Enantioselective enzymatic desymmetrization of prochiral 1,3-diols and enzymatic resolution of monoprotected 1,3-diols based on α-tetralone and related multifunctional scaffolds

Article abstract of DOI:10.1016/j.tetasy.2008.10.024

Novel multifunctional chemotypes based on α-tetralone, α-indanone, and chromanone have been synthesized by a chemo-enzymatic approach by applying an enzymatic irreversible transesterification strategy. The scaffolds synthesized can be further elaborated with subsequent enzymatic as well as chemical transformations for the generation of new sets of structurally related organic molecules.

Full text of DOI:10.1016/j.tetasy.2008.10.024

Tetrahedron: Asymmetry 19 (2008) 2497–2507
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Enantioselective enzymatic desymmetrization of prochiral 1,3-diols and
enzymatic resolution of monoprotected 1,3-diols based on
and related multifunctional scaffolds
a-tetralone
*
Tridib Mahapatra, Tapas Das, Samik Nanda
Department of Chemistry, Indian Institute of Technology, Kharagpur 721 302, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 2 October 2008
Accepted 22 October 2008
Novel multifunctional chemotypes based on
a-tetralone, a-indanone, and chromanone have been syn-
thesized by a chemo-enzymatic approach by applying an enzymatic irreversible transesterification strat-
egy. The scaffolds synthesized can be further elaborated with subsequent enzymatic as well as chemical
transformations for the generation of new sets of structurally related organic molecules.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
scaffolds as there are already many natural products based on
chromanone (flavonoids and homoisoflavonoids) and
We have designed and synthesized the -bishydroxymethylated
derivative of -tetralone and chromanone mainly due to the fol-
a
-tetralone.6
In recent years, much of the pharmaceutical industry has
moved away from natural products research, focusing instead on
increasingly narrow regions of chemical structure space which cor-
respond to existing orally bioavailable synthetic drugs. The quest
for natural products such as molecules with drug-like libraries is
increasing day by day. These natural product-like molecules offer
the advantages of easy synthesis and access to analogues, however,
the library members are skeletally diverse, structurally complex,
stereochemically rich, and densely functionalized. The Diversity-
Oriented Synthesis (DOS) has emerged as a powerful approach to
obtain complex molecules for biological studies.1 The utility of
DOS relies on the development of chemical methodologies for
the synthesis of novel structural types with high levels of skeletal
and stereochemical complexity.2 Polyketide and terpenoid natural
products possess a broad range of biological activities and both ste-
reochemical and skeletal diversity, and have served as an inspira-
tion for complex chemical library design.3 Combinatorial
biocatalysis is one of the tools of Diversity-Oriented Synthesis
(DOS), which uses enzymes as efficient catalyst for the generation
of a small molecule library based on a small molecular scaffold.4
Although biotransformations have become an established method
in organic chemical synthesis,5 biocatalysis could, from organic
chemist’s perspective, have a much bigger impact in this area.
In our combinatorial biocatalysis project, we need to design and
synthesize various small molecular multifunctional scaffolds
which will lead us to a natural product-like library after biocata-
a,a
a
lowing reasons: (a) the bishydroxymethyl group was chosen
mainly to adopt a EED (enzymatic enantioselective desymmetriza-
tion) strategy to generate a quaternary stereocenter adjacent to the
keto functionality; (b) the keto functionality can be further con-
verted to numerous functionalities by an array of biocatalytic
transformations (ketoreduction, transamination, and hydrocyna-
tion to name a few); and (c) finally, the existing aromatic ring
can undergo a biocatalytic oxidation reaction with arene di-oxy-
genase type enzymes to generate further diversity (Scheme 1).
2. Results and discussion
2.1. Synthesis of bishydroxymethylated tetralone and
chromanones
The bishydroxymethyl group was introduced via base-catalyzed
condensation reaction with formalin and the parent tetralone or
chromanone. When a methanolic solution of the parent tetralone
and chromanone was treated with K2CO3 and excess formalin,
the required bishydroxymethylated compounds were obtained in
excellent yields (80–94% yield).7 Commercially available tetralones
are used, whereas chromanones are synthesized as follows: Prop-
erly substituted phenols are alkylated with 3-bromopropionic acid
in the presence of NaH in DMF to afford the acids in moderate
yield.8 Acids were treated with oxalyl chloride in DCM to yield
the acid chlorides, the acid chlorides were then subjected to ring
closure on treatment with SnCl4 to afford the required chroma-
nones in good yield (Scheme 2).9
lytic modification. We choose chromanone and a-tetralone-based
* Corresponding author.
E-mail address: snanda@chem.iitkgp.ernet.in (S. Nanda).
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.10.024

2498
T. Mahapatra et al. / Tetrahedron: Asymmetry 19 (2008) 2497–2507
X
Y
Arene di-oxygenase
EED ( Transesterification)
Y
O
X = C, O
Y = OH
Keto reduction, transamination, hydrocynation
Scheme 1. Multifunctional small molecular scaffolds based on tetralone and chromanone.
O
O
O
OH
(COCl)2, DCM
SnCl4
NaH, DMF
CO2H
CO2H
Br
X
X
X
X = H, OMe, Cl, -(OMe)2, methylenedioxy
Y
Y
O
K2CO3, MeOH
HCHO, H2O
OH
OH
O
Y = C, O
Scheme 2. Synthesis of chromanones and bishydroxymethylated derivative of chromanone and tetralone.
We have also taken four commercially available 1-indanones
and synthesized the respective bishydroxymethyl derivatives to
access more chemotypes based on the indanone scaffold.
in organic solvent. When a trial run was conducted with compound
6 by using CAL-B lipase and vinyl acetate and isopropenyl acetate
as the acyl donors, the corresponding monoacetate was obtained in
good yield with moderate enantioselectivity (Schemes 3 and 4).
The EED of 2,2-disubstituted propane-1,3-diols using well-
known acyl donors, that is, vinyl and isopropenyl acetates, is a
well-established process that generates a quaternary stereocenter
with excellent asymmetric control. Although it has proven to be
successful, it usually suffers from low reactivity in few cases, the
reason being that racemization of the products via acyl group
migration occurs under different reaction conditions such as acidic
or hydrogenolytic ones. Furthermore, this migration has also been
observed for the products of the transesterification of other poly-
hydroxylated compounds such as different meso 1,2-diols.11 Our
initial attempts to generate quaternary stereocenters by applying
EED strategy on a tetralone-based small scaffold yielded mixed
2.2. Enantioselective enzymatic desymmetrization (EED) of
compounds 1–13
Enantioselective enzymatic desymmetrizations (EEDs) belong
to the field of asymmetric synthesis, and accordingly, a maximum
yield of 100% can be attained. For this reason, they constitute a
very interesting alternative to kinetic resolutions for the prepara-
tion of optically active compounds, which is reflected in the
increasing number of enzymatic desymmetrizations applied to or-
ganic synthesis recently published in the literature.10 We initially
planned to carry out EEDs on compounds 1–13 by an irreversible
acylation reaction (transesterification) with a suitable acyl donor
R1
O
Y
X
O
OH
OH
OH
OH
OH
OH
R2
O
O
O
4: R1 = R2 = OMe
1: X = H
2: X = OMe
3: X = Cl
6: Y = H
7: Y = OMe
1
2
5
: R = R = Methylenedioxy
OMe
O
OH
OH
OH
OH
OH
OH
MeO
z
O
OMe
O
10
: Z = H
9
8
11: Z = Cl
12: Z = OMe
13: Z = 6-Me
Scheme 3. Bishydroxymethyl derivatives of chromanone, 1-tetralone, and 1-indanone.

T. Mahapatra et al. / Tetrahedron: Asymmetry 19 (2008) 2497–2507
2499
2.3. Enzymatic kinetic resolutions of monoprotected silyl
ethers
R
OAc
OH
OH
OAc
OH
The monoprotected silyl ethers were subjected to a lipase-cata-
lyzed irreversible transesterification reaction with a suitable acyl
donor in organic solvents as depicted in Scheme 6.
We have first chosen two substrates 19 (TBS protected) and 32
(TBDPS protected), and carried out CAL-B-catalyzed kinetic resolu-
tion with vinyl acetate as acyl donor in organic solvent (DIPE). The
substrate 19 shows low enantioselectivity when compared with
substrate 32. The respective acetate obtained from compound 32
showed excellent enantioselectivity (ee: approx. 96%), whereas
the slow reacting enantiomer of 32 shows 42% ee. In the case of
CAL-B, DIPE
70%, ee = 58%
O
O
R = H, Me
Scheme 4. EED of 2,2-bis-hydroxymethyl-3,4-dihydro-2H-naphthalen-1-one.
success. The reaction yield and enantioselectivity were moderate,
and the reaction suffers from some side product formation in the
form of diacetates. We presume that acyl migration may be
responsible for the low enantioselectivity. Hence, we have chosen
vinyl benzoate as a transesterification agent and carried out the
same reaction with compound 6. We thought that as vinyl ester
is linked to an aromatic moiety, acyl migrations are hampered
since the formation of the corresponding ortho ester intermediate
involves a greater loss in resonance energy as compared to the case
of aliphatic acyl chains.12 But the observed enantioselectivity is not
so encouraging to carry out same reaction with other substrates
(Scheme 5).
It should be noted that only one enantiomer can be generated
by employing this strategy, whereas the other enantiomer seems
to be virtually inaccessible by this method. At this stage we
thought to desymmetrize the prochiral diols 1–13 at the beginning
by selective monoprotection at one of the alcohol functionalities.
The monoprotected diols serve as precursor for enzymatic kinetic
resolution by applying an irreversible transesterification strategy.
The fast reacting enantiomer of the monoprotected diols 1–13 will
undergo enzymatic acylation, whereas the slow reacting enantio-
mer will remain intact, hence making both enantiomers accessible
with excellent stereocontrol. The diols are monoprotected as their
silyl ethers when treated with imidazole and corresponding silyl
chloride (1.5 equiv each) in DCM. All the monoprotected silyl
ethers are well characterized by 1H and 13C NMR techniques.
Table 1
CAL-B-catalyzed transesterification of compounds 27–39
Entry
Substrate
Conversion(c)
ees (%)
eep (%)
Eb
a
a
1
2
3
4
5
6
7
8
9
10
11
12
13
27
28
29
30
31
32
33
34
35
36
37
38
39
29.5
30.1
26.7
37.3
34.5
30.0
31.4
33.3
39.2
36.4
35.1
35.9
32.9
41
40
32
56
50
42
44
48
60
56
52
52
48
98
93
88
94
95
98
96
96
93
98
96
93
98
148
41
21.4
57
64.2
150
76
79
51
174
82.4
46.3
160
a
Ees were calculated by chiral HPLC (Diacel, Chiral AS-H column, hexane–iso-
propanol, 98:2, flow rate: 0.8 ml/min).
b
Enantioselectivities of the reactions (E)14 were determined from the following
equation: E = ln[1 ꢀ c(1 + eep)]/ln[1 ꢀ c(1 ꢀ eep)], where eep = product ee,
ees = substrate ee; c = ees/(ees + eep)%. Enantioselectivities of the reaction (E) were
determined using the
‘SELECTIVITY’ program developed by Faber, K.; Hönig, H.;
Kleewein, A. (http://www.cis.TUGraz.at/orgc/).
O
CAL-B
OH
OCOPh
OH
+
O
DIPE
OH
O
O
Yield = 75%; ee = 50%
Scheme 5. EED reaction of compound 6 with vinyl benzoate.
X
O
X
OH
OH
Imidazole
OR
DCM, DMAP
TBS-Cl or
TBDPS-Cl
OH
O
14-26
27-39
X = C, O
n = 0, 1; 1-13
R = TBS
, TBDPDS
R1
OAc
OR
OR
OH
+
CAL-B, DIPE
molecular sieves
(R 1 = H, Me)
OAC
O
O
40-52
Scheme 6. Lipase-catalyzed kinetic resolution of monosilyl-protected alcohols.

2500
T. Mahapatra et al. / Tetrahedron: Asymmetry 19 (2008) 2497–2507
compound 19, both the respective acetate and the alcohol were ob-
tained in low enantiomeric excess (30%). The reason behind the
observation is not clear to us, but we assume that in the case of
The acetate group in 45 was deprotected with K2CO3/MeOH to
afford compound 55. The alcohol functionality in 55 was protected
as its p-toluenesulfonate ester 56 by treatment with Ts-Cl, Et3N,
and DMAP (cat). Reductive deoxygenation of the p-toluenesulfo-
nate ester and ketone reduction were achieved by treatment of
56 with LAH to afford 57 in good yield. Oxidation of 57 under
Swern conditions afforded compound 58. Removal of the TBDPS
group was achieved by treating 58 with TBAF to yield the known
compound (R)-59.
19, the TBS group as well as the a-tetralone group is similar in size
hence causing poor binding in the enzyme active site as predicted
by the Kazlauskas empirical rule for enantiopreference of certain
lipases toward primary alcohols.13 Subsequently we have used
compounds 27–39 for CAL-B-catalyzed irreversible acylation reac-
tion to generate quaternary stereocenters. The results are summa-
rized in Table 1. From Table 1 it is noticed that substrates 27–39
yield the respective acetate with good enantioselectivity (88–
98%), whereas the slow reacting enantiomeric alcohols are ob-
tained with poor enantioselectivity (32–60%).
3. Conclusion
In conclusion, we have described an efficient enzymatic resolu-
tion strategy for 2,2-disubstituted 1,3-propanediols based on 1-tet-
ralone, 1-indanone, and chroman-4-one scaffolds. The enzymatic
irreversible transesterification protocol generates a quaternary ste-
reocenter adjacent to the carbonyl group of 1-tetralone and related
scaffolds. Further biocatalytic transformation of the carbonyl func-
tionality to create more diversity is currently ongoing in our group.
2.4. Determination of absolute configuration of the product
acetate
Absolute configuration of the product acetate was confirmed by
X-ray crystal analysis of the acetate obtained from compound 32
after enzymatic transesterification. The X-ray crystal structure of
compound 45 is given in Figure 1, and it is clearly evident from
the ORTEP diagram that the newly generated stereocenter has
(S)-configuration. The stereochemical assignment was further con-
firmed by chemical transformation of compound 45 to (R)-2-
hydroxymethyl-2-methyl-3,4-dihydro-2H-naphthalen-1-one (59,
Scheme 7) and by comparing its optical rotation value and HPLC
retention time with that of the known compound reported in the
literature.15
4. Experimental
Unless otherwise stated, materials were obtained from com-
mercial suppliers and used without further purification. THF and
diethyl ether were distilled from sodium benzophenone ketyl.
Dichloromethane (DCM), dimethylformamide (DMF), and dimeth-
ylsulfoxide (DMSO) were distilled from calcium hydride. Diisopro-
pyl ether (DIPE) was refluxed over P2O5 and distilled prior to use.
Vinyl acetate and isopropenyl acetate were freshly distilled prior
to use. Lipase (from Candida rugosa, type VII, 1440
lipase (from Porcine pancreas, type II, 6 g of protein), lipase (from
Rhizopus niveus), lipase (from wheat germ, type I, 8.2 g of protein),
lg of protein),
l
l
and CAL-B (immobilized on acrylic resin) were obtained from Sig-
ma and used as obtained. Lipase AK (from Pseudomonas fluorescens)
and lipase PS (from Burkholderia cepacia) were obtained from Wako
pure chemicals, Japan. Reactions were monitored by thin-layer
chromatography (TLC) carried out on 0.25 mm silica gel plates
(Merck) with UV light, ethanolic anisaldehyde, and phosphomolyb-
dic acid/heat as developing agents. Silicagel 100–200 mesh was
used for column chromatography. Yields refer to chromatographi-
cally and spectroscopically homogeneous materials unless other-
wise stated. NMR spectra were recorded on Bruker 400 MHz
spectrometers at 25 °C in CDCl3 using TMS as the internal standard.
Chemical shifts are shown in d. 13C NMR spectra were recorded
with a complete proton decoupling environment. The chemical
shift value is listed as dH and dC for 1H and 13C, respectively. Mass
spectroscopic analysis was performed in the Central Research
Facility (CRF), IIT-Kharagpur. Optical rotations were measured on
a JASCO Dip 360 digital polarimeter. Chiral HPLC was performed
using Chiral AS-H, OJ-H, and OD-H columns (0.46 ꢁ 25 cm, Daicel
Figure 1. ORTEP diagram of compound 45.
O
O
O
TBDPSO
TBDPSO
TBDPSO
TsO
a
b
AcO
HO
45
55
O
56
OH
O
TBDPSO
TBDPSO
HO
c
d
e
57
58
59
Scheme 7. Reagents and conditions: (a) K2CO3, MEOH; rt; (b) Ts-Cl, Et3N, DMAP; (c) LAH/THF, reflux; (d) (COCl)2, Me2SO, Et3N, ꢀ78 °C; (e) TBAF-THF, rt.

T. Mahapatra et al. / Tetrahedron: Asymmetry 19 (2008) 2497–2507
2501
industries) with Shimadzu ProminenceLC-20AT chromatograph
coupled with UV–vis detector (254 nm). Eluting solvent used had
different ratios of hexane and 2-propanol.
rated under reduced pressure. The residue was taken in ethyl ace-
tate, and washed successively with water and brine. The organic
layer was dried over MgSO4 and evaporated under reduced pres-
sure. The product was purified by flash chromatography to afford
(g) of diol. dH: 8.0 (d, J = 8.0 Hz, 1H, ArH), 7.5 (t, J = 8.0 Hz, 1H,
ArH), 7.35 (t, J = 8.0 Hz, 1H, ArH), 7.2 (d, J = 8.0 Hz, 1H, ArH), 4.0
(d, J = 12.0 Hz, 2H, –CH2OH), 3.8 (d, J = 12.0 Hz, 2H, –CH2OH), 3.0
(t, J = 6.5 Hz, 2H, C4–H), 2.0 (t, J = 6.5 Hz, 2H, C3–H). dC: 202.7
(C@O), 143.82, 133.9, 131.8, 128.85, 127.56, 126.65, 64.6
(–CH2OH), 63.55 (–CH2OH), 51.4 (C2), 26.32 (C4), 25.0 (C3).
4.1. 3,3-Bis-hydroxymethyl-chroman-4-one 1
Chroman-4-one (250 mg, 1.68 mmol) was taken in MeOH
(10 ml) and K2CO3 (466 mg, 3.38 mmol), and water (10 ml) was
added to it at once. Formalin solution (37%, 0.56 ml, 6.75 mmol)
was added to the reaction mixture and it was heated at 50 °C for
2–3 h. After completion of the reaction, as indicated by TLC, MeOH
was evaporated under reduced pressure. The residue was taken in
ethyl acetate, and washed successively with water and brine. The
organic layer was dried with MgSO4 and evaporated under reduced
pressure. The product was purified by flash chromatography to af-
ford (g) of diol. dH: 7.86 (d, J = 8.0 Hz, 1H, ArH), 7.53 (t, J = 8.0 Hz,
1H, ArH), 7.1 (t, J = 8.0 Hz, 1H, ArH), 7.0 (d, J = 8.0 Hz, 1H, ArH),
4.4 (s, 2H, –OCH2), 3.96 (d, J = 10.0 Hz, 2H, –CH2OH), 3.87 (d,
J = 10.0 Hz, 2H, –CH2OH). dC: 195.7 (C@O), 161.36, 153.4, 136.5,
127.47, 121.64, 117.9, 70.04 (C2), 61.6 (–CH2OH), 60.9 (–CH2OH),
51.9 (C3).
4.7. 2,2-Bis-hydroxymethyl-6-methoxy-3,4-dihydro-2H-
naphthalen-1-one 7
The diol was prepared from 6-methoxy-a-tetralone as de-
scribed earlier. dH: 7.95 (d, J = 8.0 Hz, 1H, ArH), 6.95 (d, J = 8.0 Hz,
1H, ArH), 6.65 (s, 1H, ArH), 4.0 (d, J = 12.0 Hz, 2H, –CH2OH), 3.85
(s, 3H, –OMe), 3.8 (d, J = 12.0 Hz, 2H, –CH2OH), 3.0 (t, J = 6.5 Hz,
2H, C4–H), 2.0 (t, J = 6.5 Hz, 2H, C3–H). dC: 201.5 (C@O), 164.0,
146.5, 130.05, 125.2, 113.54, 112.3, 64.6 (–CH2OH), 63.6 (–CH2OH),
55.4 (–OMe), 50.9 (C2), 26.24 (C4), 25.21 (C3).
4.2. 7-Methoxy-3,3-bis-hydroxymethyl-chroman-4-one 2
4.8. 2,2-Bis-hydroxymethyl-7-methoxy-3,4-dihydro-2H-
naphthalen-1-one 8
The diol was prepared from 7-methoxy-chroman-4-one as de-
scribed earlier. dH: 7.78 (d, J = 8.4 Hz, 1H, ArH), 6.6 (d, J = 8.4 Hz,
1H, ArH), 6.4 (s, 1H, ArH), 4.38 (s, 2H, –OCH2), 3.9 (d, J = 11.2 Hz,
2H, –CH2OH), 3.85 (s, 3H, –OMe), 3.82 (d, J = 11.2 Hz, 2H, –CH2OH).
dC: 194.97 (C@O), 166.57, 163.46, 129.0, 110.65, 100.51, 69.14 (C2),
62.12 (–CH2OH), 62.00 (–CH2OH), 55.68 (–OMe), 50.8 (C3).
The diol was prepared from 7-methoxy-a-tetralone as de-
scribed earlier. dH: 7.5 (d, J = 2.8 Hz, 1H, ArH), 7.2 (d, J = 8.0 Hz,
1H, ArH), 7.1 (dd, J = 8.0 Hz, 2.8 Hz, 1H, ArH), 4.0 (d, J = 12.0 Hz,
2H, –CH2OH), 3.85 (s, 3H, –OMe), 3.8 (d, J = 12.0 Hz, 2H, –CH2OH),
3.0 (t, J = 6.5 Hz, 2H, C4–H), 2.0 (t, J = 6.5 Hz, 2H, C3–H). dC: 202.8
(C@O), 158.2, 136.35, 132.25, 130.5, 122.45, 109.44, 64.5
(–CH2OH), 63.7 (–CH2OH), 55.3 (OMe), 51.02 (C2), 26.44 (C4),
24.07 (C3).
4.3. 7-Chloro-3,3-bis-hydroxymethyl-chroman-4-one 3
The diol was prepared from 7-chloro-chroman-4-one as de-
scribed earlier. dH: 7.78 (d, J = 6.0 Hz, 1H, ArH), 7.0 (2H, ArH), 4.4
(s, 2H, –OCH2), 3.94 (d, J = 10.0 Hz, 2H, –CH2OH), 3.83 (d,
J = 10.0 Hz, 2H, –CH2OH). dC: 195.14 (C@O), 161.88, 142.72,
128.61, 125.26, 122.7, 118.12, 69.39 (C2), 62.26 (–CH2OH), 62.06
(–CH2OH), 51.53 (C3).
4.9. 2,2-Bis-hydroxymethyl-5,8-dimethoxy-3,4-dihydro-2H-
naphthalen-1-one 9
The diol was prepared from 5,8-dimethoxy-a-tetralone as de-
scribed earlier. dH: 7.0 (d, J = 9.2 Hz, 1H, ArH), 6.8 (d, J = 9.2 Hz,
1H, ArH), 4.0 (d, J = 12.0 Hz, 2H, –CH2OH), 3.85 (s, 6H, –OMe), 3.8
(d, J = 12.0 Hz, 2H, –CH2OH), 2.9 (t, J = 6.4 Hz, 2H, C4–H), 1.8 (t,
J = 6.4 Hz, 2H, C3–H). dC: 203.12 (C@O), 154.24, 150.06, 134.1,
121.68, 115.8, 109.98, 65.2 (–CH2OH), 65.0 (–CH2OH), 56.2
(–OMe), 55.8 (–OMe), 51.7 (C2), 25.35 (C4), 19.38 (C3).
4.4. 6,7-Dimethoxy-3,3-bis-hydroxymethyl-chroman-4-one 4
The diol was prepared from 6,7-dimethoxy-chroman-4-one as
described earlier. dH: 7.22 (s, 1H, ArH), 6.43 (s, 1H, ArH), 4.5 (s,
2H, –OCH2), 4.0–3.8 (10H). dC: 195.0 (C@O), 158.13, 157.01,
144.95, 112.25, 106.47, 99.88, 69.4 (C2), 62.19 (–CH2OH), 56.31
(–OMe), 56.13 (–OMe), 50.64 (C3).
4.10. 2,2-Bis-hydroxymethyl-indan-1-one 10
The diol was prepared from 1-indanone as described earlier. dH:
7.6 (d, J = 8.0 Hz, 1H, ArH), 7.55 (t, J = 6.4 Hz, 1H, ArH), 7.45 (d,
J = 8.0 Hz, 1H, ArH), 7.34 (t, J = 6.4 Hz, 1H, ArH), 3.8 (s, 4H, –CH2OH),
3.0 (s, 2H, C3–H). dC: 209.9 (C@O), 153.9, 135.5, 135.1, 127.57,
126.4, 123.6, 64.95 (–CH2OH), 64.75 (–CH2OH), 56.4 (C2), 33.9 (C3).
4.5. 7,7-Bis-hydroxymethyl-6,7-dihydro-[1,3]dioxolo[4,5-
g]chromen-8-one 5
The diol was prepared from 6,7-dihydro-[1,3]dioxolo[4,5-
g]chromen-8-one as described earlier. dH: 7.13 (s, 1H, ArH), 6.43
(s, 1H, ArH), 6.0 (s, 2H, –O–CH2–O–), 4.33 (s, 2H, –OCH2), 3.91 (d,
J = 11.0 Hz, 2H, –CH2OH), 3.80 (d, J = 11.0 Hz, 2H, –CH2OH). dC:
194. 94 (C@O), 160.6, 155.9, 128.4, 126.22, 103.8, 102.13, 98.2
(–O–CH2–O), 69.3 (C2), 62.07 (–CH2OH), 50.58 (C3).
4.11. 5-Chloro-2,2-bis-hydroxymethyl-indan-1-one 11
The diol was prepared from 5-chloro-1-indanone as described
earlier. dH: 7.6 (d, J = 8.0 Hz, 1H, ArH), 7.45 (s, 1H, ArH), 7.27 (d,
J = 8.0 Hz, 1H, ArH), 3.8 (s, 4H, –CH2OH), 3.1 (s, 2H, C3–H). dC:
208.48 (C@O), 155.53, 142.11, 134.5, 128.37, 126.9, 125.06, 64.66
(–CH2OH), 64.42 (–CH2OH), 57.04 (C2), 33.79 (C3).
4.6. 2,2-Bis-hydroxymethyl-3,4-dihydro-2H-naphthalen-
1-one 6
a-Tetralone (250 mg, 1.71 mmol) was taken in MeOH (10 ml)
4.12. 2,2-Bis-hydroxymethyl-5-methoxy-indan-1-one 12
and K2CO3 (447 mg, 3.42 mmol), and water (10 ml) was added to
it at once. Formalin solution (37%, 0.542 ml, 6.84 mmol) was added
to the reaction mixture and then heated at 50 °C for 2–3 h. After
completion of the reaction, as indicated by TLC, MeOH was evapo-
The diol was prepared from 5-methoxy-1-indanone as de-
scribed earlier. dH: 7.7 (d, J = 5.6 Hz, 1H, ArH), 6.9 (m, 2H, ArH),
3.92 (s, 4H, –CH2OH), 3.86 (s, 3H, –OMe), 3.03 (s, 2H, C3–H). dC:

2502
T. Mahapatra et al. / Tetrahedron: Asymmetry 19 (2008) 2497–2507
209.46 (C@O), 154.28, 146.37, 137.29, 136.71, 126.34, 124.48,
64.32 (–CH2OH), 64.24 (–CH2OH), 56.88 (C2), 55.86 (OMe), 32.46
(C3).
4.19. 3-(tert-Butyl-diphenyl-silanyloxymethyl)-7-chloro-3-
hydroxymethyl-chroman-4-one 29
dH: 7.77 (d, J = 8.2 Hz, 1H, ArH), 7.74–7.65 (m, 4H, ArH), 7.59–
7.25 (m, 6H, ArH), 7.0 (m, 2H, ArH), 4.65 (d, J = 12.0 Hz, 1H, –O–
CH2), 4.55 (d, J = 12.0 Hz, 1H, –O–CH2), 4.2–3.8 (m, 4H, –CH2OH
and –CH2OTBDMS), 1.0 (s, 9H, –Si–tBu). dC: 193.84 (C@O), 161.82,
142.20, 135.58, 134.97,132.40, 129.98, 128.59, 124.88, 122.38,
117.98, 70.04 (C2), 62.63 (–CH2OTBDPS), 62.26 (–CH2OH), 52.8
(C3), 26.74, 19.29.
4.13. 2,2-Bis-hydroxymethyl-6-methyl-indan-1-one 13
The diol was prepared from 6-methoxy-1-indanone as de-
scribed earlier. dH: 7.5–7.32 (m, 3H, ArH), 3.83 (s, 2H, –CH2OH),
3.81 (s, 2H, –CH2OH), 3.1 (s, 2H, C3–H), 2.36 (s, 3H, –Me). dC:
210.0 (C@O), 151.37, 137.54, 136.81, 136.14, 126.36, 123.90,
64.84 (–CH2OH), 64.66 (–CH2OH), 56.71 (C2), 33.45 (C3), 20.97
(Me).
4.20. 3-(tert-Butyl-dimethyl-silanyloxymethyl)-3-
hydroxymethyl-6,7-dimethoxy-chroman-4-one 17
4.14. 3-(tert-Butyl-dimethyl-silanyloxymethyl)-3-
hydroxymethyl-chroman-4-one 14
dH: 7.21 (s, 1H, ArH), 6.43 (s, 1H, ArH), 4.52 (d, J = 12.0 Hz, 1H,
–O–CH2), 4.40 (d, J = 12.0 Hz, 1H, –O–CH2), 3.9–3.82 (10H), 0.9 (s,
9H, –Si–tBu), 0.07 (s, 6H, –SiMe2). dC: 193.54 (C@O), 158.2,
156.49, 144.65, 112.37, 106.52, 99.88, 69.8 (C2), 62.99
(–CH2OTBDMS), 62.32 (–CH2OH), 56.27 (–OMe), 56.12 (–OMe),
51.19 (C3), 25.71, 18.14, ꢀ5.70, ꢀ5.75.
dH: 7.86 (d, J = 8.0 Hz, 1H, ArH), 7.5 (t, J = 8.0 Hz, 1H, ArH), 7.0 (m,
2H, ArH), 4.56 (d, J = 11.6 Hz, 1H, –O–CH2), 4.46 (d, J = 11.6 Hz, 1H,
–O–CH2), 3.95–3.84 (m, 4H, –CH2OH and –CH2OTBDMS), 0.88
(s, 9H, –Si–tBu), 0.06 (s, 6H, Si–Me2). dC: 194.94 (C@O), 161.54,
136.27, 127.27, 121.49, 120.15, 117.88, 69.36 (C2), 62.75
(–CH2OTBDMS), 62.2 (–CH2OH), 51.9 (C3), 25.7, 18.13, ꢀ5.73,
ꢀ5.78.
4.21. 3-(tert-Butyl-diphenyl-silanyloxymethyl)-3-
hydroxymethyl-6,7-dimethoxy-chroman-4-one 30
4.15. 3-(tert-Butyl-diphenyl-silanyloxymethyl)-3-
hydroxymethyl-chroman-4-one 27
dH: 7.67–7.61 (m, 4H, ArH), 7.43–7.34 (m, 6H, ArH), 7.18 (s, 1H,
ArH), 6.39 (s, 1H, ArH), 4.63 (d, J = 12.0 Hz, 1H, –O–CH2), 4.46 (d,
J = 12.0 Hz, 1H, –O–CH2), 4.0–3.83 (10H), 0.9 (s, 9H, –Si–tBu). dC:
193.52 (C@O), 158.2, 156.6, 144.76, 135.59, 132.72, 129.89,
127.81, 112.57, 106.78, 99.91, 70.11 (C2), 62.72 (–CH2OTBDPS),
62.65 (–CH2OH), 56.31 (–OMe), 56.21 (OMe), 51.71 (C3), 26.80,
19.34.
dH: 7.7 (d, J = 8.0 Hz, 1H, ArH), 7.6(m, 4H, ArH), 7.5–7.3 (m, 7H,
ArH), 7.0 (m, 2H, ArH), 4.68 (d, J = 12.0 Hz, 1H, –O–CH2), 4.52 (d,
J = 12.0 Hz, 1H, –O–CH2), 4.0 (d, J = 12.0 Hz, 1H), 3.9–3.8 (m, 3H),
1.05 (s, 9H, Si–tBu). dC: 194.9 (C@O), 161.45, 136.2, 135.8, 134.75,
132.45, 129.84, 127.77, 121.53, 119.8, 117.8, 69.7 (C2), 62.5
(–CH2OTBDPS), 62.3 (–CH2OH), 52.27 (C3), 26.62, 19.23.
4.22. 7-(tert-Butyl-dimethyl-silanyloxymethyl)-7-hydroxy-
methyl-6,7-dihydro-[1,3]dioxolo[4,5-g]chromen-8-one 18
4.16. 3-(tert-Butyl-dimethyl-silanyloxymethyl)-3-
hydroxymethyl-7-methoxy-chroman-4-one 15
dH: 7.2 (s, 1H, ArH), 6.4 (s, 1H, ArH), 5.9 (s, 2H, –O–CH2–O–), 4.51
(d, J = 12.0 Hz, 1H, –O–CH2), 4. 37 (d, J = 12.0 Hz, 1H, –O–CH2), 3.9–
3.8 (m, 4H, –CH2OTBDMS and –CH2OH), 0.8 (s, 9H, –Si–tBu), 0.02 (s,
6H, –SiMe2). dC: 193.17 (C@O), 159.76, 154.60, 149.69, 128.72,
103.94, 102.1, 98.17 (–O–CH2–O–), 69.82 (C2), 62.80
(–CH2OTBDMS), 62.23 (–CH2OH), 51.17 (C3), 25.69, 19.68, ꢀ5.73,
ꢀ5.78.
dH: 7.78 (d, J = 8.8 Hz, 1H, ArH), 6.58 (dd, J = 8.8, 2.4 Hz, 1H, ArH),
6.4 (d, J = 2.4 Hz, 1H, ArH), 4.56 (d, J = 11.2 Hz, 1H, –OCH2), 4.42 (d,
J = 11.2 Hz, 1H, –OCH2), 3.9 (d, J = 10.0 Hz, 2H), 3.85–3.80 (m, 5H),
0.9 (s, 9H, –Si–tBu), 0.06 (s, 6H, Si–Me2). dC: 193.58 (C@O), 166.28,
163.61, 128.97, 114.04, 110.35, 100.48, 69.6 (C2), 62.86
(–CH2OTBDMS), 62.22 (–CH2OH), 55.6 (–OMe), 51.4 (C3), 25.7,
18.13, ꢀ5.72, ꢀ5.77.
4.23. 7-(tert-Butyl-diphenyl-silanyloxymethyl)-7-hydroxy-
methyl-6,7-dihydro-[1,3]dioxolo[4,5-g]chromen-8-one 31
4.17. 3-(tert-Butyl-diphenyl-silanyloxymethyl)-3-
hydroxymethyl-7-methoxy-chroman-4-one 28
dH: 7.67–7.6 (m, 4H, ArH), 7.44–7.2 (m, 6H, ArH), 7.1 (s, 1H, ArH),
6.4 (s, 1H, ArH), 5.96 (s, 2H, –O–CH2–O), 4.63 (d, J = 12.0 Hz, 1H,
–O–CH2), 4.44 (d, J = 12.0 Hz, 1H, –O–CH2), 4.0–3.84 (m, 4H,
–CH2OTBDPS and –CH2OH), 1.0 (s, 9H, –Si–tBu). dC: 193.22 (C@O),
159.71, 154.62, 143.21, 135.55, 132.51, 129.85, 127.76, 113.77,
103.96, 102.01, 98.1 (–O–CH2–O–), 69.92 (C2), 62.45
(–CH2OTBDPS), 62.42 (–CH2OH), 51.53 (C3), 26.7, 19.2.
dH: 7.78 (d, J = 8.8 Hz, 1H, ArH), 7.65 (m, 4H, ArH), 7.4–7.3 (m,
6H, ArH), 6.58 (dd, J = 8.8, 2.0 Hz, 1H, ArH), 6.4 (d, J = 2.0 Hz, 1H,
ArH), 4.66 (d, J = 11.2 Hz, 1H, –OCH2), 4.48 (d, J = 11.2 Hz, 1H,
–OCH2), 4.1–3.8 (m, 7H), 1.05 (s, 9H, Si–tBu). dC: 193.56 (C@O),
166.26, 163.515, 135.54,132.56, 129.82, 128.98, 127.73, 114.1,
110.22, 100.5, 69.76 (C2), 62.47 (–CH2OTBDPS), 62.45 (–CH2OH),
55.61 (–OMe), 51.77 (C3), 26.69, 19.25.
4.24. 2-(tert-Butyl-dimethyl-silanyloxymethyl)-2-
hydroxymethyl-3,4-dihydro-2H-naphthalen-1-one 19
4.18. 3-(tert-Butyl-dimethyl-silanyloxymethyl)-7-chloro-3-
hydroxymethyl-chroman-4-one 16
Diol 6 (250 mg, 1.21 mmol) was dissolved in anhydrous DCM
(10 ml) and cooled to 0 °C. Imidazole (100 mg, 1.5 mmol) and
DMAP (catalytic) were added to the reaction mixture followed by
addition of TBS-Cl (220 mg, 1.5 mmol). The reaction mixture was
allowed to warm at room temperature for 6 h, after which water
was added to it and the organic layer was washed with brine and
dried over MgSO4. Evaporation and purification yielded the mono
TBS protected alcohol in 80% yield. dH: 7.97 (d, J = 8.0 Hz, 1H,
ArH), 7.47 (t, J = 8.0 Hz, 1H, ArH), 7.3 (t, J = 8.0 Hz, 1H, ArH), 7.24
dH: 7.78 (d, J = 8.0 Hz, 1H, ArH), 7.0 (m, 2H, ArH), 4.59 (d,
J = 12.0 Hz, 1H, –O–CH2), 4.48 (d, J = 12.0 Hz, 1H, –O–CH2), 3.96–
3.82 (m, 4H, –CH2OH and –CH2OTBDMS), 2.6 (br s, 1H), 0.9 (s,
9H, Si–tBu), 0.06 (s, 6H, –SiMe2). dC: 193.84 (C@O), 161.86,
142.19, 134.94, 128.52, 122.35, 117.95, 69.78 (C2), 62.8
(–CH2OTBDMS), 62.14 (–CH2OH), 51.94 (C3), 29.64, 18.11, ꢀ5.74,
ꢀ5.79.

T. Mahapatra et al. / Tetrahedron: Asymmetry 19 (2008) 2497–2507
2503
(d, J = 8.0 Hz, 1H, ArH), 4.0 (d, J = 10.0 Hz, 1H), 3.8 (m, 3H), 3.1–3.0
(m, 2H, –C4–H), 2.17–2.1 (m, 2H, C3–H), 0.86 (s, 9H, –Si–tBu), 0.058
(s, 3H, –Si–Me), 0.028 (s, 3H, –Si–Me). dC: 201.76 (C@O), 144.04,
133.69, 131.94, 128.77, 127.455, 126.59, 65.6 (–CH2OTBDMS),
64.38 (–CH2OH), 51.5 (C2), 26.78 (C4), 25.68 (C3), 25.11, 18.06,
ꢀ5.69, ꢀ5.77.
–CH2OTBDPS), 3.88–3.79 (m, 5H), 2.9 (m, 2H, C4–H), 2.2 (m, 2H,
C3–H), 1.0 (s, 9H, Si–tBu). dC: 200.42 (C@O), 163.86, 146.5,
135.58, 132.94, 129.9, 127.7, 127.6 125.6, 113.3, 112.4, 65.7 (–
CH2OTBDPS), 64.3 (–CH2OH), 55.4 (–OMe), 51.4 (C2), 26.95 (C4),
26.76 (C3), 25.47, 19.26.
4.30. 2-(tert-Butyl-dimethyl-silanyloxymethyl)-2-hydroxy-
methyl-5,8-dimethoxy-3,4-dihydro-2H-naphthalen-1-one 22
4.25. 2-(tert-Butyl-diphenyl-silanyloxymethyl)-2-
hydroxymethyl-3,4-dihydro-2H-naphthalen-1-one 32
dH: 6.98 (d, J = 8.2 Hz, 1H, ArH), 6.76 (d, J = 8.2 Hz, 1H, ArH), 3.94
(d, J = 10.0 Hz, 1H), 3.81 (s, 3H, –OMe), 3.80 (s, 3H, –OMe),
3.75–3.70 (m, 3H), 2.89 (m, 2H, C4–H), 2.0 (m, 2H, C3–H), 0.85 (s,
9H, Si–tBu), 0.02 (s, 6H, SiMe2). dC: 202.05 (C@O), 154.18, 149.97,
134.7, 122.17, 115.59, 109.77, 65.62 (–CH2OTBDMS), 63.72
(–CH2OH), 56.11 (–OMe), 55.88 (–OMe), 52.38 (C2), 25.67 (C4),
25.55 (C3), 19.41, 18.05, ꢀ5.67, ꢀ5.76.
Diol 6 (250 mg, 1.21 mmol) was taken in anhydrous DCM
(10 ml) and cooled to 0 °C. Imidazole (100 mg, 1.5 mmol) and
DMAP (catalytic) were added to the reaction mixture followed by
the addition of TBDPS-Cl (400 mg, 1.5 mmol). The reaction mixture
was allowed to warm at room temperature for 6 h, after which
water was added to it and the organic layer was washed with brine
and dried over MgSO4. Evaporation and purification yielded the
mono TBDPS-protected alcohol in 80% yield. dH: 7.98 (d,
J = 8.0 Hz, 1H, ArH), 7.6–7.4 (m, 10H, ArH), 7.3–7.19 (m, 3H, ArH),
4.0 (d, J = 10.4 Hz, 1H, –CH2OTBDPS), 3.93 (d, J = 10.0 Hz, 2H,
–CH2OH), 3.82 (d, J = 10.4 Hz, 1H, –CH2OTBDPS), 3.0 (m, 2H, –C4–
H), 2.22 (m, 2H, C3–H), 1.0 (s, 9H, –Si–tBu). dC: 201.68 (C@O),
143.9, 135.58, 135.564, 134.75, 133.68, 132.05, 129.8, 128.72,
127.72, 126.61, 65.6 (–CH2OTBDPS), 64.5 (–CH2OH), 51.9 (C2),
26.94 (C4), 26.5 (C3), 25.03, 19.24.
4.31. 2-(tert-Butyl-diphenyl-silanyloxymethyl)-2-hydroxy-
methyl-5,8-dimethoxy-3,4-dihydro-2H-naphthalen-1-one 35
dH: 7.7–7.5 (m, 4H, ArH), 7.48–7.3 (m, 6H, ArH), 7.0 (d, J = 8.2 Hz,
1H, ArH), 6.75 (d, J = 8.2 Hz, 1H, ArH), 4.0 (d, J = 10.0 Hz, 1H), 3.80 (s,
3H, –OMe), 3.79 (s, 3H, –OMe), 3.78–3.75 (m, 3H), 3.0 (m, 2H, C4–
H), 2.2 (m, 2H, C3–H), 1.0 (s, 9H, Si–tBu). dC: 201.97 (C@O), 154.2,
150.1, 135.64, 134.6, 133.09, 129.75, 127.73, 122.54, 115.72,
109.87, 65.77 (–CH2OTBDPS), 64.43 (–CH2OH), 56.18 (–OMe),
56.03 (–OMe), 52.85 (C2), 26.78 (C4), 25.78, 19.48, 19.32.
4.26. 2-(tert-Butyl-dimethyl-silanyloxymethyl)-2-hydroxy-
methyl-7-methoxy-3,4-dihydro-2H-naphthalen-1-one 20
4.32. 2-(tert-Butyl-dimethyl-silanyloxymethyl)-2-
dH: 7.4 (d, J = 2.8 Hz, 1H, ArH), 7.16 (d, J = 8.0 Hz, 1H, ArH), 7.05
(dd, J = 8.0, 2.8 Hz, 1H, ArH), 4.0 (d, J = 10.0 Hz, 1H), 3.81–3.76 (m,
6H), 3.0 (m, 1H, –C4–H), 2.94 (m, 1H, –C4–H), 2.12(m, 2H,
–C3–H), 0.86 (s, 9H, –Si–tBu), 0.06 (s, 3H, –SiMe), 0.03 (s, 3H,
–SiMe). dC: 201.6 (C@O), 158.26, 136.65, 132.62, 129.9, 122.2,
109.2, 65.64 (–CH2OTBDMS), 64.32 (–CH2OH), 55.43 (–OMe),
51.36 (C2), 26.94 (C4), 25.69 (C3), 24.28, 18.07, ꢀ5.67, ꢀ5.75.
hydroxymethyl-indan-1-one 23
dH: 7.60 (d, J = 8.0 Hz, 1H, ArH), 7.55 (t, J = 8.0 Hz, 1H, ArH), 7.46
(d, J = 8.0 Hz, 1H, ArH), 7.28 (t, J = 8.0 Hz, 1H, ArH), 4.0–3.77 (m, 4H,
–CH2OTBDMS and –CH2OH), 3.26 (d, J = 16.0 Hz, 1H, C3–H), 3.06 (d,
J = 16.0 Hz, 1H, C3–H), 0.75 (s, 9H, Si–tBu), 0.025 (s, 6H, SiMe2). dC:
209.29 (C@O), 154.38, 136.66, 135.18, 127.31, 126.55, 123.85,
66.07 (–CH2OTBDMS), 65.34 (–CH2OH), 56.99 (C2), 33.92 (C3),
25.69, 18.0, ꢀ5.64, ꢀ5.7.
4.27. 2-(tert-Butyl-diphenyl-silanyloxymethyl)-2-hydroxy-
methyl-7-methoxy-3,4-dihydro-2H-naphthalen-1-one 33
4.33. 2-(tert-Butyl-diphenyl-silanyloxymethyl)-2-
dH: 7.7–7.6 (m, 5H, ArH), 7.44–7.35 (m, 6H, ArH), 7.1–7.0 (m, 2H,
ArH), 4.0 (d, J = 10.0 Hz, 1H, –CH2OTBDPS), 3.93 (d, J = 10.0 Hz, 1H,
–CH2OTBDPS), 3.84–3.80 (m, 5H), 2.92 (m, 2H, –C4–H), 2.2 (m, 2H,
C3–H), 1.04 (s, 9H, –Si–tBu). dC: 201.62 (C@O), 158.26, 136.52,
135.6, 134.75, 132.71, 129.81, 127.72, 127.6, 122.25, 109.15,
65.61 (–CH2OTBDPS), 64.4 (–CH2OH), 55.43 (–OMe), 51.76 (C2),
27.08 (C4), 26.74 (C3), 24.2, 19.26.
hydroxymethyl-indan-1-one 36
dH: 7.8 (d, J = 8.6 Hz, 1H, ArH), 7.6–7.2 (m, 13H, ArH), 4.0–3.78
(m, 4H, –CH2OTBDPS and –CH2OH), 3.33 (d, J = 17.2 Hz, 1H, C3–
H), 3.08 (d, J = 17.2 Hz, 1H, C3–H), 1.0 (s, 9H, Si–tBu). dC: 209.44
(C@O), 154.32, 136.83, 135.56, 135.15, 132.98, 129.72, 127.68,
127.30, 126.46, 123.81, 66.52 (–CH2OTBDPS), 64.88 (–CH2OH),
56.94 (C2), 34.12 (C3), 26.66, 19.14.
4.28. 2-(tert-Butyl-dimethyl-silanyloxymethyl)-2-hydroxy-
methyl-6-methoxy-3,4-dihydro-2H-naphthalen-1-one 21
4.34. 2-(tert-Butyl-dimethyl-silanyloxymethyl)-5-chloro-2-
hydroxymethyl-indan-1-one 24
dH: 7.93 (d, J = 8.8 Hz, 1H, ArH), 6.8 (d, J = 8.8 Hz, 1H, ArH), 6.67
(s, 1H, ArH), 4.0 (d, J = 10.0 Hz, 1H, –CH2OTBDMS), 3.84 (s, 3H,
–OMe), 3.76 (m, 3H), 3.02 (m, 1H, C4–H), 2.9 (m, 1H, C4–H), 2.1
(t, J = 6.0 Hz, 2H, C3–H), 0.8 (s, 9H, –Si–tBu), 0.05 (s, 3H, –SiMe),
0.02 (s, 3H, –SiMe). dC: 200.5 (C@O), 163.84, 146.63, 129.92,
125.54, 113.35, 112.32, 65.71 (–CH2OTBDMS), 64.24 (–CH2OH),
55.39 (–OMe), 51.01 (C2), 26.78 (C4), 25.69 (C3), 25.55, 18.07,
ꢀ5.67, ꢀ5.76.
dH: 7.65(d, J = 8.0 Hz, 1H, ArH), 7.48 (s, 1H, ArH), 7.34 (d, J = 8.0 Hz,
1H, ArH), 3.84–3.78 (m, 4H, –CH2OTBDMS and –CH2OH), 3.25 (d,
J = 16.0 Hz, 1H, C3–H), 3.08 (d, J = 16.0 Hz, 1H, C3–H), 0.75 (s, 9H,
Si–tBu), 0.003 (s, 6H, SiMe2). dC: 207.73 (C@O), 155.77, 141.75,
135.17, 128.18, 126.75, 124.93, 66.0 (–CH2OTBDMS), 65.26
(–CH2OH), 57.32 (C2), 33.66 (C3), 25.59, 18.01, ꢀ5.65, ꢀ5.71.
4.35. 2-(tert-Butyl-diphenyl-silanyloxymethyl)-5-chloro-2-
4.29. 2-(tert-Butyl-diphenyl-silanyloxymethyl)-2-hydroxy-
methyl-6-methoxy-3,4-dihydro-2H-naphthalen-1-one 34
hydroxymethyl-indan-1-one 37
dH: 7.7 (d, J = 8.0 Hz, 1H, ArH), 7.5–7.2 (m, 12H, ArH), 4.0–3.75
(m, 4H, –CH2OTBDPS and –CH2OH), 3.3 (d, J = 16.0 Hz, 1H, C3–H),
3.1 (d, J = 16.0 Hz, 1H, C3–H), 0.9 (s, 9H, Si–tBu). dC: 207.90
(C@O), 155.82, 141.74, 135.61, 132.95, 129.86, 128.19, 127.78,
dH: 7.94 (d, J = 8.8 Hz, 1H, ArH), 7.64 (m, 4H, ArH), 7.40 (m, 6H,
ArH), 6.80 (d, J = 8.8 Hz, 1H, ArH), 6.64 (s, 1H, ArH), 4.0 (d,
J = 10.0 Hz, 1H, –CH2OTBDPS), 3.91 (d, J = 10.0 Hz, 1H,

2504
T. Mahapatra et al. / Tetrahedron: Asymmetry 19 (2008) 2497–2507
126.72, 124.94, 124.18, 66.51 (–CH2OTBDPS), 64.78 (–CH2OH),
57.47 (C2), 33.88 (C3), 26.63, 19.22.
4.41. Acetic acid (S)-3-(tert-butyl-diphenyl-silanyloxymethyl)-
7-methoxy-4-oxo-chroman-3-ylmethyl ester 41
4.36. 2-(tert-Butyl-dimethyl-silanyloxymethyl)-5-methoxy-2-
hydroxymethyl-indan-1-one 25
dH: 7.75 (d, J = 8.8 Hz, 1H, ArH), 7.7–7.5 (m, 4H ArH), 7.5–7.4 (m,
6H, ArH), 6.6 (dd, J = 8.8 Hz, 2.4 Hz, 1H, ArH), 6.38 (d, J = 2.4 Hz, 1H,
ArH), 4.66–4.4 (m, 4H), 3.9–3.76 (m, 5H), 1.98 (s, 3H, –OCOMe),
1.03 (s, 9H, OSitBu). dC: 190.42 (C@O), 170.56 (–OCOMe), 166.01,
163.13, 135.54, 132.59, 129.78, 129.75, 127.69, 114.18, 110.21,
100.54, 70.16(C2), 62.64 (CH2–OCOMe), 62.15 (–CH2–OTBDPS),
55.59 (–OMe), 50.52 (C3), 26.67 (–OCOMe), 20.67, 19.22.
dH: 7.82 (d, J = 7.8 Hz, 1H, ArH), 6.9–6.8 (m, 2H, ArH), 4.0–3.77
(m, 7H, –CH2OTBDMS and –CH2OH, –OMe), 3.32 (d, J = 17.2 Hz,
1H, C3–H), 3.0 (d, J = 17.2 Hz, 1H, C3–H), 0.9 (s, 9H, –Si–tBu), 0.09
(s, 6H, SiMe2). dC: 207.30 (C@O), 166.73, 157.29, 133.54, 133.45,
128.78, 109.56, 65.48 (–CH2OTBDMS), 65.40 (–CH2OH), 55.46
(–OMe), 55.04 (C2), 33.83 (C3), 27.53, 19.48, ꢀ5.62, ꢀ5.64.
½
a 2D8
ꢂ
¼ þ14:2 (c 0.1, MeOH). HPLC (Daicel Chiralcel AS-H, hexane/
i-PrOH = 49:1, flow rate = 0.8 ml/min) tR = 6.32 min (minor, as-
sumed R), tR = 6.78 min (major, assumed S). HRMS m/z [M+Na]+
found 541.2010; calculated 541.2017 for C30H34O6Si
4.37. 2-(tert-Butyl-diphenyl-silanyloxymethyl)-5-methoxy-2-
hydroxymethyl-indan-1-one 38
4.42. Acetic acid (S)-3-(tert-butyl-diphenyl-silanyloxymethyl)-
dH: 7.8 (d, J = 7.8 Hz, 1H, ArH), 7.6–7.3 (m, 10H, ArH), 6.88 (m,
2H, ArH), 4.0–3.77 (m, 7H, –CH2OTBDPS and –CH2OH, –OMe), 3.3
(d, J = 17.2 Hz, 1H, C3–H), 3.0 (d, J = 17.2 Hz, 1H, C3–H), 0.9 (s,
9H, –Si–tBu). dC: 207.30 (C@O), 165.73, 157.28, 135.56, 133.06,
129.98, 129.69, 127.65, 125.56, 115.46, 109.52, 66.44
(–CH2OTBDPS), 65.10 (–CH2OH), 56.96 (–OMe), 55.64 (C2), 34.13
(C3), 26.59, 19.18.
7-chloro-4-oxo-chroman-3-ylmethyl ester 42
dH: 7.80 (d, J = 8.0 Hz, 1H, ArH), 7.7–7.4 (m, 10H, ArH), 7.0 (m,
2H, ArH), 4.6 (d, J = 11.2 Hz, 1H, –OCH2), 4.52 (dd, J = 11.2, 1.6 Hz,
2H, –CH2OAc), 4.4 (d, J = 11.2 Hz, 1H, –OCH2), 3.88 (d, J = 10.4 Hz,
1H, –CH2OTBDPS), 3.8 (d, J = 10.4 Hz, 1H, –CH2OTBDPS), 1.98 (s,
3H, –OCOMe), 1.06 (s, 9H, OSitBu). dC: 190.91 (C@O), 170.48
(–OCOMe), 161.43, 141.91, 135.50, 134.72, 132.37, 129.87,
128.76, 127.74, 122.45, 117.86, 70.28 (C2), 62.32 (CH2–OCOMe),
61.94 (–CH2–OTBDPS), 50.84 (C3), 26.63(–OCOMe), 20.64, 19.20.
4.38. 2-(tert-Butyl-dimethyl-silanyloxymethyl)-6-methyl-2-
hydroxymethyl-indan-1-one 26
½
a 2D8
ꢂ
¼ þ12:8 (c 1.0, MeOH). HPLC (Daicel Chiralcel AS-H, hexane/
dH: 7.3 (m, 3H, ArH), 3.9–3.7 (m, 4H, –CH2OTBDMS and
–CH2OH), 3.3, (d, J = 17.2 Hz, 1H, C3–H), 3.06 (d, J = 17.2 Hz, 1H,
C3–H), 2.44 (s, 3H, –Me), 0.9 (s, 9H, Si–tBu), 0.06 (s, 6H, SiMe2).
dC: 207.27 (C@O), 152.68, 138.44, 136.38, 132.43, 127.71, 123.92,
67.09 (–CH2OTBDMS), 65.55 (–CH2OH), 56.38 (C2), 32.71 (C3),
27.38 (–Me), 21.92, 19.89, ꢀ5.12, ꢀ5.42.
i-PrOH = 49:1, flow rate = 0.8 ml/min) tR = 3.42 min (minor, as-
sumed R), tR = 4.31 min (major, assumed S). HRMS m/z [M+Na]+
found 545.1514; calculated 545.1521 for C29H31ClO5Si.
4.43. Acetic acid (S)-3-(tert-butyl-diphenyl-silanyloxymethyl)-
6,7-dimethoxy-4-oxo-chroman-3-ylmethyl ester 43
4.39. 2-(tert-Butyl-diphenyl-silanyloxymethyl)-6-methyl-2-
hydroxymethyl-indan-1-one 39
dH: 7.6–7.5 (m, 4H, ArH), 7.5–7.3 (m, 6H, ArH), 7.23 (s, 1H,
ArH), 6.39 (s, 1H, ArH), 4.6 (d, J = 11.2 Hz, 1H, –OCH2), 4.5 (q,
J = 11.2 Hz, 2H, –CH2–OAc), 4.42 (d, J = 11.2 Hz, 1H, –OCH2), 3.93
(d, J = 10.4 Hz, 1H, –CH2OTBDPS), 3.91(s, 3H, OMe), 3.90 (s, 3H,
OMe), 3.80 (d, J = 10.4 Hz, 1H, –CH2OTBDPS), 1.99 (s, 3H,
–OCOMe), 1.04 (s, 9H, OSitBu). dC: 190.45 (C@O), 170.60
(–OCOMe), 157.66, 156.17, 144.67, 135.55, 132.60, 129.79,
112.52, 109.67, 106.90, 99.80, 70.34 (C2), 62.72 (CH2–OCOMe),
62.25 (–CH2–OTBDPS), 56.25 (–OMe), 56.13 (–OMe), 50.39 (C3),
dH: 7.7–7.3 (m, 13H, ArH), 3.9–3.7 (m, 4H, –CH2OTBDPS and
–CH2OH), 3.3, (d, J = 17.2 Hz, 1H, C3–H), 3.02 (d, J = 17.2 Hz, 1H,
C3–H), 2.4 (s, 3H, –Me), 0.9 (s, 9H, Si–tBu). dC: 209.47 (C@O),
151.67, 137.21, 136.89, 135.56, 135.52, 133.0, 132.84, 129.71,
127.67, 123.72, 66.49 (–CH2OTBDPS), 65.02 (–CH2OH), 57.24 (C2),
33.74 (C3), 29.66 (–Me), 21.02, 19.17.
26.68 (–OCOMe), 20.71, 19.24. ½a D28
¼ þ3:6 (c 0.18, MeOH). HPLC
ꢂ
4.40. Acetic acid (S)-3-(tert-butyl-diphenyl-silanyloxymethyl)-
4-oxo-chroman-3-ylmethyl ester 40
(Daicel Chiralcel AS-H, hexane/i-PrOH = 49:1, flow rate = 0.8 ml/
min) tR = 8.54 min (minor, assumed R), tR = 10.12 min (major,
assumed S). HRMS m/z [M+Na]+ found 571.2130; calculated
571.2122 for C31H36O7Si.
In a typical resolution experiment, a solution of 27–39 (50 mg)
in anhydrous diisopropyl ether (5 ml) was stirred with vinyl ace-
tate (20 equiv) and powdered molecular sieves (25 mg, 4 Å) fol-
lowed by the addition of CAL-B (50 mg). The reaction mixture
was stirred in an orbit shaker (250 rpm) at room temperature for
12–36 h. After 50% conversion (by TLC analysis), the reaction mix-
ture was filtered through a pad of Celite and evaporated to dryness.
The alcohols and their acetates 40–52 were isolated by flash chro-
matography. dH: 7.8 (d, J = 7.2 Hz, 1H, ArH), 7.7–7.5 (m, 4H, ArH),
7.5–7.3 (m, 7H, ArH), 7.0 (m, 2H, ArH), 4.6–4.4 (m, 4H, –OCH2–
and –CH2–OAc)), 3.8 (m, 2H, –CH2–OTBDPS), 2.0 (s, 3H, OCOMe),
1.0 (s, 9H, SitBu) dC: 191.89 (C@O), 170.84 (–CH2–O–COMe),
136.01, 135.53, 135.46, 129.81, 127.72, 127.68, 127.53, 127.61,
120.98, 117.75, 69.87 (C2), 62.49 (CH2–OCOMe), 61.93 (–CH2–
4.44. Acetic acid (S)-7-(tert-butyl-diphenyl-silanyloxymethyl)-
8-oxo-7,8-dihydro-6H-[1,3]dioxolo[4,5-g]chromen-7-ylmethyl
ester 44
dH: 7.7–7.5 (m, 4H, ArH), 7.4 (m, 6H, ArH), 7.20 (s, 1H, ArH),
6.39 (s, 1H, ArH), 5.97 (s, 2H, –O–CH2–O), 4.59 (d, J = 11.6 Hz,
1H, –O–CH2), 4.48 (q, J = 11.2 Hz, 2H, –CH2OAc), 3.88 (d,
J = 10.4 Hz, 1H, –CH2OTBDPS), 3.78 (d, J = 10.4 Hz, 1H,
–CH2OTBDPS), 1.98 (s, 3H, –OCOMe), 1.04 (s, 9H, OSitBu). dC:
190.15 (C@O), 170.57 (–OCOMe), 159.24, 154.33, 143.26, 135.54,
132.54, 129.80, 127.71, 113.90, 104.33, 101.98, 98.08 (–O–CH2–
O), 70.31 (C2), 62.64 (CH2–OCOMe), 62.12 (–CH2–OTBDPS), 50.31
OTBDPS), 50.87 (C3), 26.58 (–OCOMe), 20.69, 19.21. ½a D28
ꢂ
¼ þ11:0
(C3), 26.68 (–OCOMe), 20.69, 19.23. ½a D28
¼ þ3:90 (c 0.36, MeOH).
ꢂ
(c 0.2, MeOH). HPLC (Daicel Chiralcel AS-H, hexane/i-PrOH = 49:1,
flow rate = 0.8 ml/min) tR = 4.25 min (minor, assumed R),
tR = 5.05 min (major, assumed S). HRMS m/z [M+Na]+ found
511.1911; calculated 511.1921 for C29H32O5Si.
HPLC (Daicel Chiralcel AS-H, hexane/i-PrOH = 49:1, flow
rate = 0.8 ml/min) tR = 9.27 min (minor, assumed R), tR = 12.24 min
(major, assumed S). HRMS m/z [M+Na]+ found 555.1813; calcu-
lated 555.1809 for C30H32O7Si.

T. Mahapatra et al. / Tetrahedron: Asymmetry 19 (2008) 2497–2507
2505
4.45. Acetic acid (S)-2-(tert-butyl-diphenyl-silanyloxymethyl)-
4.49. Acetic acid (S)-2-(tert-butyl-diphenyl-silanyloxymethyl)-
1-oxo-1,2,3,4-tetrahydro-naphthalen-2-ylmethyl ester 45
1-oxo-indan-2-ylmethyl ester 49
dH: 8.0 (d, J = 8.0 Hz, 1H, ArH), 7.78–7.6 (m, 4H, ArH), 7.5–7.1 (m,
9H, ArH), 4.51 (d, J = 10.8 Hz, 1H, –CH2–OAc), 4.38 (d, J = 10.8 Hz,
1H, –CH2–OAc), 3.84 (m, 2H, –CH2OTBDPS), 2.9 (m, 2H, C4), 2.3
(m, 2H, C3), 1.97 (s, 3H, –OCOMe), 1.07 (s, 9H, OSitBu). dC: 197.81
(C1), 170.79 (–OCOMe), 143.15, 135.56, 134.72, 132.85, 129.72,
129.59, 128.65, 127.66, 127.63, 126.64, 65.59 (–CH2–OCOMe),
64.35 (–CH2–OTBDPS), 50.87 (C2), 27.09 (C4), 26.66 (–OCOMe),
dH: 7.78 (d, J = 8.0 Hz, 1H, ArH), 7.7–7.3 (m, 13H, ArH), 4.27 (d,
J = 10.8 Hz, 1H, –CH2–OAc), 4.24 (d, J = 10.8 Hz, 1H, –CH2–OAc),
3.88 (d, J = 9.6 Hz, 1H, –CH2–OTBDPS), 3.74 (d, J = 9.6 Hz, 1H,
–CH2–OTBDPS), 3.34 (d, J = 17.2 Hz, 1H, C3), 3.14 (d, J = 17.2 Hz,
1H, C3), 1.90 (s, 3H, –OCOMe), 0.85 (s, 9H, OSitBu). dC: 206.24
(C1), 170.76 (–OCOMe), 153.54, 136.83, 135.53, 134.95,
132.91, 129.72, 127.65, 127.29, 126.29, 123.92, 66.02 (–CH2–
OCOMe), 65.22 (–CH2–OTBDPS), 55.21 (C2), 34.03 (C3), 26.46
24.91 (C3), 20.77, 19.21. ½a D28
¼ þ6:7 (c 0.2, MeOH). HPLC (Daicel
ꢂ
Chiralcel AS-H, hexane/i-PrOH = 49:1, flow rate = 0.8 ml/min)
tR = 4.57 min (minor, assumed R), tR = 5.45 min (major, assumed
S). HRMS m/z [M+Na]+ found 509.2115; calculated 509.2118 for
C30H34O4Si.
(–OCOMe), 20.64, 19.09. ½a D28
¼ þ15:8 (c 0.24, MeOH). HPLC (Daicel
ꢂ
Chiralcel AS-H, hexane/i-PrOH = 49:1, flow rate = 0.8 ml/min)
tR = 4.67 min (minor, assumed R), tR = 5.32 min (major, assumed
S). HRMS m/z [M+Na]+ found 495.1956; calculated 495.1962 for
C29H32O4Si.
4.46. Acetic acid (S)-2-(tert-butyl-diphenyl-silanyloxymethyl)-
7-methoxy-1-oxo-1,2,3,4-tetrahydro-naphthalen-2-ylmethyl
ester 46
4.50. Acetic acid (S)-2-(tert-butyl-diphenyl-silanyloxymethyl)-
5-chloro-1-oxo-indan-2-ylmethyl ester 50
dH: 7.78 (m, 1H, ArH), 7.6–7.5 (m, 4H, ArH), 7.5–7.0 (m, 8H, ArH),
4.54 (d, J = 11.0 Hz, 1H, –CH2–OAc), 4.42 (d, J = 11.0 Hz, 1H, –CH2–
OAc), 3.86 (m, 5H), 2.9 (t, J = 6.2 Hz, 2H, C4), 2.3 (m, 2H, C3), 2.02 (s,
3H, –OCOMe), 1.09 (s, 9H, OSitBu). dC: 197.75 (C1), 170.82
(–OCOMe), 158.31, 135.76, 134.73, 132.868,, 132.77, 129.89,
129.73, 127.66, 121.96, 109.41, 65.59 (–CH2–OCOMe), 64.27
(–CH2–OTBDPS), 55.44 (–OMe), 50.74 (C2), 27.27 (C4), 26.67
dH: 7.69 (d, J = 6.4 Hz, 1H, ArH), 7.6–7.3 (m, 12H, ArH), 4.2 (m,
2H, –CH2–OAc), 3.87 (d, J = 9.6 Hz, 1H, –CH2–OTBDPS), 3.70 (d,
J = 9.6 Hz, 1H, –CH2–OTBDPS), 3.26 (d, J = 17.2 Hz, 1H, C3), 3.15
(d, J = 17.2 Hz, 1H, C3), 1.90 (s, 3H, –OCOMe), 0.9 (s, 9H, OSitBu).
dC: 204.85 (C1), 170.65 (–OCOMe), 155.01, 141.49, 135.51,
132.76, 130.83, 129.79, 128.74, 127.69, 126.50, 124.98, 65.95
(–CH2–OCOMe), 65.03 (–CH2–OTBDPS), 55.50 (C2), 33.73 (C3),
(–OCOMe), 24.10 (C3), 20.79, 19.23. ½a D28
ꢂ
¼ þ23:8 (c 0.2, MeOH).
26.47 (–OCOMe), 20.62, 19.10. ½a D28
¼ þ13:1 (c 0.2, MeOH). HPLC
ꢂ
HPLC (Daicel Chiralcel AS-H, hexane/i-PrOH = 49:1, flow
rate = 0.8 ml/min) tR = 5.67 min (minor, assumed R), tR = 6.45 min
(major, assumed S). HRMS m/z [M+Na]+ found 539.2216; calculated
539.2224 for C31H36O5Si.
(Daicel Chiralcel AS-H, hexane/i-PrOH = 49:1, flow rate = 0.8 ml/
min) tR = 4.04 min (minor, assumed R), tR = 4.60 min (major,
assumed S). HRMS m/z [M+Na]+ found 529.1578; calculated
529.1572 for C29H31ClO4Si.
4.47. Acetic acid (S)-2-(tert-butyl-diphenyl-silanyloxymethyl)-
6-methoxy-1-oxo-1,2,3,4-tetrahydro-naphthalen-2-ylmethyl
ester 47
4.51. Acetic acid (S)-2-(tert-butyl-diphenyl-silanyloxymethyl)-
5-methoxy-1-oxo-indan-2-ylmethyl ester 51
dH: 7.72 (d, J = 8.0 Hz, 1H, ArH), 7.6 (m, 4H, ArH), 7.5–7.3 (m, 6H,
ArH), 6.9 (m, 2H, ArH), 4.30 (d, J = 10.8 Hz, 1H, –CH2–OAc), 4.23 (d,
J = 10.8 Hz, 1H, –CH2–OAc), 3.99 (s, 3H, –OMe), 3.8 (m, 2H,
–CH2–OTBDPS), 3.29 (d, J = 17.2 Hz, 1H, C3–H), 3.07 (d,
J = 17.2 Hz, 1H, C3–H), 1.91 (s, 3H, –OCOMe), 0.92 (s, 9H, OSitBu).
dC: 204.13 (C1), 170.86 (–OCOMe), 165.64, 156.53, 135.64,
133.13, 130.23, 129.78, 127.73, 125.73, 115.36, 109.57, 66.09
(CH2–OCOMe), 65.47 (–CH2–OTBDPS), 34.07 (C3), 26.62 (–OCOMe),
dH: 7.95 (d, J = 8.0 Hz, 1H, ArH), 7.7–7.5 (m, 4H, ArH), 7.5–7.3 (m,
6H, ArH), 6.9–6.6 (m, 2H, ArH), 4.50 (d, J = 10.8 Hz, 1H, –CH2–OAc),
4.35 (d, J = 10.8 Hz, 1H, –CH2–OAc), 3.87–3.81 (m, 5H), 2.9 (t,
J = 6.0 Hz, 2H, C4), 2.28 (m, 2H, C3), 1.99 (s, 3H, –OCOMe), 1.01
(s, 9H, OSitBu). dC: 196.49 (C1), 170.92 (–OCOMe), 163.63, 145.79,
135.65, 133.00, 130.28, 129.78, 127.70, 125.89, 113.36, 112.37,
65.86 (–CH2–OCOMe), 64.51 (–CH2–OTBDPS), 55.46 (–OMe),
50.74 (C2), 27.12 (C4), 26.77 (–OCOMe), 25.41 (C3), 20.89, 19.32.
20.75, 19.24.
½
a 2D8
ꢂ
¼ þ18:3 (c 0.4, MeOH). HPLC (Daicel
½
a 2D8
ꢂ
¼ þ11:10 (c 0.2, MeOH). HPLC (Daicel Chiralcel AS-H, hex-
Chiralcel AS-H, hexane/i-PrOH = 49:1, flow rate = 0.8 ml/min)
tR = 6.15 min (minor, assumed R), tR = 7.29 min (major, assumed
S). HRMS m/z [M+Na]+ found 525.2073; calculated 525.2067 for
C30H34O5Si.
ane/i-PrOH = 49:1, flow rate = 0.8 ml/min) tR = 5.87 min (minor,
assumed R), tR = 6.89 min (major, assumed S). HRMS m/z [M+Na]+
found 539.2218 calculated 539.2224 for C31H36O5Si.
4.48. Acetic acid (S)-2-(tert-butyl-diphenyl-silanyloxymethyl)-
5,8-dimethoxy-1-oxo-1,2,3,4-tetrahydro-naphthalen-2-
ylmethyl ester 48
4.52. Acetic acid (S)-2-(tert-butyl-diphenyl-silanyloxymethyl)-
6-methyl-1-oxo-indan-2-ylmethyl ester 52
dH: 7.6–7.4 (m, 13H, ArH), 4.30 (d, J = 11.0 Hz, 1H, –CH2–OAc),
4.24 (d, J = 11.0 Hz, 1H, –CH2–OAc), 3.86 (d, J = 9.4 Hz, 1H, –CH2–
OTBDPS), 3.75 (d, J = 9.4 Hz, 1H, –CH2–OTBDPS), 3.28 (d,
J = 17.2 Hz, 1H, C3–H), 3.07 (d, J = 17.2 Hz, 1H, C3–H), 2.6 (s, 3H,
–Me), 1.90 (s, 3H, –OCOMe), 0.88 (s, 9H, OSitBu). dC: 206.19 (C1),
170.79 (–OCOMe), 150.90, 137.26, 136.27, 135.58, 132.88, 133.08,
129.76, 127.71, 126.05, 123.92, 66.12 (CH2–OCOMe), 65.39
(–CH2–OTBDPS), 55.66 (C2), 33.73 (C3), 26.61 (–OCOMe), 21.06
dH: 7.64–7.5 (m, 4H, ArH), 7.5–7.3 (m, 6H, ArH), 7.0 (d, J = 9.0 Hz,
1H, ArH), 6.89 (d, J = 9.0 Hz, 1H, ArH), 4.46 (d, J = 11.2 Hz, 1H, –CH2–
OAc), 4.40 (d, J = 11.2 Hz, 1H, –CH2–OAc), 3.9–3.75 (m, 8H), 2.85
(m, 2H, C4), 2.25 (m, 2H, C3), 1.96 (s, 3H, –OCOMe), 1.0 (s, 9H, OSit-
Bu). dC: 197.92 (C1), 170.87 (–OCOMe), 153.94, 149.92, 135.55,
133.52, 132.95, 129.62, 127.61, 122.69, 115.06, 109.98, 65.66
(–CH2–OCOMe), 64.26 (–CH2–OTBDPS), 56.18 (–OMe), 55.89
(–OMe), 51.49 (C2), 26.62 (C4), 26.22 (–OCOMe), 20.83 (C3),
(–Ar–CH3), 20.69, 19.22. ½a D28
¼ þ10:6 (c 0.4, MeOH). HPLC (Daicel
ꢂ
19.34, 19.21. ½a D28
ꢂ
¼ þ13:3 (c 0.4, MeOH). HPLC (Daicel Chiralcel
Chiralcel AS-H, hexane/i-PrOH = 49:1, flow rate = 0.8 ml/min)
tR = 4.42 min (minor, assumed R), tR = 5.14 min (major, assumed
S). HRMS m/z [M+Na]+ found 509.2113; calculated 509.2118 for
C30H34O4Si.
AS-H, hexane/i-PrOH = 49:1, flow rate = 0.8 ml/min) tR = 8.31 min
(minor, assumed R), tR = 9.49 min (major, assumed S). HRMS m/z
[M+Na]+ found 569.2323; calculated 569.2329 for C32H38O6Si.

2506
T. Mahapatra et al. / Tetrahedron: Asymmetry 19 (2008) 2497–2507
4.53. Acetic acid 2-hydroxymethyl-1-oxo-1,2,3,4-tetrahydro-
naphthalen-2-ylmethyl ester 53
4.56. (R)-2-(tert-Butyl-diphenyl-silanyloxymethyl)-2-methyl-
3,4-dihydro-2H-naphthalen-1-one 58
In a typical EED reaction, diol 6 (50 mg, 0.24 mmol) was taken
in 2 ml of anhydrous DIPE, followed by the addition of CAL-B
(30 mg), vinyl acetate (20 equiv) and molecular sieves (4 Å). The
reaction mixture was kept under an argon atmosphere until an
appreciable amount of conversion was achieved (as measured by
TLC). The reaction mixture was filtered, and the solvent was evap-
orated in vacuo. The product was purified by preparative TLC (hex-
ane/EtOAc, 3:1). dH: 7.99 (d, J = 8.0 Hz, 1H, ArH), 7.49 (t, J = 7.6 Hz,
1H, ArH), 7.31 (t, J = 7.6 Hz, 1H, ArH), 7.24 (d, J = 8.0 Hz, 1H, ArH),
4.41 (d, J = 11.2 Hz, 1H, –CH2OAc), 4.31 (d, J = 11.2 Hz, 1H,
–CH2OAc), 3.77 (s, 2H, –CH2OH), 3.0 (m, 2H, C4–H), 2.5 (br, 1H,
–OH), 2.12 (t, J = 6.4 Hz, 2H, C3–H), 2.02 (s, 3H, –OCOMe). dC:
200.52 (C@O), 170.99 (–OCOMe), 144.82, 133.94, 130.84, 128.45,
127.26, 126.46, 64.68 (–CH2OAc), 63.06 (–CH2OH), 50.68 (C2),
29.63 (C4), 25.80 (C3), 20.78 (–OCOMe). HPLC (Daicel Chiralcel
OJ-H, hexane/i-PrOH = 9:1, flow rate = 1.0 ml/min) tR = 15.08 min
(major), tR = 16.17 min (minor).
Oxalyl chloride (0.1 ml, 1.17 mmol) was taken in DCM (15 ml)
at ꢀ78 °C. To this cold solution, DMSO (0.16 ml, 2.34 mmol) was
slowly added and the mixture was kept for 5 min at the same tem-
perature. Alcohol 57 (335 mg, 0.78 mmol) in DCM (3 ml) was
added to the solution. The temperature was maintained at
ꢀ78 °C for a further 1 h. Triethylamine (0.43 ml, 3.17 mmol) was
then added and the reaction mixture was allowed to attain room
temperature. Water was added to the solution, and the mixture
was extracted with DCM. The organic extract was washed succes-
sively with aq NaHCO3 and brine and dried over Na2SO4. The or-
ganic extract was evaporated and purified by column
chromatography to afford the ketone 58 in 90% yield. dH: 8.0 (d,
J = 8.0 Hz, 1H, ArH), 7.7–7.1 (m,13H, ArH), 3.98 (d, J = 9.8 Hz, 1H,
–CH2OTBDPS), 3.62 (d, J = 9.8 Hz, 1H, – CH2OTBDPS), 2.98 (t,
J = 6.8 Hz, 2H, C4–H), 2.4 (m, 1H, C3–H), 2.0 (m, 1H, C3–H), 1.2 (s,
3H, –Me), 1.0 (s, 9H). dC: 201.19, 143.72, 135.73, 133.56, 133.39,
132.26, 129.61, 128.66, 127.80, 127.65, 126.56, 68.77
(–CH2OTBDPS), 47.51 (C2), 31.74 (C4), 26.80 (C3), 25.51, 19.62,
4.54. Benzoic acid 2-hydroxymethyl-1-oxo-1,2,3,4-tetrahydro-
naphthalen-2-ylmethyl ester 54
19.37. ½a 2D8
¼ þ21:2 (c 0.9, MeOH).
ꢂ
Acknowledgments
In a typical EED reaction, diol 6 (50 mg, 0.24 mmol) was
dissolved in 2 ml of anhyd DIPE, followed by the addition of
CAL-B (30 mg), vinyl benzoate (20 equiv), and molecular sieve
(4 Å). The reaction mixture was kept under an argon atmosphere
until an appreciable amount of conversion was achieved (as mea-
sured by TLC). The reaction mixture was filtered, and the solvent
was evaporated in vacuo. The product was purified by preparative
TLC (hexane/EtOAc, 3:1). dH: 8.03 (d, J = 8.0 Hz, 1H, ArH), 7.98 (d,
J = 7.8 Hz, 2H, ArH), and 7.6–7.2 (m, 6H, ArH), 4.7 (d, J = 11.2 Hz,
1H, –CH2OCOPh), 4.58 (d, J = 11.2 Hz, 1H, –CH2OCOPh), 3.9 (m,
2H, –CH2OH), 3.0 (m, 2H, C4–H), 2.2 (m, 2H, C3–H). dC: 200.68
(C@O), 171.56 (–OCOPh), 134.48, 132.27, 130.46, 129.76, 129.54,
129.28, 128.76, 128.43, 127.68, 127.25, 69.83, 65.44, 49.2 (C2),
29.78 (C4), 26.57 (C3). HPLC (Daicel Chiralcel OJ-H, hexane/
i-PrOH = 9:1, flow rate = 1.0 ml/min) tR = 17.18 min (major),
tR = 19.53 min (minor).
We thank the DST (New Delhi, India) for providing financial
support (DST Fast track scheme and IPHRA). T.M. and T.D. are
thankful to CSIR (New Delhi, India) for a research fellowship. We
thank Prof. D. Mal (Department of Chemistry, IIT-Kharagpur) and
his lab members for their kind help in our early days of research.
Special thanks goes to Mr. Lalit Rajput (Department of Chemistry,
IIT-Kharagpur) for X-Ray analysis.
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