β-Hydroxy-α-tosyloxy esters as chiral building blocks for the enantioselective synthesis of benzo-annulated oxa-heterocycles: scope and limitations

Article abstract of DOI:10.1016/j.tet.2008.03.001

The enantioselective synthesis of benzo-annulated oxa-heterocycles 2,3-dihydrobenzofuran and 1-benzopyran derivatives is described using β-hydroxy-α-tosyloxy esters as chiral building blocks, which are easily accessible through the regioselective α-tosyla

Full text of DOI:10.1016/j.tet.2008.03.001

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Tetrahedron 64 (2008) 4162e4173
www.elsevier.com/locate/tet
b-Hydroxy-a-tosyloxy esters as chiral building blocks for the
enantioselective synthesis of benzo-annulated oxa-heterocycles:
scope and limitations*
*
Sajal Kumar Das, Gautam Panda
Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow-226001, UP, India
Received 17 December 2007; received in revised form 29 February 2008; accepted 1 March 2008
Available online 7 March 2008
Abstract
The enantioselective synthesis of benzo-annulated oxa-heterocycles 2,3-dihydrobenzofuran and 1-benzopyran derivatives is described using
b-hydroxy-a-tosyloxy esters as chiral building blocks, which are easily accessible through the regioselective a-tosylation of Sharpless asymmet-
ric dihydroxylation-derived syn-2,3-dihydroxy esters.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
product-like small molecules (Fig. 1)6e11 containing 2,3-dihy-
drobenzofuran, 1-benzopyran, and 1-benzoxepin frame works.
Since the pioneering report of Sharpless on the regio-
selective arenesulfonylation of the a-hydroxy group of
syn-2,3-dihydroxy esters,12 the resulting trifunctional b-hy-
droxy-a-arenesulfonyloxy esters have been extensively used
for their conversions into the corresponding a-azido-b-hydroxy
esters12,13 and glycidic esters.12,14 The only other synthetic
utility we are aware of is their use in the synthesis of a combi-
natorial library of tetrahydroquinoline based polycyclic
molecules.15 Thus, despite their easy accessibility and multi-
functionalities, b-hydroxy-a-arenesulfonyloxy esters have not
been largely utilized for benzo-annulated heterocycle synthe-
sis. This paper describes our efforts toward generation of
benzo-annulated oxa-heterocycles through phenoxide ion me-
diated intramolecular SN2 reaction on the tosyloxy group of
b-hydroxy-a-tosyloxy esters and ring opening of syn-glycidic
esters, which were derived from b-hydroxy-a-tosyloxy esters.
Over the past several years, organic synthesis of natural
product-like molecules have received significant attention
due to the growing use of small-molecule libraries for studies
of protein function and discovery of novel drug leads.1 Small-
molecule libraries generated from the core scaffolds derived
from natural products are proving to be a valuable source of
biologically active compounds that provide new probes for
molecular targets. In this context, new methodologies have
to be designed for stereoselective synthesis of small-molecule
libraries with distinct skeletal frame works via diversity-ori-
ented synthesis (DOS).2
Following our interest in the field of diversity-oriented syn-
thesis of benzo-annulated heterocycles as privileged struc-
tures, we recently employed naturally occurring a-amino
acids as chiral pools that provided an access to a large array
of benzofused heterocycles.3e5 As part of our research pro-
gram related to the diversity-oriented synthesis (DOS), we be-
came interested in the enantioselective synthesis of natural
2. Results and discussion
Initially, we focused our attention on a stereoselective syn-
thesis of 2,3-dihydro-3-hydroxy-2-[1-hydroxy-1-(methyl)-eth-
yl]benzofuran ring system, which constitutes the core skeleton
of a number of biologically important natural products (Fig. 1,
*
CDRI communication number 7330.
* Corresponding author. Tel.: þ91 522 2612411/18x4385/4469/4474; fax:
þ91 522 2623405.
E-mail address: gautam.panda@gmail.com (G. Panda).
0040-4020/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.03.001

S.K. Das, G. Panda / Tetrahedron 64 (2008) 4162e4173
4163
O
Conversion of diol 12a into b-hydroxy-a-tosyloxy ester 13a
was achieved by the regioselective a-tosylation of diol 12a
with tosyl chloride (1.05 equiv) and triethyl amine in dry
CH2Cl2 at 0 ꢀC for 72 h.12 All the products were well charac-
terized by NMR and MS studies.
Next, hydroxyl group of 13a was protected as its tert-butyl
dimethylsilyl ether by using tert-butyl dimethylsilyl triflate in
the presence of 2,6-lutidine affording 14a with excellent yield
(Scheme 2). Catalytic debenzylation of 14a with hydrogen and
10% Pd/C in ethyl acetate followed by cyclization of the re-
sulting debenzylated product in the presence of anhydrous
K2CO3 in dry acetone afforded 2,3-dihydrobenzofuran deriva-
tive 15a in good yield. Treatment of the ester 15a with an ex-
cess of methylmagnesium iodide furnished the tertiary alcohol
16a. Finally, removal of the TBDMS of 16a with TBAF in dry
THF afforded 17a in 91% yield.
O
O
O
OH
OH
O
OH
2, Vaginol7
O
OH
1, Xanthoarnol6
O
OMe
HO
O
OH
OH
OH
O
OH
OH
OMe
4, Avicenol A9
3, Brosimacutin G8
OH
OH
O
OH
OH
O
O
O
HO
HO
7, Helliannuol D11
5, Megapodiol10
6, Helliannuol E11
OBn
OH
Diversity of
intramolecular
ring formation
Ring nature and ring
substituents diversity
CO2Et
( )n
*
*
OBn
O
OTs
O
a
OTs
c
b
Ring size
diversity
13a
OH
Configurational
diversity
CO2Et
8, Enantiomerically enriched
β-hydroxy-α-tosyloxy ester
n = 0, 1 and 2.
CO2Et
OTBDMS
OTBDMS
OTBDMS
14a
15a
16a
O
d
Figure 1. Bioactive natural products (1e7) containing benzo-annulated oxa-
heterocycles and the synthetic versatility of b-hydroxy-a-tosyloxy esters (8)
in our synthetic strategy.
OH
OH
17a
Scheme 2. Reagents and conditions: (a) TBDMS-OTf, 2,6-lutidine, 0 ꢀCert,
6 h, 85%; (b) (i) H2, 10% Pd/C, EtOAc, 4 h; (ii) anhyd K2CO3, dry acetone,
6 h, 69% (based on two steps); (c) MeMgI, dry ether, reflux, 4 h, 77%; (d)
TBAF, dry THF, 0 ꢀC, 5 h, 91%.
compounds 1e4). Although these compounds were known for
a long time, these compounds have not been the subjects of
much organic synthesis. The only successful synthetic study
of the natural products in this family, we are aware of are
the recent reports by Snider et al.16
After the enantioselective synthesis of 2,3-dihydrobenzo-
furan derivative 17a, our next attention was to synthesize
structurally related dihydronaphthofuran analog of 17a.
Thus, commercially available 2-hydroxy-1-naphthaldehyde
9b was converted into 17b using the same reaction sequence
as that described for the synthesis of 17a (Scheme 3).
Our model synthesis to obtain enantiopure 2,3-dihydro-3-
hydroxy-2-[1-hydroxy-1-(methyl)-ethyl]-benzofuran deriva-
tive is shown in Scheme 1. Benzylation of commercially
available 2-hydroxybenzaldehyde 9a with benzyl bromide
and anhydrous K2CO3 in dry acetone under reflux condition
followed by Wittig olefination of the resulting 2-benzyloxy-
benzaldehyde 10a with (carbethoxymethylene)triphenyl-
phosphorane in dry CH2Cl2 at room temperature furnished
the corresponding trans cinnamate ester 11a. The trans cinna-
mate ester 11a was then subjected to Sharpless asymmetric di-
hydroxylation17 with AD-mix-a in t-BuOH/H2O (1:1) at 0 ꢀC
for 28 h furnishing enantiopure dihydroxyl derivatives 12a in
good yield and high enantiomeric excess (92%, ee>99%).
OH
OBn
OBn
a
c
b
CHO
CHO
CO2Et
11b
9b
10b
OBn
OH
OBn
OTs
OBn
OTs
d
e
CO2Et
CO2Et
CO2Et
OTBDMS
14b
OH
12b
OH
13b
OBn
OH
OBn
OH
OBn
O
O
a
b
c
g
f
OH
CO2Et
CHO
CO2Et
CHO
CO2Et
9a
12a
10a
11a
OH
OH
OTBDMS
17b
15b
OBn
OTs
d
Scheme 3. Reagents and conditions: (a) BnBr, anhyd K2CO3, dry acetone, re-
flux, 4 h, 83%; (b) Ph3P]CHCO2Et, dry CH2Cl2, rt, 2 h, 80%. (c) AD-mix-a,
t-BuOH/H2O (1:1), 0 ꢀC, 28 h, 93%; (d) TsCl, dry Et3N, dry CH2Cl2, 0 ꢀC,
72 h, 94%; (e) TBDMS-OTf, 2,6-lutidine, 0 ꢀCert, 6 h, 88%; (f) (i) H2,
10% Pd/C, EtOAc, 4 h; (ii) anhyd K2CO3, dry acetone, 6 h, 72% (based on
two steps); (c) (i) MeMgI, dry ether, reflux, 4 h; (ii) TBAF, dry THF, 0 ꢀC,
5 h, 74% for two steps.
CO2Et
13a
OH
Scheme 1. Reagents and conditions: (a) BnBr, anhyd K2CO3, dry acetone, re-
flux, 4 h, 85%; (b) Ph3P]CHCO2Et, dry CH2Cl2, rt, 2 h, 78%; (c) AD-mix-a,
t-BuOH/H2O (1:1), 0 ꢀC, 28 h, 92%; (d) TsCl, dry Et3N, dry CH2Cl2, 0 ꢀC,
72 h, 87%.

4164
S.K. Das, G. Panda / Tetrahedron 64 (2008) 4162e4173
OBn
OTBDMS
The successful synthesis of enantiomerically pure 17a,17b
O
CO2Et
a
c
b
23
encouraged us to initiate further application of this strategy on
homologated analog of 13a for the synthesis of other 2,3-dihy-
drobenzofuran and 1-benzopyran derivatives. Toward that di-
rection, aldehyde 10a was converted into olefin 18 by Wittig
reaction with methyltriphenylphosphonium iodide and potas-
sium tert-butoxide in dry THF (Scheme 4). Olefin 18 was con-
verted into primary alcohol 19 by hydroboration with 9-BBN
and oxidation with hydrogen peroxide and NaOH. Compound
19 was oxidized to its corresponding aldehyde 20 by PCC in
dry CH2Cl2. With aldehyde 20 in hand, next work was the con-
version of it into b-hydroxy-a-tosyloxy ester 23 using a similar
reaction sequence as that described for the synthesis of 13a.
CO2Et
OTBDMS
27
28
OTs
OH
OH
O
O
d
OH
OTBDMS
29
30
Scheme 6. Reagents and conditions: (a) TBDMS-OTf, 2,6-lutidine, 0 ꢀCert,
6 h, 89%; (b) (i) H2, 10% Pd/C, EtOAc, 4 h; (ii) anhyd K2CO3, dry acetone,
8 h (70%, based on two steps); (c) MeMgI, dry ether, reflux, 4 h, 91%; (d)
TBAF, dry THF, 0 ꢀC, 5 h, 87%.
The successful utilization of b-hydroxy-a-tosyloxy esters
in the synthesis of novel 2,3-dihydrobenzofurans and 1-benzo-
pyran derivative inspired us to initiate further application of
this strategy for the synthesis of another structurally related
1-benzopyran and 1-benzoxepin derivatives by using a b-hy-
droxy-a-tosyloxy ester 36 homologated by one more carbon
atom. The synthesis of 36 was achieved from aldehyde 20
by following the same reaction sequence as that described
for 23 (Scheme 7).
OBn
CHO
OBn
OBn
d
c
b
a
10a
OH
20
18
19
OBn
OH
OBn
OH
OBn
e
f
CO2Et
CO2Et
CO2Et
22
21
23
OH
OTs
Scheme 4. Reagents and conditions: (a) methyltriphenylphosphonium iodide,
t-BuOK, dry THF, 0 ꢀCert, 2 h, 80%; (b) (i) 9-BBN, dry THF, 0 ꢀCert, over-
night; (ii) NaOH/H2O2, reflux, 2 h, 96%; (c) PCC, dry CH2Cl2, 2 h, 0 ꢀCert,
76%; (d) Ph3P]CHCO2Et, dry CH2Cl2, rt, overnight, 75%; (e) AD-mix-a, t-
BuOH/H2O (1:1), 0 ꢀC, 40 h, 89%; (f) TsCl, dry Et3N, dry CH2Cl2, 0 ꢀC, 72 h,
85%.
OBn
OBn
OBn
b
a
c
20
OH
CHO
31
OBn
33
32
OBn
d
f
e
OH
CO2Et
CO2Et
35
34
OBn
OH
With the availability of 23, its conversion into 2,3-dihydro-
benzofuran derivative (Scheme 5) was first attempted. Accord-
ingly, treatment of b-hydroxy-a-tosyloxy ester 23 with
anhydrous K2CO3 in absolute ethanol furnished epoxy ester
24 in good yield. Next, debenzylation of 24 under hydrogen
atmosphere using 10% Pd/C as catalyst followed by anhydrous
K2CO3 induced phenoxide ion mediated intramolecular 5-exo-
tet epoxide ring opening produced enantiomerically pure
dihydrobenzofuran based a-hydroxy ester 25, which on meth-
ylmagnesium iodide Grignard reaction furnished 26. To the
best of our knowledge, this is the first report of phenoxide
ion mediated intramolecular ring opening of syn-glycidic ester.
OTs
CO2Et
36
OH
Scheme 7. Reagents and conditions: (a) methyltriphenylphosphonium iodide,
t-BuOK, dry THF, 0 ꢀCert, 2 h, 88%; (b) (i) 9-BBN, dry THF, 0 ꢀCert, over-
night; (ii) NaOH/H2O2, reflux, 2 h, 96%; (c) PCC, dry DCM, 2 h, 0 ꢀCert,
72%; (d) Ph3P]CHCO2Et, dry DCM, rt, overnight, 77%; (e) AD-mix-a, t-
BuOH/H2O (1:1), 0 ꢀC, 40 h, 87%; (f) TsCl, dry Et3N, dry DCM, 0 ꢀC,
72 h, 80%.
With the availability of 36, attention was first turned to its
elaboration into 1-benzopyran derivative (Scheme 8). Thus, b-
hydroxy-a-tosyloxy ester 36 was converted into 1-benzopyran
derivative 39 using a similar reaction sequence as that de-
scribed for the synthesis of 26.
OBn
OH
O
OH
O
a
b
c
23
O
CO2Et
OH
26
24
CO2Et 25
OH
Scheme 5. Reagents and conditions: (a) anhyd K2CO3, ethanol, rt, 8 h, 75%;
(b) (i) H2, 10% Pd/C, ethyl acetate, 2 h; (ii) anhyd K2CO3, dry acetone, rt,
6 h, 81% (for two steps); (c) MeMgI, dry ether, reflux, 4 h, 88%.
OBn
O
b
a
c
CO2Et
O
CO2Et
36
37
38
OH
After the effective utilization of 23 in the synthesis of enan-
tiomerically pure 26, we wanted to further utilize it for the
synthesis of 1-benzopyran derivative involving phenoxide
ion mediated intramolecular SN2 reaction of tosyloxy group.
Thus, 23 was converted into 1-benzopyran derivative 30 using
a similar reaction sequence as that described for the synthesis
of 17a (Scheme 6).
O
OH
39
Scheme 8. Reagents and conditions: (a) anhyd K2CO3, ethanol, 8 h, 78%; (b)
(i) H2, 10% Pd/C, ethyl acetate, 2 h; (ii) anhyd K2CO3, dry acetone, 6 h, (68%,
for two steps); (c) MeMgI, dry ether, reflux, 4 h, 83%.

S.K. Das, G. Panda / Tetrahedron 64 (2008) 4162e4173
4165
O-
performed over silica gel (60e120 mesh) procured from
Qualigens (India) using freshly distilled solvents. Mass spectra
were recorded as electron spray ionization (ESI-MS) or fast
atom bombardment spectra (FABMS) on a JEOL SX 102
spectrometer using argon/xenon as the FAB gas. Elemental
analyses were done on Varian EL-III CHN analyzer. Melting
points were determined on COMPLAB melting point appara-
tus and are uncorrected. IR spectra were recorded on a Per-
kineElmer FT-IR RXI spectrometer. 1H NMR and 13C
NMR spectra were recorded on Brucker DPX-200 (operating
at 200 MHz for 1H and 50 MHz for 13C) or DPX-300 (operat-
X
OBn
a
OTs
CO2Et
OTBDMS
OTs
CO2Et
OTBDMS
b
36
40
CO2Et
OH
O
X
41, not formed
Scheme 9. Reagents and conditions: (a) TBDMS-OTf, 2,6-lutidine, 0 ꢀCert,
8 h, 85%; (b) (i) H2, 10% Pd/C, ethyl acetate; (ii) anhyd K2CO3, dry acetone,
reflux, 15 h.
1
ing at 300 MHz for H and 75 MHz for 13C) spectrometer
using CDCl3 or acetone-d6 as solvent. Tetramethylsilane
(0.00 ppm) served as an internal standard in H NMR and
In an attempt to utilize b-hydroxy-a-tosyloxy ester 36 for
the synthesis of 1-benzoxepin derivative, 36 was converted
into 40, which was first debenzylated and subsequently treated
with anhydrous K2CO3 (as described for the synthesis of
15a,15b and 28). To our dismay, the reaction did not proceed
at all to give 41 and the starting phenolic derivative remained
unchanged. Varying the base, solvent, reaction time, and tem-
perature did not give any fruitful result. This is perhaps for the
easy formation of five- and six-membered rings over seven-
membered ones (Scheme 9).
1
CDCl3 (77.0 ppm) in 13C NMR. All spectra were recorded
at 25 ꢀC. Coupling constants (J values) are given in hertz
(Hz). Chemical shifts are expressed in parts per million. The
enantiomeric excess was determined by LichroCART Chira-
dex column (250ꢁ4 mm, 5 mm) using water and methanol as
eluent at 25 ꢀC. Optical rotations were measured at the sodium
D-line at ambient temperature, with a Perkin Elmer 141
polarimeter.
4.2. 2-Benzyloxy-benzaldehyde (10a)
3. Conclusion
To a solution of commercially available 2-hydroxybenz-
aldehyde (10 mL, 95.64 mmol) in dry acetone (200 mL) was
added anhydrous K2CO3 (20.0 g, 144.70 mmol) and benzyl
bromide (13.0 mL, 109.52 mmol) and refluxed for 4 h. The
mixture was then filtered through Celite and the filter cake
was well washed with acetone (200 mL). The filtrate was con-
centrated and the resulting residue was redissolved in ethyl ac-
etate (300 mL), washed with water (2ꢁ100 mL) and brine
(100 mL). The organic layer was dried over anhydrous
Na2SO4, filtered, and then concentrated in vacuo. Purification
of the crude product by silica gel column chromatography (4%
ethyl acetate in hexane) afforded 10a (17.25 g, 85%) as a color-
less oil. Rf: 0.52 (20% ethyl acetate in hexane). IR (neat):
In summary, an efficient enantioselective synthesis of ‘nat-
ural product-like’ benzo-annulated oxa-heterocycles 2,3-dihy-
drobenzofuran and 1-benzopyran is described using b-
hydroxy-a-tosyloxy esters as chiral building blocks, which
are easily accessible through regioselective a-tosylation of
Sharpless asymmetric dihydroxylation-derived syn-2,3-dihy-
droxy esters. However, the methodology was not feasible to
synthesize 1-benzoxepine derivatives. The ease of the reaction
sequence, as well as the commercial availability of large array
of starting 2-hydroxyaromatic aldehydes, makes this process
a practical method for the preparation of ‘natural product-
like’ 2,3-dihydrobenzofuran and 1-benzopyran derivatives. In
addition, the scope of the reaction sequence is much broader,
and the synthesis of various substituted aromatic and hetero-
aromatic nuclei can be envisioned from the starting hydroxy
aldehydes.
2874, 1680, 1597, 1237, 991, 755 cmꢂ1
.
1H NMR
(200 MHz, CDCl3): d 10.55 (s, 1H), 7.85 (dd, 1H, J1¼2.0,
J2¼7.9), 7.52e7.36 (m, 6H), 7.06e7.02 (m, 2H), 5.17 (s,
2H). 13C NMR (75 MHz, CDCl3): d 189.5, 160.9, 135.9,
135.8, 128.6, 128.2, 128.1, 127.1, 124.9, 120.8, 112.9, 70.2.
MS (ESI): m/z 212 [M]þ, 91 [C6H5CH2]þ. Anal. Calcd for
C14H12O2: C, 79.22; H, 5.70. Found: C, 79.37; H, 5.88. The
above spectroscopic data are in full agreement with the
literature data.18
4. Experimental
4.1. General methods
All dry reactions were carried out under argon or nitrogen
in oven-dried glassware using standard gas-light syringes, can-
nulas, and septa. All reagents and solvents were dried prior to
use according to the standard methods. Commercial reagents
were used without further purification unless otherwise stated.
Reactions were monitored on silica gel TLC plates (coated
with TLC grade silica gel, obtained from Merck). Detecting
agents used (for TLC) were iodine vapors and/or spraying
with an aqueous solution of vanillin in 10% sulfuric acid fol-
lowed by heating at 150 ꢀC. Column chromatography was
4.3. 2-Benzyloxy-naphthalene-1-carbaldehyde (10b)
Using commercially available 2-hydroxy-1-naphthaldehyde
(2.0 g, 11.61 mmol), the title compound was prepared in the
same manner as that described for 10a. Purification of the
crude product by silica gel column chromatography (4% ethyl
acetate in hexane) afforded 10b (2.52 g, 83%) as a light-
yellow solid. Mp: 118e119 ꢀC. Rf: 0.49 (20% ethyl acetate
in hexane). IR (KBr): 2886, 1660, 1589, 1510, 1347, 1269,

4166
S.K. Das, G. Panda / Tetrahedron 64 (2008) 4162e4173
1220, 1147, 1055, 807, 750 cmꢂ1
.
1H NMR (200 MHz,
were clear and then cooled to 0 ꢀC. A solution of cinnamate
CDCl3): d 10.96 (s, 1H), 9.28 (d, 1H, J¼8.6), 8.01 (d, 1H,
J¼9.1), 7.75 (d, 1H, J¼8.0), 7.65e7.57 (m, 1H), 7.43e7.28
(m, 7H), 5.31 (s, 2H). 13C NMR (50 MHz, CDCl3): d 192.5,
163.6, 137.9, 136.4, 131.9, 130.3, 129.2, 129.1, 128.8,
128.6, 127.8, 125.4, 125.3, 117.6, 114.4, 71.9. MS (ESI):
m/z 263 [Mþ1]þ, 91 [C6H5CH2]þ. Anal. Calcd for C18H14O2:
C, 82.42; H, 5.38. Found: C, 82.51; H, 5.49. The above spec-
troscopic data are in full agreement with the literature data.19
ester 11a (1.0 g, 3.54 mmol) in tert-butyl alcohol (5 mL)
was added 0 ꢀC. The reaction mixture was stirred at the
same temperature for 28 h. The reaction was quenched at
0 ꢀC by the addition of sodium sulfite (5.1 g), warmed to
room temperature, and further stirred for 1 h. The reaction
mixture was then extracted with ethyl acetate (3ꢁ50 mL).
The combined organic layer was washed with aqueous 2 N
KOH solution (50 mL), water (50 mL), and brine (50 mL).
The organic layer was dried over anhydrous Na2SO4, filtered,
and then concentrated in vacuo. Purification of the crude prod-
uct by silica gel column chromatography (25% ethyl acetate in
hexane) afforded 12a (1.03 g, 92%) as a colorless solid. Mp:
96e97 ꢀC. Rf: 0.35 (40% ethyl acetate in hexane). [a]2D5
þ8.4 (c 0.9, CHCl3). The enantiomeric excess was estimated
to be >99% by chiral HPLC analysis (instrument: HP1100,
column: LichroCART Chiradex column 250ꢁ4 mm, 5 mm),
flow rate: 0.5 mL/min, detection: UV 254 nm (eluent: metha-
nol/H2O). IR (KBr): 3537, 3512, 2982, 1722, 1601, 1496,
4.4. (2E)-3-(2-Benzyloxy-phenyl)-acrylic acid ethyl ester
(11a)
To a solution of 10a (1.50 g, 7.06 mmol) in dichlorome-
thane (20 mL) was added (carbethoxymethylene)triphenyl-
phosphorane (3.0 g, 8.60 mmol) at room temperature. The
reaction mixture was stirred at room temperature for 2 h. Sol-
vent was removed under reduced pressure and the residue was
purified by silica gel column chromatography (4% ethyl ace-
tate in hexane) to afford 11a (1.55 g, 78%) as a colorless
gum. Rf: 0.58 (20% ethyl acetate in hexane). IR (KBr):
1456, 1386, 1290, 1240, 1111, 1049, 760, 736 cmꢂ1 1H
.
NMR (300 MHz, CDCl3): d 7.45e7.24 (m, 7H), 7.03e6.93
(m, 2H), 5.42 (s, 1H), 5.10 (d, 1H, J¼11.8), 5.09 (d, 1H,
J¼11.8), 4.50 (s, 1H), 4.27e4.17 (m, 2H), 3.13 (br s, 1H),
3.01 (br s, 1H), 1.22 (t, 3H, J¼7.1). 13C NMR (75 MHz,
CDCl3): d 173.0, 155.1, 136.7, 128.8, 128.5, 127.9, 127.2,
127.0, 121.0, 111.5, 73.2, 70.3, 70.0, 61.9, 14.0. MS (ESI):
m/z 339 [MþNa]þ, 334 [MþNH4]þ, 299 [MꢂOH]þ, 91
[C6H5CH2]þ. Anal. Calcd for C18H20O5: C, 68.34; H, 6.37.
Found: C, 68.29; H, 6.51.
2937, 1715, 1502, 1277, 1179, 1066, 758 cmꢂ1 1H NMR
.
(300 MHz, CDCl3): d 8.08 (d, 1H, J¼16.1), 7.54 (dd, 1H,
J1¼1.3, J2¼7.6), 7.44e7.25 (m, 6H), 6.99e6.93 (m, 1H),
6.53 (d, 1H, J¼16.1), 5.17 (s, 2H), 4.24 (q, 2H, J¼7.1), 1.32
(t, 3H, J¼7.1). 13C NMR (75 MHz, CDCl3): d 167.4, 157.3,
139.8, 136.6, 131.3, 128.6, 128.6, 127.9, 127.1, 123.9,
121.0, 118.8, 112.8, 70.3, 60.2, 14.3. MS (FAB): m/z 283
[Mþ1]þ, 237 [MꢂOEt]þ. Anal. Calcd for C18H18O3: C,
76.57; H, 6.43. Found: C, 76.46; H, 6.34.
4.7. 3-(2-Benzyloxy-naphthalen-1-yl)-2,3-dihydroxy-
4.5. (2E)-3-(2-Benzyloxy-naphthalen-1-yl)-acrylic acid ethyl
ester (11b)
propionic acid ethyl ester (12b)
Starting from 1.25 g (3.76 mmol) of 11b, the title com-
pound was prepared in the same manner as that described
for 12a. Purification of the crude product by silica gel column
chromatography (25% ethyl acetate in hexane) afforded 12b
(1.28 g, 93%) as a colorless gum. Rf: 0.37 (40% ethyl acetate
in hexane). [a]2D5 ꢂ4.4 (c 1.13, CHCl3). The enantiomeric ex-
cess was estimated to be >99% by chiral HPLC analysis as
that described for 12a. IR (KBr): 3509, 1720, 1250, 1125,
Using 1.5 g (5.71 mmol) of 10b, the title compound was
prepared in the same manner as that described for 11a. Purifi-
cation of the crude product by silica gel column chromatogra-
phy (4% ethyl acetate in hexane) afforded 11b (1.51 g, 80%)
as a colorless semi-solid. Rf: 0.50 (20% ethyl acetate in hex-
ane). IR (KBr): 2927, 2363, 1707, 1592, 1267, 1165, 1044,
745 cmꢂ1
.
1H NMR (200 MHz, CDCl3): d 1H NMR
1
(200 MHz, CDCl3): d 8.38 (d, 1H, J¼16.1), 8.19 (d, 1H,
J¼8.5), 7.79e7.75 (m, 2H), 7.55e7.24 (m, 8H), 6.78 (d,
1H, J¼16.1), 5.29 (s, 2H), 4.30 (q, 2H, J¼7.1), 1.35 (t, 3H,
J¼7.1). 13C NMR (50 MHz, CDCl3): d 168.2, 155.9, 138.1,
137.1, 131.7, 130.0, 129.6, 129.0, 128.4, 127.8, 127.5,
127.0, 124.5, 124.2, 123.9, 118.1, 114.9, 71.6, 60.8, 14.8.
MS (ESI): m/z 333 [M]þ, 287 [MꢂOEt]þ. Anal. Calcd for
C22H20O3: C, 79.50; H, 6.06. Found: C, 79.59; H, 6.18.
1048, 757, 742 cmꢂ1. H NMR (300 MHz, CDCl3): d 8.04
(d, 1H, J¼8.6), 7.78 (d, 2H, J¼8.8), 7.52e7.29 (m, 8H),
5.82 (d, 1H, J¼4.3), 5.25 (s, 2H), 4.88 (br s, 1H), 4.56 (d,
1H, J¼4.7), 4.13e3.98 (m, 2H), 3.26 (br s, 1H), 1.01 (t, 3H,
J¼7.1). 13C NMR (75 MHz, CDCl3): d 172.6, 155.0, 136.1,
131.7, 130.1, 129.5, 128.8, 128.7, 128.4, 127.5, 127.1,
123.9, 122.5, 119.8, 114.9, 74.4, 72.3, 72.1, 61.7, 13.7. MS
(ESI): m/z 389 [MþNa]þ, 384 [MþNH4]þ, 349 [MꢂOH]þ,
91 [C6H5CH2]þ. Anal. Calcd for C22H22O5: C, 72.12; H,
6.05. Found: C, 72.19; H, 6.18.
4.6. (2R,3S)-3-(2-Benzyloxy-phenyl)-2,3-dihydroxy-propionic
acid ethyl ester (12a)
4.8. (2R,3S)-3-(2-Benzyloxy-phenyl)-3-hydroxy-2-(toluene-
To a stirred solution of tert-butyl alcohol (18 mL) and water
(18 mL) were added AD-mix-a (5.0 g) and methanesulfon-
amide (0.34 g, 3.54 mmol) at room temperature. The mixture
was vigorously stirred at room temperature until both phases
4-sulfonyloxy)-propionic acid ethyl ester (13a)
To a solution of diol 12a (1.0 g, 3.16 mmol) in dry CH2Cl2
(20 mL) at 0 ꢀC was added dry triethyl amine (0.75 mL,

S.K. Das, G. Panda / Tetrahedron 64 (2008) 4162e4173
4167
5.37 mmol) followed by tosyl chloride (0.62 g, 3.25 mmol)
and kept in the refrigerator for 3 days. The reaction mixture
was diluted with H2O (50 mL), and extracted with CH2Cl2
(2ꢁ50 mL). The combined organic layers were washed with
brine (50 mL) and dried over anhydrous Na2SO4. The solvent
was removed under reduced pressure and purification of the
crude product by silica gel column chromatography (18%
ethyl acetate in hexane) afforded 13a (1.30 g, 87%) as a white
solid. Mp: 105e106 ꢀC. Rf: 0.41 (40% ethyl acetate in hex-
ane). [a]2D5 þ62.8 (c 1.5, CHCl3). IR (KBr): 3436, 2989,
2364, 1749, 1618, 1509, 1445, 1284, 1204, 1039, 826,
and purification of the crude product by silica gel column
chromatography (6% ethyl acetate in hexane) afforded 14a
(1.05 g, 85%) as a colorless solid. Mp: 75e76 ꢀC. Rf: 0.52
(20% ethyl acetate in hexane). [a]2D5 þ45.4 (c 2.34, CHCl3).
IR (KBr): 2930, 2362, 1764, 1597, 1370, 1220, 1181, 1039,
1
901, 758 cmꢂ1. H NMR (300 MHz, CDCl3): d 7.41e7.31
(m, 8H), 7.18e7.12 (m, 1H), 7.04 (d, 2H, J¼8.1), 6.89e
6.84 (m, 1H), 6.69 (d, 1H, J¼7.9), 5.62 (d, 1H, J¼2.8), 5.04
(d, 1H, J¼3.1), 5.01 (d, 1H, J1¼12.0), 4.98 (d, 1H, J1¼
12.0), 4.19e4.05 (m, 2H), 2.16 (s, 3H), 1.17 (t, 3H, J¼7.1),
0.84 (s, 9H), ꢂ0.04 (s, 3H), ꢂ0.19 (s, 3H). 13C NMR
(75 MHz, CDCl3): d 167.1, 154.2, 143.9, 136.7, 132.9,
129.2, 129.0, 128.7, 128.5, 127.8, 127.6, 127.0, 126.7,
120.6, 110.9, 79.8, 69.6, 69.1, 61.5, 25.5, 21.5, 18.0, 13.7,
ꢂ4.9, ꢂ5.6. MS (ESI): m/z 608 [MþNa]þ, 602 [MþNH4]þ.
Anal. Calcd for C31H40O7SSi: C, 63.67; H, 6.89. Found: C,
63.56; H, 7.07.
730 cmꢂ1 1H NMR (300 MHz, CDCl3): d 7.44e7.18 (m,
.
9H), 7.08 (d, 2H, J¼8.2), 6.91 (d, 1H, J¼7.0), 6.77 (d, 1H,
J¼8.2), 5.39 (s, 1H), 5.23 (d, 1H, J¼3.6), 5.00 (d, 1H,
J¼13.0), 4.99 (d, 1H, J¼13.0), 4.13 (q, 2H, J¼7.1), 2.82 (br
s, 1H), 2.38 (s, 3H), 1.15 (t, 3H, J¼7.1). 13C NMR
(75 MHz, CDCl3): d 167.1, 155.0, 144.4, 136.4, 132.7,
129.4, 129.1, 128.6, 128.0, 127.7, 127.1, 126.0, 121.1, 111.4,
79.3, 70.6, 70.0, 61.8, 21.5, 13.8. MS (ESI): m/z 493
[MþNa]þ, 488 [MþNH4]þ, 453 [MꢂOH]þ. Anal. Calcd for
C25H26O7S: C, 63.81; H, 5.57. Found: C, 63.98; 5.50.
4.11. (2R,3S)-3-(2-Benzyloxy-naphthalen-1-yl)-3-(tert-butyl-
dimethyl-silanyloxy)-2-(toluene-4-sulfonyloxy)-propionic
acid ethyl ester (14b)
4.9. (2R,3S)-3-(2-Benzyloxy-naphthalen-1-yl)-3-hydroxy-
2-(toluene-4-sulfonyloxy)-propionic acid ethyl ester (13b)
Starting from 1.0 g (1.92 mmol) of 13b, the title compound
was prepared in the same manner as that described for 14a.
Purification of the crude product by silica gel column chroma-
tography (6% ethyl acetate in hexane) afforded 14b (1.07 g,
88%) as a colorless semi-solid. Rf: 0.54 (20% ethyl acetate
in hexane). [a]2D5 þ60.0 (c 1.73, CHCl3). IR (KBr): 2932,
2360, 1741, 1460, 1375, 1248, 1180, 1028, 885, 840,
Starting from 1.0 g (2.72 mmol) of 12b, the title compound
was prepared in the same manner as that described for 13a.
Purification of the crude product by silica gel column chroma-
tography (18% ethyl acetate in hexane) afforded 13b (1.34 g,
94%) as a colorless solid. Mp: 109e110 ꢀC. Rf: 0.44 (40%
ethyl acetate in hexane). [a]2D5 þ54.7 (c 2.3, CHCl3). IR
(KBr): 3502, 2923, 2363, 1767, 1597, 1367, 1169, 1040,
737 cmꢂ1 1H NMR (300 MHz, CDCl3): d 8.61 (d, 1H,
.
J¼8.5), 7.61 (d, 2H, J¼8.6), 7.48e7.22 (m, 9H), 7.08 (d,
1H, J¼9.1), 6.87 (d, 1H, J¼8.1), 6.27 (d, 1H, J¼5.2), 5.22
(d, 1H, J¼5.2), 5.13 (s, 2H), 3.96 (q, 2H, J¼7.1), 2.28 (s,
3H), 0.98 (t, 3H, J¼7.1), 0.75 (s, 9H), ꢂ0.03 (s, 3H), ꢂ0.42
(s, 3H). 13C NMR (75 MHz, CDCl3): d 166.8, 152.6, 143.9,
136.8, 133.1, 132.5, 130.3, 129.5, 128.9, 128.6, 127.9,
127.7, 127.3, 127.2, 126.9, 125.8, 123.5, 119.4, 112.9, 81.3,
70.9, 69.3, 61.4, 25.5, 21.4, 17.9, 13.6, ꢂ5.4, ꢂ5.6. MS
(ESI): m/z 658 [MþNa]þ, 652 [MþNH4]þ. Anal. Calcd for
C35H42O7SSi: C, 66.22; H, 6.67. Found: C, 66.10; H, 6.43.
1
889, 856, 726 cmꢂ1. H NMR (300 MHz, CDCl3): d 7.81 (d,
1H, J¼8.5), 7.70e7.66 (m, 2H), 7.50 (d, 1H, J¼6.9), 7.44e
7.27 (m, 7H), 7.18 (d, 1H, J¼9.1), 6.87 (d, 1H, J¼8.1), 5.91
(d, 1H, J¼5.1), 5.22 (d, 1H, J¼5.1), 5.18 (s, 2H), 4.34 (br s,
1H), 3.94 (q, 2H, J¼7.1), 2.22 (s, 3H), 0.94 (t, 3H, J¼7.1).
13C NMR (75 MHz, CDCl3): d 166.7, 155.1, 144.3, 135.8,
132.1, 131.0, 130.5, 129.1, 128.7, 128.5, 128.3, 127.6, 127.3,
127.2, 123.8, 121.8, 117.2, 80.5, 71.6, 70.4, 61.6, 21.4, 13.5.
MS (ESI): m/z 543 [MþNa]þ, 538 [MþNH4]þ, 503
[MꢂOH]þ. Anal. Calcd for C29H28O7S: C, 66.91; H, 5.42.
Found: C, 67.11; H, 5.55.
4.12. (2S,3S)-3-(tert-Butyl-dimethyl-silanyloxy)-2,3-dihydro-
benzofuran-2-carboxylic acid ethyl ester (15a)
4.10. (2R,3S)-3-(2-Benzyloxy-phenyl)-3-(tert-butyl-dimethyl-
silanyloxy)-2-(toluene-4-sulfonyloxy)-propionic acid ethyl
ester (14a)
To a stirred solution of 14a (1.0 g, 1.71 mmol) in ethyl ac-
etate (20 mL) was added 10% Pd/C (100 mg). After stirring
for 4 h at room temperature under pressure of a hydrogen bal-
loon, the reaction mixture was filtered through a pad of Cel-
iteÒ and the filtrate was concentrated under reduced pressure
to get the corresponding debenzylated product (0.733 g) as
a colorless semi-solid, which was used for the next step with-
out further purification.
To a stirring solution of the above debenzylated product in
dry acetone (20 mL), was added anhydrous K2CO3 (0.35 g,
2.53 mmol) and the mixture was stirred for 6 h at room tem-
perature. After removing acetone from the reaction mixture
under reduced pressure, water (10 mL) was added to the
To a stirring solution of 13a (1.0 g, 2.12 mmol) in dry
CH2Cl2 (30 mL) at 0 ꢀC were added 2,6-lutidine (0.48 mL,
4.14 mmol) and TBDMS-OTf (0.73 mL, 3.18 mmol), succes-
sively. The reaction mixture was then stirred at room temper-
ature for 6 h. The reaction was quenched with a saturated
aqueous NH4Cl solution (20 mL) and extracted with CH2Cl2
(3ꢁ25 mL). The combined organic layers were washed with
water (50 mL), brine (50 mL), and dried over anhydrous
Na2SO4. The solvent was removed under reduced pressure

4168
S.K. Das, G. Panda / Tetrahedron 64 (2008) 4162e4173
resulting residue and extracted with ethyl acetate (3ꢁ20 mL)
and washed with brine (1ꢁ20 mL). The organic layer was
dried over Na2SO4, filtered, and concentrated under reduced
pressure. Purification of the crude product by silica gel column
chromatography (4% ethyl acetate in hexane) afforded 15a
(0.384 g, 69%, for two steps) as a colorless semi-solid. Rf:
0.42 (10% ethyl acetate in hexane). [a]2D5 þ62.6 (c 1.31,
CHCl3). IR (KBr): 2932, 2361, 1752, 1471, 1217, 1082,
7.20 (t, 1H, J¼7.7), 6.88 (t, 1H, J¼7.3), 6.78 (d, 1H,
J¼8.0), 5.53 (d, 1H, J¼2.4), 4.26 (d, 1H, J¼2.8), 1.29 (s,
3H), 1.10 (s, 3H), 0.88 (s, 9H), 0.20 (s, 6H). 13C NMR
(75 MHz, acetone-d6): d 161.3, 130.4, 130.1, 126.2, 120.8,
110.3, 97.7, 74.6, 71.1, 27.1, 26.0, 24.6, 18.3, ꢂ3.8, ꢂ4.2.
MS (ESI): m/z 332 [MþNa]þ. Anal. Calcd for C17H28O3Si:
C, 66.19; H, 9.15. Found: C, 66.26; H, 9.31.
1
842, 758 cmꢂ1. H NMR (300 MHz, CDCl3): d 7.28e7.24
4.15. (2S,3S)-2-(1-Hydroxy-1-methyl-ethyl)-2,3-dihydro-
benzofuran-3-ol (17a)
(m, 2H), 6.97e6.93 (m, 2H), 5.51 (d, 1H, J¼3.1), 4.92 (d,
1H, J¼3.1), 4.29e4.22 (m, 2H), 1.31 (t, 3H, J¼7.1), 0.92 (s,
9H), 0.19 (s, 6H). 13C NMR (75 MHz, CDCl3): d 169.8,
159.5, 130.4, 127.1, 125.3, 121.5, 110.7, 87.5, 76.8, 61.7,
25.7, 18.0, 14.1, ꢂ4.4, ꢂ4.5. MS (ESI): m/z 346 [MþNa]þ.
Anal. Calcd for C17H26O4Si: C, 63.32; H, 8.13. Found: C,
63.39; H, 8.25.
To an ice-cooled solution of 16a (80.5 mg, 0.26 mmol) in
dry THF (5 mL) was added tetra-n-butylammonium fluoride
(TBAF) (1 M in THF, 0.60 mL). After being stirred at 0 ꢀC
for 5 h, the reaction mixture was diluted with ethyl acetate
(25 mL), washed with water (25 mL) and brine (25 mL).
The combined organic layer was dried over Na2SO4, filtered,
and concentrated under reduced pressure. Purification of the
crude product by silica gel column chromatography (30%
ethyl acetate in hexane) afforded 17a (46 mg, 91%) as a color-
less solid. Mp: 95e96 ꢀC. Rf: 0.55 (60% ethyl acetate in hex-
ane). [a]2D5 þ93.3 (c 0.9, CHCl3). IR (KBr): 3462, 3194, 2932,
4.13. (1S,2S)-1-(tert-Butyl-dimethyl-silanyloxy)-1,2-dihydro-
naphtho[2,1-b]furan-2-carboxylic acid ethyl ester (15b)
Starting from 0.85 g (1.34 mmol) of 14b, the title com-
pound was prepared in two steps in the same manner as that
described for 15a. Purification of the crude product by silica
gel column chromatography (4% ethyl acetate in hexane) af-
forded 15b (0.362 g, 72%) as a colorless solid. Mp: 92e
93 ꢀC. Rf: 0.44 (10% ethyl acetate in hexane). [a]2D5 þ37.7
(c 1.43, CHCl3). IR (KBr): 2932, 2855, 2362, 1750, 1460,
2362, 1598, 1477, 1234, 1178, 1047, 750 cmꢂ1 1H NMR
.
(300 MHz, acetone-d6): d 7.33 (d, 1H, J¼7.4), 7.19e7.13
(m, 1H), 6.87e6.82 (m, 1H), 6.74 (d, 1H, J¼8.0), 5.39 (d,
1H, J¼4.5), 4.74 (br s, 1H), 4.24 (d, 1H, J¼4.6), 3.74 (br s,
1H), 1.25 (s, 3H), 1.22 (s, 3H). 13C NMR (75 MHz, ace-
tone-d6): d 162.1, 132.1, 131.3, 127.3, 122.1, 111.4, 98.6,
74.4, 72.2, 26.9, 26.8. MS (ESI): m/z 217 [MþNa]þ. Anal.
Calcd for C11H14O3: C, 68.02; H, 7.27. Found: C, 68.16; H,
7.50.
1366, 1259, 1195, 1072, 885, 840, 743 cmꢂ1 1H NMR
.
(300 MHz, CDCl3): d 7.87e7.83 (m, 3H), 7.57e7.52 (m,
1H), 7.41e7.36 (m, 1H), 7.31 (d, 1H, J¼8.8), 6.04 (d, 1H,
J¼2.1), 5.17 (d, 1H, J¼2.1), 4.36e4.25 (m, 2H), 1.35 (t, 3H,
J¼7.1), 0.97 (s, 9H), 0.36 (s, 3H), 0.25 (s, 3H). 13C NMR
(75 MHz, CDCl3): d 169.8, 158.1, 132.1, 130.7, 130.0,
129.0, 127.2, 123.6, 122.6, 118.6, 112.7, 88.2, 77.6, 61.9,
25.8, 18.2, 14.2, ꢂ3.9, ꢂ4.7. MS (ESI): m/z 395 [MþNa]þ.
Anal. Calcd for C21H28O4Si: C, 67.71; H, 7.58. Found: C,
67.56; H, 7.66.
4.16. (2S,3S)-2-(1-Hydroxy-1-methyl-ethyl)-1,2-dihydro-
naphtho[2,1-b]furan-1-ol (17b)
Starting from 0.205 mg (0.55 mmol) of 15b, the title com-
pound was prepared in two steps. First step is the Grignard
reaction as that described for 16a and the second step depro-
tection of TBDMS group as that described for 16a. The inter-
mediate tertiary alcohol resulting from the Grignard reaction
was not much stable and hence used for the next step (depro-
tection of TBDMS group) without purification by silica gel
column chromatography. Purification of the crude product
of the final step by silica gel column chromatography (30%
ethyl acetate in hexane) afforded 17b (113 mg, 74%, for
two steps) as a colorless semi-solid. Rf: 0.58 (60% ethyl ace-
tate in hexane). [a]2D5 þ46.7 (c 1.97, CHCl3). IR (KBr): 3355,
2925, 2360, 1595, 1488, 1457, 1257, 1050, 757 cmꢂ1 1H
NMR (300 MHz, acetone-d6): d 8.03 (d, 1H, J¼8.3), 7.85e
7.78 (m, 2H), 7.50e7.45 (m, 1H), 7.33e7.28 (m, 1H), 7.09
(d, 1H, J¼8.0), 5.85 (d, 1H, J¼3.6), 4.68 (br s, 1H), 4.43
(d, 1H, J¼3.6), 3.71 (br s, 1H), 1.32 (s, 3H), 1.28 (s, 3H).
13C NMR (75 MHz, acetone-d6): d 160.3, 133.3, 132.8,
131.4, 130.5, 128.6, 124.8, 124.7, 122.6, 114.2, 100.0, 74.6,
72.3, 27.1, 26.6. MS (ESI): m/z 267 [MþNa]þ. Anal.
Calcd for C15H16O3: C, 73.75; H, 6.60. Found: C, 73.86; H,
6.73.
4.14. 2-[(2S,3S)-3-(tert-Butyl-dimethyl-silanyloxy)-2,
3-dihydro-benzofuran-2-yl]-propan-2-ol (16a)
To a freshly prepared, magnetically stirred, ice-cold sus-
pension of methylmagnesium iodide [prepared from methyl
iodide (0.56 mL, 7.0 mmol) and magnesium (0.17 g,
7.0 mmol) in 10 mL of dry ether] was added a solution of ester
15a (0.154 g, 0.46 mmol) in dry THF (10 mL). The reaction
mixture was refluxed for 4 h, cooled, and quenched with aque-
ous NH4Cl solution (10 mL). The mixture was extracted with
ethyl acetate (2ꢁ25 mL), washed with water (25 mL) and
brine (25 mL). The combined organic layer was dried over
Na2SO4, filtered, and concentrated under reduced pressure.
Purification of the crude product by silica gel column chroma-
tography (8% ethyl acetate in hexane) afforded 16a (0.112 g,
77%) as a colorless semi-solid. Rf: 0.54 (20% ethyl acetate
in hexane). [a]2D5 þ93.1 (c 2.04, CHCl3). IR (KBr): 3462,
3194, 2932, 2362, 1598, 1477, 1234, 1178, 1047, 750 cmꢂ1
.
1H NMR (300 MHz, acetone-d6): d 7.33 (d, 1H, J¼7.3),

S.K. Das, G. Panda / Tetrahedron 64 (2008) 4162e4173
4169
4.17. 2-Benzyloxystyrene (18)
sieve (3.85 g) and PCC (3.85 g, 17.86 mmol) at 0 ꢀC and
the mixture was stirred at room temperature for 2 h. After
evaporating dichloromethane, the reaction mixture was diluted
with ether (50 mL) and filtered through a small pad of silica
gel. Concentration of the filtrate and purification of the residue
by silica gel column chromatography (4% ethyl acetate in
hexane) afforded 20 (2.25 g, 76%) as a colorless gum. Rf:
0.55 (20% ethyl acetate in hexane). IR (neat): 3035, 2950,
To a suspension of methyltriphenylphosphonium iodide
(17.15 g, 42.42 mmol) in dry THF (100 mL) under a nitrogen
atmosphere at 0 ꢀC was added t-BuOK (4.76 g, 42.42 mmol).
The reaction mixture was stirred for 15 min at 0 ꢀC and then
warmed to room temperature while stirring was continued for
45 min. The solution was then recooled to 0 ꢀC, and a solu-
tion of aldehyde 10a (6.0 g, 28.27 mmol) in dry THF
(50 mL) was added dropwise. The reaction mixture was
then warmed to room temperature and stirred for an addi-
tional 2 h. The reaction was quenched with saturated aqueous
NH4Cl solution (50 mL) and extracted with Et2O
(3ꢁ100 mL). The combined organic extracts were washed
with brine (200 mL), dried (Na2SO4), and concentrated in va-
cuo. The residue was purified by silica gel column chroma-
tography (2% ethyl acetate in hexane) to give alkene 18
(4.75 g, 80%) as colorless oil. Rf: 0.46 (10% ethyl acetate
in hexane). IR (neat): 3065, 3030, 2360, 1597, 1489, 1452,
2360, 1720, 1597, 1500, 1230, 758 cmꢂ1
.
1H NMR
(300 MHz, CDCl3): d 9.81 (t, 1H, J¼1.9), 7.50e7.35 (m,
6H), 7.25e7.27 (m, 1H), 7.09e7.05 (m, 2H), 5.14 (s, 2H),
3.79 (d, 2H, J¼1.9). 13C NMR (75 MHz, CDCl3): d 199.5,
156.4, 136.5, 131.1, 128.6, 128.3, 127.6, 126.9, 121.3,
120.8, 111.5, 69.6, 45.2. MS (FAB): m/z 226 [M]þ-. Anal.
Calcd for C15H14O2: C, 79.62; H, 6.24. Found: C, 79.73; H,
6.33.
4.20. (2E)-4-(2-Benzyloxy-phenyl)-but-2-enoic acid ethyl
ester (21)
1237, 1014, 751 cmꢂ1
.
1H NMR (300 MHz, CDCl3):
d 7.51e7.30 (m, 6H), 7.22e7.08 (m, 2H), 6.96e6.90 (m,
2H), 5.75 (dd, 1H, J1¼17.7, J2¼1.4), 5.25 (dd, 1H,
J1¼11.2, J2¼1.4), 5.08 (s, 2H). 13C NMR (75 MHz,
CDCl3): d 155.9, 137.1, 131.6, 128.8, 128.5, 127.8, 127.3,
126.5, 121.0, 114.4, 112.5, 70.3. MS (ESI): m/z 211
[Mþ1]þ. Anal. Calcd for C15H14O: C, 85.68; H, 6.71.
Found: C, 85.56; H, 6.79.
Starting from 2.0 g (8.83 mmol) of 20, the title compound
was prepared in the same manner as that described for 11a.
Purification of the crude product by silica gel column chroma-
tography (6% ethyl acetate in hexane) afforded 21 (1.96 g,
75%) as a colorless gum. Rf: 0.58 (20% ethyl acetate in hex-
1
ane). IR (neat): 2368, 1720, 1502, 1253, 1045, 750 cmꢂ1. H
NMR (300 MHz, CDCl3): d 7.40e7.26 (m, 6H), 7.20e7.07
(m, 2H), 6.92e6.87 (m, 2H), 5.77 (d, 1H, J¼15.5), 5.03 (s,
2H), 4.14 (q, 2H, J¼7.1), 3.55e3.53 (m, 2H), 1.24 (t, 3H,
J¼7.1). 13C NMR (75 MHz, CDCl3): d 166.51, 156.32,
147.10, 136.98, 130.20, 128.42, 127.91, 127.75, 127.14,
126.54, 121.88, 120.83, 111.72, 69.86, 59.98, 32.97, 14.16.
MS (ESI): m/z 319 [MþNa]þ. Anal. Calcd for C19H20O3: C,
77.00; H, 6.80. Found: C, 77.09; H, 6.65.
4.18. 2-(2-Benzyloxy-phenyl)-ethanol (19)
To a stirring solution of 18 (4.0 g, 19.02 mmol) in anhy-
drous THF (30 mL) was added a 0.5 M THF solution of 9-
BBN (60 mL) dropwise under a nitrogen atmosphere at 0 ꢀC
and the mixture was stirred at room temperature overnight.
H2O (5 mL) was added followed by 3 N NaOH solution
(40 mL) and 30% aqueous hydrogen peroxide solution
(30 mL). The reaction mixture was stirred for 2 h at 50 ꢀC.
The mixture was extracted with ethyl acetate (2ꢁ50 mL),
washed with water (150 mL) and brine (150 mL). The com-
bined organic layer was dried over Na2SO4, filtered, and con-
centrated under reduced pressure. Purification of the crude
product by silica gel column chromatography (8% ethyl ace-
tate in hexane) afforded alcohol 19 (4.15 g, 96%) as a colorless
gum. Rf: 0.32 (20% ethyl acetate in hexane). IR (neat): 3429,
4.21. (2R,3S)-4-(2-Benzyloxy-phenyl)-2,3-dihydroxy-butyric
acid ethyl ester (22)
Starting from 1.85 g (6.24 mmol) of 21, the title compound
was prepared in the same manner as that described for 12a.
Purification of the crude product by silica gel column chroma-
tography (25% ethyl acetate in hexane) afforded 22 (1.83 g,
89%) as a colorless semi-solid. Rf: 0.41 (40% ethyl acetate
in hexane). The enantiomeric excess was estimated to be
>99% by chiral HPLC analysis as that described for 12a.
[a]2D5 ꢂ15.3 (c 2.4, CHCl3). IR (KBr): 3346, 2927, 2362,
1601, 1462, 1247, 1046, 758 cmꢂ1 1H NMR (300 MHz,
.
CDCl3): d 7.54e7.41 (m, 5H), 7.32e7.27 (m, 2H), 7.05e
7.00 (m, 2H), 5.14 (s, 2H), 3.92 (t, 3H, J¼6.6), 3.05 (t, 3H,
J¼6.6), 2.48 (br s, 1H). 13C NMR (75 MHz, CDCl3):
d 156.5, 136.9, 130.8, 128.4, 127.7, 127.5, 127.2, 127.0,
120.7, 111.6, 69.7, 62.3, 33.9. MS (FAB): m/z 228 [M]þ,
211 [MꢂOH]þ. Anal. Calcd for C15H16O2: C, 78.92; H,
7.06. Found: C, 79.08; H, 7.14.
1759, 1497, 1453, 1240, 122, 749 cmꢂ1
.
1H NMR
(300 MHz, CDCl3): d 7.43e7.27 (m, 5H), 7.24e7.15 (m,
2H), 6.93e6.88 (m, 2H), 5.08 (s, 2H), 4.31e4.25 (m, 1H),
4.19 (q, 2H, J¼7.1), 4.05 (d, 1H, J¼1.65), 3.10e2.91 (m,
2H), 2.56 (br s, 2H), 1.22 (t, 3H, J¼7.1). 13C NMR
(75 MHz, CDCl3): d 173.4, 156.6, 136.9, 131.4, 128.5,
127.9, 127.8, 127.1, 126.4, 121.0, 111.8, 72.6, 72.3, 70.0,
61.7, 35.1, 14.0. MS (ESI): m/z 353 [MþNa]þ, 348, 331,
313, 295. Anal. Calcd for C19H22O5: C, 69.07; H, 6.71. Found:
C, 69.17; H, 6.56.
4.19. (2-Benzyloxy-phenyl)-acetaldehyde (20)
To a stirring solution of 19 (3.0 g, 13.14 mmol) in anhy-
˚
drous dichloromethane (50 mL) was added 4 A molecular

4170
S.K. Das, G. Panda / Tetrahedron 64 (2008) 4162e4173
4.22. (2R,3S)-4-(2-Benzyloxy-phenyl)-3-hydroxy-2-(toluene-
4-sulfonyloxy)-butyric acid ethyl ester (23)
d 7.15 (d, 1H, J¼7.1), 7.08 (t, 1H, J¼7.6), 6.85e6.80 (m,
1H), 6.75 (d, 1H, J¼7.9), 5.11e5.05 (m, 1H), 4.33e4.25
(m, 3H), 3.42e3.24 (m, 2H), 2.96 (d, 1H, J¼6.9), 1.30 (t,
3H, J¼7.1). 13C NMR (75 MHz, CDCl3): d 172.0, 159.5,
127.9, 126.4, 124.7, 120.7, 109.1, 82.4, 72.4, 62.1, 31.3,
14.1. MS (ESI): m/z 245 [MþNa]þ, 241. Anal. Calcd for
C12H14O4: C, 64.85; H, 6.35. Found: C, 64.76; H, 6.48.
Starting from 1.5 g (4.54 mmol) of 22, the title compound
was prepared in the same manner as that described for 13a.
Purification of the crude product by silica gel column chroma-
tography (18% ethyl acetate in hexane) afforded 23 (1.87 g,
85%) as a colorless semi-solid. Rf: 0.46 (40% ethyl acetate
in hexane). [a]2D5 ꢂ10.1 (c 2.1, CHCl3). IR (KBr): 3464,
4.25. (1S)-1-[(2R)-2,3-Dihydro-benzofuran-2-yl]-2-methyl-
propane-1,2-diol (26)
3022, 2401, 1756, 1599, 1494, 1373, 1217, 1028, 762 cmꢂ1
.
1H NMR (300 MHz, CDCl3): d 7.81 (d, 2H, J¼8.3), 7.37e
7.28 (m, 7H), 7.20e7.09 (m, 2H), 6.89e6.85 (m, 2H), 5.06
(s, 2H), 4.87 (d, 1H, J¼2.7), 4.36e4.35 (m, 1H), 4.10e4.02
(m, 2H), 2.92e2.83 (m, 2H), 2.40 (s, 3H), 2.39 (br s, 1H),
1.12 (t, 3H, J¼7.1). 13C NMR (75 MHz, CDCl3): d 167.18,
156.56, 145.09, 136.73, 133.15, 131.41, 129.68, 128.62,
128.29, 128.14, 127.90, 127.06, 125.46, 121.05, 111.77,
79.49, 71.56, 69.97, 61.88, 34.74, 21.63, 13.86. MS (ESI):
m/z 507 [MþNa]þ, 502 [MþNH4]þ, 485 [M]þ. Anal. Calcd
for C26H28O7S: C, 64.45; H, 5.82. Found: C, 64.61; H, 5.90.
Starting from 0.125 g (0.562 mmol) of 26, the title com-
pound was prepared in the same manner as that described
for 16a. Purification of the crude product by silica gel column
chromatography (30% ethyl acetate in hexane) afforded 26
(0.103 g, 88%) as a white solid. Mp: 89e90 ꢀC. Rf: 0.57
(60% ethyl acetate in hexane). [a]2D5 ꢂ55.9 (c 1.42, CHCl3).
IR (KBr): 3431, 2925, 2363, 1729, 1634, 1332, 1224, 1163,
1
755, 678 cmꢂ1. H NMR (300 MHz, CDCl3): d 7.18 (d, 1H,
J¼7.2), 7.10 (t, 1H, J¼7.6), 6.86 (dd, 1H, J1¼7.0, J2¼7.5),
6.76 (d, 1H, J¼7.9), 5.04 (m, 1H), 3.45e3.37 (m, 2H),
3.25e3.16 (m, 1H), 2.66 (br s, 2H), 1.39 (s, 3H), 1.33 (s,
3H). 13C NMR (75 MHz, CDCl3): d 158.9, 127.8, 126.8,
124.9, 121.0, 109.2, 82.7, 77.2, 72.8, 32.6, 26.6. MS (ESI):
m/z 231 [MþNa]þ, 226. Anal. Calcd for C12H16O3: C,
69.21; H, 7.74. Found: C, 69.42; H, 7.79.
4.23. (2S,3S)-3-(2-Benzyloxybenzyl)-oxirane-2-carboxylic
acid ethyl ester (24)
A solution of tosylate 23 (0.5 g, 1.03 mmol) in dry metha-
nol (25 mL) was treated with anhydrous K2CO3 (0.21 g,
1.52 mmol) and the resulting suspension stirred vigorously at
room temperature for 8 h. After removing acetone from the re-
action mixture under reduced pressure, water (20 mL) was
added to the resulting residue and extracted with ethyl acetate
(3ꢁ20 m) and washed with brine (1ꢁ30 mL). The organic
layer was dried over Na2SO4, filtered, and concentrated under
reduced pressure to give light-yellow oil. Purification of the
crude product by silica gel column chromatography (10%
ethyl acetate in hexane) afforded 24 (0.24 g, 75%) as a color-
less gum. Rf: 0.54 (20% ethyl acetate in hexane). [a]2D5 þ38.4
(c 1.9, CHCl3). IR (KBr): 3020, 2363, 1742, 1495, 1216,
4.26. (2R,3S)-4-(2-Benzyloxy-phenyl)-3-(tert-butyl-dimethyl-
silanyloxy)-2-(toluene-4-sulfonyloxy)-butyric acid ethyl ester
(27)
Starting from 0.75 g (1.54 mmol) of 23, the title compound
was prepared in the same manner as that described for 14a.
Purification of the crude product by silica gel column chroma-
tography (8% ethyl acetate in hexane) afforded 27 (0.82 g,
89%) as a colorless semi-solid. Rf: 0.55 (20% ethyl acetate
in hexane). [a]2D5 ꢂ7.2 (c 0.92, CHCl3). IR (KBr): 2931,
758 cmꢂ1
.
1H NMR (300 MHz, CDCl3): d 7.43e7.29 (m,
2360, 1745, 1495, 1370, 1216, 1031, 758, 671 cmꢂ1 1H
.
5H), 7.23e7.12 (m, 2H), 6.92e6.87 (m, 2H), 5.09 (s, 2H),
4.29e4.17 (m, 2H), 3.55e3.50 (m, 2H), 3.22e3.15 (m, 1H),
3.01e2.93 (m, 1H), 1.27 (t, 3H, J¼7.1). 13C NMR (75 MHz,
CDCl3): d 168.3, 156.5, 136.9, 130.6, 128.5, 128.1, 127.8,
127.1, 125.3, 120.9, 111.6, 69.8, 61.4, 56.8, 52.9, 28.7, 14.1.
MS (ESI): m/z 345 [MþNa]þ. Anal. Calcd for C19H20O4: C,
73.06; H, 6.45. Found: C, 72.89; H, 6.31.
NMR (300 MHz, CDCl3): d 7.79 (d, 2H, J¼8.3), 7.45e7.27
(m, 7H), 7.19e7.09 (m, 2H), 6.88e6.82 (m, 2H), 5.07 (s,
2H), 4.74 (d, 1H, J¼3.4), 4.51e4.48 (m, 1H), 4.02e3.95
(m, 2H), 3.02e2.96 (m, 1H), 2.83e2.77 (m, 1H), 2.41 (s,
3H), 1.12 (t, 3H, J¼7.1), 0.74 (s, 9H), ꢂ0.21 (s, 3H), ꢂ0.44
(s, 3H). 13C NMR (75 MHz, CDCl3): d 167.5, 156.9, 144.6,
137.0, 133.9, 132.6, 129.5, 128.6, 128.0, 127.9, 127.5,
125.4, 120.7, 111.3, 79.4, 71.2, 69.9, 61.5, 35.2, 25.6, 21.6,
17.8, 13.8, ꢂ5.3. MS (ESI): m/z 621 [MþNa]þ, 617, 599.
Anal. Calcd for C32H42O7SSi: C, 64.18; H, 7.07. Found: C,
64.06; H, 7.20.
4.24. (S)-[(2R)-2,3-Dihydro-benzofuran-2-yl]-hydroxy-acetic
acid ethyl ester (25)
Starting from 0.225 g (0.72 mmol) of 24, the title com-
pound was prepared in the same manner as that described
for 15a. Purification of the crude product by silica gel column
chromatography (10% ethyl acetate in hexane) afforded 25
(0.13 g, 81%, for two steps) as a white solid. Mp: 80e
81 ꢀC. Rf: 0.35 (20% ethyl acetate in hexane). [a]2D5 ꢂ76.9
(c 1.13, CHCl3). IR (KBr): 3437, 2929, 2364, 1728, 1483,
4.27. (2S,3S)-3-(tert-Butyl-dimethyl-silanyloxy)-chroman-
2-carboxylic acid ethyl ester (28)
Starting from 0.5 g (0.83 mmol) of 27, the title compound
was prepared in the same manner as that described for 15a.
Purification of the crude product by silica gel column chroma-
tography (4% ethyl acetate in hexane) afforded 28 (0.195 g,
1
1233, 1136, 1014, 754 cmꢂ1. H NMR (300 MHz, CDCl3):

S.K. Das, G. Panda / Tetrahedron 64 (2008) 4162e4173
4171
70%; based on two steps) as a colorless viscous liquid. Rf: 0.48
(10% ethyl acetate in hexane). [a]2D5 þ51.2 (c 2.5, CHCl3). IR
(neat): 3069, 2908, 2370, 1597, 1494, 1453, 1241, 1022,
749 cmꢂ1 1H NMR (300 MHz, CDCl3): d 7.44e7.28 (m,
.
(neat): 2932, 1751, 1250, 1197, 1119, 838, 756 cmꢂ1
.
1H
5H), 7.20e7.14 (m, 2H), 6.93e6.89 (m, 2H), 6.08e5.95 (m,
1H), 5.08 (s, 2H), 5.05e5.02 (m, 2H), 3.45 (d, 2H, J¼6.6).
13C NMR (75 MHz, CDCl3): d 156.4, 137.4, 137.0, 129.9,
129.0, 128.5, 127.7, 127.3, 127.1, 120.8, 115.4, 111.7, 69.9,
34.4. MS (ESI): m/z 225 [Mþ1]þ, 91 [C6H5CH2]þ. Anal.
Calcd for C16H16O: C, 85.68; H, 7.19. Found: C, 85.76; H,
7.30.
NMR (300 MHz, CDCl3): d 7.16e7.11 (m, 1H), 7.05e7.03
(m, 1H), 6.93e6.88 (m, 2H), 4.43e4.38 (m, 2H), 4.34e4.21
(m, 2H), 3.03e2.84 (m, 2H), 1.33 (t, 3H, J¼7.1), 0.91 (s,
9H), 0.15 (s, 3H), 0.12 (s, 3H). 13C NMR (75 MHz, CDCl3):
d 169.6, 152.8, 129.6, 127.5, 121.1, 119.3, 116.3, 78.76,
65.62, 61.32, 33.73, 25.51, 17.79, 13.96, ꢂ4.50, ꢂ5.10. MS
(ESI): m/z 360 [MþNa]þ, 337 [M]þ. Anal. Calcd for
C18H28O4Si: C, 64.25; H, 8.39. Found: C, 64.36; H, 8.43.
4.31. 3-(2-Benzyloxy-phenyl)-propan-1-ol (32)
4.28. 2-[(2S,3S)-3-(tert-Butyl-dimethyl-silanyloxy)-chroman-
2-yl]-propan-2-ol (29)
Starting from 3.0 g (13.37 mmol) of 31, the title compound
was prepared in the same manner as that described for 19. Pu-
rification of the crude product by silica gel column chromatog-
raphy (8% ethyl acetate in hexane) afforded 32 (3.12 g, 96%)
as a colorless gum. Rf: 0.32 (20% ethyl acetate in hexane). IR
Starting from 0.15 g (0.44 mmol) of 28, the title compound
was prepared in the same manner as that described for 16a.
Purification of the crude product by silica gel column chroma-
tography (5% ethyl acetate in hexane) afforded 29 (0.132 g,
91%) as a colorless semi-solid. Rf: 0.36 (10% ethyl acetate
in hexane). [a]2D5 þ94.4 (c 1.56, CHCl3). IR (KBr): 3512,
2933, 2362, 1586, 1489, 1363, 1248, 1089, 1049, 840,
1
(neat): 3421, 1594, 1452, 1351, 1239, 1040, 750 cmꢂ1. H
NMR (300 MHz, CDCl3): d 7.41e7.25 (m, 5H), 7.16e7.10
(m, 2H), 6.91e6.86 (m, 2H), 5.03 (s, 2H), 3.54 (t, 2H, J¼
6.3), 2.74 (t, 2H, J¼7.3), 2.01 (s, 1H), 1.87e1.78 (m, 2H).
13C NMR (75 MHz, CDCl3): d 156.5, 137.1, 130.4, 130.1,
128.5, 127.8, 127.1, 127.0, 120.9, 111.7, 70.0, 61.8, 32.8,
26.1. MS (FAB): m/z 242 [M]þ. Anal. Calcd for C16H18O2:
C, 79.31; H, 7.49. Found: C, 79.39; H, 7.61.
755 cmꢂ1 1H NMR (300 MHz, CDCl3): d 7.16e7.06 (m,
.
2H), 6.93e6.84 (m, 2H), 4.32e4.24 (m, 1H), 4.17 (s, 1H),
3.67 (d, 1H, J¼9.0), 3.10e2.91 (m, 2H), 1.41 (s, 3H), 1.39
(s, 3H), 0.98 (s, 9H), 0.26 (s, 3H), 0.25 (s, 3H). 13C NMR
(75 MHz, CDCl3): d 153.9, 129.4, 127.5, 120.78, 120.1,
116.2, 82.8, 72.2, 68.5, 36.4, 27.0, 25.7, 23.7, 17.7, ꢂ3.2,
ꢂ4.8. MS (ESI): m/z 346 [MþNa]þ, 323 [M]þ. Anal. Calcd
for C18H30O3Si: C, 67.03; H, 9.38. Found: C, 67.13; H, 9.11.
4.32. 3-(2-Benzyloxy-phenyl)-propionaldehyde (33)
Starting from 3.0 g (12.38 mmol) of 32, the title compound
was prepared in the same manner as that described for 20. Pu-
rification of the crude product by silica gel column chromatog-
raphy (5% ethyl acetate in hexane) afforded 33 (2.14 g, 72%)
as a colorless oil. Rf: 0.55 (20% ethyl acetate in hexane). IR
(neat): 3032, 2930, 2360, 1710, 1600, 1501, 1240,
4.29. (2S,3S)-2-(1-Hydroxy-1-methyl-ethyl)-chroman-
3-ol (30)
1
Starting from 0.102 g (0.31 mmol) of 29, the title com-
pound was prepared in the same manner as that described
for 17a. Purification of the crude product by silica gel column
chromatography (30% ethyl acetate in hexane) afforded 30
(56 mg, 87%) as a colorless solid. Mp: 115e116 ꢀC. Rf: 0.65
(60% ethyl acetate in hexane). [a]2D5 þ85.2 (c 0.95, CHCl3).
IR (KBr): 3343, 2925, 2361, 1587, 1486, 1457, 1242, 1043,
751 cmꢂ1. H NMR (200 MHz, CDCl3): d 9.77 (t, 1H, J¼
1.9), 7.41e7.32 (m, 5H), 7.23e7.15 (m, 2H), 6.93e6.87 (m,
2H), 5.08 (s, 2H), 3.00 (t, 2H, J¼7.3), 2.75 (t, 2H, J¼7.3),
2.01 (s, 1H), 1.87e1.78 (m, 2H). 13C NMR (50 MHz,
CDCl3): d 202.9, 157.0, 137.6, 130.6, 129.4, 129.1, 128.4,
128.1, 127.6, 121.3, 112.1, 70.3, 44.3, 24.0. MS (FAB): m/z
240 [M]þ. Anal. Calcd for C16H16O2: C, 79.97; H, 6.71.
Found: C, 79.93; H, 6.79.
755 cmꢂ1 1H NMR (300 MHz, acetone-d6): d 7.07e7.04
.
(m, 2H), 6.86e6.75 (m, 2H), 5.10 (s, 1H), 4.62 (s, 1H),
4.16e4.08 (m, 1H), 3.57 (d, 1H, J¼9.0), 3.06e2.99 (m,
1H), 2.83e2.75 (m, 1H), 1.38 (s, 3H), 1.32 (s, 3H). 13C
NMR (75 MHz, acetone-d6): d 156.0, 131.4, 129.2, 122.9,
122.5, 117.8, 84.9, 74.6, 67.5, 36.8, 29.4, 25.0. MS (ESI):
m/z 231 [MþNa]þ, 226 [MþNH4]þ. Anal. Calcd for
C12H16O3: C, 69.21; H, 7.74. Found: C, 69.29; H, 7.98.
4.33. (2E)-5-(2-Benzyloxy-phenyl)-pent-2-enoic acid ethyl
ester (34)
Starting from 2.0 g (8.32 mmol) of 33, the title compound
was prepared in the same manner as that described for 11a.
Purification of the crude product by silica gel column chroma-
tography (5% ethyl acetate in hexane) afforded 34 (2.0 g,
77%) as a colorless oil. Rf: 0.58 (20% ethyl acetate in hexane).
4.30. 2-Benzyloxy allylbenzene (31)
IR (neat): 2361, 1717, 1495, 1453, 1240, 1039, 749 cmꢂ1. H
1
Starting from 4.0 g (17.67 mmol) of 20, the title compound
was prepared in the same manner as that described for 18. Pu-
rification of the crude product by silica gel column chromatog-
raphy (2% ethyl acetate in hexane) afforded 31 (3.50 g, 88%)
as a colorless oil. Rf: 0.46 (10% ethyl acetate in hexane). IR
NMR (200 MHz, CDCl3): d 7.41e7.21 (m, 5H), 7.16e6.98
(m, 2H), 6.92e6.88 (m, 3H), 5.81 (d, 1H, J¼15.6), 5.07 (s,
2H), 4.16 (m, 2H), 2.82 (t, 2H, J¼7.9), 2.57e2.46 (m, 2H),
1.26 (t, 3H, J¼7.1). 13C NMR (50 MHz, CDCl3): d 167.2,
157.0, 149.3, 137.7, 130.4, 130.0, 129.0, 128.2, 127.9,

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S.K. Das, G. Panda / Tetrahedron 64 (2008) 4162e4173
127.5, 121.9, 121.2, 112.0, 70.2, 60.6, 32.9, 29.6, 14.7. MS
(ESI): m/z 311 [Mþ1]þ. Anal. Calcd for C20H22O3: C,
77.39; H, 7.14. Found: C, 77.51; H, 7.09.
CDCl3): d 7.44e7.31 (m, 5H), 7.16e7.14 (m, 2H), 6.91e
6.87 (m, 2H), 5.08 (s, 2H), 4.17e4.04 (m, 2H), 3.39 (d, 1H,
J¼4.5), 3.19e3.17 (m, 1H), 2.89e2.80 (m, 2H), 2.07e1.92
(m, 2H), 1.23 (t, 3H, J¼7.1). 13C NMR (75 MHz, CDCl3):
d 168.2, 156.5, 137.2, 130.1, 129.3, 128.5, 127.8, 127.4,
127.1, 120.8, 111.6, 69.8, 61.3, 57.3, 52.9, 27.5, 26.9, 14.1.
MS (FAB): m/z 327 [Mþ1]þ. Anal. Calcd for C20H22O4: C,
73.60; H, 6.79. Found: C, 73.75; H, 6.53.
4.34. (2R,3S)-5-(2-Benzyloxy-phenyl)-2,3-dihydroxy-
pentanoic acid ethyl ester (35)
Starting from 1.85 g (5.96 mmol) of 34, the title compound
was prepared in the same manner as that described for 12a.
Purification of the crude product by silica gel column chroma-
tography (25% ethyl acetate in hexane) afforded 35 (1.78 g,
87%) as a colorless semi-solid. Rf: 0.38 (40% ethyl acetate
in hexane). [a]2D5 ꢂ18.75 (c 1.71, CHCl3). The enantiomeric
excess was estimated to be >99% by chiral HPLC analysis
as that described for 12a. IR (KBr): 3431, 2933, 1731, 1595,
4.37. (S)-[(2R)-Chroman-2-yl]-hydroxy-acetic acid ethyl
ester (38)
Starting from 0.45 g (1.38 mmol) of 37, the title compound
was prepared in the same manner as that described for 15a.
Purification of the crude product by silica gel column chroma-
tography (15% ethyl acetate in hexane) afforded 38 (0.221 g,
68%; based on two steps) as a colorless semi-solid. Rf: 0.39
(20% ethyl acetate in hexane). [a]2D5 ꢂ80.86 (c 1.77,
CHCl3). IR (KBr): 3446, 2928, 1739, 1487, 1234, 1131,
1492, 1449, 1238, 1023, 754 cmꢂ1 1H NMR (300 MHz,
.
CDCl3): d 7.44e7.31 (m, 5H), 7.19e7.14 (m, 2H), 6.93e
6.88 (m, 2H), 5.08 (s, 2H), 4.27e4.20 (m, 2H), 4.06 (dd,
1H, J1¼2.0, J2¼5.6), 3.04 (d, 1H, J¼5.7), 2.88e2.79 (m,
2H), 2.14 (d, 1H, J¼8.4), 1.95e1.90 (m, 2H), 1.27 (t, 3H,
J¼7.1). 13C NMR (75 MHz, CDCl3): d 173.5, 156.5, 137.2,
130.2, 130.2, 128.6, 127.9, 127.2, 127.2, 120.9, 111.8, 73.3,
71.9, 70.0, 61.9, 34.0, 26.4, 14.1. MS (ESI): m/z 367
[MþNa]þ, 362, 345. Anal. Calcd for C20H24O5: C, 69.75;
H, 7.02. Found: C, 69.65; H, 7.12.
756 cmꢂ1 1H NMR (300 MHz, CDCl3): d 7.09e7.03 (m,
.
2H), 6.87e6.75 (m, 2H), 4.38e4.24 (m, 4H), 3.04e2.99
(m, 1H), 2.95e2.78 (m, 2H), 2.24e2.09 (m, 1H), 2.04e1.96
(m, 1H), 1.32 (t, 3H, J¼7.1). 13C NMR (75 MHz, CDCl3):
d 172.4, 154.4, 129.3, 127.2, 121.5, 120.4, 116.7, 76.4,
72.9, 61.9, 24.7, 23.5, 14.1. MS (FAB): m/z 237 [Mþ1]þ.
Anal. Calcd for C13H16O4: C, 66.09; H, 6.83. Found: C,
66.17; H, 6.99.
4.35. (2R,3S)-5-(2-Benzyloxy-phenyl)-3-hydroxy-2-(toluene-
4-sulfonyloxy)-pentanoic acid ethyl ester (36)
4.38. (1S)-1-[(2R)-Chroman-2-yl]-2-methyl-propane-1,2-diol
(39)
Starting from 1.55 g (4.50 mmol) of 35, the title compound
was prepared in the same manner as that described for 13a.
Purification of the crude product by silica gel column chroma-
tography (15% ethyl acetate in hexane) afforded 36 (1.79 g,
80%) as a colorless gum. Rf: 0.41 (40% ethyl acetate in hex-
ane). [a]2D5 ꢂ1.5 (c 1.15, CHCl3). IR (KBr): 3407, 2924,
1H NMR (300 MHz, CDCl3): d 7.77 (d, 2H, J¼8.3), 7.42e
7.24 (m, 7H), 7.18e7.08 (m, 2H), 6.91e6.86 (m, 2H), 5.05
(s, 2H), 4.81 (d, 1H, J¼3.3), 4.08e4.04 (m, 2H), 3.96e3.93
(m, 1H), 2.80e2.70 (m, 2H), 2.39 (s, 3H), 1.82e1.74 (m,
2H), 1.13 (t, 3H, J¼7.1). 13C NMR (75 MHz, CDCl3):
d 167.2, 156.5, 145.1, 137.0, 133.1, 130.2, 129.7, 129.5,
128.6, 128.1, 127.9, 127.4, 127.2, 120.9, 111.7, 80.0, 70.9,
70.0, 61.8, 33.1, 25.9, 21.6, 13.8. MS (ESI): m/z 521
[MþNa]þ, 516, 499. Anal. Calcd for C27H30O7S: C, 65.04;
H, 6.06. Found: C, 65.22; H, 6.14.
Starting from 0.195 g (0.825 mmol) of 38, the title com-
pound was prepared in the same manner as that described
for 17a. Purification of the crude product by silica gel column
chromatography (30% ethyl acetate in hexane) afforded 39
(0.152 g, 83%) as a colorless oil. Rf: 0.52 (60% ethyl acetate
in hexane). [a]2D5 ꢂ93.75 (c 2.04, CHCl3). IR (neat): 3555,
2143, 1754, 1593, 1444, 1366, 1231, 1178, 1022, 755 cmꢂ1
.
3015, 2933, 2362, 1583, 1489, 1388, 1231, 1090, 756 cmꢂ1
.
1H NMR (300 MHz, CDCl3): d 7.10e7.04 (m, 2H), 6.89e
6.75 (m, 2H), 4.32e4.27 (m, 1H), 3.33 (d, 1H, J¼6.5),
2.91e2.78 (m, 4H), 2.24e2.23 (m, 1H), 1.93e1.86 (m, 1H),
1.38 (s, 3H), 1.32 (s, 3H). 13C NMR (75 MHz, CDCl3):
d 153.9, 129.7, 127.2, 122.1, 120.9, 116.6, 77.5, 76.4, 73.1,
26.6, 26.5, 24.8, 24.7. MS (ESI): m/z 246 [MþNa]þ. Anal.
Calcd for C13H18O3: C, 70.24; H, 8.16. Found: C, 70.11; H,
8.40.
4.36. (2S,3S)-3-[2-(2-Benzyloxy-phenyl)-ethyl]-oxirane-
2-carboxylic acid ethyl ester (37)
4.39. (2R,3S)-5-(2-Benzyloxy-phenyl)-3-(tert-butyl-dimethyl-
silanyloxy)-2-(toluene-4-sulfonyloxy)-pentanoic acid ethyl
ester (40)
Starting from 1.15 g (2.30 mmol) of 36, the title compound
was prepared in the same manner as that described for 24. Pu-
rification of the crude product by silica gel column chromatog-
raphy (10% ethyl acetate in hexane) afforded 37 (0.585 g,
78%) as a colorless semi-solid. Rf: 0.58 (20% ethyl acetate
in hexane). [a]2D5 þ21.87 (c 1.6, CHCl3). IR (KBr): 3021,
Starting from 1.15 g (2.30 mmol) of 36, the title compound
was prepared in the same manner as that described for 14a.
Purification of the crude product by silica gel column chroma-
tography (6% ethyl acetate in hexane) afforded 40 (1.21 g,
85%) as a colorless semi-solid. Rf: 0.58 (20% ethyl acetate
in hexane). [a]2D5 þ1.2 (c 2.10, CHCl3). IR (KBr): 3022,
2366, 1744, 1218, 1028, 767 cmꢂ1 1H NMR (300 MHz,
.

S.K. Das, G. Panda / Tetrahedron 64 (2008) 4162e4173
4173
2932, 2362, 1741, 1599, 1372, 1216, 758, 699 cmꢂ1. 1H NMR
(300 MHz, CDCl3): d 7.77 (d, 2H, J¼8.2), 7.44e7.24 (m, 7H),
7.17e7.07 (m, 2H), 6.90e6.86 (m, 2H), 5.06 (s, 2H), 4.88 (d,
1H, J¼3.9), 4.07e3.94 (m, 3H), 2.70e2.65 (m, 1H), 2.54e
2.50 (m, 1H), 2.40 (s, 3H), 1.93e1.90 (m, 1H), 1.80e1.68
(m, 1H), 1.13 (t, 3H, J¼7.1), 0.79 (s, 9H), ꢂ0.07 (s, 3H),
0.076 (s, 3H). 13C NMR (75 MHz, CDCl3): d 167.4, 156.4,
144.8, 137.3, 133.5, 129.9, 129.8, 129.6, 128.5, 128.1,
127.7, 127.2, 120.7, 111.5, 79.4, 72.1, 69.8, 61.5, 33.0, 25.8,
25.6, 21.6, 17.9, 13.8, ꢂ4.6, ꢂ4.9. MS (ESI): m/z 636
[MþNa]þ, 631, 613. Anal. Calcd for C33H44O7SSi: C,
64.67; H, 7.24. Found: C, 64.81; H, 7.19.
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Acknowledgements
This research project was supported by Department of Sci-
ence and Technology (SR/S1/OC-23/2005) New Delhi, India.
S.K.D. thanks CSIR for providing fellowship (NET-SRF).
Supplementary data
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Supplementary data associated with this article can be
found in the online version, at doi:10.1016/j.tet.2008.03.001.
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