Studies on epoxidation of enantiomerically pure 2,3-dideoxy hex-2-enitols: a convenient access to highly functionalized enantiomerically pure tetrahydrofuran derivatives

Article abstract of DOI:10.1016/j.tetasy.2006.04.022

A detailed comparative study on the epoxidation of enantiomerically pure allylic alcohols 8-14 derived from their respective glycals with Sharpless, m-CPBA and Camp's reagents was carried out in order to obtain 2,3-epoxy alcohols keeping in view the versa

Full text of DOI:10.1016/j.tetasy.2006.04.022

Tetrahedron: Asymmetry 17 (2006) 1189–1198
Studies on epoxidation of enantiomerically pure 2,3-dideoxy
hex-2-enitols: a convenient access to highly
functionalized enantiomerically pure tetrahydrofuran derivativesI
Ram Sagar, L. Vijaya Raghava Reddy and Arun K. Shaw*
Division of Medicinal and Process Chemistry, Central Drug Research Institute (CDRI), Lucknow 226 001, India
Received 21 February 2006; revised 19 April 2006; accepted 21 April 2006
Abstract—A detailed comparative study on the epoxidation of enantiomerically pure allylic alcohols 8–14 derived from their respective
glycals with Sharpless, m-CPBA and Camp’s reagents was carried out in order to obtain 2,3-epoxy alcohols keeping in view the versatility
of these synthons in synthetic chemistry for the preparation of various molecules of biological importance by suitable chemical trans-
formations. During the course of this study, the Sharpless asymmetric epoxidation reaction was found to be an unprecedented alterna-
tive, due to its mild reaction conditions, for synthesizing highly functionalized enantiomerically pure tetrahydrofuran derivatives. A
detailed mechanistic pathway of their formation has also been studied.
ꢀ 2006 Elsevier Ltd. All rights reserved.
1. Introduction
Thus, considering I as a versatile synthetic building block,
we are further interested to make the best use of I to gen-
erate 2,3-epoxy alcohols III, the precursors for obtaining
secondary amino alcohols by introducing an amino group
regio- and stereoselectively at either of the two deoxy
unsaturated carbons C-2 or C-3. The 2,3-epoxy alcohol
III could be derived from enantiomerically pure allylic
alcohol II by epoxidation. Very recently the allylic alcohols
of type II have been used for the synthesis of polyhydroxy-
lated surfactants.8 A thorough literature survey on III re-
vealed that its synthesis has not yet been reported from
II (Fig. 1). However, the synthesis of 2,3-epoxy alcohols
of type III has been reported by Sharpless et al.9 In this
communication, they reported the synthesis of IIIA from
tetrose IIA to make various hexitols. The same group has
also reported in their next article,10 the usage of 2,3-epoxy
alcohols derived from tetrose IIA towards the synthesis of
saccharides and related polyhydroxylated natural prod-
ucts. The 2,3-epoxy alcohols of type III have recently been
shown by Somfai and Lindstro¨m to be an important syn-
thon for the asymmetric synthesis of 1-deoxynojirimycin
(DNJ).11
The total synthesis of functionally and stereochemically
complex naturally occurring bioactive compounds, using
highly functionalized acyclic monosaccharide derivatives
as chiral synthons, has become almost routine for many
years.1,2 These chiral building blocks are available in vari-
ous forms and can be obtained from cyclic sugar deriva-
tives by suitable chemical transformations. One of the
most proven versatile acyclic monosaccharide chiral start-
ing materials is glycal derived unsaturated deoxy sugar
aldehydes, which we call Perlin aldehydes of the general
structure I.3 These molecules have been exploited for the
synthesis of various types of biologically active com-
pounds.4 Over the last few years we have been using these
molecules as precursors for the synthesis of terminal amino
alcohols as anti-tubercular agents.5,6 Recently we have also
shown that I, with acyl protection of its hydroxyls, under-
went almost completely diastereoselective annulations with
4-hydroxy pyrone derivatives in the presence of L-proline
to generate pyrano pyrons.7
Thus the synthetic importance of 2,3-epoxy alcohol III
prompted us to develop an alternative method for its syn-
thesis, on a preparative scale, starting from easily available
Perlin aldehyde I. Recently, we have shown the applica-
tion of 2,3-epoxy alcohols of type III for the synthesis of
q CDRI Communication No. 6803.
*
Corresponding author. Tel.: +91 9415403775; e-mail: akshaw55@
yahoo.com
0957-4166/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2006.04.022

1190
R. Sagar et al. / Tetrahedron: Asymmetry 17 (2006) 1189–1198
OH
OH
R1
OH
R3O
R3O
R3O
CH2OH
CHO
CH2OH
O
R2
II
R2
R1
R2
III
R1
I
R1 =OR, R2 =H or
R1 =H, R2 =OR, R = R3 =acyl or aryl group
O
O
OH
SPh
BnO
BnO
O
O
OAc
O
II A
III A
Figure 1.
polyhydroxylated terminal alkenic alcohols.12 Herein we
report the results of a detailed comparative study on epox-
idation of II by Sharpless,13,14 m-CPBA and m-CPBA/KF
(Camp’s reagent)15 reagents.
At this stage, we became interested in the order of selectiv-
ity in Sharpless asymmetric epoxidation of the allylic alco-
hol with other tartrate, as well as the results of the catalytic
version of SAE.17 Therefore, the first SAE of 8 was carried
out using D-(À)-DIPT (2.5 equiv). Here also, the reaction
proceeded with complete diastereoselectivity (>99%), fur-
nishing the highly functionalized epoxy derivative
[(2R,3S)-4,6-di-O-benzyl-2,3-epoxy-D-galactitol] 8b in 60%
yield after 10h of continuous stirring of the reaction mix-
ture (Scheme 3). In the study of a catalytic version of
SAE on the allylic alcohol 8, the use of 2.4 equiv of t-
BuOOH, 0.05 equiv of Ti(O–i-Pr)4 and 0.06 equiv of L-
(+)-DET did not show any results. However when the
amounts of Ti(O–i-Pr)4 and L-(+)-DET were increased to
0.10 and 0.12 equiv, respectively, keeping the amount of
t-BuOOH constant, it was noticed that the reaction took
place smoothly with the same selectivity but requiring more
time for completion (25 h, Table 1, entry 2). On further in-
crease of the amounts of Ti(O–i-Pr)4 and L-(+)-DET to
0.20 and 0.24 equiv, respectively, SAE occurred exactly at
the same rate, with the same selectivity and yield as was no-
ticed in the case when 2.0 equiv of Ti(O–i-Pr)4 and
2.5 equiv of L-(+)-DET were used for the SAE of 8.
2. Results and discussion
The starting materials required for the present study were
prepared by reduction of the appropriate Perlin aldehydes
1–7 by adapting the procedure developed by Luche16
(Scheme 1).
With the required substrates in hand, the stage was set to
carry out a detailed study on epoxidation of allylic alcohols
by the Sharpless asymmetric reaction. For this, compound
8 was submitted to Sharpless asymmetric epoxidation
(SAE) with t-BuOOH (3.0 equiv 6.0 M solution in nonane)
in the presence of Ti(O–i-Pr)4 (2.0 equiv) and L-(+)-DET
(2.5 equiv) in DCM. After exploring several trial experi-
ments at various low temperatures below 0 ꢁC, it was found
that initiating the reaction at À25 ꢁC and continuing it to
0 ꢁC for 10 h, showed almost complete diastereoselectivity
(>99%) furnishing the epoxy derivative 8a [(2S,3R)-4,6-
di-O-benzyl-2,3-epoxy-D-galactitol] in 70% yield (Scheme
2).
Thus, based on the selectivity observed in the SAE of 8 in
the temperature range À25 ꢁC to 0 ꢁC, and considering the
OR3
OR3
NaBH4 (0.5 equiv.)
CeCl3.7H2O (1.0 equiv.)
R4O
R4O
CHO
OH
EtOH, rt, 70-78% yields
R2
R2
R1
R1
1. R1=OBn, R2=R3=H, R4=Bn
2. R1=R3=H, R2=OBn, R4=Bn
3. R1=OBn, R2=H, R3=R4=Bn
4. R1=H, R2=OBn, R3=R4=Bn
8. R1=OBn, R2=R3=H, R4=Bn
9. R1=R3=H, R2=OBn, R4=Bn
10. R1=OBn, R2=H, R3=R4=Bn
11. R1=H, R2=OBn, R3=R4=Bn
12. R1=OBn, R2=H, R3=Ac, R4=Bn
13. R1=OAc, R2=H, R3=R4=Ac
14. R1=H, R2=OAc, R3=R4=Ac
5. R1=OBn, R2=H, R3=Ac, R4=Bn
6. R1=OAc, R2=H, R3=R4=Ac
7. R1=H, R2=OAc, R3=R4=Ac
Scheme 1. Reduction of a,b-unsaturated enals to allylic alcohols.

R. Sagar et al. / Tetrahedron: Asymmetry 17 (2006) 1189–1198
1191
OR3
OR3
R1
Ti(O-i-Pr)4, L-(+)-DET
t-BuOOH, MS 4 Å
R4O
R4O
OH
OH
O
R1
DCM, -25 ˚C to 0 °C
R2
R2
8. R1=OBn, R2=R3=H, R4=Bn
9. R1=R3=H, R2=OBn, R4=Bn
10. R1=OBn, R2=H, R3=R4=Bn
11. R1=H, R2=OBn, R3=R4=Bn
12. R1=OBn, R2=H, R3=Ac, R4=Bn
13. R1=OAc, R2=H, R3=R4=Ac
14. R1=H, R2=OAc, R3=R4=Ac
8a. R1=OBn, R2=R3=H, R4=Bn
9a. R1=R3=H, R2=OBn, R4=Bn
10a. R1=OBn, R2=H, R3=R4=Bn
11a. R1=H, R2=OBn, R3=R4=Bn
12a. R1=OBn, R2=H, R3=Ac, R4=Bn
13a. R1=OAc, R2=H, R3=R4=Ac
14a. R1=H, R2=OAc, R3=R4=Ac
Scheme 2. Sharpless asymmetric epoxidation of allylic alcohols using L-(+)-DET.
OR3
OR3
Ti(O-i-Pr)4, D-(-)-DIPT
t-BuOOH, MS 4 Å
R4O
R4O
OH
OH
O
DCM, -25 ˚C to 0 °C, 10 h
R2
R1
R2
R1
1
2
3
4
8. R1=OBn, R2=R3=H, R4=Bn
Scheme 3. Sharpless asymmetric epoxidation of 8 using D-(À)-DIPT.
(60%)
8b. R =OBn, R =R =H, R =Bn
Table 1. Results of catalytic Sharpless asymmetric epoxidation (2.4 equiv of t-BuOOH, 0.20 equiv of Ti(O–i-Pr)4 and 0.24 equiv of L-(+)-DET)
Entry
Substrate
Temp (ꢁC)
Time (h)
Product
dra 2S,3R:2R,3S
Yieldb (%)
1c
2d
3
8
8
À25 to 0
À25 to 0
À25 to 0
À25 to 0
À25 to 0
À25 to 0
À25 to 0
À25 to 0
20
25
10
10
15
6
No reaction
99:1
8a
8a
62
70
60
68
70
6
8
99:1
1:99
99:1
99:1
99:1
99:1
4e
5
8
8b
9a
9
6
10
10
11
10a
10ag
11a
7f
8h
24
36
60
a Determined by 1H NMR of the crude material.
b Isolated yields of pure isomer.
c 2.4 equiv of t-BuOOH, 0.05 equiv of Ti(O–i-Pr)4 and 0.06 equiv of L-(+)-DET were used.
d 2.4 equiv of t-BuOOH, 0.10 equiv of Ti(O–i-Pr)4 and 0.12 equiv of L-(+)-DET were used.
e
D-(À)-DIPT was used in this case.
f 3.0 equiv of t-BuOOH, 2.0 equiv of Ti(O–i-Pr)4 and 2.5 equiv of L-(+)-DET were used.
g Compound 15 was isolated in 70% yield along with 10a.
h 10% starting material was recovered.
diastereoselectivity as the main criteria, the protocol of cat-
alytic SAE (2.4 equiv of t-BuOOH, 0.20 equiv of Ti(O–i-
Pr)4 and 0.24 equiv of L-(+)-DET) was extended to other
allylic alcohols 9–14 using L-(+)-DET (Table 1). Com-
pounds 12, 13 and 14, containing acyl protection, did not
undergo SAE, even after prolonged hours of continuous
stirring.
cyclized compound 15, indicated the presence of only two
benzyl groups and the absence of a third one, which was
present in the starting material 10. It was also noticed that
the epoxide protons were absent at d 3.18–2.97 in 15. Fur-
thermore, its DEPT 13C NMR spectrum showed the pres-
ence of 4-methylene carbons and 4-methine carbons in
between d 82.6 and 65.1. These spectroscopic data implied
that intramolecular SN2 type opening of the in situ formed
epoxide occurred due to the participation of C-6-O-benzyl
oxygen with concomitant debenzylation forming a tetrahy-
drofuran ring.
In the case of compound 10, when Ti(O–i-Pr)4 (2.0 equiv),
L-(+)-DET (2.5 equiv) and t-BuOOH (3.0 equiv) were
used, epoxide 10a was isolated in 6%, along with tetra-
hydrofuran derivative 15 (Scheme 4) in 70% yield (Table
1 entry 7). The appearance of ten aromatic protons be-
tween d 7.34 and 7.30 and four benzylic protons at d
Based on the structure of 10a there were two possible path-
ways for the formation of either of the two different tetra-
hydrofuran derivatives. This could be either 2,5-anhydro
1
4.67–4.49 as a multiplet in the H NMR spectrum of the

1192
R. Sagar et al. / Tetrahedron: Asymmetry 17 (2006) 1189–1198
derivative if the C-5 oxygen participates in epoxide opening
or 3,6-anhydro derivative if the C-6 oxygen participates in
epoxide opening. 1H NMR and 13C NMR spectrum signals
assigned for 15 were reconfirmed on the basis of its HSQC
spectrum. Its HMBC spectrum showed long range correla-
tions as depicted in Figure 2. All the HMBC correlations in
Figure 2 were in support of the structure of 3,6-anhydro
derivative 15, and ruled out the formation of 2,5-anhydro
derivative based on the argument that the benzylic protons
did not show any correlation with C-(6), suggesting the
absence of –CH2Ph at this position.
support from Sharpless et al.’s earlier reports.18 Here,
although the author alluded the participation of oxygen
atom of the C(6) benzyloxy group in the titanium-catalyzed
ring opening of epoxide IIIA, during its formation by
asymmetric epoxidation of its substrate to form a tetrahy-
drofuran derivative, the product was left uncharacterized.
A thorough literature survey revealed that carbohydrates
were extensively used as precursors in a tetrahydrofuran
synthesis. The catalytic hydrogenation of glycals19 and
thioglycosides,20 nitrous acid deamination of 2-amino-2-
deoxyaldoses,21 acid-catalyzed dehydration of acyclic aldi-
tols,22 reduction of glycosyl halides,23 dehydration of sug-
ars catalyzed by pyridinium salts,24 reductive cleavage of
glycosides25 and intramolecular cyclization of bromode-
oxyaldonolactones and bromodeoxyalditols26 are the liter-
ature reports for the preparation of anhydroalditols. Very
few of these methods26 were able to synthesize 3,6-anhy-
dro-galactitols in an enatiomerically pure form and in good
yields, which are not otherwise available in enantiomeri-
cally pure form from galactitol by simple treatment with
acid.27
OH
O
H
2
3
OH
6
(S)
(S)
1
H
H
H
H
H
H
4
5
(R)
H
(S)
C
O
O
C
H
H
H
We also submitted compound 10 to SAE in the presence of
D-(À)-DIPT (2.5 equiv) expecting to obtain 3,6-anhydro-L-
galactitol (Scheme 5). The reaction was completed in 24 h
furnishing the expected enantiomerically pure product 17
in 75% yield. The structure of this product was confirmed
by comparing the spectral data with that of compound
15 and finally by preparing its diacetate derivative 18.
"
" HMBC correlations
Figure 2. Selected HMBC correlations of 15.
Structure 15 was further confirmed by preparing its diace-
tate derivative 16 (Scheme 4) whose H NMR spectrum
1
showed ddd (J = 8.1, 4.8 and 2.2 Hz) at d 5.31 for carbinol
proton at C-2. This multiplicity is only possible for H-2
proton in 16. Thus, the detailed spectral study of the new
tetrahydrofuran derivative 15 and its diacetate derivative
16 unequivocally established it as 3,6-anhydro-D-galactitol
15. Our seemingly contradictory finding gained further
These enantiomerically pure, highly functionalized tetrahy-
drofuran derivatives, which are of great value because of
their industrial applications and biological properties,28
can be effectively utilized as potential synthons for the
preparation of biologically active compounds. We feel that
OR
O
OBn
OR
Ti(O-i-Pr)4, L-(+)-DET
t-BuOOH, MS 4 Å
BnO
H
OH
+
10a (6%)
DCM, -25 °C to 0 °C, 24 h
H
BnO
BnO
OBn
15 R=H (70%)
16 R=Ac
10
Ac2O,
Pyridine, 0 °C
Scheme 4. Sharpless asymmetric epoxidation of 10 using L-(+)-DET.
O
H
OBn
Ti(O-i-Pr)4, D-(-)-DIPT
t-BuOOH, MS 4 Å
BnO
OR
OH
OR
OBn
DCM, -25 °C to 0 °C, 24 h
BnO
+
10b (trace)
H
BnO
17 R=H (75%)
18 R=Ac
Ac2O,
10
Pyridine, 0 °C
Scheme 5. Sharpless asymmetric epoxidation of 10 using D-(À)-DIPT.

R. Sagar et al. / Tetrahedron: Asymmetry 17 (2006) 1189–1198
1193
these moieties can be of great interest to a chemist as it has
various sites of diversification to play around as illustrated
in Figure 3.
of olefins at room temperature to furnish the resulting
epoxides in very good yield plausibly due to the inactiva-
tion of any acid-catalyzed side reaction. This reagent was
used for diastereoselective one-step epoxidation of gly-
cals.29 Hence, we also tried this reagent for the epoxidation
of the above studied allylic alcohols. However this method
ended with almost similar results to that of m-CPBA med-
iated epoxidation apart from the non-participation of acet-
ylated compounds 12, 13 and 14 as they are less reactive
allylic alcohols.
OH
O
OH
Bn
O
OBn
In order to ascertain the mechanistic pathway of the forma-
tion of 3,6-anhydrogalactitols 15 and 17, compound (2S,
3R/2R,3S)-4,5,6-tri-O-benzyl-2,3-epoxy-D-galactitol 10a/
10b, an inseparable diastereomeric mixture of an epoxide
prepared by m-CPBA mediated epoxidation of 10, was stir-
red with t-BuOOH (3.0 equiv, 6.0 M solution in nonane) in
the presence of Ti(O–i-Pr)4 (2.0 equiv) and L-(+)-DET
(2.5 equiv) in DCM under SAE conditions. This reaction
mixture on continuous stirring for 12 h, provided a diaste-
reomeric mixture of 3,6-anhydrogalactitols 15 or 17 (60/
40,30 1H NMR) confirming the involvement of epoxide
intermediate during the cyclization process. It is worth
mentioning here that absence of any one of the Sharpless
reagents did not yield the 3,6-anhydrogalactitols 15 or 17.
Figure 3. Arrows showing sites of diversification.
In light of the above findings, we were further interested to
carry out epoxidation of all the above studied enantiomeri-
cally pure allylic alcohols (8–14) by m-CPBA with a view to
compare the selectivity and yield of each reaction with that
of SAE of the same substrate. The comparative study of
epoxidation with m-CPBA (Scheme 6) was initiated using
allylic alcohol 8. The reaction was completed at room tem-
perature producing chromatographically pure inseparable
diastereomeric mixture of epoxide 8a/8b (29/71) in 75%
yield. All the allylic alcohols including acyl protected allylic
alcohols 12, 13 and 14, which did not undergo SAE, under-
went m-CPBA epoxidation furnishing the diastereomeric
mixture of their respective epoxides (Table 2).
3. Conclusion
With these results in hand we came across a literature re-
port that m-CPBA/KF complex (Camp’s reagent) sus-
pended in DCM can be used as a mild epoxidizing agent
In conclusion, our approach towards the synthesis of 2,3-
epoxyalcohols III, from Perlin aldehydes I is new and
OR3
OR3
OR3
m-CPBA
(2.5 equiv.)
R4O
R4O
R4O
OH
OH
+
OH
DCM. rt
O
O
R2
R1
R2
a
R1 R2
R1
b
8. R1=OBn, R2=R3=H, R4=Bn
9. R1=R3=H, R2=OBn, R4=Bn
8a/8b. R1=OBn, R2=R3=H, R4=Bn
9a/9b. R1=R3=H, R2=OBn, R4=Bn
10. R1=OBn, R2=H, R3=R4=Bn
11. R1=H, R2=OBn, R3=R4=Bn
10a/10b. R1=OBn, R2=H, R3=R4=Bn
11a/11b. R1=H, R2=OBn, R3=R4=Bn
12a/12b. R1=OBn, R2=H, R3=Ac, R4=Bn
13a/13b. R1=OAc, R2=H, R3=R4=Ac
14a/14b. R1=H, R2=OAc, R3=R4=Ac
12. R1=OBn, R2=H, R3=Ac, R4=Bn
13. R1=OAc, R2=H, R3=R4=Ac
14. R1=H, R2=OAc, R3=R4=Ac
Scheme 6. Epoxidation with m-CPBA.
Table 2. Results of m-CPBA mediate epoxidation at room temperature (30 ꢁC)
Entry
Substrate
Time (h)
Product
dra 2S,3R:2R,3S
Yieldb (%)
1
2
3
4
5
6
7
8
4
3
3
3
5
8a/8b
9a/9b
29:71
58:42
60:40
28:72
32:68
66:34
37:63
75
73
70
80
67
44
45
9
10
11
12
13
14
10a/10b
11a/11b
12a/12b
13a/13b
14a/14b
120
115
a Determined by 1H NMR of the crude material.
b Isolated yields of inseparable diastereomers.

1194
R. Sagar et al. / Tetrahedron: Asymmetry 17 (2006) 1189–1198
proved to be a very simple and general method. This
approach involved two steps for reaching the required
2,3-epoxyalcohol from I. The SAE reaction of 10 with
t-BuOOH (3.0 equiv) in the presence of Ti(O–i-Pr)4
(2.0 equiv), L-(+)-DET or D-(À)-DIPT (2.5 equiv) resulted
in intramolecular SN2 opening of the in situ formed 2,3-
epoxy alcohol 10a or 10b by C(6) benzyloxy group with
concomitant debenzylation resulting in enantiomerically
pure, highly functionalized valuable tetrahydrofuran deriv-
ative 15 or 17, which are important structural motifs found
in various bioactive natural products such as antibiotics,
terpene polyethers, Annonaceous acetogenins, etc.31 Thus,
by changing the ratio of Sharpless reagents we were able
to obtain different products (2,3-epoxy alcohols or tetra-
hydrofurans) by applying the same reaction protocol.
The extensive efforts in the preparation of polysubstituted
tetrahydrofurans, not withstanding the established proce-
dures in the literature, manifest their significance. All these
2,3-epoxy alcohols as well as 3,6-anhydro-galactitols re-
ported herein were very stable and also prepared in gram
scale (up to 10.0 g). These novel carbohydrate derivatives
will certainly find wide applications in synthetic organic
chemistry. Their further applications in synthetic and
medicinal chemistry are currently underway in our
laboratory.
ring, a 6.0 M solution of t-BuOOH (0.20 mL, 1.2 mmol)
was added and the temperature of the reaction raised to
0 ꢁC and was left for stirring till the completion of the reac-
tion. After completion, a 10% solution of tartaric acid
(10 mL) was added to quench the reaction at 0 ꢁC and stir-
red for 0.5 h. The solution was filtered through a Celite
pad. The organic layer from the filtrate was separated using
a separating funnel and concentrated to get the mixture res-
idue. The residue was dissolved in Et2O (20 mL) and stirred
with 4% NaOH in brine solution (15 mL) at 0 ꢁC for 0.75 h
to hydrolyze and remove excess of diethyl tartrate. Later,
the ether layer was separated using separating funnel,
washed with brine, dried over Na2SO4 and concentrated
to get the crude product. The crude product was purified
by column chromatography to afford diastereomeric pure
epoxide 8a. A similar reaction protocol was adopted for
compounds 9, 10 and 11.
Substrate 10 (1.0 equiv) was subjected to SAE with
t-BuOOH (3.0 equiv) in the presence of Ti(O–i-Pr)4
(2.0 equiv) and L-(+)-DET or D-(À)-DIPT (2.5 equiv) to
obtain THF derivative 15 or 17.
4.3. General procedure for epoxidation with m-CPBA
To a well stirred solution of allylic alcohol 8 in dry DCM at
rt, m-CPBA (107 mg, 0.62 mmol) was added and was con-
tinued stirring at the same temperature till the completion
of the reaction. Once the reaction was complete excess of
saturated NaHCO3 solution was added and left for stirring
for 1 h to neutralize unused m-CPBA. Later, the reaction
mixture was extracted with ethyl acetate (4 · 5 mL) and
the combined organic layer was dried over anhydrous
Na2SO4 and concentrated to give the crude product, which
on column chromatography yielded a diastereomeric mix-
ture of product 8a/8b in 78% yield.
4. Experimental
4.1. General
All the reactions were monitored by warming the CeSO4
(1% in 2 M H2SO4) sprayed precoated silica gel TLC plates
at 100 ꢁC. NMR spectra were recorded on Bruker Avance
DPX 200 FT, Bruker Robotics and Bruker DRX 300 Spec-
trometers at 200, 300 MHz (1H) and 50, 75 MHz (13C). For
13C NMR reference, CDCl3 appeared at 77.4 ppm, unless
otherwise stated. Mass spectra were recorded on a JEOL
SX 102/DA 6000 mass spectrometer using argon/xenon
(6 kV, 100 mA) as the FAB gas. Organic solvents were dried
by standard methods. Ti(O-i-Pr)4, L-(+)-diethyl tartrate, D-
(À)-diethyl tartrate and t-BuOOH were purchased from Al-
drich chemical co. Allylic alcohols 8–14 were synthesized in
the laboratory. IR spectra were recorded on Perkin–Elmer
881 and FTIR-8210 PC Shimadzu Spectrophotometers.
Optical rotations were determined on an Autopol III polar-
imeter using a 1 dm cell at 28 ꢁC in methanol or chloroform
as the solvent; concentrations mentioned are in g/100 mL.
Elemental analyses were carried out on Carlo-Erba-1108
and Vario EL III instruments. The minor diastereomers
4.4. General procedure for epoxidation with m-CPBA-KF
complex
A solution of m-CPBA (107 mg, 0.62 mmol) in dry CH2Cl2
(10 mL) was dried by passing it over Na2SO4. The resulting
solution was then taken in the r.b. flask (100 mL) contain-
ing anhydrous KF (726.2 mg, 12.5 mmol) and left for stir-
ring at room temperature for 30 min. To this, allylic
alcohol 8 (82 mg, 0.25 mmol) was added slowly and stirring
continued until the completion of the reaction. The reac-
tion mixture after the completion of the reaction was fil-
tered through Celite pad and concentrated under reduced
pressure to get the crude product, which on column chro-
matography yielded inseparable diastereomeric mixture
8a/8b.
are marked as D in the assignment of H NMR and 13C
NMR spectra of diastereoisomeric mixtures.
1
4.2. General procedure for catalytic Sharpless asymmetric
epoxidation
4.4.1. (2S,3R)-4,6-Di-O-benzyl-2,3-epoxy-D-galactitol 8a.
Oil, eluent for column chromatography: EtOAc/hexane
(3/7, v/v), Rf 0.30 (1/1 EtOAc/hexane); [a]D À26.47 (c
0.170, CHCl3); IR (neat, cmÀ1): 3403 (O–H str), 3031
(@C–H str), 2923, 2869 (–C–H str), 1495, 1454 (C@C
A solution of Ti(O–i-Pr)4 (0.029 mL, 0.10 mmol) and
L-(+)-diethyltartrate (0.020 mL, 0.12 mmol) in CH2Cl2
(5 mL) was stirred at À25 ꢁC for 0.5 h in the presence of
1
str), 1218 (C–O str of epoxide), 1093 (C–O str); H NMR
˚
MS 4 A. To this mixture, a solution of compound 8
(200 MHz, CDCl3): d 7.32–7.25 (m, 10H, ArH), 4.68–4.50
(m, 4H, 2 · CH2Ph), 3.93 (m, 1H, H-5), 3.76 (dd,
J1a,1b = 12.7 Hz and J1a,2 = 2.6 Hz, 1H, H-1a), 3.62–3.47
(164 mg, 0.5 mmol) in CH2Cl2 (5 mL) was added and the
mixture stirred at the same temperature. After 0.5 h of stir-

R. Sagar et al. / Tetrahedron: Asymmetry 17 (2006) 1189–1198
1195
(m, 4H, H-1b, H-6a, H-6b and H-4), 3.14 (dd, J3,4 = 5.1 Hz
and J3,2 = 2.2 Hz, 1H, H-3), 3.08 (m, 1H, H-2); 13C NMR
(50 MHz, CDCl3): d 138.3, 138.2 (Ar qC), 128.8, 128.3,
128.2 (ArC), 77.3 (C-4), 74.0, 73.8 (2 · CH2Ph), 71.2
(C-5), 71.0 (C-1), 61.5 (C-6), 57.2 (C-3), 55.1 (C-2); FAB
MS calcd for C20H24O5 m/z 344; found 345 [M+1]+Å,
325, 253 [MÀCH2Ph]+Å, 181. Elemental analysis calcd for
C20H24O5ÆH2O (362.43) C, 66.28; H, 7.23. Found: C,
66.91; H, 7.43.
1H, H-6b), 3.14 (dd, J3,4 = 4.5 Hz and J3,2 = 2.0 Hz 1H,
H-3), 3.06–3.05 (m, 1H, H-2); 13C NMR (50 MHz, CDCl3):
d 138.2, 138.0 (Ar qC), 128.3, 128.1, 128.0, 127.8, 127.7
(ArC), 78.2 (C-4), 76.6 (C-5), 73.6, 73.4, 73.3 (3 · CH2Ph),
69.1 (C-1), 61.3 (C-6), 56.8 (C-3), 54.8 (C-2); FAB MS
calcd for C27H30O5 m/z 434; found 435 [M+1]+Å, 343
[MÀCH2Ph]+Å.
4.4.5. (2S,3R/2R,3S)-4,5,6-Tri-O-benzyl-2,3-epoxy-D-galac-
titol 10a/10b. Oil, eluent for column chromatography:
EtOAc/hexane (3/22, v/v), Rf 0.42 (3/7 EtOAc/hexane);
IR (neat, cmÀ1): 3446 (O–H str), 3065, 3030 (@C–H str),
2919 (–C–H str), 1496, 1454 (C@C str), 1216 (C–O str of
4.4.2. (2R,3S)-4,6-Di-O-benzyl-2,3-epoxy-D-galactitol 8b.
.Oil, eluent for column chromatography: EtOAc/hexane
(3/7, v/v), Rf 0.32 (1/1 EtOAc/hexane); [a]D = À16.4 (c
0.073, CHCl3); IR (neat, cmÀ1): 3431 (O–H str), 3029
(@C–H str), 2922 (–C–H str), 1653, 1495, 1456 (C@C
1
epoxide), 1097 (C–O str); H NMR (200 MHz, CDCl3): d
7.31–7.25 (m, 15H, ArH), 4.77–4.48 (m, 6H, 3 · CH2Ph),
3.82–3.30 (m, 6H, H-1, H-4, H-5 and H-6), 3.20 (dd,
J3,4 = 6.8 Hz and J3,2 = 2.2 Hz 1H, Hb-3), 3.14 (dd,
J3,4 = 4.6 Hz and J3,2 = 2.2 Hz 1H, Ha-3), 3.07 (m, 1H,
Ha-2), 2.95 (m, 1H, Hb-2); 13C NMR (50 MHz, CDCl3):
d 138.5, 138.4 (Ar qC), 128.7, 128.4, 128.3 128.0 (ArC),
79.6 (C-4), 78.6 (CD-4), 77.0 (C-5), 74.0, 73.8, 73.6
(3 · CH2Ph), 69.6 (C-1), 61.6 (C-6), 57.1 (C-3), 56.8 (CD-
3), 55.1 (C-2), 54.8 (CD-2); FAB MS calcd for C27H30O5
m/z 434; found 434 [M]+Å, 343 [MÀCH2Ph]+Å, 271, 253
[M+1À2CH2Ph]+Å, 231, 189, 165. Elemental analysis calcd
for C27H30O5 (434.54) C, 74.63; H, 6.95. Found: C, 74.61;
H, 7.00.
1
str), 1218 (C–O str of epoxide), 1091 (C–O str); H NMR
(200 MHz, CDCl3): d 7.40–7.28 (m, 10H, ArH), 4.88–4.49
(m, 4H, 2 · CH2Ph), 3.87 (m, 1H, H-5), 3.72 (dd,
J1a,1b = 12.6 Hz and J1a,2 = 3.3 Hz, 1H, H-1a), 3.61–3.53
(m, 3H, H-1b, H-6a and H-6b), 3.31 (dd, J4,3 = 7.1 Hz
and J4,5 = 4.7 Hz, 1H, H-4), 3.18 (dd, J3,4 = 7.1 Hz and
J3,2 = 2.2 Hz, 1H, H-3), 2.97 (dd, J = 5.9 Hz and
J = 3.5 Hz, 1H, H-2); 13C NMR (50 MHz, CDCl3): d
138.2, 138.0 (Ar qC), 129.0, 128.8, 128.4, 128.2 (ArC),
80.0 (C-4), 74.0, 72.8 (2 · CH2Ph), 71.5 (C-5), 70.7 (C-1),
61.5 (C-6), 56.9 (C-2), 54.8 (C-3); FAB MS calcd for
C20H24O5 m/z 344; found 345, 325 [MÀ17]+Å, 253
[MÀCH2Ph]+Å, 221, 181. Elemental analysis calcd for
C20H24O5ÆH2O (362.43) C, 66.28; H, 7.23. Found: C,
66.69; H, 7.49.
4.4.6. (2S,3R)-4,5,6-Tri-O-benzyl-2,3-epoxy-D-glucitol 11a.
Oil, eluent for column chromatography: EtOAc/hexane
(3/17, v/v), Rf 0.38 (3/7 EtOAc/hexane); [a]D = +10.5 (c
0.057, CHCl3); IR (neat, cmÀ1): 3432 (O–H str), 3063,
3031 (@C–H str), 2924, 2865 (–C–H str), 1604, 1496,
1454 (C@C str), 1211 (C–O str of epoxide), 1097 (C–O
4.4.3. (2S,3R)-4,6-Di-O-benzyl-2,3-epoxy-D-glucitol 9a.
Oil, eluent for column chromatography: EtOAc/hexane
(3/7, v/v), Rf 0.37 (1/1 EtOAc/hexane); [a]D = +12.1 (c
0.066, CHCl3); IR (neat, cmÀ1): 3398 (O–H str), 3031
(@C–H str), 2921, 2870 (–C–H str), 1655, 1605, 1496
1
str); H NMR (300 MHz, CDCl3): d 7.38–7.28 (m, 15H,
ArH), 4.85–4.54 (m, 6H, 3 · CH2Ph), 3.82–3.71 (m, 3H,
H-1a, H-1b, H-5), 3.67–3.53 (m, 2H, H-6a, H-6b), 3.45
(br t, J = 6.0 Hz 1H, H-4), 3.22 (dd, J3,4 = 9.0 Hz and
J3,2 = 3.0 Hz 1H, H-3), 3.01 (ddd, J2,1a = 9.0 Hz,
J2,1b = 6.0 and J2,3 = 3.0 Hz 1H, H-2); 13C NMR
(50 MHz, CDCl3): d 138.5, 138.4 (Ar qC), 128.8, 128.7,
128.3, 128.2, 128.1, 128.0 (ArC), 79.4 (C-4), 78.9 (C-5),
73.8, 73.1, 73.0 (3 · CH2Ph), 69.2 (C-1), 61.6 (C-6), 57.1
(C-3), 55.7 (C-2); ES MS Calcd for C27H30O5 m/z 434;
found 435 [M+1]+Å, 343 [MÀCH2Ph]+Å.
1
(C@C str), 1214 (C–O str of epoxide), 1096 (C–O str); H
NMR (200 MHz, CDCl3): d 7.30–7.25 (m, 10H, ArH),
4.82–4.48 (m, 4H, 2 · CH2Ph), 3.90 (m, 1H, H-5), 3.74
(dd, J1a,1b = 12.5 Hz and J1a,2 = 3.3 Hz, 1H, H-1a), 3.66–
3.59 (m, 2H, H-1b and H-6a), 3.57 (dd, J6b,6a = 10.6 Hz
and J6b,5 = 4.6 Hz, 1H, H-6b), 3.25 (br t, J = 6.9 Hz, 1H,
H-4), 3.16 (dd, J3,4 = 7.0 Hz and J3,2 = 2.0 Hz, 1H, H-3),
3.00 (m, 1H, H-2); 13C NMR (50 MHz, CDCl3): d 138.3,
138.0 (Ar qC), 128.9, 128.8, 128.3, 128.2 (ArC), 80.0 (C-
4), 73.9 (C-1), 72.8 (CH2Ph), 71.1 (C-5), 71.0 (CH2Ph),
61.7 (C-6), 57.2 (C-3), 55.5 (C-2); FAB MS calcd for
C20H24O5 m/z 344; found 345 [M+1]+Å, 327 [MÀ17]+Å 253
[MÀCH2Ph]+Å, 203, 181. Elemental analysis calcd for
C20H24O5ÆH2O (362.43) C, 66.28; H, 7.23. Found: C,
66.17; H, 6.83.
4.4.7.
(2R,3S)-4,5,6-Tri-O-benzyl-2,3-epoxy-D-glucitol
11b. It was isolated as an oil from the mixture of 11a/
11b during its repeated silica gel column chromatographic
purification using EtOAc/hexane (3/22, v/v) as eluent, Rf
0.48 (3/7 EtOAc/hexane); [a]D = À22.8 (c 0.136, CHCl3);
IR (neat, cmÀ1): 3446 (O–H str), 3029 (@C–H str), 2920,
2869 (–C–H str), 1603, 1496, 1454 (C@C str), 1216 (C–O
str of epoxides), 1096 (C–O str); 1H NMR (200 MHz,
CDCl3): d 7.31–7.26 (m, 15H, ArH), 4.77–4.51 (m, 6H,
3 · CH2Ph), 3.81–3.39 (m, 6H, H-1, H-4, H-5 and H-6),
3.20 (dd, J3,4 = 6.8 Hz and J3,2 = 1.6 Hz, 1H, H-3), 2.98
(m, 1H, H-2); 13C NMR (50 MHz, CDCl3): d 138.6 (Ar
qC), 128.8, 128.3, 128.1 (ArC), 79.5 (C-4), 79.0 (C-5),
73.8, 73.1, 73.0 (3 · CH2Ph), 69.3 (C-1), 61.7 (C-6), 57.1
(C-3), 55.8 (C-2); FAB MS calcd for C27H30O5 m/z 434;
4.4.4.
(2S,3R)-4,5,6-Tri-O-benzyl-2,3-epoxy-D-galactitol
10a. Oil, eluent for column chromatography: EtOAc/hex-
ane (3/22, v/v), Rf 0.42 (3/7 EtOAc/hexane); [a]D = À20.3
(c 0.123, CHCl3); IR (neat, cmÀ1): 3413 (O–H str), 3065,
3013 (@C–H str), 2933, 2875 (–C–H str), 1606, 1456,
1455 (C@C str), 1217 (C–O str of epoxide), 1091 (C–O
1
str); H NMR (200 MHz, CDCl3): d 7.31–7.25 (m, 15H,
ArH), 4.76–4.48 (m, 6H, 3 · CH2Ph), 3.82–3.75 (m, 1H,
H-4), 3.67–3.62 (m, 3H, H-1a, H-1b, H-5), 3.59–3.55 (m,
1H, H-6a), 3.46 (dd, J6b,6a = 12.6 Hz and J6b,5 = 4.1 Hz

1196
R. Sagar et al. / Tetrahedron: Asymmetry 17 (2006) 1189–1198
found 435 [M+1]+Å, 419 [M+2ÀH2O] 348 [MÀCH2Ph]+Å,
253 [M+1À2 · CH2Ph]+Å, 221, 207, 181. Elemental analysis
calcd for C27H30O5Æ0.5H2O (443.55) C, 73.11; H, 7.04.
Found: C, 72.80; H, 6.56.
J1b,2 = 3.3 Hz, 1H, H-1b), 3.19 (dd, J3,4 = 5.4 Hz and
J3,2 = 2.1 Hz, 1H, H-3), 3.08 (dd, J2,1 = 5.5 Hz and
J2,3 = 2.8 Hz, 1H, H-2), 2.13, 2.12, 2.07 (3 · OCOCH3);
13C NMR (50 MHz, CDCl3): d 170.8, 170.5 and 170.2
(3 · COCH3), 71.1 (C-4), 70.7 (C-5), 62.3 (C-1), 61.0 (C-
6), 56.1 (C-3), 54.3 (C-2), 21.0 (3 · OCOCH3); FAB MS
calcd for C12H18O8 m/z 290; found 291 [M+1]+Å, 273
[MÀH2O]+Å, 259 [MÀCH2OH]+Å, 231 [MÀOCOCH3]+Å,
173 [MÀ2OCOCH3]+Å.
4.4.8. (2S,3R/2R,3S)-4,6-Di-O-benzyl-5-O-acetyl-2,3-epoxy-
D-galactitol 12a/12b. Oil, eluent for column chromatogra-
phy, 3:17 EtOAc/hexane v/v, Rf 0.48 (2/3 EtOAc/hexane);
IR (neat, cmÀ1): 3467 (O–H str), 3017 (@C–H str), 2924,
2871 (–C–H str), 1738 (C@O str), 1496, 1454 (C@C str),
1374 (C–H def of CH3), 1238 (C–O str of epoxides), 1057
4.4.11. (2S,3R/2R,3S)-4,5,6-Tri-O-acetyl-2,3-epoxy-D-gluc-
itol 14a/14b. Oil, eluent for column chromatography:
EtOAc/hexane (7/13) v/v, Rf 0.23 (1/1 EtOAc/hexane);
IR (neat, cmÀ1): 3486 (O–H str), 2930 (C–H str), 1745
(C@O str), 1373 (C–H def of CH3), 1219 (C–O str of epox-
ides), 1047 (C–O str); 1H NMR (200 MHz, CDCl3): d 5.36–
5.25 (m, 1H, H-5), 5.02 (br t, J4,3=5 = 5.8 Hz, 1H, H-4),
4.36 (dd, J6a,6b = 12.2 Hz and J6a,5 = 3.4 Hz, 1H, H-6a),
4.19 (dd, J6b,6a = 12.2 Hz and J6b,5 = 6.2 Hz, 1H, H-6b),
3.88 (dd, J1a,1b = 12.8 Hz and J1a,2 = 2.8 Hz, 1H, H-1a),
3.69 (dd, J1b,1a = 12.8 Hz and J1b,2 = 3.7 Hz, 1H, H-1b),
3.24 (dd, J3,4 = 5.8 Hz and J3,2 = 2.0 Hz, 1H, H-3), 3.19
(m, 1H, HD-3), 3.09 (m, 1H, H-2), 2.10, 2.08, 2.07
(3 · OCOCH3); 13C NMR (50 MHz, CDCl3): d 171.0,
170.4 and 170.1 (3 · COCH3), 71.2 (C-4), 71.0 (CD-4),
70.8 (C-5), 70.8 (CD-5), 62.2 (C-1), 62.1 (CD-1), 61.1
(C-6), 61.0 (CD-6), 56.5 (C-3), 54.0 (C-2), 52.6 (CD-2),
21.1 (3 · OCOCDH3), 21.0 (3 · OCOCH3); FAB MS calcd
for C12H18O8 m/z 290; found 291 [M+1]+Å, 259
[MÀCH2OH]+Å, 231 [MÀOCOCH3]+Å, 219, 154. Elemental
analysis calcd for C12H18O8ÆH2O (308.29) C, 46.75; H,
6.53. Found: C, 47.00; H, 5.86.
1
(C–O str); H NMR (200 MHz, CDCl3): d 7.31–7.25 (m,
10H, ArH), 5.28–5.20 (m, 1H, H-5), 4.68–4.47 (m, 4H,
2 · CH2Ph), 3.75–3.37 (m, 5H, H-4, H-1a, H-1b, H-6a
and H-6b), 3.08 (dd, J3,4 = 9.0 Hz and J3,2 = 2.6 Hz, 1H,
H-3), 3.03–2.96 (m, 1H, H-2), 2.09 (s, 3H, COCH3); 13C
NMR (50 MHz, CDCl3): d 171.0 (COCH3), 138.2, 138.1
(Ar qC), 128.8, 128.2 (ArC), 78.4 (C-5), 75.5 (CD-5), 74.3
(CH2Ph), 73.7 (CH2PhD), 73.1 (C-4), 72.4 (CD-4), 72.7
(CH2Ph), 68.5 (C-1), 68.1 (CD-1), 61.8 (C-6), 57.0 (C-3),
56.4 (CD-3), 55.0 (C-2), 54.6 (CD-2), 21.4 (COCH3); FAB
MS calcd for C22H26O6 m/z 386; found 387 [M+1]+Å, 369
[M+1ÀH2O]+Å, 355 [MÀCH2OH]+Å, 295 [MÀCH2Ph]+Å,
279, 181. Elemental analysis calcd for C22H26O6Æ0.5H2O
(395.46) C, 66.81; H, 6.88. Found: C, 66.60; H, 6.83.
4.4.9. (2S,3R/2R,3S)-4,5,6-Tri-O-acetyl-2,3-epoxy-D-galac-
titol (13a/13b). Oil, eluent for column chromatography:
EtOAc/hexane (7/13, v/v), Rf 0.23 (1/1 EtOAc/hexane);
IR (neat, cmÀ1): 3478 (O–H str), 2934 (C–H str), 1745
1
(C@O str), 1374 (C–H def of CH3), 1225 (C–O str); H
NMR (200 MHz, CDCl3): d 5.42–5.31 (m, 1H, H-5), 5.06
(br t, J4,3=5 = 5.2 Hz, 1H, H-4), 5.03 (br t, J4,3=5 = 4.0
Hz, 1H, HD-4), 4.38 (dd, J6a,6b = 12.0 Hz and J6a,5
4.1 Hz, 1H, H-6a), 4.32 (dd, J6a,6b = 11.0 Hz and J6a,5
=
=
4.4.12. 3,6-Anhydro-4,5-di-O-benzyl-D-galactitol 15. Oil,
eluent for column chromatography: EtOAc/hexane (7/13,
v/v), [a]D = +25.00 (c 0.140, CHCl3); Rf 0.18 (3/7
EtOAc/hexane); IR (neat, cmÀ1): 3429 (O–H str), 3066,
3015 (@C–H str), 2928 (–C–H str), 1496, 1455 (C@C str),
1217, 1087 (C–O str); 1H NMR (300 MHz, CDCl3): d
7.34–7.30 (m, 10H, ArH), 4.67–4.49 (m, 4H, 2 · CH2Ph),
4.16 (m, 1H, H-4), 4.13–4.10 (m, 2H, H-5 and H-6a),
4.03–3.98 (m, 2H, H-2 and H-3), 3.89–3.79 (m, 2H, H-6b
and H-1a), 3.69 (dd, J1b,1a = 11.1 Hz and J1b,2 = 3.9 Hz,
1H, H-1b); 13C NMR (50 MHz, CDCl3): d 137.9, 137.8
(Ar qC), 129.0, 128.9, 128.5, 128.3, 128.2, 128.0 (ArC),
82.70 (C-5), 82.0 (C-4), 80.9 (C-3), 72.6 (CH2Ph), 72.1
(C-6), 71.9 (CH2Ph), 70.1 (C-2), 65.1 (C-1); FAB MS calcd
for C20H24O5 m/z 344; found 345 [M+1]+Å, 325, 253
[MÀCH2Ph]+Å, 203, 181, 154. Elemental analysis calcd
for C20H24O5ÆH2O (362.43) C, 66.28; H, 7.23. Found: C,
66.49; H, 6.89.
4.9 Hz, 1H, HD-6a), 4.12 (dd, J6b,6a = 12.0 Hz and
J6b,5 = 2.5 Hz, 1H, H-6b), 4.09 (dd, J6b,6a = 11.0 Hz and
J6b,5 = 2.5 Hz, 1H, HD-6b), 3.74–3.62 (m, 2H, H-1a and
H-1b), 3.20 (dd, J3,4 = 5.4 Hz and J3,2 = 2.2 Hz, 1H, H-
3), 3.12–3.08 (m, 1H, H-2), 2.13, 2.12, 2.10 (3 · OCOCH3);
13C NMR (50 MHz, CDCl3): d 170.8, 170.5 and 170.2
(3 · COCH3), 71.1 (C-4), 70.7 (C-5), 70.1 (CD-4), 70.0
(CD-5), 62.3 (C-1), 62.0 (CD-1), 61.0 (C-6), 60.9 (CD-6),
56.8 (CD-3), 56.1 (C-3), 54.3 (C-2), 52.7 (CD-2), 21.0
(3 · OCOCH3); FAB MS calcd for C12H18O8 m/z 290;
found 291 [M+1]+Å, 259 [MÀCH2OH]+Å, 231
[MÀOCOCH3]+Å, 219, 202, 165. Elemental analysis calcd
for C12H18O8ÆH2O (308.29) C, 46.75; H, 6.53. Found: C,
46.85; H, 5.77.
4.4.10.
(2R,3S)-4,5,6-Tri-O-acetyl-2,3-epoxy-D-galactitol
13b. Compound 13b was isolated as an oil from the mix-
ture of 13a/13b during its repeated silica gel column chro-
matographic purification using EtOAc/hexane (7/13, v/v),
as eluent, Rf 0.23 (1/1 EtOAc/hexane); IR (neat, cmÀ1):
3466 (O–H str), 2924 (C–H str), 1746 (C@O str), 1374
4.4.13. 3,6-Anhydro-1,2-di-O-acetyl-4,5-di-O-benzyl-D-gala-
ctitol 16. Oil, eluent for column chromatography:
EtOAc/hexane (1/9, v/v), [a]D = +15.55 (c 0.090, CHCl3);
1H NMR (200 MHz, CDCl3): d 7.39–7.26 (m, 10H,
1
(C–H def of CH3), 1225 (C–O str); H NMR (200 MHz,
ArH), 5.31 (ddd, J2,3 = 8.1 Hz, J2,1b = 4.8 Hz and J2,1a
=
CDCl3): d 5.38–5.31 (m, 1H, H-5), 5.06 (br t, J4,3=5
5.2 Hz, 1H, H-4), 4.38 (dd, J6a,6b = 12.1 Hz and J6a,5
4.1 Hz, 1H, H-6a), 4.12 (dd, J6b,6a = 12.1 Hz and J6b,5
6.2 Hz, 1H, H-6b), 3.87 (dd, J1a,1b = 12.8 Hz and J1a,2
=
=
=
=
2.2 Hz, 1H, H-2), 4.65 (dd, J1a,1b = 12.3 Hz and J1a,2
=
2.2 Hz, 1H, H-1a), 4.56–4.39 (m, 4H, 2 · CH2Ph), 4.19
(dd, J1b,1a = 12.0 Hz and J1b,2 = 4.8 Hz, 1H, H-1b), 4.18
(m, 1H. H-4), 4.12–4.01 (m, 2H, H-3 and H-5), 3.99–3.94
2.8 Hz, 1H, H-1a), 3.71 (dd, J1b,1a = 12.8 Hz and
(m, 1H, H-6a), 3.87 (dd, J6b,6a = 12.8 Hz and J6b,5 =

R. Sagar et al. / Tetrahedron: Asymmetry 17 (2006) 1189–1198
1197
Derivatives in the Asymmetric Synthesis of Natural Products.
In Fortschr. Chem. Org. Naturst.; Springer: Wien, 1980, p 1;
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3161–3213; (f) Casiraghi, G.; Zanardi, F.; Rassu, G.; Spanu,
P. Chem. Rev. 1995, 95, 1677–1716; (g) Hudlicky, T. Chem.
Rev. 1996, 96, 3–30; (h) Wu, Y.-L.; Wu, W.-L.; Li, Y.-L.;
Sun, X.-L.; Peng, Z.-H. Pure Appl. Chem. 1996, 68, 727–734;
4.4 Hz, 1H, H-6b), 2.05 (s, 3H, COCH3), 1.94 (s, 3H,
COCH3); 13C NMR (50 MHz, CDCl3): d 171.2, 170.0
(2 · COCH3), 137.9, 137.6 (Ar qC), 128.9, 128.5, 128.4,
128.0 (ArC), 81.6 (C-5), 81.2 (C-4), 78.7 (C-2), 72.5
(CH2Ph), 72.3 (C-6), 71.8 (CH2Ph), 69.5 (C-3), 63.7
(C-1), 21.3, 21.2 (2 · COCH3).
4.4.14. 3,6-Anhydro-4,5-di-O-benzyl-L-galactitol (17). Oil,
eluent for column chromatography: EtOAc/hexane (8/17,
v/v), Rf 0.20 (1/1 EtOAc/hexane); [a]D = +2.0 (c 0.100,
CHCl3); IR (neat, cmÀ1): 3422 (O–H str), 3066, 3015
(@C–H str), 2927, 2857 (–C–H str), 1496, 1456 (C@C
´
´
´
(i) H-Lopez, A. M.; P-Gonzalez, M. S.; S-Garcıa, F.; L-
Herrera, F. J. J. Org. Chem. 1998, 63, 9630–9634.
3. (a) Gonzalez, F.; Lesage, S.; Perlin, A. S. Carbohydr. Res.
1975, 42, 267–274; (b) Sagar, R.; Pathak, R.; Shaw, A. K.
Carbohydr. Res. 2004, 339, 2031–2035; (c) Saquib, M.; Sagar,
R.; Shaw, A. K. Carbohydr. Res. 2006, 341, 1052–1056.
4. (a) Horton, D.; Liav, A. Carbohydr. Res. 1972, 24, 105–113;
(b) Kaluza, Z.; Chmielewski, M.; Pedersen, E. B. Heterocy-
cles 1988, 27, 1313–1316; (c) Wengel, J.; Lau, J.; Pedersen, E.
B. Synthesis 1989, 829–832; (d) Lau, J.; Pedersen, E. B. Chem.
Scr. 1989, 29, 67–70; (e) Walczak, K.; Pedersen, E. B.
Synthesis 1991, 959–962; (f) Lau, J.; Wengel, J.; Pedersen, E.
B.; Vestergaard, B. F. Synthesis 1991, 1183–1190; (g) Hirata,
N.; Yamagiwa, Y.; Kamikawa, T. J. Chem. Soc. Perkin
Trans. 1 1991, 2279–2280; (h) Wengel, J.; Pedersen, E. B.;
Vestergaard, B. F. Synthesis 1992, 319–322; (i) Lellouche,
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1
str), 1216, 1098 (C–O str); H NMR (200 MHz, CDCl3):
d 7.38–7.28 (m, 10H, ArH), 4.54–4.49 (m, 4H, 2 · CH2Ph),
4.18 (m, 1H, H-4), 4.09–4.00 (m, 2H, H-5 and H-6a), 3.91–
3.80 (m, 3H, H-2, H-3 and H-1a), 3.70 (dd, J6b,6a = 11.6 Hz
and J6b,5 = 3.8 Hz, 1H, H-6b); 3.62 (dd, J1b,1a = 11.8 Hz
and J1b,2 = 5.0 Hz, 1H, H-1b); 13C NMR (50 MHz,
CDCl3): d 138.0, 137.7 (Ar qC), 129.0, 128.9, 128.3, 128.2
(ArC), 85.5 (C-5), 83.7 (C-4), 83.0 (C-3), 72.2 (CH2Ph),
71.8 (C-6), 71.7 (C-2), 71.6 (CH2Ph), 64.0 (C-1); FAB
MS calcd for C20H24O5 m/z 344; found 345 [M+1]+Å,
323, 281, 257, 239. Elemental analysis calcd for C20H24O5Æ
H2O (362.43) C, 66.28; H, 7.23. Found: C, 66.38; H, 7.36.
4.4.15. 3,6-Anhydro-1,2-di-O-acetyl-4,5-di-O-benzyl-L-gala-
ctitol (18). Oil, eluent for column chromatography
EtOAc/hexane (1/9, v/v), [a]D = +19.1 (c 0.068, CHCl3);
1H NMR (200 MHz, CDCl3): d 7.39–7.28 (m, 10H,
5. Pathak, R.; Shaw, A. K.; Bhaduri, A. P.; Chandrasekhar, K.
V. G.; Srivastava, A.; Srivastava, K. K.; Chaturvedi, V.;
Srivastava, R.; Srivastava, B. S.; Arora, S.; Sinha, S. Bioorg.
Med. Chem. 2002, 10, 1695–1702.
6. Pathak, R.; Pant, C. S.; Shaw, A. K.; Bhaduri, A. P.;
Gaikward, A. N.; Sinha, S.; Srivastava, A.; Srivastava, K. K.;
Chaturvedi, V.; Srivastava, R.; Srivastava, B. S. Bioorg. Med.
Chem. 2002, 10, 3187–3196.
ArH), 5.22 (ddd, J2,3 = 7.5 Hz, J2,1b = 5.7 Hz and J2,1a
=
2.6 Hz, 1H, H-2), 4.56–4.49 (m, 4H, 2 · CH2Ph), 4.48
(dd, J1a,1b = 10.0 Hz and J1a,2 = 2.5 Hz, 1H, H-1a), 4.17
(dd, J1b,1a = 12.2 Hz and J1b,2 = 5.6 Hz, 1H, H-1b), 4.05–
3.99 (m, 4H, H-3, H-4, H-5 and H-6a), 3.92 (dd,
J6b,6a = 10.1 Hz and J6b,5 = 4.0 Hz, 1H, H-6b), 2.05 (s,
3H, COCH3), 2.00 (s, 3H, COCH3).
7. Sagar, R.; Singh, P.; Kumar, R.; Maulik, P. R.; Shaw, A. K.
Carbohydr. Res. 2005, 340, 1287–1300.
8. Andersson, K. N.; Blomberg, E.; Somfai, P. J. Org. Chem.
2004, 69, 3746–3752.
Acknowledgements
9. Behrens, C. H.; Sharpless, K. B. Aldrichim. Acta 1983, 16, 67–
79.
10. Katsuki, T.; Lee, A. W. M.; Ma, P.; Martin, V. S.;
Masamune, S.; Sharpless, K. B.; Tuddenham, D.; Walker,
F. J. J. Org. Chem. 1982, 47, 1373–1378.
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stro¨m, U. M. Tetrahedron 2003, 59, 1293–1299.
We are thankful to a referee for his constructive comments
on this article, Sophisticated Analytical Instrument Facility
(SAIF) CDRI for providing spectral data and Mr. Anup
Kishore Pandey for technical assistance. R.S. is thankful
to DOD and LVRR to CSIR, New Delhi, for financial
assistance.
12. Reddy, L. V. R.; Sagar, R.; Shaw, A. K. Tetrahedron Lett.
2006, 47, 1753–1756.
13. (a) Lee, A. W. M.; Martin, V. S.; Masamune, S.; Sharpless,
K. B.; Walker, F. J. J. Am. Chem. Soc. 1982, 104, 3515–3516;
(b) Organic reactions; Leo A, Paquette et al., Eds.; John
Wiley & Sons, 1996; Vol. 48, pp 1–45.
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