A general approach to medium-sized ring ethers via hydrolytic and oxidative kinetic resolutions: stereoselective syntheses of (-)-cis-lauthisan and (+)-isolaurepan

Article abstract of DOI:10.1016/j.tet.2009.01.062

A short and enantioselective approach to medium ring ethers and its application to the syntheses of (-)-cis-lauthisan and (+)-isolaurepan are described. The synthetic strategy features Jacobson's Hydrolytic Kinetic Resolution (HKR), oxidative resolution of secondary alcohol, and highly diastereoselective Et₃SiH/TMSOTf-promoted reductive cyclization of a hydroxy ketone to give exclusively the different medium-sized cis-disubstituted cyclic ethers.

Full text of DOI:10.1016/j.tet.2009.01.062

Tetrahedron 65 (2009) 2226–2231
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A general approach to medium-sized ring ethers via hydrolytic and oxidative
kinetic resolutions: stereoselective syntheses of (ꢀ)-cis-lauthisan and
(þ)-isolaurepan
*
Divya Tripathi, Satyendra Kumar Pandey, Pradeep Kumar
Division of Organic Chemistry, National Chemical Laboratory, Pune 411008, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A short and enantioselective approach to medium ring ethers and its application to the syntheses of
(ꢀ)-cis-lauthisan and (þ)-isolaurepan are described. The synthetic strategy features Jacobson’s Hydro-
lytic Kinetic Resolution (HKR), oxidative resolution of secondary alcohol, and highly diastereoselective
Et3SiH/TMSOTf-promoted reductive cyclization of a hydroxy ketone to give exclusively the different
medium-sized cis-disubstituted cyclic ethers.
Received 20 October 2008
Received in revised form 27 December 2008
Accepted 13 January 2009
Available online 20 January 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Jacobson’s Hydrolytic Kinetic Resolution
(HKR)
Oxidative resolution of secondary alcohol
cis-Reductive cyclization
Ring ether
Oxepanes
1. Introduction
(þ)-laurencin 2, isolated from the extracts of Laurencia glandulifera
(Fig. 1). Several strategies have been employed for the stereo-
Polyfunctionalized medium-sized cyclic ethers have attracted
much attention from synthetic and medicinal chemists due to their
presence in a wide range of biologically active natural products,
including ladder marine toxins, lauroxanes, antibiotic, etc.1 These
ethers constitute important structural features present in a number
of biologically active marine natural products, particularly from
Laurencia red algae.2 Many compounds of this class contain a seven
or eight-membered cyclic ether ring usually with cis stereochem-
istry in the alkyl substituents.
selective preparation of racemic6 and enantioriched7 cis-lauthisan,
most of them require multistep synthesis or take place with
moderate cis selectivities.
(þ)-Isolaurepan 3 is a fully saturated analogue of the core of
(þ)-isolaurepinnacin 4 and other chiral oxepane derivatives.8 Kot-
suki et al. reported the first total synthesis of (þ)-isolaurepan via
cis-selective reduction mediated by triethylsilane/TiCl4.9a A few
more groups have described its formal synthesis by different
In view of the increasing number of biologically active marine
natural products containing medium and large sized cyclic ether
derivatives, much attention has been focused on efficient ap-
proaches toward these systems. However, their synthesis is gen-
erally difficult via standard cyclization methodologies.3
Nevertheless, the challenge in their efficient construction has led to
the development of several strategies for their synthesis,4,5 mainly
in racemic form.
Br
O
O
OAc
(-)- lauthisan 1
(+)-laurencin 2
(ꢀ)-Lauthisan 1, isolated from a sample of sea alga Laurencia
O
O
obtusa is
a fully saturated core of the natural derivative
H
H
H
H
Cl
Br
(+)-isolaurepan 3
(+)-isolaurepinnacin 4
* Corresponding author. Tel.: þ91 20 25902050; fax: þ91 20 25902629.
E-mail address: pk.tripathi@ncl.res.in (P. Kumar).
Figure 1.
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.01.062

D. Tripathi et al. / Tetrahedron 65 (2009) 2226–2231
2227
approaches.10 Although there have been a number of reports on the
a
5
5
+
OH
O
5
stereoselective construction of racemic cis-2,7-disubstituted oxe-
panes, literature describing synthetic strategies for its non-racemic
derivatives is rather scarce. Thus development of a general strategy
for the enantioselective synthesis of the functionalized medium
ring ether skeleton present in many Laurencia non-terpenoid me-
tabolites is highly desirable.
O
O
OH
11
10
(R)-10
b
c
11
OPiv
5
5
OH
(R)-10
As part of our research on the asymmetric synthesis of bioactive
molecules,11 we became interested in developing a general route,
which could be useful in the synthesis of a wide variety of func-
tionalized non-racemic cis-disubstituted cyclic ether-based mole-
cules. In our preliminary communication we reported a total
synthesis of (þ)-isolaurepan 3.12 Herein we wish to report a general
route to cis-disubstituted cyclic ether-based molecules and its ap-
plication to the synthesis of (ꢀ)-cis-lauthisan 1 and (þ)-isolaurepan
3 using HKR, oxidative resolution of secondary alcohol, and cis-
selective reduction with triethylsilane as the key steps.
Scheme 2. Reagents and conditions: (a) (R,R)-Salen-Co-(OAc) (0.5 mol %), dist. H2O
(0.55 equiv), 0 ꢁC, 14 h, 45% for (R)-10, 43% for 11; (b) (i) PivCl, Et3N, cat. DMAP, rt, 2 h;
(ii) MsCl, Et3N, DMAP, 0 ꢁC to rt, 1 h; (c) K2CO3, MeOH, rt, overnight (61% for three
steps).
displacement of the mesylate furnished epoxide (R)-10 in 61%
overall yield (Scheme 2).
With enantiomerically pure epoxide (R)-10 in hand, we sub-
jected it to copper-catalyzed (CuI) regioselective opening with the
Grignard reagent, derived from benzyl protected bromopentanol
and Mg in THF at ꢀ78 ꢁC to obtain alcohol 12 in 72% yield (Scheme
3). Silyl protection of the newly generated secondary alcohol 12
with tert-butyldimethylsilyl chloride in the presence of imidazole
and catalytic amount of DMAP afforded 13 in 94% yield. Sub-
sequently the terminal benzyl group was deprotected using 20%
Pd(OH)2/H2, which led to compound 14 in excellent yield. Alcohol
14 was subjected to Swern oxidation14 to give aldehyde which on
Grignard reaction with EtMgBr in dry THF at 0 ꢁC furnished com-
pound 15 in 87% yield. Oxidation of free hydroxyl group 15 with IBX
(15/16) and silyl deprotection of 16 by treatment with p-TSA in
methanol afforded 17 in excellent yield. In order to generate cis-
disubstituted cyclic ether, 17 was treated with Et3SiH and TMSOTf
in the next step, which promoted reductive cyclization9b to give
exclusively the cis-disubstituted cyclic eight-membered ether,
(ꢀ)-lauthisan 1 as the target compound in 42% yield. The physical
and spectroscopic data of 1 were identical with those reported in
the literature.15
2. Results and discussion
Our retrosynthetic approach for the synthesis of cis-di-
substituted cyclic ether-based molecule 5 was envisioned via ret-
rosynthetic route as shown in Scheme 1. The hydroxy-keto
derivative 6 was visualized as a synthetic intermediate from which
(ꢀ)-cis-lauthisan 1 and (þ)-isolaurepan 3 could be synthesized. The
hydroxy-keto derivative 6 could be obtained from alcohol 7, which
in turn could be easily synthesized from the enantiomerically pure
terminal epoxide 8 or aldehyde 9.
O
n
R1
R2
R2
*
*
n
O
*
OP
R1
5
6
O
R1
O
R1
*
or
R1
OH
n
*
8
H
OH
OTBS
OP
7
c
9
a
b
(R)-10
OBn
5
5
Scheme 1. Retrosynthetic route to medium-sized ring ethers.
OBn
5
5
12
13
O
OH
OTBS
OTBS
OTBS
e
d
2.1. Synthesis of (L)-lauthisan
OH
5
5
5
5
5
5
14
15
16
The synthesis of (ꢀ)-cis-lauthisan 1 started from racemic ep-
oxide 10, which was subjected to Jacobsen’s HKR by using (R,R)-
Salen-CoIIIOAc catalyst (Fig. 2) to give chiral epoxide (R)-10 along
with chiral (S)-diol 11 as single isomer (Scheme 2).13 The chiral
epoxide (R)-10 was easily isolated from the more polar chiral diol 11
by silica gel column chromatography.
We thought it would be appropriate to convert diol 11 into the
required epoxide (R)-10 by means of an internal nucleophilic sub-
stitution of a secondary mesylate. Accordingly, the chemoselective
pivalation of diol 11 with pivaloyl chloride, followed by mesylation
of the secondary hydroxyl and treatment of the crude mesylate
product with K2CO3 in methanol led to the deprotection of the
pivaloyl ester. Concomitant ring closure by intramolecular SN2
O
OH
g
f
5
5
O
17
1
Scheme 3. Reagents and conditions: (a) C6H5CH2O-(CH2)5MgBr, CuI, THF, ꢀ78 ꢁC, 2 h,
72%; (b) TBSCl, imidazole, cat. DMAP, dry CH2Cl2, 8 h, 0 ꢁC, 94%; (c) 20% Pd(OH)2/H2,
EtOAc, 1 atm, 12 h, 89%; (d) (i) (COCl)2, DMSO, Et3N, dry CH2Cl2, ꢀ78 ꢁC to ꢀ60 ꢁC, 2 h;
(ii) n-C2H5MgBr, THF, 0 ꢁC to rt, 1 h, 87%; (e) IBX, EtOAc, 80 ꢁC, 90%; (f) p-TSA, MeOH, rt,
30 min, 96%; (g) Et3SiH, TMSOTf, CH2Cl2, 0 ꢁC, 1 h, 42%.
2.2. Synthesis of (D)-isolaurepan
Our synthetic strategy for the synthesis of (þ)-isolaurepan 3 is
shown in Scheme 4. The synthesis started from chiral epoxide (S)-
10 prepared from Jacobsen’s HKR of the racemic epoxide 10 by
using (S,S)-Salen-CoIIIAc complex. The copper-catalyzed (CuI)
regioselective opening of chiral epoxide (S)-10 with Grignard re-
agent derived from p-methoxybenzyl protected bromobutanol and
Mg in THF gave rise to the required alcohol fragment (S)-20, albeit
in low yield (30%). This prompted us to find another suitable route
to this fragment with an improved yield. As illustrated in Scheme 4,
the synthesis of this fragment commenced with commercially
available 1,6-hexanediol 18. Thus selective monohydroxyl
H
N
H
N
Co
t-Bu
t-Bu
O
O
OAc
t-Bu
t-Bu
Figure 2. (R,R)-Salen-CoIIIOAc complex.

2228
D. Tripathi et al. / Tetrahedron 65 (2009) 2226–2231
protection of 18 with p-methoxybenzyl bromide in the presence of
NaH gave the monoprotected diol 19 in 85% yield. This was then
oxidized to the corresponding aldehyde under Swern conditions
and subsequently treated with the Grignard reagent derived from
1-bromohexane and Mg in THF at 0 ꢁC to furnish the racemic al-
cohol 20 in 91% yield.
OTBS
OTBS
a
b
(S)-20
OH
e
OPMB
4
4
5
5
22
23
OH
OTBS
O
OTBS
c
d
5
4
5
4
24
25
OH
a
5
4
5
OH
O
OPMB
c
O
f
(S)-10
(S)-20
O
5
4
OH
b
26
3
HO
OPMB
HO
d
OH
4
4
5
4
OPMB
Scheme 5. Reagents and conditions: (a) TBS-OTf, 2,6-lutidine, dry CH2Cl2, 30 min, 0 ꢁC,
85%; (b) DDQ, CH2Cl2/H2O (18:1), rt, 1 h, 94%; (c) (i) (COCl)2, DMSO, Et3N, dry CH2Cl2,
ꢀ78 ꢁC to ꢀ60 ꢁC, 2 h, 90%; (ii) n-C3H7MgBr, THF, 0 ꢁC to rt, 1 h, 62%; (d) IBX, EtOAc,
80 ꢁC; 92% (e) p-TSA, MeOH, rt, 30 min; (f) Et3SiH, TMSOTf, CH2Cl2, 0 ꢁC, 1 h, 84%.
18
19
20
OH
O
+
4
OPMB
4
5
OPMB
5
(S)-20
21
OH
O
e
5
4
OPMB
4
OPMB
5
HOTf
n
n
n
TMSOTf
21
20
Scheme 4. Reagents and conditions: (a) p-CH3OC6H4-CH2O(CH2)4MgBr, CuI, THF,
ꢀ38 ꢁC, 2 h, 30%; (b) p-CH3OC6H4CH2Br, NaH, dry DMF, cat. TBAI, 0 ꢁC to rt, 1 h, 85%; (c)
R1
+O
R2
R1
n = 2, 3
O
R2
R1
O
R2
HO
HO
OTMS
TMS
-OTf
(i) (COCl)2, DMSO, Et3N, dry CH2Cl2, ꢀ78 ꢁC to ꢀ60 ꢁC, 2 h; (ii) n-C6H13MgBr, THF, 0 ꢁ
C
to rt, 1 h, 91%; (d) (S,S)-Salen-MnIII(Cl) (0.02 equiv), KBr (0.8 equiv), PhI(OAC)2
(0.7 equiv), H2O/CH2Cl2 2:1, rt, 30 min., 45% for (S)-20 and 43% for 21; (e) NaBH4,
MeOH, 4 h, 89%.
Et3SiH
(axial approach)
n
n
n
O
HOTf
R1
R2
O
R2
R2
O
R1
R1
TMSO+
H
+
B
A
With substantial amounts of racemic alcohol 20 in hand, our
next aim was to resolve this alcohol to obtain enantiomerically pure
(S)-20. As illustrated in Scheme 4, the racemic alcohol 20 was
subjected to oxidative resolution16 using (S,S)-Salen-MnIIICl as
catalyst (Fig. 3) to give the required optically active alcohol (S)-20 in
45% yield and 93% ee along with the oxidized compound 21 in 43%
yield, which was easily isolated from the polar alcohol (S)-20 using
silica gel chromatography. Ketone 21 was recycled by conversion
into the racemic alcohol 20 in 89% yield by reduction with NaBH4 in
MeOH.
As shown in Scheme 5, hydroxyl protection of (S)-20 with tert-
butyldimethylsilyl triflate in the presence of 2,6-lutidine afforded
silyl ether 22 in 85% yield. Subsequent p-methoxybenzyl depro-
tection of the primary alcohol was carried out with DDQ in DCM/
H2O (18:1) to give the required alcohol 23 in 94% yield. Alcohol 23
was oxidized to the corresponding aldehyde by Swern oxidation
followed by Grignard reaction with 1-bromopropane and Mg in
THF at 0 ꢁC to give the desired compound 24 in 62% yield. The
newly formed secondary alcohol was oxidized using IBX to give
ketone 25, which on treatment with p-TSA in methanol afforded
the required deprotected precursor 26.
Scheme 6. Mechanistic pathway for the reductive cyclization process.
A general possible mechanistic pathway explaining the forma-
tion of major cis diastereomer in the cyclization step is shown in
Scheme 6. Activation of carbonyl group of the hydroxy ketone by
TMSOTf favors the intramolecular nucleophilic addition of the hy-
droxyl group, which eventually leads to the carboxonium in-
termediate A through an acetal precursor. The axial approach of
Et3SiH17 to A, a seven-membered twist-chair-like transition state
(Fig. 4) affording cis diastereomer B, is certainly favored because of
the higher stability of the resulting chair-like transition state.
Similar reasons could explain the major formation of the cis isomer
in the case of eight-membered cyclic ether (ꢀ)-lauthisan 1.
Et3SiH
(axial approach)
R1
O
R2
R2
O
R1
In order to generate the cis-disubstituted cyclic ether, ketone 26
was treated with Et3SiH and TMSOTf, which promoted reductive
cyclization to give exclusively, the cis-disubstituted cyclic seven-
membered ether, (þ)-isolaurepan 3 in 84% yield. The configuration
of the newly generated centers in 3 can be deduced by 1H NMR and
NOE experiments.9a The physical and spectroscopic data of 3 were
identical with those reported in the literature.9a
B
A
Chair form
Twist-chair form
Figure 4. Stereochemical pathway for the reductive cyclization in a seven-membered
ring.
3. Conclusions
In conclusion we have developed a new and short approach to
cis-disubstituted oxepanes in high enantiomeric excess using
Jacobsen Co and Mn and (R,R)- and (S,S)-based Salen catalysts. The
R and S configurations of the cis ring can be manipulated simply by
changing the catalyst in the resolution step. High yielding reaction
steps have been employed. The synthetic strategy described here
has significant potential for stereochemical variations and further
extension to other stereoisomers and analogues.
H
H
N
N
Mn
Cl
t-Bu
O
O
t-Bu
t-Bu
t-Bu
Figure 3. (S,S)-Salen-MnIII (Cl).

D. Tripathi et al. / Tetrahedron 65 (2009) 2226–2231
2229
4. Experimental
4.1.4. (R)-7-(tert-Butyldimethylsilyloxy)tridecan-1-ol (14)
Compound 13 (4 g) was dissolved in dry EtOAc (10 mL) and 20%
Pd(OH)2 (70 mg) was added carefully. The reaction mixture was
stirred under an atmosphere of H2 filled in a balloon for 12 h at
room temperature. The mixture was filtered and concentrated
under reduced pressure. The residue was purified by silica gel
4.1. General methods
Solvents were purified and dried by standard procedures before
use. Melting points are uncorrected. Optical rotations were mea-
sured using sodium D line on JASCO-181 digital polarimeter. In-
frared spectra were recorded on a Perkin–Elmer model 683 grating
infrared spectrometer. 1H NMR (200 MHz, 500 MHz) and 13C NMR
(50 MHz, 125 MHz) spectra were recorded in CDCl3 solution with
residual CHCl3 (¼7.27 ppm and ¼77.00 ppm), respectively, as in-
ternal standard. Elemental analyses were carried out on a Carlo
Erba CHNS-O analyzer. Petroleum ether of boiling range 60–80 ꢁC
was used. Column chromatography was performed on silica gel
(60–120 and 100–200 mesh) using a mixture of petroleum ether/
ethyl acetate.
column chromatography using EtOAc/pet ether (18:2) as eluent to
25
give 14 (2.8 g) in 89% yield. [
n
a]
þ2.92 (c 1.02, CHCl3); IR (CHCl3)
D
¼3440, 3018, 2931, 1471, 1361, 1255, 1215, 1049 cmꢀ1
;
1H NMR
(200 MHz, CDCl3):
d
¼0.04 (s, 6H), 0.85–0.92 (m, 12H), 1.27–1.49 (m,
20H), 3.65 (t, J¼6.5 Hz, 2H), 3.60 (m, 1H); 13C NMR (50 MHz, CDCl3):
d
¼ꢀ5.4, ꢀ4.5, 14.0, 18.1, 22.6, 25.3, 25.6, 25.8, 25.9, 29.4, 31.8, 32.7,
37.1, 62.8, 72.3. Anal. Calcd for C19H42O2Si (330.62): C, 69.02; H,
12.80%. Found: C, 69.21; H, 12.69%.
4.1.5. (9R)-9-(tert-Butyldimethylsilyloxy)pentadecan-3-ol (15)
To a solution of oxalyl chloride (1.13 mL, 12.7 mmol) in dry
CH2Cl2 (100 mL) at ꢀ78 ꢁC was added dropwise dry DMSO (5.4 mL,
76.22 mmol) in CH2Cl2 (20 mL). After 30 min, alcohol 14 (2.8 g,
8.46 mmol) in CH2Cl2 (20 mL) was added over 10 min giving a co-
pious white precipitate. After stirring for 1 h at ꢀ78 ꢁC the reaction
mixture was brought to ꢀ60 ꢁC and Et3N (5.31 mL, 38.11 mmol) was
added slowly and stirred for 30 min allowing the reaction mixture
to warm to room temperature. The reaction mixture was diluted
with water (50 mL) and CH2Cl2. The organic layer was separated
and washed with water and brine, dried (Na2SO4), and passed
through short pad of Celite. The filtrate was concentrated to give
the crude aldehyde as pale yellow oil, which was used as such for
the next step without purification.
To a stirred solution of the above crude aldehyde was added
a solution of Grignard reagent dropwise at 0 ꢁC, prepared from
ethyl bromide (1.18 mL, 15.82 mmol) and Mg-turning (0.72 g,
23.73 mmol) in dry THF. The mixture was warmed to rt over 1 h and
poured into a saturated NH4Cl solution. The layers were separated
and the aqueous layer was extracted with EtOAc (3ꢂ30 mL). The
combined EtOAc extracts were dried over Na2SO4. The extracts
were concentrated to near dryness and purified on silica gel column
4.1.1. 2-Hexyloxirane (R)-10
The racemic 2-hexyloxirane 10 was resolved to (R)-2-hexylox-
irane {(R)-10} in high enantiomeric excess by the HKR method
following a literature procedure.13 Colorless oil, [
a
]
þ13.46 (neat);
25
D
24
lit.13
[a
]
þ14.0 (neat); 1H NMR (200 MHz, CDCl3):
d
¼0.88 (t,
D
J¼6.8 Hz, 3H), 1.26–1.51 (m, 10H), 2.44–2.48 (m, 1H), 2.72–2.77 (m,
1H), 2.87–2.93 (m, 1H); 13C NMR (50 MHz, CDCl3):
25.9, 29.1, 31.7, 32.5, 47.1, 52.3.
d¼13.9, 22.5,
4.1.2. (R)-1-(Benzyloxy)tridecan-7-ol (12)
To a stirred solution of (R)-10 (4.8 g, 37.38 mmol) and CuI
(0.306 g, 3.73 mmol) in dry THF (30 mL) was added Grignard re-
agent prepared from benzyl protected bromopentanol (19.23 g,
74.76 mmol) and Mg-turning (2.72 g, 112.14 mmol) in dry THF,
dropwise at ꢀ78 ꢁC. The mixture was warmed to ꢀ78 ꢁC over 2 h
and poured into a saturated NH4Cl solution. The layers were sep-
arated and the aqueous layer was extracted with EtOAc (3ꢂ50 mL).
The combined EtOAc extracts were dried over Na2SO4. The extracts
were concentrated to near dryness and purified on silica gel column
chromatography (EtOAc/petroleum ether, 1:9) to give 12 as color-
25
less oil (8.26 g, 72%). [
a
]
þ1.85 (c 1.08, CHCl3); IR (CHCl3)
n
¼3426,
1H
¼0.90 (t, J¼6.9 Hz, 3H), 1.29–1.43 (m,
16H), 1.61–1.63 (m, 4H), 3.47 (t, J¼6.9 Hz, 2H), 3.60–3.63 (m, 1H),
4.51 (s, 2H), 7.27–7.37 (m, 5H); 13C NMR (50 MHz, CDCl3):
chromatography (EtOAc/petroleum ether, 1:9) to give 15 as color-
D
25
3011, 2857, 2930, 1712, 1454, 1364, 1277, 1216, 1099, 755 cmꢀ1
NMR (200 MHz, CDCl3):
;
less oil (2.64 g, 87%). [
a
]
þ3.16 (c 0.98, CHCl3); IR (CHCl3)
n
¼3616,
1H NMR
¼0.04 (s, 6H), 0.87–0.92 (m, 15H), 1.27–1.52 (m,
22H), 3.50–3.66 (m, 2H); 13C NMR (50 MHz, CDCl3):
D
d
3443, 3019, 2932, 2400, 1463, 1377, 1215, 1049 cmꢀ1
(200 MHz, CDCl3):
;
d
d¼14.0,
d¼ꢀ4.5, 9.8,
22.5, 25.5, 26.1, 29.3, 29.4, 29.6, 31.7, 70.4, 71.8, 72.8, 127.4, 127.5,
128.3, 138.5. Anal. Calcd for C20H34O2 (306.48): C, 78.38; H, 11.18%.
Found: C, 78.52; H, 11.35%.
14.1, 18.1, 22.6, 25.3, 25.7, 26.0, 29.5, 29.5, 29.9, 30.1, 31.9, 36.9, 37.1,
37.2. Anal. Calcd for C21H46O2Si (358.67): C, 70.32; H,12.93%. Found:
C, 70.19; H, 12.78%.
4.1.3. (R)-(1-(Benzyloxy)tridecan-7-yloxy)(tert-butyl)-
dimethylsilane (13)
4.1.6. (R)-9-(tert-Butyldimethylsilyloxy)pentadecan-3-one (16)
To a solution of 15 (2.0 g, 5.57 mmol) in EtOAc (5 mL) in 25 mL
R.B. flask was added IBX (4.68 g,16.72 mmol) in one portion and the
reaction mixture was refluxed for 3 h. The reaction mixture was
filtered through a pad of Celite and the filtrate was concentrated to
Imidazole (1.59 g, 23.49 mmol) and catalytic amount of DMAP
were added to a stirred solution of alcohol 12 (3.2 g, 10.44 mmol)
in CH2Cl2 (25 mL). tert-Butyl dimethylchlorosilane (2.04 g,
13.57 mmol) was then added to this solution at 0 ꢁC, and the
reaction mixture was stirred at room temperature for 8 h. After
this time, the reaction mixture was quenched with saturated
aqueous NH4Cl and extracted with CH2Cl2 (3ꢂ30 mL). The organic
extracts were washed with brine, dried (Na2SO4), and concen-
trated. Silica gel column chromatography of the crude product
give the crude aldehyde 16 (1.78 g) in 90% yield, which was used
25
without any further purification. [
a
]
D
ꢀ2.39 (c 1.06, CHCl3); IR
(CHCl3)
n
¼2932, 1710, 1462, 1255, 1215, 1051 cmꢀ1
;
1H NMR
(200 MHz, CDCl3):
d
¼0.03 (s, 6H), 0.88–0.92 (m, 12H), 1.05 (t,
J¼7.3 Hz, 3H), 1.27–1.38 (m, 18H), 2.40–2.44 (m, 4H) 3.52–3.64 (m,
1H); 13C NMR (50 MHz, CDCl3):
d
¼ꢀ4.5, 7.9, 14.1, 18.1, 22.6, 23.9,
(petroleum ether/EtOAc 19:1) provided 13 (4.13 g, 94%) as a col-
25.1, 25.3, 25.9, 29.5, 31.9, 35.8, 36.8, 37.1, 42.34, 72.2, 211.9. Anal.
Calcd for C21H44O2Si (356.66): C, 70.72; H, 12.43%. Found: C, 70.58;
H, 12.61%.
25
orless liquid. [
a
]
þ1.35 (c 0.92, CHCl3); IR (CHCl3)
n
¼3018, 2932,
1H NMR (200 MHz,
¼0.04 (s, 6H), 0.88–0.92 (m, 12H), 1.27–1.49 (m, 20H),
3.60–3.63 (m, 1H), 3.65 (t, J¼6.5 Hz, 2H), 4.51 (s, 2H), 7.31–7.37
(m, 5H); 13C NMR (50 MHz, CDCl3):
D
1463, 1361, 1255, 1215, 1092, 1028 cmꢀ1
CDCl3):
;
d
4.1.7. (R)-9-Hydroxypentadecan-3-one (17)
d
¼ꢀ4.4, 14.1, 18.1, 22.6, 25.3,
To a stirred solution of compound 16 (1.0 g) in MeOH was added
a catalytic amount of p-TSA at room temperature and the reaction
mixture stirred for 30 min at the same temperature. The mixture
was filtered through a Celite pad, washed with MeOH, and
25.9, 26.2, 26.9, 29.5, 29.7, 31.9, 37.1, 70.5, 72.3, 72.8, 127.4, 127.6,
128.2, 138.6. Anal. Calcd for C26H48O2Si (420.74): C, 74.22; H,
11.50%. Found: C, 74.35; H, 11.39%.

2230
D. Tripathi et al. / Tetrahedron 65 (2009) 2226–2231
25
concentrated to give 17 (651.8 mg) in 96% yield. [
a]
ꢀ4.92 (c 1.06,
separated and the aqueous layer was extracted with EtOAc
(3ꢂ50 mL). The combined EtOAc extracts were dried over Na2SO4.
The extracts were concentrated to near dryness and purified on
silica gel column chromatography (EtOAc/petroleum ether, 1:9) to
give 20 as colorless oil (7.2 g, 91%).
A mixture of substrate 20 (7.0 g, 21.70 mmol), catalyst (S,S)-
Salen-MnIII (Cl) (276 mg, 0.43 mmol), additive, KBr (207 mg,
1.73 mmol), CH2Cl2 (5 mL), and water (10 mL) was stirred in a 5 mL
tube for a few minutes at room temperature. The oxidant PhI(OAc)2
(4.89 g, 15.19 mmol) was added and the mixture was stirred for
30 min until the completion of reaction. The products were extrac-
ted by using diethyl ether giving yields as 45% for (S)-20 (3.15 g) and
43% for 21 (3 g). The conversion and ee values were determined by
chiral HPLC. The ee was measured by HPLC using a Chiralcel OD
D
CHCl3); IR (CHCl3)
1047 cmꢀ1 1H NMR (200 MHz, CDCl3):
1.05 (t, J¼7.4 Hz, 3H), 1.28–1.42 (m, 12H), 1.55–1.63 (m, 6H), 2.37–
2.48 (m, 4H) 3.56–3.58 (m, 1H); 13C NMR (50 MHz, CDCl3):
n
¼3421, 3019, 2932, 2858, 2400, 1709, 1461, 1215,
;
d
¼0.89 (t, J¼6.7 Hz, 3H),
d
¼7.8,
14.0, 22.5, 23.7, 25.3, 25.5, 29.3, 31.7, 35.8, 37.1, 37.4, 42.2, 71.7, 211.9.
Anal. Calcd for C15H30O2 (242.40): C, 74.32; H, 12.47%. Found: C,
74.51; H, 12.37%.
4.1.8. (2S,8R)-2-Ethyl-8-hexyloxocane: (þ)-cis-lauthisan (1)
To a solution of hydroxy ketone 17 (400 mg, 1.65 mmol) in dry
CH2Cl2 (4 mL), TMSOTf (0.328 mL, 1.81 mmol), followed by Et3SiH
(0.58 mL, 3.63 mmol), was added dropwise at 0 ꢁC. The reaction
mixture was stirred for 1 h at 0 ꢁC and quenched with a saturated
aqueous solution of NH4Cl. After workup and flash chromatography
(eluent EtOAc/hexane 1:40), pure (ꢀ)-cis-lauthisan 1 (157 mg) was
obtained as a colorless oil, in 42% yield (EtOAc/petroleum ether
column (isopropyl alcohol/petroleum ether¼1:99); flow, 1.0 mL/
25
min. Compound (S)-20: [
a
]
þ2.35 (c 1.7, CHCl3); IR (CHCl3)
n
¼3426,
D
3011, 2857, 2930, 1712, 1454, 1364, 1277, 1216 cmꢀ1
(200 MHz, CDCl3):
;
1H NMR
24
20
1:19). [
(CHCl3)
a
n
]
ꢀ3.92 (c 0.15, CHCl3); lit.15
[
a
]
D ꢀ4.0 (c 0.15, CHCl3); IR
d
¼0.89 (t, J¼6.7 Hz, 3H), 1.22–1.61 (m, 18H), 3.44
D
¼2910, 2860, 1460, 1090 cmꢀ1; 1H NMR (200 MHz, CDCl3):
(t, J¼6.4 Hz, 2H), 3.57 (m, 1H), 3.80 (s, 3H), 4.43 (s, 2H), 6.90 (d,
d
¼0.88 (t, J¼7.5 Hz, 3H), 0.93 (t, J¼7.5 Hz, 3H), 1.8–1.2 (m, 22H),
J¼8.7 Hz, 2H), 7.29 (d, J¼8.7 Hz, 2H); 13C NMR (50 MHz, CDCl3):
3.35–3.57 (m, 1H), 3.43–3.45 (m, 1H); 13C NMR (50 MHz, CDCl3):
d
¼14.0, 22.5, 25.4, 25.6, 26.2, 29.3, 29.6, 31.8, 37.4, 55.2, 55.2, 69.9,
d
¼10.9, 14.2, 22.7, 24.2, 26.4, 27.2, 29.6, 30.0, 32.0, 33.5, 33.7, 37.1,
71.8, 72.4, 113.6, 127.1, 129.2, 130.6, 158.9. Anal. Calcd for C20H34O3
(322.48): C, 74.49; H, 10.63%. Found: C, 74.26; H, 10.85%.
79.6, 81.1.
4.1.9. 6-(4-Methoxybenzyloxy) hexan-1-ol (19)
4.1.11. Conversion of compound 21 to 20
To a solution of 1,5-hexanediol 18 (8.0 g, 67.79 mmol) in dry
DMF (200 mL) was added sodium hydride (60%, 2.44 g,
45.76 mmol) at 0 ꢁC. The reaction mixture was stirred at room
temperature for 30 min after which it was again cooled to 0 ꢁC. To
this was added slowly p-methoxybenzyl bromide (9.55 g,
61.01 mmol) and tetra-N-butylammonium iodide (cat.) with further
stirring for 1 h at the same temperature. The reaction mixture was
quenched with addition of cold water at 0 ꢁC. The two phases were
separated and the aqueous phase was extracted with EtOAc
(3ꢂ100 mL). The combined organic layers were washed with water
and brine, dried (Na2SO4), and concentrated. The residual oil was
purified by silica gel column chromatography using petroleum
ether/EtOAc (8:2) as eluent to furnish the mono-PMB protected
To a solution of 21 (3 g, 10.79 mmol) in EtOH (10 mL) was added
NaBH4 (1.22 g, 32.37 mmol). After stirring for 4 h at room temper-
ature, the reaction mixture was quenched with 10% AcOH aqueous
solution. After the removal of solvents under reduced pressure, the
mixture was added to water (20 mL) and extracted with ether
(250 mL). The organic layer was washed with brine, dried over
anhydrous MgSO4, and concentrated to give a residue, which was
purified by silica gel column chromatography to give 20 (2.68 g) in
89% yield.
4.1.12. (S)-tert-Butyl(1-(4-methoxybenzyloxy)dodecan-6-
yloxy)dimethylsilane (22)
To a stirred solution of alcohol (S)-20 (4.83 g, 3.10 mmol) in
CH2Cl2 (50 mL) and 2,6-lutidine (0.58 g, 1.08 mL, 5.43 mmol) was
added TBS-OTf (1.22 g, 4.65 mmol) at 0 ꢁC and the mixture was
stirred at the same temperature for 30 min. The reaction mixture
was quenched with water and extracted with CH2Cl2 (3ꢂ50 mL).
The combined organic layers were washed with brine, dried
(Na2SO4), and concentrated. Silica gel column chromatography of
alcohol 19 (13.54 g, 85%) as a colorless oil. IR (CHCl3)
2938,1718,1496,1454,1216,1096 cmꢀ1; 1H NMR (200 MHz, CDCl3):
¼1.32–1.60 (m, 6H), 3.43 (t, J¼6.5 Hz, 2H), 3.62 (t, J¼6.4 Hz, 2H),
3.79 (d, 3H), 4.05–4.13 (m, 1H), 4.42 (s, 1H), 4.61 (s, 1H), 6.84–6.90
(m, 2H), 7.23–7.31 (m, 2H); 13C NMR (50 MHz, CDCl3):
n
¼3402, 3009,
d
d¼13.4, 20.2,
24.8, 25.2, 28.9, 31.8, 54.5, 113.1, 127.86, 129.9, 132.5, 158.4. Anal.
Calcd for C13H20O3 (224.30): C, 69.61; H, 8.99%. Found: C, 69.48; H,
9.12%.
the crude product using petroleum ether/EtOAc (19:1) as eluent
25
gave compound 22 as a yellow syrup, 85% yield. [
CHCl3); IR (CHCl3)
1028, 836, 759 cmꢀ1
a
]
þ2.85 (c 1.4,
D
n
¼3018, 2857, 2932, 1463, 1361, 1255, 1215, 1092,
4.1.10. (S)-1-(4-Methoxybenzyloxy)dodecan-6-ols: (S)-20 and 21
To a solution of oxalyl chloride (5.60 g, 29.4 mmol) in dry CH2Cl2
(100 mL) at ꢀ78 ꢁC was added dropwise dry DMSO (6.88 g, 6.2 mL,
88.21 mmol) in CH2Cl2 (20 mL). After 30 min, alcohol 19 (7.0 g,
29.40 mmol) in CH2Cl2 (20 mL) was added over 10 min giving
a copious white precipitate. After stirring for 1 h at ꢀ78 ꢁC the re-
action mixture was brought to ꢀ60 ꢁC and Et3N (5.72 g, 7.88 mL,
132.32 mmol) was added slowly and stirred for 30 min allowing the
reaction mixture to warm to room temperature. The reaction
mixture was diluted with water (150 mL) and CH2Cl2. The organic
layer was separated and washed with water and brine, dried
(Na2SO4), and passed through short pad of Celite. The filtrate was
concentrated to give the aldehyde as pale yellow oil, which was
used as such for the next step without purification.
;
1H NMR (400 MHz, CDCl3):
d¼0.04 (s, 6H),
0.87–0.92 (m, 12H), 1.27–1.37 (m, 12H), 1.55–1.60 (m, 6H), 3.44 (t,
J¼6.7 Hz, 2H), 3.59–3.64 (m, 1H), 3.81 (s, 3H), 4.44 (s, 2H), 6.91 (d,
J¼8.8 Hz, 2H), 7.29 (d, J¼8.8 Hz, 2H); 13C NMR (50 MHz, CDCl3):
d
¼ꢀ4.4, 14.1, 18.1, 22.6, 25.2, 25.3, 25.9, 26.4, 29.5, 29.8, 31.9, 37.1,
55.2, 70.1, 72.3, 72.5, 113.7, 129.2, 130.7, 159.1. Anal. Calcd for
C26H48O3Si (436.74): C, 71.50; H, 11.08%. Found: C, 71.68; H, 11.10%.
4.1.13. (S)-6-(tert-Butyldimethylsilyloxy)dodecan-1-ol (23)
To a stirring solution of PMB ether 22 (4.8 g, 2.77 mmol) in
CH2Cl2/H2O (18:1) was added DDQ (756 mg, 3.33 mmol). The
resulting mixture was stirred for 1 h at rt. The mixture was poured
into saturated aqueous NaHCO3 and further diluted with CH2Cl2.
The layers were separated and the aqueous layer was extracted
with CH2Cl2 (2ꢂ30 mL). The combined organic layers were dried
(Na2SO4), filtered, and concentrated. The residue was then filtered
through a pad of Celite and washed with 50% EtOAc/hexane
(20 mL). The solvents were removed under reduced pressure to
give the crude product mixture as yellow oil. Silica gel column
To a stirred solution of the above crude aldehyde in dry THF
(50 mL) was added Grignard reagent prepared from a solution of 1-
bromohexane (6.08 g, 36.84 mmol) and Mg-turning (0.78 g,
31.93 mmol), dropwise at 0 ꢁC. The mixture was warmed to rt over
1 h and poured into a saturated NH4Cl solution. The layers were

D. Tripathi et al. / Tetrahedron 65 (2009) 2226–2231
2231
chromatography of the crude product using petroleum ether/EtOAc
Department of Science & Technology, New Delhi is gratefully
acknowledged.
25
(7:3) as eluent afforded 23 (3.27 g) as colorless oil in 94% yield. [
þ5.24 (c 1.62, CHCl3); IR (CHCl3) ¼3626, 3018, 2857, 2931, 1471,
1361, 1255, 1215, 1049 cmꢀ1; 1H NMR (200 MHz, CDCl3):
a]
D
n
d
¼0.04 (s,
6H), 0.87–0.92 (m, 12H), 1.27–1.37 (m, 12), 1.55–1.60 (m, 6H), 3.44
References and notes
(t, J¼6.7 Hz, 2H), 3.59–3.64 (m, 1H); 13C NMR (50 MHz, CDCl3):
d
¼ꢀ4.4, 14.1, 22.7, 25.4, 25.9, 29.6, 30.92, 31.8, 32.2, 37.1, 37.2, 62.8,
1. (a) Yasumoto, T.; Murata, M. Chem. Rev. 1993, 93, 1897; (b) Faulkner, D. J. Nat.
Prod. Rep. 2002, 19, 1 and preceding issues.
72.4. Anal. Calcd for C18H40O2Si (316.59): C, 68.29; H,12.73%. Found:
C, 68.38; H, 12.61%.
2. (a) Moore, R. E. In Marine Natural Products; Scheuer, P. J., Ed.; Academic: New
York, NY, 1978; Vol. 1, Chapter 2; (b) Erickson, K. K. In Marine Natural Products;
Scheuer, P. J., Ed.; Academic: New York, NY, 1983; Vol. 5, p 131; (c) Faulkner, D. J.
Nat. Prod. Rep. 1984, 1, 251; Faulkner, D. J. Nat. Prod. Rep. 1986, 3, 1; Faulkner, D. J.
Nat. Prod. Rep. 1988, 5, 613.
3. Illuminati, G.; Mandolini, L. Acc. Chem. Res. 1981, 14, 95.
4. Blunt, J. W.; Copp, B. R.; Munro, M. H. G.; Northcote, P. T.; Prinsep, M. R. Nat.
Prod. Rep. 2003, 20, 1 and earlier reviews in the same series.
5. General reviews: (a) Elliott, M. C. J. Chem. Soc., Perkin Trans. 1 2002, 85, 2301 and
earlier reviews in the same series; (b) Yet, L. Chem. Rev. 2000, 100, 2963; (c)
Hoberg, J. O. Tetrahedron 1998, 54, 12631.
6. (a) Coster, M. J.; De Voss, J. J. Org. Lett. 2002, 4, 3047; (b) Udding, J. H.; Gies-
selink, J. P. M.; Hiemstra, H.; Speckamp, W. N. J. Org. Chem. 1994, 59, 6671; (c)
Nicolaou, K. C.; McGarry, D. G.; Somers, P. K.; Kim, B. H.; Ogilvie, W. W.; Prasad,
C. V. C.; Veale, C. A.; Hark, R. R. J. Am. Chem. Soc. 1990, 112, 6263; (d) Nicolaou, K.
C.; McGarry, D. G.; Somers, P. K.; Veale, C. A.; Furst, G. T. J. Am. Chem. Soc. 1987,
109, 2504.
4.1.14. (9S)-9-(tert-Butyldimethylsilyloxy)pentadecan-4-ol (24)
Compound 24 was prepared following the procedure described
25
for compound 15 in 62% yield as a yellow syrup. [
CHCl3); IR (CHCl3)
1049 cmꢀ1; 1H NMR (400 MHz, CDCl3):
0.88 (t, J¼6.8 Hz, 3H), 0.94 (t, J¼6.6 Hz, 3H), 1.27–1.32 (m, 14H),
1.39–1.44 (m, 8H), 3.61 (m, 2H); 13C NMR (50 MHz, CDCl3):
a
]
þ2.08 (c 0.96,
D
n
¼3616, 3443, 3019, 2932, 2400,1463,1377,1215,
d
¼0.04 (s, 6H), 0.89 (s, 9H),
d
¼0.5,
18.6, 18.9, 22.2, 23.0, 27.5, 28.9, 29.9, 30.1, 30.8, 34.4, 36.8, 41.7, 41.9,
47.7, 49.6, 81.6, 81.8, 82.1. Anal. Calcd for C21H46O2Si (358.67): C,
70.32; H, 12.93%. Found: C, 70.48; H, 12.81%.
7. (þ)-cis-Lauthisan: (a) Rhee, H. J.; Beom, H. Y.; Kim, H. D. Tetrahedron Lett. 2004,
45, 8019; (b) Kim, H.; Ziani-Cherif, Ch.; Oh, J.; Cha, J. K. J. Org. Chem. 1995, 60,
792; (c) Paquette, L. A.; Sweeney, T. J. Tetrahedron 1990, 46, 4487; (d) Tsushima,
K.; Murai, A. Chem. Lett. 1990, 761; (e) Paquette, L. A.; Sweeney, T. J. J. Org. Chem.
1990, 55, 1703; (f) Carling, R. W.; Holmes, A. B. J. Chem. Soc., Chem. Commun.
1986, 565 (ꢀ)-cis-Lauthisan; (g) Suh, Y. G.; Koo, B. A.; Kim, E. N.; Choi, N. S.
Tetrahedron Lett. 1995, 36, 2089.
8. (a) Yuasa, Y.; Sato, W.; Shibuya, S. Synth. Commun. 1997, 27, 573; (b) Mujica, M.
T.; Afonso, M. M.; Galindo, A.; Palenzuela, J. A. J. Org. Chem. 1998, 63, 9728; (c)
Matsumura, R.; Suzuki, T.; Sato, K.; Inotsume, T.; Hagiwara, H.; Hoshi, T.; Kamat,
V. P.; Ando, M. Tetrahedron Lett. 2000, 41, 7697.
4.1.15. (S)-9-(tert-Butyldimethylsilyloxy)pentadecan-4-one (25)
Compound 25 was prepared following the procedure described
25
for compound 16 in 92% yield as a yellow syrup. [
a]
þ4.0 (c 1.02,
D
CHCl3); IR (CHCl3)
n
¼2932, 2400, 1710, 1215, 1051, 759 cmꢀ1
;
1H
NMR (400 MHz, CDCl3):
d
¼0.03 (s, 3H), 0.04 (s, 3H), 0.88 (s, 9H),
0.92 (t, J¼7.4 Hz, 6H), 1.27–1.30 (m, 10H), 1.39–1.41 (m, 4H), 1.59–
1.61 (m, 4H), 2.36–2.39 (m, 4H), 3.60 (m, 1H); 13C NMR (100 MHz,
CDCl3):
d
¼0.5, 18.6, 18.9, 22.2, 23.0, 27.5, 28.9, 29.9, 30.1, 30.8, 34.4,
36.8, 41.7, 41.9, 47.7, 49.6, 81.6, 81.8, 82.1, 216.3. Anal. Calcd for
C21H44O2Si (356.66): C, 70.72; H, 12.43%. Found: C, 70.58; H, 12.61%.
9. (a) Kotsuki, H.; Ushio, Y.; Kadota, I.; Ochi, M. J. Org. Chem. 1989, 54, 5153; (b)
Carreno, M. C.; Mazery, R. D.; Urbano, A.; Colobert, F.; Solladie, G. J. Org. Chem.
2003, 68, 7779.
10. (a) Carreno, M. C.; Mazery, R. D.; Urbano, A.; Colobert, F.; Solladie, G. Org. Lett.
2004, 6, 297; (b) Prasad, K. R.; Anbarasan, P. Tetrahedron: Asymmetry 2007, 18,
1419; (c) Carling, R. W.; Clark, J. S.; Holmes, A. B. J. Chem. Soc., Perkin Trans. 1
1992, 75, 83.
11. (a) Pandey, S. K.; Pandey, M.; Kumar, P. Tetrahedron Lett. 2008, 49, 2397; (b)
Gupta, P.; Kumar, P. Eur. J. Org. Chem. 2008, 1195 and references cited therein.
12. Tripathi, D.; Kumar, P. Tetrahedron Lett. 2008, 49, 7012.
13. Tokunaga, M.; Larrow, F. J.; Kakiuchi, F.; Jacobsen, E. N. Science 1997, 277, 936.
14. For reviews on the Swern oxidation, see: (a) Tidwell, T. T. Synthesis 1990, 857;
(b) Tidwell, T. T. Org. React. 1990, 39, 297.
15. Carreno, M. C.; Mazery, R. D.; Urbano, A.; Colobert, F.; Solladie, G. Org. Lett.
2005, 7, 2039.
4.1.16. (2S,7R)-2-Pentyl-7-propyloxepane: (þ)-isolaurepan (3)
Compound 3 was prepared following the procedure described
25
for compound 1 in 84% yield as a yellow syrup. [
a
]
þ1.5 (c 0.97,
D
24
CHCl3); lit.7
2850, 1465, 1455, 1375, 1340,1140, 1100 cmꢀ1
CDCl3):
¼0.88 (t, J¼6.8 Hz, 3H), 0.90 (t, J¼7.0 Hz, 3H), 1.26–1.44 (m,
10H), 1.47–1.55 (m, 8H), 1.65–1.73 (m, 4H), 3.37–3.39 (m, 2H); 13C
NMR (50 MHz, CDCl3):
[
a
]
D
þ1.5 (c 0.97, CHCl3); IR (CHCl3)
n
¼2950, 2920,
;
1H NMR (400 MHz,
d
d
¼14.0, 19.4, 22.6, 25.3, 26.2, 29.3, 31.8, 36.8,
36.9, 37.4, 39.6, 80.0, 80.3.
16. For oxidative resolution of secondary alcohols see: (a) Sun, W.; Wang, H. W.;
Xia, C. G.; Li, J. W.; Zhao, P. Q. Angew. Chem., Int. Ed. 2003, 42, 1042; (b) Li, Z.;
Tang, Z. H.; Hu, X. X.; Xia, C. G. Chem.dEur. J. 2005, 11, 1210.
Acknowledgements
17. (a) Homma, K.; Mukaiyama, T. Chem. Lett. 1989, 259; (b) Nicolaou, K. C.; Hwang,
C. K.; Duggan, M. E.; Nugiel, D. A.; Abe, Y.; Reddy, K. B.; DeFrees, S. A.; Reddy, D.
R.; Awartani, R. A.; Conley, S. R.; Rutjes, F. P. J. T.; Theodorakis, E. A. J. Am. Chem.
Soc. 1995, 117, 10227; (c) Nicolaou, K. C.; Hwang, C. K.; Nugiel, D. A. J. Am. Chem.
Soc. 1989, 111, 4136.
D.T. and S.K.P. thank UGC and CSIR New Delhi, respectively, for
the award of Senior Research Fellowship. Financial support for
funding the project (Grant No. SR/S1/OC-40/2003) from the