Synthesis of (-)-galantinic acid via iterative hydrolytic kinetic resolution and tethered aminohydroxylation

Article abstract of DOI:10.1016/j.tet.2010.02.093

A new synthetic strategy for (-)-galantinic acid is reported using iterative hydrolytic kinetic resolution and tethered aminohydroxylation as the key steps.

Full text of DOI:10.1016/j.tet.2010.02.093

Tetrahedron 66 (2010) 3159–3164
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of (ꢀ)-galantinic acid via iterative hydrolytic kinetic resolution and
tethered aminohydroxylation
*
Abhishek Dubey, Shruti V. Kauloorkar, Pradeep Kumar
Division of Organic Chemistry, National Chemical Laboratory, Homi Bhabha Road, Pune 411008, Maharashtra, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 6 January 2010
Received in revised form 25 February 2010
Accepted 26 February 2010
Available online 6 March 2010
A new synthetic strategy for (ꢀ)-galantinic acid is reported using iterative hydrolytic kinetic resolution
and tethered aminohydroxylation as the key steps.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Iterative hydrolytic kinetic resolution
Tethered aminohydroxylation
1,3-Diol
1,2-Aminoalcohol
Selectivity
1. Introduction
syntheses known for galantinic acid derive the asymmetry from
chiral pool starting materials, such as serine aldehyde and mannitol
(ꢀ)-Galantinic acid 1, a nonproteinogenic amino acid, is a key
component of the peptide antibiotic galantin I 2, isolated from
a culture broth of Bacillus pulvifaciens.1 The originally proposed
tetrahydropyranoid structure 3 of galantinic acid was later shown
to be incorrect by total synthesis and was revised to 1 by Sakai and
Ohfune2 who also reported its first total synthesis3(Fig. 1). The
etc.4a–f However, synthetic approaches involving achiral substrate
as starting materials are rather scarce.4g–h
As a part of our research programme aimed at developing
enantioselective synthesis of biologically active aminoalcohols,5 we
became interested in devising a new route to (ꢀ)-galantinic acid
based on synthetic protocol developed by us for 1,3-diol6 using
OH
OH
H2N
O
O
HOOC
OH
HO
OH
NH2
1
3
H2N
O
revised structure
originally proposed
structure
CH3
NH
OH
OH
OH OH
O
CH3
O
H
N
H
N
H2N
O
O
N
N
H
H
H
N
H
NH2
N
NH2
OH
O
N
H
N
H
NH2
HO
O
Galantin I
2
Figure 1. Structures of galantinic acid 1, galantin I 2 and originally proposed structure of galantinic acid 3.
potent biological activity and unique structure with an array of
functionalities makes galantinic acid an attractive synthetic target
of considerable interest. Various methods for its synthesis have
been reported in the literature.4 Most of the enantioselective
hydrolytic kinetic resolution7 (HKR) and also by tethered amino-
hydroxylation (TA).8 The tethered aminohydroxylation has
emerged as a powerful method of preparing vicinal aminoalcohols
in a regio- and stereoselective manner. This method overcomes the
problem of low regioselectivity mainly encountered during the
asymmetric aminohydroxylation,9 a recent discovery of Sharpless
to introduce amine and alcohol functionality in a single step in
* Corresponding author. Tel.: þ91 20 25902050; fax: þ91 20 25902629.
E-mail address: pk.tripathi@ncl.res.in (P. Kumar).
0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.02.093

3160
A. Dubey et al. / Tetrahedron 66 (2010) 3159–3164
enantio- and stereoselective way. Herein, we report a new syn-
thesis of (ꢀ)-galantinic acid employing iterative hydrolytic kinetic
resolution and tethered aminohydroxylation as the key steps.
methanol furnished the carbamate 14 in 95% yield. The carbamate
14 was subjected to TA8 using tert-butyl hypochlorite as the
oxidant, potassium osmate, NaOH, diisopropylethylamine and
propanol as the solvent. However, we could isolate only 15% of the
protected aminoalcohol 15 along with starting material and
unidentified side products as major compounds. The limited life
time of N-chlorocarbamates, produced in situ by the action of NaOH
and t-BuOCl on a primary carbamate and chlorination of the alkene
unit as a competing side reaction in the TA reaction may be
responsible for lowering the yield.8e Therefore, we turned our
attention on replacement of the chlorine of the N-chlorocarbamate
by N-O–CO-R group. Accordingly, alcohol 13 was reacted with CDI
in pyridine, followed by the addition of hydroxylamine hydro-
chloride, to afford the hydroxycarbamate 16 in excellent yield. The
resulting hydroxycarbamate 16 was then treated with 2,4,6-tri-
2. Results and discussion
The synthesis of (ꢀ)-galantinic acid started from commercially
available 1,3-propanediol 4 as illustrated in Scheme 1. Thus selec-
tive mono hydroxy protection of 4 with p-methoxybenzyl chloride
in the presence of NaH gave the mono protected diol 5 in 86% yield,
which was oxidized to the corresponding aldehyde under Swern
oxidation conditions10 followed by Corey–Chaykovsky reaction11
with dimethylsulfoxonium methylide to afford the racemic
epoxide 6 in 71% yield. Epoxide 6 was subjected to Jacobsen HKR7
using (R,R)-Salen–CoIII–OAc complex as a catalyst to give the
OH
O
O
a
b
c
OH
HO
OH
PMBO
OH
PMBO
PMBO
PMBO
OTBS
6
7a
5
4
7b
OTBS
O
OH
8
g
f
e
d
PMBO
PMBO
OH
PMBO
10
anti:syn 1.2:1
9
O
OTBS O
O
OTBS
NH2
j
OTBS
O
O
OTBS
O
i
h
PMBO
OH
PMBO
PMBO
PMBO
NH
15
13
k
11
14
OH
OTBS
OH
PMBO
12
O
O
OTBS O
O
C6H2Cl3
OH
NH
OTBS O
NH
OTBS O
16
PMBO
OH
n
l
m
O
NH
OH
PMBO
PMBO
15
17
syn:anti 13:1
OTBS O
O
O
OTBS
O
OTBS O
OH
p
q
o
HOOC
PMBO
OTBS
HO
OTBS
HO
OTBS
OH
NH
NH
NH
NH2
Galantinic acid
1
O
O
18
19
20
Scheme 1. Reagents and conditions: (a) PMBCl, NaH, TBAI, 0 ꢁC, DMF, 6 h, 86%; (b) (i) Oxalyl chloride, DMSO, Et3N, ꢀ78 ꢁC, 4 h; (ii) Trimethylsufoxonium iodide, DMSO, NaH, 0 ꢁC, 5 h,
71%; (c) (R,R)–Salen–CoIII–(OAc) (0.5 mol %), distd H2O (0.60 equiv), 0 ꢁC, 24 h, (47% for 7a, 48% for 7b); (d) Vinylmagnesium bromide, CuI, THF, ꢀ40 ꢁC, 4 h, 90%; (e) TBSCl, imidazole,
DCM, 6 h, 95%; (f) mCPBA, DCM, 0 ꢁC,10 h, 88% (g) (S,S)-Salen–CoIII–(OAc)(0.5 mol %), distd H2O (0.55 equiv), THF (0.55 equiv), 0 ꢁC, 22 h, (48% for 11); (h) (CH3)3SþIꢀ, n-BuLi, ꢀ20 ꢁC, 4 h,
85%; (i) Cl3CCONCO, K2CO3, CH2Cl2:CH3OH (1.5:1), 4 h, 95%; (j) NaOH, t-BuOCl, iPr2EtN, potassium osmate, 2.5 h,15%; (k) CDI, pyridine, NH2OH.HCl, 40 ꢁC, 85%; (l) 2,4,6-trichlorobenzoyl
chloride, Et3N, 0 ꢁC, 1 h, 90%; (m) K2OsO4.2H2O, t-BuOH: H2O (3:1), 40 ml/mmol; 3 h, 75%; (n) TBSCl, imidazole, DCM, 2 h, 85%; (o) DDQ, THF: H2O (18:1), 0 ꢁC, 3 h, 93%; (p) (i) Oxalyl
chloride, DMSO, Et3N, ꢀ78 ꢁC, 1.5 h; (ii) NaClO2, DMSO, NaH2PO4, 12 h, 73% for two step; (q) (i) K2CO3, methanol, 0 ꢁC, 6 h; (ii) acidified with 2 N HCl, 55% for two steps.
enantiopure epoxide 7a in 47% yield (>98% ee), which was easily
isolated from the more polar diol 7b by column chromatography.
With enantiomerically pure epoxide in hand our next aim was to
construct the 1,3-anti-diol. Thus epoxide 7a was treated with
vinylmagnesium bromide in the presence of CuI to give the
homoallylic alcohol 8 in 90% yield.6 The hydroxyl group was
protected as TBS ether followed by epoxidation with mCPBA to give
10 in 88% yield. The epoxide was found to be a mixture of two di-
astereomers (anti/syn 1.2:1). To construct diastereomerically pure
epoxide6 by means of Jacobsen HKR, the epoxide 10 was treated
with (S,S)-Salen–CoIII–OAc complex (0.5 mol %) and water in
(0.55 equiv) in THF (0.55 equiv) to afford the epoxide 11 as a single
diastereomer (as determined from 1H and 13C NMR spectral anal-
ysis). Epoxide 11 was treated with excess of dimethylsulfonium
methylide12 (generated from trimethylsulphonium iodide and
n-BuLi) to furnish the allylic alcohol 13 in 85% yield. Alcohol 13 was
then reacted with trichloroacetyl isocyanate in CH2Cl2 to give the
corresponding isocyanate, which on treatment with aq K2CO3 and
chlorobenzoyl chloride to give 17 in 90% yield. Compound 17 was
subjected to tethered aminohydroxylation under modified and
optimized reaction conditions. Thus by increasing the dilution of
reaction from 20 ml/mmol to 40 ml/mmol and slow addition of
potassium osmate to the solution of 17 in t-BuOH/H2O, we could get
the protected aminoalcohol 15 in 75% yield with complete regio-
and very good diastereoselectivity (syn/anti 13:1, determined from
1H NMR). The diastereomeric mixture could easily be separated by
column chromatography. The key step in the TA as depicted in
Figure 2 is the intramolecular addition of the RN]Os]O fragment
across the alkene leading to syn or anti relative stereochemistry.
Between the two possible conformations A and B of tethered [3þ2]
cycloaddition, equilibrium is more shifted toward the conformation
A over B, due to steric interaction between bulky R group and
alkene in B thus leading to major syn product.
With required framework in hand our next task was to protect
the newly generated alcohol with TBS chloride to give the TBS ether
18 in 85% yield. The PMB group was removed by DDQ to afford the

A. Dubey et al. / Tetrahedron 66 (2010) 3159–3164
3161
O
mono-PMB protected alcohol 5 (11.09 g, 86%) as colorless oil;
Anal. Calcd for C11H16O3 (196.24): C, 67.32; H, 8.22%; found: C,
67.41; H, 8.19%; Rf (80% EtOAc/pet. ether) 0.51; IR (neat, cmꢀ1):
nmax 3410, 2940, 2863, 1612, 1513, 1249, 1175, 1098; 1H NMR
O
H
H
R
N
H
Os
O
H
H
O
O
O
H
O
H
N
Os
O
(500 MHz, CDCl3): d 2.22–2.27 (2H, m), 2.82 (1H, br s), 4.02 (2H, t,
O
H
R
O
J¼5.27 Hz), 4.15 (2H, t, J¼5.67 Hz), 4.20 (3H,s), 4.85 (2H, s), 7.28
(2H, d, J¼10 Hz), 7.65 (2H, d, J¼9.8 Hz); 13C NMR (125 MHz,
B
A
CDCl3):
d 32.2, 55.2, 61.5, 68.7, 72.8, 113.8 (2-carbons), 129.2 (2-
OTBS
carbons), 130.2, 159.2; MS (ESI) m/z: 219 [MþNa]þ.
R =
syn
PMBO
anti
4.1.2. 2-(2-(4-Methoxybenzyloxy)ethyl)oxirane (6). (i) Swern oxi-
dation. To a solution of oxalyl chloride (3.33 mL, 38.21 mmol) in dry
CH2Cl2 (50 mL) at ꢀ78 ꢁC was added dropwise dry DMSO (5.42 mL,
76.43 mmol) in CH2Cl2 (20 mL). After 30 min, alcohol 5 (5.0 g,
25.47 mmol) in CH2Cl2 (20 mL) was added over 10 min giving co-
pious white precipitate. After stirring for 1 h at ꢀ78 ꢁC, the reaction
mixture was brought to ꢀ60 ꢁC and Et3N (15.62 mL, 112.24 mmol)
was added slowly and stirred for 30 min allowing the reaction
mixture to warm to room temperature. The reaction mixture was
then diluted with water (100 mL) and CH2Cl2. The organic layer was
separated and washed with water and brine, dried over Na2SO4,
and passed through short pad of Celite. The filtrate was concen-
trated to give the aldehyde (4.70 g, 95%) as pale yellow oil, which
was used as such for the next step without purification.
Figure 2. Depicts the origin of steroselectivity.
alcohol 19 in 93% yield. The alcohol was oxidized to the aldehyde
under Swern oxidation conditions followed by subsequent oxida-
tion using NaClO2 to give the acid 20 in 73% yield. This was further
subjected to hydrolysis with K2CO3 in methanol to furnish the
crude aminoalcohol. Subsequent acidification by 2 N HCl produced
(ꢀ)-galantinic acid 1 in 55% yield from two steps. The physical and
spectroscopic data of 1 were in complete agreement with those
described in literature.2 The overall yield of the target compound 1
was found to be 1.52% from fifteen steps.
(ii) To
a solution of trimethylsulfoxonium iodide (7.98 g,
3. Conclusion
36.29 mmol) in dry DMSO was added NaH (0.87 g, 36.29 mmol).
After 1 h, aldehyde (4.7 g, 24.19 mmol) dissolved in THF was added
at 25 ꢁC. After stirring for 5 h ice was added to the reaction mixture
and the reaction mixture was extracted with water, brine, dried
over Na2SO4. Solvent was removed under pressure and the crude
product was purified by silica gel column chromatography using
petroleum ether/EtOAc (95:5) to get pure epoxide 6 (3.77 g, 71%) as
colorless liquid; Anal. Calcd for C12H16O3 (208.25): C, 69.21; H,
7.74%; found: C, 69.24; H, 7.70%; Rf (20% EtOAc/pet. ether) 0.72; IR
(neat, cmꢀ1): nmax 3490, 2940, 2863,1612,1513,1249,1175,1098; 1H
We have developed a new synthetic approach to (ꢀ)-galantinic
acid using iterative hydrolytic kinetic resolution and tethered
aminohydroxylation as key steps.
4. Experimental
4.1. General
All reactions were carried out under argon or nitrogen in oven-
dried glassware using standard gas-light syringes, cannulas, and
septa. Melting points are uncorrected. Solvents and reagents were
purified and dried by standard methods prior to use. Optical rota-
tions were measured at room temperature sodium D line on JASCO-
181 digital polarimeter. IR spectra were recorded on an FTIR
instrument. 1H NMR spectra were recorded at 200 MHz, 400 MHz,
and 500 MHz and are reported in parts per million (delta) down-
field relative to CDCl3 as internal standard and 13C NMR spectra
were recorded at 50 MHz, 100 MHz, and 125 MHz and are assigned
in parts per million (delta) relative to CDCl3. Column chromato-
graphy was performed on silica gel (100–200 and 230–400 mesh)
using a mixture of petroleum ether and ethyl acetate as the eluent.
Microanalytical data were obtained using a Carlo–Erba CHNS-0 EA
1108 elemental analyzer. Enantiomeric excess was determined
using chiral HPLC.
NMR (200 MHz, CDCl3): d 1.70–1.91 (2H, m), 2.53–2.57 (1H, m),
2.78–2.83 (1H, m), 3.07–3.11 (1H, m), 3.62 (2H, t, J¼6.95 Hz), 3.83
(3H, s), 4.48 (2H, s), 6.88–6.93 (2H, d, J¼8.72 Hz), 7.29–7.31 (2H, d,
J¼8.72 Hz); 13C NMR (50 MHz, CDCl3):
d 32.8, 47.0, 50.0, 55.1, 66.6,
72.6,113.7 (2-carbons),129.2 (2-carbons),130.2 159.1; MS (ESI) m/z:
231 [MþNa]þ.
4.1.3. (R)-2-(2-(4-Methoxybenzyloxy)ethyl)oxirane (7a). Racemic
epoxide (ꢃ)-6 (8.0 g, 38.41 mmol), THF (583
(S,S)-Salen–CoIII–OAc catalyst (127 mg, 0.192 mmol, 0.5 mol %) and
the solution was cooled to 0 ꢁC. Every 5 min, H2O (50
L) was added
until 414 L (0.60 equiv, 23.04 mmol) had been added; after an-
mL) were added to
m
m
other 5 min the ice bath was removed and the reaction was stirred
at room temperature for 24 h. The reaction mixture was concen-
trated and purified through silica gel column chromatography us-
ing petroleum ether/EtOAc (95:5) as eluent to furnish the epoxide
(R)-7a as a single stereoisomer as a yellow colored liquid. Contin-
ued chromatography with petroleum ether/EtOAc (6:4) provided
4.1.1. 3-(4-Methoxybenzyloxy)propan-1-ol (5). To a solution of 1,3-
propanediol 4 (5.0 g, 65.71 mmol) in dry DMF (200 mL) was
added sodium hydride (60%, 2.90 g, 72.28 mmol) at 0 ꢁC. The
reaction mixture was then stirred at room temperature for
30 min after which it was again cooled to 0 ꢁC. To this was added
slowly p-methoxybenzyl chloride (11.32 g, 10.75 mL, 72.28 mmol)
and tetra n-butylammonium iodide (2.6 g, 6.57 mmol) with fur-
ther stirring for 6 h at the same temperature. The reaction was
quenched with addition of cold water at 0 ꢁC. The two phases
were separated and the aqueous phase was extracted with EtOAc
(3ꢂ100 mL). The combined organic layers were washed with
water (3ꢂ100 mL), brine, dried over Na2SO4, and concentrated.
The residual oil was purified by silica gel column chromatogra-
phy using petroleum ether/EtOAc (6:4) as eluent to furnish the
the diol (S)-7b as a brown colored liquid as a single enantiomer.
25
(R)-7a: Yield: 3.84 g, 48%; [
a
]
ꢀ12.98 (c 1, CHCl3); HPLC: Chiracel
D
OD-H column (2-propanol/petroleum ether¼4:96, flow rate
0.5 mL/min,
l
¼220 nm). Retention time (min): 18.59 (major) and
19.4 (minor). The racemic standard was prepared in the same way
with racemic epoxide, ee>98%.
4.1.4. (S)-1-(4-Methoxybenzyloxy)hex-5-en-3-ol (8). A round bot-
tomed flask was charged with copper(I)iodide (0.274 mg,
1.44 mmol), gently heated under vacuum and slowly cooled with
a flow of argon and THF (20 mL) was added. This suspension was
cooled to ꢀ40 ꢁC, stirred and vinylmagnesium bromide (1 M in THF,
28.8 mL, 28.8 mmol) was added to it. A solution of epoxide (R)-7a

3162
A. Dubey et al. / Tetrahedron 66 (2010) 3159–3164
(3.0 g, 14.40 mmol) in THF (15 mL) was added to the above reagent
and the mixture was stirred at ꢀ40 ꢁC for 4 h. After consumption of
starting material, the reaction mixture was quenched with a satu-
rated aqueous solution of NH4Cl. The water layer was extracted
with EtOAc (3ꢂ50 mL). The combined organic layer was washed
with brine, dried over Na2SO4, and concentrated. Purification of
crude product by silica gel column chromatography using petro-
leum ether/EtOAc (9:1) as eluent afforded (S)-8 (3.06 g, 90%) as
a colorless liquid; Anal. Calcd for C14H20O3 (236.31): C, 71.16; H,
(2H, m), 1.77–1.90 (2H, m), 2.43–2.51 (1H, m), 2.74–2.82 (1H, m),
2.98–3.11 (1H, m), 3.51 (2H, t, J¼6.44 Hz), 3.81 (3H, s), 4.04–4.11
(1H, m), 4.42 (2H, Abq, J¼11.54 Hz), 6.88 (2H, d, J¼8.72 Hz), 7.26
(2H, d, J¼8.72 Hz); 13C NMR (50 MHz, CDCl3):
d
ꢀ4.9, ꢀ4.7, 18.0,
25.8 (3-carbons), 37.7, 40.6, 47.7, 49.7, 55.2, 66.3, 67.5, 72.6, 113.8 (2-
carbons), 129.3 (2-carbons), 130.5, 159.1; MS (ESI) m/z: 389
[MþNa]þ, 405[MþK]þ.
4.1.8. (3S,5R)-5-(tert-Butyldimethylsilyloxy)-7-(4-methoxybenzyloxy)-
hept-1-en-3-ol (13). To a stirred solution of dry THF was added
trimethylsulfoniumiodide (13.91 g, 68.19 mmol) at ꢀ20 ꢁC. The re-
action mixture was stirred for 20 min followed by addition of
n-BuLi (42.6 ml, 1.6 M, 68.19 mmol). After 40 min, epoxide 11 (5.0 g,
13.63 mmol) in THF was added dropwise. The reaction mixture was
stirred at ꢀ20 ꢁC for 3 h and quenched by saturated solution of
ammonium chloride. The two phases were separated and the
aqueous phase was extracted with EtOAc (3ꢂ50 mL). The combined
organic layers were washed with water (3ꢂ50 mL), brine, dried
over Na2SO4 and concentrated. The residual oil was purified by
silica gel column chromatography using petroleum ether/EtOAc
(8:2) as eluent to furnish the allylic alcohol 13 (4.41 g, 85%) as
8.53%; found: C, 71.21; H, 8.47%; Rf (30% EtOAc/pet. ether) 0.69;
25
[
a]
ꢀ5.98 (c 1.35, CHCl3); IR (neat, cmꢀ1): nmax 3386, 1640, 1603,
D
1493, 1453, 1243; 1H NMR (200 MHz, CDCl3):
d 1.74–1.80 (2H, m),
2.21–2.28 (2H, m), 2.74 (1H, br s), 3.56–3.76 (2H, m), 3.81 (3H, s),
3.84–3.93 (1H, m), 4.46 (2H, s), 5.06–5.17 (2H, m), 5.74–5.94 (1H,
m), 6.88 (2H, d, J¼8.72 Hz), 7.26 (2H, d, J¼8.72 Hz); 13C NMR
(125 MHz, CDCl3):
d 35.8, 41.9, 55.2, 68.7, 70.5, 72.9, 113.8 (2-car-
bons), 117.5, 129.3 (2-carbons), 130.0 134.9, 159.2; MS (ESI) m/z: 259
[MþNa]þ.
4.1.5. (S)-tert-Butyl(1-(4-methoxybenzyloxy)hex-5-en-3-yloxy)-
dimethylsilane (9). To
a stirred solution of alcohol 8 (5 g,
21.86 mmol) in CH2Cl2 was added imidazole (2.88 g, 42.37 mmol).
To this solution t-butyl dimethylchlorosilane (4.78 g, 31.77 mmol)
was added at 0 ꢁC and the reaction was stirred at room temperature
for 6 h. The reaction mixture was quenched with a saturated
aqueous solution of NH4Cl and extracted with CH2Cl2. The extract
was washed with brine, dried over Na2SO4, and concentrated. Pu-
rification of crude product by silica gel column chromatography
using petroleum ether/EtOAc (95:5) as eluent afforded (S)-9 (7.04 g,
95%); as a colorless liquid; Anal. Calcd for C20H34O3Si (350.57): C,
colorless oil; Anal. Calcd for C21H36O4Si (380.59): C, 66.27; H, 9.53%;
25
found: C, 66.32; H, 9.47%; Rf (30% EtOAc/pet. ether) 0.69; [a]
D
ꢀ5.25 (c 1.3, CHCl3); IR (neat, cmꢀ1): nmax 3430, 3018, 2957, 2931,
2859, 1652, 1471, 1379, 1256, 1212, 1101, 1036, 971, 869, 758; 1H
NMR (200 MHz, CDCl3): d 0.09 (3H, s), 0.11 (3H, s), 0.9 (9H, s), 1.63–
1.73 (2H, m), 1.85–1.97 (2H, m), 2.44–2.94 (1H, br s), 3.5 (2H, t,
J¼6.44 Hz), 3.81 (3H, s), 4.06–4.31 (2H, m), 4.43 (2H, Abq,
J¼11.49 Hz), 5.04–5.29 (2H, m), 5.76–5.92 (1H, m), 6.88 (2H, d,
J¼8.71 Hz), 7.25 (2H, d, J¼8.72 Hz); 13C NMR (50 MHz, CDCl3):
68.52; H, 9.78%; found: C, 68.49; H, 9.73%; Rf (10% EtOAc/pet. ether)
d
ꢀ4.7, ꢀ4.3, 17.9, 25.8 (3-carbons), 36.4, 42.4, 55.2, 68.4, 68.6, 69.6,
25
0.78; [
a
]
þ16.12 (c 1.65, CHCl3); IR (neat, cmꢀ1): nmax 1641, 1606,
72.3, 113.8, 113.9, 129.3 (2-carbons), 130.4, 140.0, 141.1, 159.2; MS
D
1491, 1462; 1H NMR (200 MHz, CDCl3):
d
0.05 (3H, s), 0.06 (3H, s),
(ESI) m/z: 403 [Mþ23]þ.
0.89 (9H, s), 1.63–1.80 (2H, m), 2.19–2.26 (2H, m), 3.51 (2H, t,
J¼6.32 Hz), 3.81 (3H, s), 3.84–3.95 (1H, m), 4.43 (2H, Abq,
J¼11.5 Hz), 4.48–5.09 (2H, m), 5.71–5.92 (1H, m), 6.89 (2H, d,
J¼8.71 Hz), 7.27 (2H, d, J¼8.72 Hz); 13C NMR (50 MHz, CDCl3):
4.1.9. (3S,5R)-5-(tert-Butyldimethylsilyloxy)-7-(4-methoxybenzyloxy)-
hept-1-en-3-yl carbamate (14). Trichloroacetyl isocyanate (0.594 g,
0.37 mL, 3.15 mmol) was added dropwise to a solution of the
alcohol 13 (1.0 g, 2.62 mmol) in dry dichloromethane 3.93 mL
(1.5 mL/mmol) at 0 ꢁC. After stirring for 2 h, or until TLC showed
no starting material present, the mixture was concentrated under
reduced pressure. The residue was dissolved in methanol 5.24 mL
(2 mL/mmol), cooled to 0 ꢁC and an aqueous potassium carbonate
solution (1.09 g, 7.86 mmol, 2 mL/mmol) was added. The cooling
bath was removed and the mixture was allowed to stir for 4 h, by
which time TLC showed complete conversion. Methanol was
evaporated under reduced pressure and the aqueous residue was
extracted with dichloromethane (25 mLꢂ3). The combined or-
ganics were washed with brine (10 mL), dried over Na2SO4, and
concentrated under reduced pressure to yield the crude carba-
mate, which was purified by flash column chromatography on
silica gel using petroleum ether/EtOAc (7:3) as eluent to give
carbamate 14 (1.05 g, 95%) as colorless oil; Anal.. Calcd for
d
ꢀ4.7, ꢀ4.4, 18.1, 25.9 (3-carbons), 36.7, 42.3, 55.2, 66.7, 68.9, 72.6,
113.7 (2-carbons), 116.9, 129.3 (2-carbons), 130.7, 134.9, 159.1; MS
(ESI) m/z: 373 [MþNa]þ.
4.1.6. tert-Butyl((R)-4-(4-methoxybenzyloxy)-1-((S)-oxiran-2-yl)bu-
tan-2-yloxy)dimethylsilane (10). To a stirred solution of olefin 9
(5 g, 14.26 mmol) in CH2Cl2 (100 mL) at 0 ꢁC was added m-CPBA
(50%) (5.41 g, 6.38 mmol). The reaction mixture was stirred at room
temperature for 10 h and quenched by saturated NaHCO3 solution,
extracted with CH2Cl2, washed with satd NaHCO3 and brine, dried
over Na2SO4, concentrated and purified by silica gel column chro-
matography using petroleum ether/EtOAc (9:1) as eluent to yield
the epoxide 10 as a colorless liquid in diastereomeric mixture (anti/
syn¼1.2:1). Yield: 4.6 g, 88%.
4.1.7. tert-Butyl((R)-4-(4-methoxybenzyloxy)-1-((S)-oxiran-2-yl)bu-
tan-2-yloxy)dimethylsilane (11). A solution of epoxide 10 (4 g,
10.92 mmol) and (S,S)-Salen–CoIII–OAc (0.036 g, 0.055 mmol) in
THF (0.4 mL) was stirred at 0 ꢁC for 5 min, and then distilled water
C22H37NO5Si (423.62): C, 62.38; H, 8.80; N, 3.31%; found: C,
25
62.32; H, 8.75; N, 3.3%; Rf (30% EtOAc/pet. ether) 0.44; [
a
]
ꢀ5.0
D
(c 1, CHCl3); IR (neat, cmꢀ1); IR (neat, cmꢀ1): nmax 3370, 1692,
1308, 1276, 1140, 974, 771, 699; 1H NMR (200 MHz, CDCl3):
d
0.04
(108
m
L, 6.01 mmol) was added. After stirring for 24 h, it was con-
(3H, s), 0.06 (3H, s), 0.88 (9H, s), 1.67–1.86 (4H, m), 3.52 (2H, t,
J¼6.69 Hz), 3.81 (3H, s), 3.87–3.98 (1H, m), 4.42 (2H, s), 4.80 (1H,
br s), 5.12–5.30 (3H, m), 5.71–5.90 (1H, m), 6.88 (2H, d, J¼8.33),
centrated and purified by silica gel column chromatography using
petroleum ether/EtOAc (9:1) as eluent to afford 11 (1.84 g, 46%) as
a yellow colored liquid, Continued chromatography with pet. ether/
EtOAc (3:2) provided the diol 12 as a brown colored liquid as
a single diastereomer. Compound 11: Anal. Calcd for C20H34O4Si
7.26 (2H, d, J¼8.72 Hz); 13C NMR (50 MHz, CDCl3):
d
ꢀ4.9, ꢀ4.6,
18.0, 25.8 (3-carbons), 37.6, 42.1, 55.2, 66.2, 66.4, 72.5, 72.6, 113.7
(2-carbons), 115.7, 129.2 (2-carbons), 130.5, 136.9, 156.3, 159; MS
(ESI) m/z: 446.63 [MþNa]þ.
(366.57): C, 52.67; H, 9.2%; found: C, 52.74; H, 9.11%; Rf (20% EtOAc/
25
pet. ether) 0.68; [
a
]
ꢀ14.0 (c 1, CHCl3); IR (neat, cmꢀ1): nmax 2960,
D
2860, 1470, 1410, 1340, 1250, 1095, 1035, 840, 780; 1H NMR
(200 MHz, CDCl3): 0.06 (3H, s), 0.08 (3H, s), 0.89 (9H, s), 1.62–1.72
4.1.10. (3S,5R)-5-(tert-Butyldimethylsilyloxy)-7-(4-methoxybenzyl-
oxy)hept-1-en-3-yl hydroxycarbamate (16). N,N-Carbodiimidazole

A. Dubey et al. / Tetrahedron 66 (2010) 3159–3164
3163
(1.70 g, 10.50 mmol) was added to the alcohol 13 (2.0 g, 5.25 mmol)
in pyridine at 40 ꢁC. Hydroxylamine hydrochloride (0.803 g,
11.56 mmol) was added after complete adduct formation between
alcohol and CDI (w4 h). The reaction was stirred for 24 h at 40 ꢁC,
quenched with 1 M HCl, partitioned and aqueous layer extracted
with diethyl ether and ethyl acetate. The combined organic layer
was washed with water and brine, dried. The solvent was
azeotropically removed with toluene. The crude product was
purified by flash column chromatography on silica gel using pe-
troleum ether/EtOAc (8:2) as eluent to give hydroxylamine 16
(1.96 g, 85%) as colorless oil; Anal.. Calcd for C22H37NO6Si (439.62):
(1H, br s), 3.46–3.64 (5H, m), 3.80 (3H, s), 4.04–4.09 (1H, m), 4.36–
4.56 (3H, m), 6.59–6.66 (1H,br s), 6.88 (d, J¼8.71 Hz, 2H), 7.25 (d,
J¼8.71 Hz, 2H); 13C NMR (125 MHz, CDCl3): ꢀ4.8, ꢀ4.5, 18.0, 25.8
(3-carbons), 37.8, 43.0, 55.2, 59.6, 63.5, 65.9, 66.1, 72.6, 75.9, 113.8
(2-carbons), 129.3 (2-carbons), 130.3, 159.1, 159.5; MS (ESI) m/z:
462 [MþNa]þ.
4.1.13. (4R,5R)-5-((R)-2-(tert-Butyldimethylsilyloxy)-4-(4-methoxy-
benzyloxy)butyl)-4-((tert-butyldimethylsilyloxy)methyl)oxazolidin-
2-one (18). To a stirred solution of alcohol 15 (0.20 g, 0.454 mmol)
in CH2Cl2 was added imidazole (46 mg, 0.682 mmol). To this solu-
tion tert-butyl dimethylchlorosilane (102 mg, 0.682 mmol) was
added at 0 ꢁC and the reaction was stirred at room temperature for
6 h. The reaction mixture was quenched with a saturated aqueous
solution of NH4Cl and extracted with CH2Cl2. The extract was
washed with brine, dried (Na2SO4), concentrated, and purified us-
ing silica gel chromatography of crude product using EtOAc/
petroleum ether (2:8) as eluent to give the protected amino-
hydroxylated product 21 (0.214 g, 85%) as a thick colorless liquid;
Anal. Calcd for C28H51NO6Si2 (553.38): C, 60.72; H, 9.28; N, 2.53%;
C, 60.11; H, 8.48; N, 3.19%; found: C, 60.17; H, 8.56; N, 3.2%; Rf (40%
25
EtOAc/pet. ether) 0.48; [
a]
ꢀ11.40 (c 1, CHCl3); IR (neat, cmꢀ1):
D
nmax 3253, 1700, 1516, 1306, 1256, 1138, 971, 771, 694; 1H NMR
(200 MHz, CDCl3): d 0.03 (3H, s), 0.05 (3H, s), 0.88 (9H, s), 1.71–1.88
(4H, m), 3.52 (2H, t, J¼6.31 Hz), 3.81 (3H, s), 3.85–3.97 (1H, m), 4.41
(2H, ABq, J¼11.49 Hz), 5.14–5.33 (3H, m), 5.75–5.86 (1H, m), 6.88
(2H, d, J¼8.69 Hz), 7.25 (2H, d, J¼8.69 Hz), 7.35 (1H, br s,); 13C NMR
(50 MHz, CDCl3):
d
ꢀ4.6, ꢀ4.5, 18.0, 25.8 (3-carbons), 36.6, 41.9,
55.2, 66.3, 66.4, 72.6, 73.8, 113.7 (2-carbons), 117.0, 129.5 (2-car-
bons), 130.2, 136.2, 158.4, 159.1; MS (ESI) m/z: 462 [MþNa]þ,
478 [MþK]þ.
found: C, 60.67; H, 9.35; N, 2.47%; Rf (30% EtOAc/pet. ether) 0.50;
25
[a
]
ꢀ33.33 (c 1, CHCl3); IR (neat, cmꢀ1): nmax 3289, 2900, 1690,
D
1101, 1044, 971, 869, 769; 1H NMR (500 MHz, CDCl3):
d 0.06–0.07
4.1.11. (3S,5R)-5-(tert-Butyldimethylsilyloxy)-7-(4-methoxybenzyl-
oxy)hept-1-en-3-yl-2,4,6-trichlorobenzoyloxycarb-amate (17). To an
ice-cold solution of hydroxycarbamate 16 (1.0 g, 2.27 mmol) in
Et2O (4:1; 5 ml/mmol) was added Et3N (0.348 mL, 2.50 mmol),
before the addition of the 2,4,6-trichlorobenzoyl chloride
(0.355 mL, 2.27 mmol) in small portions. The reaction was
quenched with HCl (1 M aq soln, 25 mL) and the aqueous layer
was extracted with Et2O (3ꢂ20 ml). The combined organic layers
were washed sequentially with water (30 ml), NaHCO3 (aq satd
soln, 30 ml) and brine (30 ml), dried (NaSO4), filtered, and
concentrated in vacuo. The crude product was purified by flash
column chromatography using petroleum ether/ethyl acetate
(97:3) as eluent to give O-trichlorobenzoyl substituted hydroxyl-
amine 17 (1.32 g, 90%) as pale yellow oil; Anal. Calcd for
(12H, m), 0.87–0.88 (18H, m), 1.59–1.95 (4H, m), 3.42–3.59 (5H, m),
3.81 (3H, s), 4.02–4.14 (1H, m), 4.4 (2H, ABq, J¼11.5 Hz), 4.46–4.45
(1H, m), 5.85 (1H, br s) 6.88 (2H, d, J¼8.69 Hz), 7.25 (2H, d,
J¼8.69 Hz); 13C NMR (125 MHz, CDCl3): ꢀ5.6 (2-carbons), ꢀ4.8,
ꢀ4.5, 18.0, 18.1, 25.7 (3-carbons), 25.8 (3-carbons), 37.9, 43.2, 55.2,
59.2, 64.4, 65.9, 66., 72.6, 76.2, 113.7 (2-carbons), 129.2 (2-carbons),
130.4, 159.1, 159.3; MS (ESI) m/z: 576 [MþNa]þ.
4.1.14. (4R,5R)-5-((R)-2-(tert-Butyldimethylsilyloxy)-4-hydroxybutyl)-
4-((tert-butyldimethylsilyloxy)methyl)oxazolidin-2-one (19). To a stir-
ring solution of PMB ether 18 (200 mg, 0.374 mmol) in CH2Cl2/
H2O (20:1) was added DDQ (170 mg, 0.749 mmol). The resulting
mixture was stirred for 3 h at 0 ꢁC. The mixture was poured into
saturated aqueous NaHCO3 and further diluted with CH2Cl2. The
layers were separated and the aqueous layer was extracted with
CH2Cl2 (2ꢂ10 mL). The combined organic layers were dried
(Na2SO4), filtered, and concentrated. The solvents were removed
under reduced pressure to give the crude product mixture as
yellow oil. Silica gel column chromatography of the crude prod-
uct using petroleum ether/EtOAc (1:1) as eluent gave 19 (0.145 g,
93%) as a colorless solid; Anal. Calcd for C20H43NO5Si2 (433.73): C,
C29H38Cl3NO7Si (647.06): C, 53.83; H, 5.92; N, 2.16%; found: C,
25
53.56; H, 6.21; N, 2.26%; Rf (10% EtOAc/pet. ether) 0.64; [
a
]
ꢀ3.19
D
(c 1.2, CHCl3); IR (neat, cmꢀ1): nmax 3425, 2965, 1760, 1740, 1652,
1471, 1101, 1036, 971, 869, 758; 1H NMR (200 MHz, CDCl3):
d
0.04
(3H, s), 0.05 (3H, s), 0.88 (9H, s), 1.66–1.87 (4H, m), 3.52 (2H, t,
J¼6.57 Hz), 3.80 (3H, s), 3.87–4.02 (1H, m), 4.41 (2H, ABq,
J¼11.89 Hz), 5.14–5.45 (3H, m), 5.72–5.88 (1H, m), 6.87 (2H, d,
J¼8.46 Hz), 7.25 (2H, d, J¼8.46 Hz), 7.38–7.40 (2H, m), 8.4 (1H, br
55.38; H, 9.99; N, 3.23%; found: C, 55.32; H, 10.02; N, 3.2%; Rf
25
s); 13C NMR (50 MHz, CDCl3):
d
ꢀ4.9, ꢀ4.4, 17.9, 25.8 (3-carbons),
(60% EtOAc/pet. ether) 0.40; mp: 63 ꢁC; [
a
]
ꢀ30.18 (c 1, CHCl3);
D
37.5, 42.0, 55.2, 66.0, 66.2, 72.5, 75.3,113.7 (2-carbons), 117.3, 128.2
(2-carbons), 129.1 (2-carbons), 130.4, 133.6, 135.5, 135.8, 137.6,
155.1, 159.0, 163; MS (ESI) m/z: 670 [MþNa]þ.
IR (neat, cmꢀ1): nmax 3251, 2929, 1688, 1451, 1101; 1H NMR
(400 MHz, CDCl3): 0.05 (6H, s), 0.11 (3H, s), 0.12 (3H, s), 0.88–
d
0.89 (18H, m), 1.66–1.72 (1H, m), 1.77–1.83 (1H, m), 1.85–1.92
(2H, m), 2.27 (1H, br s), 3.47–3.50 (1H, m), 3.59–3.60 (2H, m),
3.70–3.74 (1H, m), 3.79–3.84 (1H, m), 4.15–4.20 (1H, m), 4.50–
4.54 (1H, m), 6.14 (1H, br s); 13C NMR (100 MHz, CDCl3): ꢀ5.6 (2-
carbons), ꢀ4.9, ꢀ4.5, 17.9, 18.1, 25.7 (3-carbons), 25.8 (2-carbons),
39.2, 42.6, 59.2, 59.3, 64.3, 67.1, 76.2, 159.3; MS (ESI) m/z: 456
[MþNa]þ.
4.1.12. (4R,5R)-5-((R)-2-(tert-Butyldimethylsilyloxy)-4-(4-methoxy-
benzyloxy)butyl)-4-(hydroxymethyl)oxazolidin-2-one (15). To a so-
lution of O-trichlorobenzoyl substituted hydroxycarbamate 17
(0.50 g, 0.772 mmol) in tert-butanol and water 30 mL (3:1, 40 mL/
mmol) was added dropwise a solution of potassium osmate
dihydrate (5 mg, 0.015 mmol, 2 mol %) in water (5 mL). The re-
action was quenched by addition of sodium sulphite (200 mg/
mmol) and the solvent azeotropically removed with toluene. The
crude product was purified by flash column chromatography on
silica gel using petroleum ether/EtOAc (6:4) as eluent to afford the
aminohydroxylated product 15 (0.25 g, 75%) as colorless syrupy
oil; Anal. Calcd for C22H37NO6Si (439.62): C, 60.11; H, 8.48; N,
4.1.15. (S)-3-(tert-Butyldimethylsilyloxy)-4-((4R,5R)-4-((tert-butyldi-
methylsilyloxy)methyl)-2-oxooxazolidin-5-yl)butanoic acid (20). A so-
lution of oxalyl chloride (0.087 g, 0.060 mL, 0.691 mmol) in dry
CH2Cl2 (10 mL) at ꢀ78 ꢁC was added dropwise dry DMSO (0.108 g,
0.098 mL, 1.38 mmol) in CH2Cl2 (2 mL). After 30 min, alcohol 19
(200 mg, 0.461 mmol) in CH2Cl2 (3 mL) was added over 10 min
giving a copious white precipitate. After stirring for 1 h at ꢀ78 ꢁC
the reaction mixture was brought to ꢀ60 ꢁC and Et3N (0.205 g,
0.282 mL, 2.02 mmol) was added slowly and stirred for 30 min
allowing the reaction mixture to warm to room temperature. The
3.19%; found: C, 60.18; H, 8.41; N, 3.11%; Rf (60% EtOAc/pet. ether)
25
0.44; [
a
]
ꢀ27.33 (c 1.3, CHCl3); IR (neat, cmꢀ1): nmax 3386, 2930,
D
1698, 1490, 1435, 1285, 1072, 818, 768; 1H NMR (500 MHz, CDCl3):
d
0.07 (3H, s), 0.08 (3H, s), 0.87 (9H, s), 1.64–1.90 (4H, m), 3.13–3.34

3164
A. Dubey et al. / Tetrahedron 66 (2010) 3159–3164
reaction mixture was poured into water (10 mL) and the organic
layer was separated. The aqueous layer was extracted with CH2Cl2
(2ꢂ15 mL) and combined organic layers were washed with water
(3ꢂ10 mL), brine (20 mL), dried (Na2SO4) and passed through short
pad of silica gel. The filtrate was concentrated to give the aldehyde
(180 mg) as pale yellow syrup, which was used as such for the next
step without further purification.
(1H dt, J¼7.0, 12.25 Hz), 3.61 (1H, q, J¼8.32, 14.91 Hz), 3.91–4.21
(3H, m); MS (ESI) m/z: 194 [MþH]þ.
Acknowledgements
A.D. thanks CSIR, New Delhi for the award of Senior Research
Fellowship. We thank Dr. Ganesh Pandey, Head, organic division,
NCL for his support and encouragement.
A solution of 79% NaClO2 (56 mg, 0.625 mmol) in 1.0 mL of water
was added dropwise a stirred solution of above crude aldehyde
(180 mg, 0.416 mmol) in 0.5 mL of DMSO and NaH2PO4 (37 mg,
0.312 mmol) in 1.0 mL of water over a period of 5 min at room
temperature. The mixture was left overnight at room temperature,
then 5% aqueous solution of NaHCO3 was added. The aqueous phase
was extracted three times with CH2Cl2 and washed with brine,
dried (Na2SO4), and concentrated. Silica gel column chromatogra-
phy of the crude product using petroleum ether/EtOAc (2:8) as
eluent gave the acid 20 (0.150 g, 73%) as a yellowish solid; Anal.
Calcd for C20H41NO6Si2 (439.62): C, 53.65; H, 9.23; N, 3.13%; found:
References and notes
1. Shoji, J.; Sakajaki, R.; Koizumi, K.; Matsurra, S. J. J. Antibiot. 1975, 28, 122–125.
2. Sakai, N.; Ohfune, Y. Tetrahedron Lett. 1990, 31, 4151–4154.
3. Sakai, N.; Ohfune, Y. J. Am. Chem. Soc. 1992, 114, 998–1010.
4. (a) Ikota, N. Heterocycles 1991, 32, 521–528; (b) Kumar, J. S. R.; Datta, A. Tet-
rahedron Lett. 1999, 40, 1381–1384; (c) Kiyooka, S.; Goh, K.; Nakamura, Y.;
Takesue, H.; Hena, M. A. Tetrahedron Lett. 2000, 41, 6599–6603; (d) Moreau, X.;
Campagne, J. Tetrahedron Lett. 2001, 42, 4467–4469; (e) Bethuel, Y.; Gademann,
K. Synlett 2006, 1580–1582; (f) Nagaiah, K.; Sreenu, D.; Purnima, K. V.; Rao, R. S.;
Yadav, J. S. Synlett 2009, 1386–1392; (g) Raghavan, S.; Ramakrishna Reddy, S.
J. Org. Chem. 2003, 68, 5754–5757; (h) Pandey, S. K.; Kandula, S. R.; Kumar, P.
Tetrahedron Lett. 2004, 45, 5877–5879.
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S. V.; Kumar, P. Tetrahedron Lett. 2003, 44, 1957–1958; (c) Kondekar, N. B.; Subba
Rao, K. V.; Kumar, P. Tetrahedron Lett. 2004, 45, 5477–5479; (d) Kumar, P.; Bodas,
M. S. J. Org. Chem. 2005, 70, 360–363; (e) Pandey, S. K.; Pandey, M.; Kumar, P.
Tetrahedron Lett. 2008, 49, 3297–3299; (f) Dubey, A.; Kumar, P. Tetrahedron Lett.
2009, 50, 3425–3427 and references cited therein.
6. Kumar, P.; Gupta, P.; Naidu, S. V. Chem.dEur. J. 2006, 12, 1397–1402.
7. (a) Tokunaga, M.; Larrow, J. F.; Kakiuchi, F.; Jacobsen, E. N. Science 1997, 277,
936–938; (b) Schaus, S. E.; Brandes, B. D.; Larrow, J. F.; Tokunaga, M.; Hansen, K.
B.; Gould, A. E.; Furrow, M. E.; Jacobsen, E. N. J. Am. Chem. Soc. 2002, 124, 1307–
1315; (c) For various application of HKR in synthesis of bioactive compounds,
see review: Kumar, P.; Naidu, S. V.; Gupta, P. Tetrahedron 2007, 63, 2745–2785
account (d) Kumar, P.; Gupta, P. Synlett 2009, 1367–1382.
8. (a) Donohoe, T. J.; Johnson, P. D.; Helliwell, M.; Keenan, M. Chem. Commun.
2001, 3, 2078–2079; (b) Donohoe, T. J.; Johnson, P. D.; Cowley, A.; Keenan, M.
J. Am. Chem. Soc. 2002, 124, 12934–12935; (c) Donohoe, T. J.; Johnson, P. D.; Pye,
R. J. Org. Biomol. Chem. 2003, 1, 2025–2028; (d) Donohoe, T. J.; Johnson, P. D.;
Pye, R. J.; Keenam, M. Org. Lett. 2004, 6, 2583–2585; (e) Donohoe, T. J.; Carole, J.
R.; William, G.; Johannes, K.; Emile, R. Org. Lett. 2007, 7, 1725–1728.
9. (a) Li, G.; Chang, H. T.; Sharpless, K. B. Angew. Chem., Int. Ed. 1996, 35, 451–454;
(b) Brien, P. O. Angew. Chem., Int. Ed.1999, 38, 326–329 and referencescited therein.
10. For reviews on the Swern oxidation, see: (a) Tidwell, T. T. Synthesis 1990, 857–
870; (b) Tidwell, T. T. Org. React. 1990, 39, 297–572.
C, 53.56; H, 9.2; N, 3.18%; Rf (90% EtOAc/pet. ether) 0.37; mp: 68 ꢁC;
25
[
a]
ꢀ13.45 (c 0.5, CHCl3); IR (neat, cmꢀ1): nmax 3400, 2957, 1730,
D
1652; NMR (200 MHz, CDCl3):
d 0.06–0.13 (12H, m), 0.88 (18H, s),
1.79–1.96 (2H, m), 2.55–2.65 (2H, m), 3.47–3.55 (1H, m), 3.60–3.62
(2H, m), 4.36–4.52 (1H, m), 4.54–4.61 (1H, m), 6.09 (1H, br s), 9.82
(1H, br s) ppm; 13C NMR (100 MHz, CDCl3): ꢀ5.3 (2-carbons), ꢀ4.6,
ꢀ4.3, 18.1, 18.3, 26 (6-carbons), 39.5, 45.8, 59.4, 64.6, 67.3, 76.5,
159.6, 178.5.
4.1.16. (3S,5S,6S)-6-Amino-3,5,7-trihydroxyheptanoic acid (ꢀ)-gal-
antinic acid (1). To a stirred solution of TA product 20 (100 mg,
0.223 mmol) in methanol (3 mL) was added potassium carbonate
(92 mg, 0.67 mmol) and the reaction mixture was stirred until
completion of the starting material (almost 6 h) and methanol was
removed in vacuo. Water was added to the crude product and
extracted with ethyl acetate (3ꢂ3 mL) and dried over sodium
sulfate and concentrated to near dryness, which was subsequently
treated with 2 N HCl to afford crude crystals of 1. These were
recrystallized from H2O/MeOH to give pure (ꢀ)-galantinic acid 1
25
(23 mg, 55%); mp: 128 ꢁC (lit.3 125 ꢀ130 ꢁC); [
a]
ꢀ29.7 (c, 0.5,
D
11. Corey, E. J.; Chaykovsky, M. J. Am. Chem. Soc. 1965, 87, 1353–1364.
12. Alcaraz, L.; Harnett, J. J.; Mioskowski, C.; Martel, J. P.; Le Gall, T.; Shin, D.-S.;
Falck, J. R. Tetrahedron Lett. 1994, 35, 5449–5452.
25
H2O); (lit.2 [
a
]
ꢀ29.4); 1H NMR (500 MHz, CDCl3):
d
1.51–1.83 (2H,
D
m), 2.37 (1H, dd, J¼5.8, 13.65 Hz), 2.49 (1H dd, J¼6.5, 13.86 Hz), 3.13