group was
then protected as its benzyl ether 4 (92% yield). The racemic azido
epoxide 4 was subjected to hydrolytic kinetic resolution with (S,S)-
salen Co(III)OAc complex (0.5 mol %) and H2O (0.49 equiv), which
produced the corresponding azido diol (ꢀ)-3 (48%, 99% ee) and chi-
ral epoxide (+)-8 (50%, 97% ee) with high enantiomeric purity. The
key diol intermediate (ꢀ)-3 was readily separated from epoxide
(+)-8 by simple flash column chromatographic purification over
silica gel. The enantiomeric purity of azido diol (ꢀ)-3 was deter-
mined by chiral HPLC analysis as 99% ee.
4. Experimental section
4.1. General
Solvents were purified and dried by standard procedures before
use. Optical rotations were measured using sodium D line on a
JASCO-181 digital polarimeter. The 1H NMR and 13C NMR spectra
were recorded on Bruker AC-200 spectrometer unless mentioned
otherwise. Elemental analysis was carried out on a Carlo Erba
CHNS-O analyzer. IR spectra were recorded on a Perkin-Elmer
model 683 B and absorption is expressed in cmꢀ1. Purification
was done using column chromatography (230–400 mesh).
Scheme 3 presents the remaining steps in order to obtain the
target molecule 1 from chiral diol intermediate 3. Firstly, the pri-
mary hydroxyl group was regioselectively protected as its silyl
ether to afford 9 in 92% yield. Protection of the secondary hydroxyl
group as its benzyl ether followed by deprotection of silyl ether
OBn
OH
OBn
iv
iii
ii
BnO
BnO
BnO
N3
10
OH
N3
OR
N3
11
3, R = H
9, R = TBS
i
OH
OBn
OBn
HO
v
BnO
OH
BnO
OTs
HO
N
H
N3
OH
N3
OH
1
2, R = H (dr = 14:1)
Scheme 3. Reagents and conditions: (i) TBSCl (1.1 equiv), imidazole (1.5 equiv), CH2Cl2, 25 °C, 92%; (ii) (a) BnBr (1.1 equiv), NaH (1.5 equiv), DMF, 0 °C to 25 °C; (b) CSA
(10 mol %), CH2Cl2:MeOH (1:1), 84% (over 2 steps); (iii) (a) PCC, CH2Cl2, 4 Å MS, 25 °C; (b) CH3PPh3I (1.1 equiv), n-BuLi (1.5 equiv), THF, 0–25 °C, 81% (over 2 steps) (iv) AD-
mix-a,
tBuOH:H2O (1:1), 25 °C, 6 h, 88%; (v) (a) Bu2SnO (2 equiv), p-TsCl (1.1 equiv), Et3N (2 equiv), DMAP (10 mol %), CH2Cl2, 0–25 °C; (b)10% Pd/C, 6 M HCl, MeOH, H2
(1 atm), 25 °C, 12 h, 90%.
Please cite this article in press as: Reddi, R. N.; et al. Tetrahedron: Asymmetry (2016), http://dx.doi.org/10.1016/j.tetasy.2016.10.013

R. N. Reddi et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
3
4.2. 2-Azido-3-bromobutane-1,4-diol 6
9.13 mmol), H2O (0.08 mL, 4.47 mmol) was added at 0 °C. The reac-
tion was then allowed to stir for 12 h at 25 °C. After completion of
the reaction (monitored by TLC), the crude product was purified by
column chromatography over silica gel to give chiral azido epoxide
(+)-8, [solvent system; petroleum ether:ethyl acetate (95:5)] and
chiral azido diol (ꢀ)-3 [solvent system; petroleum ether:ethyl
acetate (6:4)] in pure form.
A mixture of cis-2-butene-1,4-diol 5 (10 g, 113.63 mmol) and
NaN3 (14.77 g, 227.27 mmol) were taken in CH3CN/H2O
(180:60 mL) after which NBS (24.13 g, 136.36 mmol) was added
slowly via solid addition funnel with stirring at 0 °C while the pro-
gress of the reaction was monitored by TLC. After completion of the
reaction (monitored by TLC), CH3CN was evaporated, the reaction
mixture was diluted with EtOAc (80 mL), and the aq. layer was
extracted with EtOAc (3 ꢂ 30 mL). The combined organic layers
were dried over anhydrous Na2SO4 and concentrated under
reduced pressure to give a crude product, which was purified by
column chromatography using petroleum ether: ethyl acetate
(50:50) to afford pure product 6 as a colorless solid in 89% yield.
Yield: 89% (21.1 g) colorless solid, mp: 52 °C; IR: (neat, cmꢀ1): mmax
1035, 1267, 2104, 3361; 1H NMR (200 MHz, CDCl3 + DMSO-d6): d
3.74–3.95 (m, 5H), 4.12–4.20 (m, 1H), 4.43–4.54 (m, 2H); 13C
NMR (50 MHz, CDCl3 + DMSO-d6): d 54.3, 62.4, 63.3, 63.4; Anal.
Calcd for C4H8BrN3O2 requires C, 22.87; H, 3.84; N, 20.01; found
C, 22.80; H, 3.82; N, 20.06.
4.6. (2R,3R)-3-Azido-4-(benzyloxy)butane-1,2-diol (ꢀ)-3
Yield: 50% (1.08 g), colorless oil; [
a
]
25 = ꢀ37.8 (c 1, CHCl3); IR
D
(CHCl3, cmꢀ1): mmax 1271, 1453, 2099, 2870, 2929, 3384; 1H NMR
(200 MHz, CDCl3): d 1.60 (br s, 1H), 2.81 (br s, 1H), 3.59–3.83 (m,
6H), 4.59 (s, 2H), 7.34 (m, 5H); 13C NMR (50 MHz, CDCl3): d 62.0,
63.4, 69.9, 71.4, 73.5, 127.7, 127.9, 128.5, 137.3; Anal. Calcd for
C11H15N3O3 requires C, 55.69; H, 6.37; N, 17.71; found C, 55.70;
H, 6.48; N, 17.65; enantiomeric purity: 99% ee determined from
HPLC analysis (Chiral OD-H column, n-hexane/ 2-propanol
(90:10), 0.5 mL/min, 254 nm) Retention time: t major = 21.25 and
tminor = 24.82 min.
4.3. rac-2-Azido-2-(oxiran-2-yl)ethanol 7
4.7. (S)-2-((S)-1-Azido-2-(benzyloxy)ethyl)oxirane (+)-8
Azido bromide 6 (8 g, 38.27 mmol) was taken in THF (50 mL)
and NaOH powder (1.83 g, 45.75 mmol) was added slowly with
stirring at 0 °C for 2 h. After completion of the reaction (monitored
by TLC), the reaction mixture was diluted with EtOAc (60 mL) and
water (50 mL). The organic layer was further separated and the aq.
layer extracted with EtOAc (3 ꢂ 20 mL). The combined organic
extracts were washed with brine, dried over anhydrous Na2SO4
and concentrated under reduced pressure to give a crude product,
which was then purified by column chromatography using petro-
leum ether:ethyl acetate (8:2) as eluents to afford 7 in 84% yield
as a colorless oil. Yield: 84% (4.14 g) colorless oil; IR (CHCl3,
cmꢀ1): mmax 1264, 2104, 2931, 3383; 1H NMR (200 MHz, CDCl3):
d 2.18 (br s, 1H), 2.80–2.90 (m, 2H), 3.09–3.15 (m, 1H), 3.44–3.52
(m, 1H), 3.65–3.90 (m, 2H); 13C NMR (50 MHz, CDCl3): d 44.2,
49.9, 61.8, 62.9; Anal. Calcd for C4H7N3O2 requires C, 37.21; H,
5.46; N, 32.54; found C, 37.28; H, 5.56; N, 32.46.
Yield: 48% (0.96 g), colorless oil; [a]
25 = +29.3 (c 1, CHCl3); IR
D
(CHCl3, cmꢀ1): mmax 1264, 1453, 2102, 2864; 1H NMR (200 MHz,
CDCl3): d 2.74–2.83 (m, 2H), 3.05–3.11 (m, 1H), 3.44–3.52 (m,
1H), 3.57–3.73 (m, 2H), 4.59 (s, 2H), 7.28–7.39 (m, 5H); 13C NMR
(50 MHz, CDCl3): d 45.0, 50.5, 61.7, 69.9, 73.4, 127.6, 127.8,
128.4, 137.4; Anal. Calcd for C11H13N3O2 requires C, 60.26; H,
5.98; N, 19.17; found C, 60.24; H, 5.90; N, 19.20; enantiomeric pur-
ity: 99% ee determined from HPLC analysis (Chiral OD-H column,
n-hexane/2-propanol (95:5), 0.5 mL/min, 254 nm) Retention time:
tminor = 13.51 and tmajor = 16.20 min.
4.8. (2R,3R)-3-Azido-4-(benzyloxy)-1-((tert-butyldimethylsilyl)
oxy)butan-2-ol 9
To a stirred solution of azido diol 3 (2 g, 8.43 mmol) in CH2Cl2
(25 mL) were added TBSCl (1.52 g, 10.11 mmol) and imidazole
(1.15 g, 16.86 mmol) at 25 °C. The resulting solution was stirred
at same temperature for 3 h, then quenched with water and
extracted with CH2Cl2 (3 ꢂ 30 mL). The combined organic extracts
were washed with brine, dried over anhydrous Na2SO4 and con-
centrated under reduced pressure to give the crude product. Col-
umn chromatographic purification with silica gel using
petroleum ether:ethyl acetate (95:5) as the eluent gave pure
mono-TBS ether 9 as a colorless oil in 92% yield (2.72 g). Yield:
4.4. rac-2-(1-Azido-2-(benzyloxy)ethyl)oxirane 4
To a suspension of sodium hydride (1.1 g, 42.63 mmol) in DMF
(50 mL), a solution of epoxy alcohol 7 (5 g, 38.75 mmol) in DMF
(10 mL) was added. To this, BnBr (7.25 g, 42.63 mmol) was added
slowly and the stirring was continued for 2 h at -40 °C. After com-
pletion of the reaction (monitored by TLC), it was quenched with
saturated NH4Cl and extracted with EtOAc (3 ꢂ 50 mL). The com-
bined organic layer was separated and dried over anhydrous
Na2SO4 and concentrated under reduced pressure. The crude pro-
duct was purified by column chromatography over silica gel using
petroleum ether:ethyl acetate (95:5) to give product 4 in 92% yield.
92%, colorless oil; [a]
25 = +33.3 (c 1, CHCl3); IR (CHCl3, cmꢀ1): mmax
D
1464, 1593, 2102, 2864, 3414; 1H NMR (200 MHz, CDCl3): d 0.00 (d,
J = 1.8 Hz, 6H), 0.81 (s, 9H), 2.47 (d, J = 6.1 Hz, 1H), 3.40–3.69 (m,
5H), 3.71–3.83 (m, 1H), 4.50 (s, 2H), 7.24 (s, 5H); 13C NMR
(125 MHz, CDCl3): ꢀ5.4, 25.7, 25.9, 62.0, 63.7, 70.5, 70.8, 73.5,
127.6, 127.8, 128.5, 137.7; HRMS (ESIMS): calcd for C17H29SiN3-
O3+Na]+ 374.1876, found 374.1875.
Yield: 92% (7.81 g), colorless oil; IR (CHCl3, cmꢀ1):
mmax 1264, 1453,
2102, 2864; 1H NMR (200 MHz, CDCl3): d 2.74–2.83 (m, 2H), 3.05–
3.11 (m, 1H), 3.44–3.52 (m, 1H), 3.57–3.73 (m, 2H), 4.59 (s, 2H),
7.28–7.39 (m, 5H); 13C NMR (50 MHz, CDCl3): d 45.0, 50.5, 61.7,
69.9, 73.5, 127.6, 127.8, 128.4, 137.4; Anal. Calcd for C11H13N3O2
requires C, 60.26; H, 5.98; N, 19.17; found C, 60.24; H, 5.90; N, 19.20.
4.9. (2R,3R0)-3-Azido-2,4-bis(benzyloxy)butan-1-ol 10
To a stirred solution of alcohol 9 (2.5 g, 7.11 mmol) in DMF
(40 mL) was added sodium hydride (0.256 g, 10.66 mmol) at 0 °C
followed by the addition of benzyl bromide (1.33 g, 7.82 mmol).
After stirring for 1 h, the reaction mixture was quenched by the
addition of ice. The aqueous layer was extracted with EtOAc
(3 ꢂ 50 mL) and the combined organic layers were washed with
water, brine, and dried over anhyd Na2SO4, after which the solvent
was distilled off under reduced pressure to give the crude benzyl
ether. The crude product was dissolved in MeOH (30 mL) after
4.5. 3-Azido-4-(benzyloxy)butane-1,2-diol (ꢀ)-3
To a solution of (S,S)-Co-salen (0.027 g, 0.5 mol %) in toluene
(2 mL), AcOH (0.02 g, 0.36 mmol) was added. The solution was
then allowed to stir at 25 °C in open air for 30 min. During this
time, the color changed from orange-red to a dark brown; it was
then dried under vacuum. To this racemic azido epoxide (2 g,
Please cite this article in press as: Reddi, R. N.; et al. Tetrahedron: Asymmetry (2016), http://dx.doi.org/10.1016/j.tetasy.2016.10.013

4
R. N. Reddi et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
which camphor sulfonic acid (10 mol %, 0.165 mg) was added and
the mixture stirred at room temperature. After completion of the
reaction as monitored by TLC, MeOH was evaporated and water
(30 mL) was added. The organic layer was separated and the aque-
ous layer was extracted with EtOAc (3 ꢂ 50 mL). The combined
organic layers were washed with water, brine, and dried over
anhyd Na2SO4, after which the solvent was distilled off under
reduced pressure to give the crude product, which was purified
by column chromatography over silica gel using EtOAc/Pet. ether
as eluent (5:95) to give pure alcohol 10 in 1.95 g (84%). Yield:
NMR (200 MHz, CDCl3): d 1.98 (s, 1H), 2.83 (br s, 1H), 3.73–3.94
(m, 7H), 4.58–4.73 (m, 4H), 7.35 (m, 10H); 13C NMR (50 MHz,
CDCl3): d 62.0, 63.3, 69.4, 71.3, 73.4, 73.9, 79.2, 127.7, 127.9,
128.0, 128.2, 128.5, 137.4, 137.5; HRMS (ESIMS): calcd for C19H23
-
N3O4+Na]+ 380.1581, found 380.1580.
4.12. 1,4-Dideoxy-1,4-imido-D-arabinitol 1
To a stirred solution of diol 2 (0.3 g, 0.58 mmol) in CH2Cl2 were
added Bu2SnO (291 mg, 1.174 mmol), p-TsCl (122 mg, 0.64 mmol),
Et3N (1.174 mmol, 0.16 ml) and DMAP (10 mol %, 7.1 mg) at 0 °C.
The reaction mixture was allowed to stir at 25 °C for 3 h. After
completion, the reaction mixture was quenched with water and
extracted with CH2Cl2. The combined organic layers were dried
over Na2SO4. After concentration, to the crude mixture in MeOH
(20 mL) was added a solution of aqueous 6 M HCl (4 mL) and 10%
Pd/C (0.1 g, 0.1 mmol). The reaction mixture was allowed to stir
under an H2 atmosphere (1 atm) for 36 h. The resulting mixture
was filtered through a Celite pad and concentrated in vacuo. The
residue was purified by column chromatography to afford 90 mg
84%, colorless oil; [a]
25 = +26.3 (c 1, CHCl3); IR (CHCl3, cmꢀ1): mmax
D
745, 1364, 1553, 2100, 2864, 3342; 1H NMR (200 MHz, CDCl3): d
2.00 (br s, 2H), 3.54–3.81 (m, 7H), 4.56 (d, J = 6.1 Hz, 4H), 7.32 (s,
10H); 13C NMR (50 MHz, CDCl3): d 60.6, 60.8, 69.2, 72.2, 73.1,
78.2, 127.4, 127.5, 127.6, 128.2, 137.4, 137.4; HRMS (ESIMS): calcd
for C18H21N3O3+Na]+ 350.1481, found 350.1489.
4.10. ((((2R,3S)-2-Azidopent-4-ene-1,3-diyl)bis(oxy))bis(methyl-
ene))dibenzene 11
To a stirred solution of alcohol 10 (1.0 g, 3.05 mmol) in CH2Cl2
(20 mL) was added PCC (0.78 g, 3.66 mmol) at 25 °C. The reaction
mixture was allowed to stir at the same temperature for 3 h. After
completion (as monitored by TLC), the reaction mixture was fil-
tered and water (20 mL) was added. The aqueous layer was
extracted with CH2Cl2 (3 ꢂ 30 mL). The combined organic layers
were washed with water, brine and dried over anhyd Na2SO4, after
which the solvent was distilled off under reduced pressure to give
the crude product. In a separate round bottomed flask, one carbon
Wittig salt (ICH3PPh3) (1.47 g, 3.66 mmol) in THF was added n-BuLi
(390 mg, 6.1 mmol, 3.85 mL of 1.6 M solution in THF) at 0 °C, which
gave a yellow solution of the Wittig ylide. The above crude alde-
hyde was added to this reaction mixture and allowed to stir at
25 °C for 8 h. After completion of the reaction, as monitored by
TLC, the reaction mixture was quenched with ice followed by the
addition of water. The THF layer was concentrated and the resul-
tant aqueous layer was extracted with EtOAc (3 ꢂ 40 mL). The
combined organic layers were dried over anhydrous Na2SO4, and
the solvent was distilled off under reduced pressure to give the
crude product, which was purified by flash column chromatogra-
phy over silica gel using EtOAc/Pet. ether as eluent (5:95) to give
(90%) of 1,4-dideoxy-1,4-imino-
salt, a colorless solid. Yield: 90%, colorless solid; Rf = 0.30 (CH2Cl2/
MeOH/EtOH/30%NH4OH 5:2:2:1); mp: 112–114 °C; [
25 = +39.2 (c
0.5, D2O); lit.11 25 = +40.1 (c 0.5, D2O); 1H NMR (500 MHz, D2O) d
3.03–3.09 (m, J = 11.9 Hz, 1H), 3.23–3.39 (m, 2H), 3.62–3.68 (m,
J = 11.7 Hz, 1H), 3.96–4.29 (m, 3H); 13C NMR (125 MHz, D2O): d
50.5, 60.5, 66.1, 75.6, 77.6; HRMS (ESIMS): Calcd for C5H12NO3
[M+H+] 134.0812, found 134.0814.
D-arabinitol 1 as its hydrochloride
a]
D
[a]
D
Acknowledgements
RNR, PKP and RGK thank CSIR New Delhi for the grant of finan-
cial support (Indus MAGIC project CSC 0123). Authors thank Dr.
Sanjeev Tambe, Chair and Head, Chemical Engineering and Process
Development Division for his constant encouragement.
References
1. (a) Fleet, G. W. J.; Nicholas, S. J.; Smith, P.-W.; Evans, S. V.; Fellows, L. E.; Nash,
R. J. Tetrahedron Lett. 1985, 26, 3127; (b) Fleet, G. W. J.; Smith, P. W. Tetrahedron
Lett. 1986, 42, 5685–5692; (c) Karpas, A.; Fleet, G. W. J.; Dwek, R. A.; Petursson,
S.; Namgoong, S. K.; Ramsden, N.-G.; Jacob, G. S.; Rademacher, T. W. Proc. Natl.
Acad. Sci. U.S.A. 1980, 85, 9229–9233.
2. (a) Sinnot, M. L. Chem. Rev. 1990, 90, 1171–1202; (b) Robinson, K. M.;
Rhinehart, B. L.; Ducep, J. B.; Danzin, C. Drugs Future 1992, 17, 705–720.
3. Furukawa, J.; Okuda, S.; Saito, K.; Hatanaka, S.-I. Phytochemistry 1985, 24, 593.
4. (a) Jones, D. W. C.; Nash, R. J.; Bell, E. A.; William, J. M. Tetrahedron Lett. 1985, 26,
3125; (b) Nash, R. J.; Bell, E. A.; Williams, J. M. Phytochemistry 1985, 24, 1620.
5. (a) Fleet, G. W. J.; Karpas, A.; Dwek, R. A.; Fellows, L. E.; Tyms, A. S.; Petursson,
S.; Namgoong, S. K.; Ramsden, N. G.; Smith, P. W.; Son, J. C.; Wilson, F. X.; Witty,
D. R.; Jacob, G. S.; Rademacher, T. W. FEBS Lett. 1988, 237, 128; (b) Behling, J. R.;
Campbell, A. L.; Babiak, K. A.; Ng, J. S.; Medich, J.; Farid, P.; Fleet, G. W. J.
Tetrahedron 1993, 49, 3359; (c) Asano, N.; Kizu, H.; Oseki, K.; Tomioka, E.;
Matsui, K.; Okamoto, M.; Baba, M. J. Med. Chem. 1995, 38, 2349.
alkene 11 in 0.80 g (81%). Yield: 81%, colorless oil; [
a]
25 = ꢀ22.3
D
(c 1, CHCl3); IR (CHCl3, cmꢀ1): mmax 760, 1259, 2102, 2864, 2937;
1H NMR (200 MHz, CDCl3): d 3.50–3.72 (m, 3H), 3.96 (dd, J = 7.8,
5.1 Hz, 1H), 4.33–4.68 (m, 5H), 5.27–5.47 (m, 2H), 5.71–5.96 (m,
1H), 7.21–7.44 (m, 12H): 13C NMR (50 MHz, CDCl3): d 61.4, 62.7,
70.6, 78.6, 118.6, 127.0, 127.2, 127.4, 127.5, 136.7, 136.8; HRMS
(ESIMS): calcd for C19H21N3O2+Na]+ 346.1526, found 346.1524.
4.11. (2R,3R,4R)-4-Azido-3,5-bis(benzyloxy)pentane-1,2-diol 2
6. (a) Go-Bit, D. W.; Langlois, N.; Leaem, T. Tetrahedron Lett. 1994, 35, 2869; (b)
Lombardo, M.; Licciulli, S.; Trombini, C. Tetrahedron Lett. 2003, 44, 9147; (c)
Kim, J.-Y.; Mu, Y.; Jin, X.; Park, S.-H.; Pham, V.-T.; Song, D.-K.; Lee, K.-Y.; Ham,
W.-H. Tetrahedron 2011, 67, 9426; (d) Choi, H. G.; Park, D.-S.; Lee, W. K.; Sim, T.
Tetrahedron Lett. 2013, 54, 5775.
7. (a) Ayad, T.; Génisson, Y.; Broussy, S.; Baltas, M.; Gorrichon, L. Eur. J. Org. Chem.
2003, 2903; (b) Concia, A. L.; Gomez, L.; Bujons, J.; Parella, T.; Vilaplana, C.;
ardona, P. J.; Joglar, J.; Clapes, P. Org. Biomol. Chem. 2013, 11, 2005.
8. (a) Reddy, R. S.; Chouthaiwale, P. V.; Suryavanshi, G.; Chavan, V. B.; Sudalai, A.
Chem. Commun. 2010, 5012; (b) Dattatray, A. D.; Sudalai, A. Tetrahedron Lett.
2012, 53, 3213–3215.
9. (a) Rawat, V.; Chouthaiwale, P. V.; Chavan, V. B.; Suryavanshi, G.; Sudalai, A.
Tetrahedron Lett. 2010, 51, 6565; (b) Chaithanya, K. I. N.; Reddy, R. S.;
Suryavanshi, G.; Sudalai, A. Tetrahedron Lett. 2011, 52, 438; (c) Shelke, A. M.;
Rawat, V.; Suryavanshi, G.; Sudalai, A. Tetrahedron: Asymmetry 2012, 23, 1534.
10. (a) da Cruz, F. P.; Newberry, S.; Jenkinson, S. F.; Wormald, M. R.; Butters, T. D.;
Alonzi, D. S.; Nakagawa, S.; Becq, F.; Norez, C.; Nash, R. J.; Kato, A.; Fleet, G. W. J.
Tetrahedron Lett. 2011, 52, 219–223; (b) Moreno-Vargas, A. J.; Robina, I.;
Demange, R.; Vogel, P. Helv. Chim. Acta 2003, 86, 1894–1913.
To a stirred solution of K3Fe(CN)6 (1.52 g, 4.65 mmol), K2CO3
(641 mg, 4.65 mmol), MeSO2-NH2 (441 mg, 4.65 mmol), and
(DHQ)2-PHAL (60 mg, 0.077 mmol) were added t-BuOH and water
(1:1, 50 ml). The mixture was stirred at 0 °C for 5 min, and then to
this solution was added K2OsO4ꢃ2H2O (5.74 mg, 1 mol %) immedi-
ately followed by the addition of alkene 11 (0.5 g, 1.55 mmol).
The reaction was stirred vigorously at 0 °C for 2–18 h. Ethyl acetate
was then added to the reaction mixture followed by quenching
with solid sodium sulfite. The layers were separated, and the aque-
ous layer was extracted with EtOAc. The combined organic layers
were washed with brine and then dried over Na2SO4. After concen-
tration, the crude mixture was purified by column chromatography
over silica gel using EtOAc/Pet. ether as eluent (4:6) to give diol 2 in
0.484 g (88%). Yield: 88%, colorless oil; [
a
]
D
25 = ꢀ36.3 (c 1, CHCl3); IR
11. Kim, I. S.; Zee, O. P.; Jung, Y. H. Org. Lett. 2006, 8, 4101.
(CHCl3, cmꢀ1): mmax 698, 737, 1100, 1453, 2098, 2924, 3438; 1H
Please cite this article in press as: Reddi, R. N.; et al. Tetrahedron: Asymmetry (2016), http://dx.doi.org/10.1016/j.tetasy.2016.10.013