Enantioselective synthesis of the tetracyclic core of platensimycin

Article abstract of DOI:10.1055/s-0030-1260002

A concise preparative method for the tetracyclic core of platensimycin in an optically active form was developed through a nine-step sequence from p-anisaldehyde without the use of protecting groups. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0030-1260002

1532
PAPER
Enantioselective Synthesis of the Tetracyclic Core of Platensimycin
S
ynthesis of the Te
o
tracyclic
C
o
h
re of Platens
e
imycin i Ueda, Kayoko Iwahashi, Kazuo Iguchi, Hisanaka Ito*
School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
Fax +81(42)6765473; E-mail: itohisa@toyaku.ac.jp
Received 4 March 2011; revised 15 March 2011
and the addition reaction of methyl groups to the ester
Abstract: A concise preparative method for the tetracyclic core of
moiety. Compound 6 could be easily obtained from p-
anisaldehyde (7) through Stobbe condensation and fol-
lowing enantioselective reduction of the C=C bond.
platensimycin in an optically active form was developed through a
nine-step sequence from p-anisaldehyde without the use of protect-
ing groups.
Key words: antibiotics, enantioselective hydrogenation, iodoether-
ification, formal synthesis
OH
O
O
O
HO2C
N
H
H
O
H
O
OH
Platensimycin (1) has received much attention due to its
biological activity and intriguing structural features. The
Merck group discovered platensimycin in 2006 in a strain
of Streptococcus platensis as a novel antibiotic compound
against MRSA and VRE.1,2 The cage-like tetracyclic core
of platensimycin is of special interest as a synthetic target.
Since the first total synthesis of platensimycin in racemic
form was reported by Nicolaou et al.,3 successful exam-
ples of the total synthesis and formal synthesis of platen-
simycin have been reported by several groups.4,5 Almost
all of them employed compound 2 as a key intermediate
for the synthesis of 1. Among them, Mulzer et al.4g and
Corey et al.4h derived compound 2 from compound 3
through the reduction of both C=C bonds and re-oxidation
for the construction of cyclohexenone moiety. During the
effort for the diastereoselective reduction of C=C bond,
Mulzer et al. employed Crabtree’s catalyst to obtain the
desired stereoisomer predominantly.4g Corey et al. ob-
tained good diastereoselectivity during the reduction of
double bond by employing a chiral catalyst for the hydro-
genation reaction.4h For the synthesis of 3 in an optically
active form, Corey et al. employed an enantioselective
1,4-addition of an isopropenyl group, followed by bromo-
etherification and intramolecular substitution for the con-
struction of the tetracyclic core.4h Herein, we describe the
formal synthesis of the optically active tetracyclic core 3
from p-anisaldehyde by using less expensive reagents in a
stereoselective and protecting-group-free manner.
H
H
platensimycin (1)
2
OH
OH
O
O
HO
H
O
OH
5
4
3
OMe
OMe
CO2H
CHO
7
CO2Me
6
Scheme 1 Synthetic plan for platensimycin
The synthesis of compound 10 is outlined in Scheme 2.
Known compound 96,7 was prepared from p-anisaldehyde
(7) through Stobbe condensation, followed by enantiose-
lective reduction of the C=C bond, and polyphosphoric
acid-mediated intramolecular Friedel–Crafts acylation.
Compound 6 was reported by Zhang et al. in an optically
active form.8 [Rh(TangPhos)(nbd)]SbF6 was used as a
catalyst for an enantioselective reduction of compound 8
affording compound 6 in 97% ee. An enantioselective re-
duction of compound 8 was also examined by using
Rh(cod)2BF4 with (R,R)-Et-DuPhos, which gave 6 in 98%
ee in quantitative yield. Masaguer et al. reported the use
of TFA and TFAA for the intramolecular Friedel–Crafts
acylation of compound 6, and 9 was obtained in 50%
yield.6 We succeeded in improving the yield at this stage
Our synthetic strategy is shown in Scheme 1. Compound
3, which was previously reported by Mulzer et al.4g and
Corey et al.,4h would be synthesized from 4 through iodo-
etherification and subsequent intramolecular substitution
reaction. Compound 4 could be prepared by the site-selec-
tive b-elimination of the tertiary hydroxy group followed
by the stereoselective reduction of the ketone moiety of
compound 5. Compound 5 would be constructed from
compound 6 by intramolecular Friedel–Crafts acylation
SYNTHESIS 2011, No. 10, pp 1532–1536
x
x.
x
x
.
2
0
1
1
Advanced online publication: 15.04.2011
DOI: 10.1055/s-0030-1260002; Art ID: F24711SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of the Tetracyclic Core of Platensimycin
1533
OH
by employing polyphosphoric acid (83% yield). For the
cleavage of the methyl ether on the aromatic ring, the
presence of the ketone moiety conjugated on the aromatic
ring is crucial. After the reduction of the ketone moiety,
the cleavage of the methyl ether was unsuccessful. There-
fore, the methyl ether was cleaved at this stage. Com-
pound 9 was treated with aqueous HBr to give compound
10 in 95% yield.
OH
1. L-Selectride
HO
2. MeMgBr
HO
2 steps, 48%
OH
OH
OLi
11
4
O
OMe
OMe
OH
OH
CO2Me
OMe
dimethyl
succinate
t-BuOK
Rh(cod)2BF4
(R,R)-Et-DuPhos
H2
10
LHMDS
MeLi
HO2C
HO2C
O
LiO
quant., 98% ee
73%
quant.
CO2Me
CO2Me
CHO
7
8
6
CO2Me
OMe
OH
12
5
Scheme 3 One-pot synthesis of compound 5
PPA
83%
HBr, H2O
95%
O
O
tion of 4 afforded compound 14 in 95% yield (diastereo-
meric ratio = 9:1). The mechanism for the diastereo-
selectivity at this stage was proposed by Corey et al.4h for
the bromoetherification of their substrate. Cyclization of
14 for the construction of the tetracyclic core 3 was
achieved by treatment of 14 with potassium tert-butoxide
in tert-butyl alcohol under refluxing conditions (98%
yield). The spectral data and optical rotation value of com-
pound 3 was identical to those reported in the literature.4h
CO2Me
CO2Me
10
9
Scheme 2 Synthesis of compound 10
For the synthesis of 4, which is a precursor of the iodo-
etherification reaction, the ketone and methoxycarbonyl
moieties of compound 10 must be converted into hydroxy
and isopropenyl groups, respectively. As shown in
Scheme 3, the reduction of the ketone moiety and the ad-
dition of the dimethyl groups to the methoxycarbonyl
moiety of compound 10 proceeded smoothly to give com-
pound 11. However, the selective elimination of the tertia-
ry hydroxy group of 11 to construct the isopropenyl group
was unsuccessful. Therefore, the elimination of the tertia-
ry hydroxy group of compound 5 was examined next. For
the preparation of compound 5, the protection of the ke-
tone moiety of 10 was required. Thus, the ketone moiety
of 10 was converted into enolate 12 in situ, and the addi-
tion of the methyl group was examined. Treatment of
compound 10 with two equivalents of lithium bis(trimeth-
ylsilyl)amide (LHMDS) at –78 °C followed by the addi-
tion of methyllithium gave compound 5 in quantitative
yield without significant racemization (96% ee). If re-
quired, compound 5 can be recrystallized to furnish al-
most enantiomerically pure 5 (99.5% ee) without
significant loss of sample (>90% yield).
OH
OH
NaBH4
O
Burgess reagent
97%
O
96%, 15:1
OH
5
13
OH
OH
H
I2, NaHCO3
95%, 9:1
t-BuOK
98%
3
HO
O
H
I
4
14
Scheme 4 Synthesis of compound 3
As shown in Scheme 4, the elimination of the tertiary hy-
droxy group of 5 for the construction of the isopropenyl
group was achieved by the use of the Burgess reagent,9
which can be easily prepared from chlorosulfonyl isocy-
anate, methanol, and triethylamine; and compound 13 was
obtained in 97% yield. The reduction of the ketone moiety
of 13 proceeded by employing sodium borohydride to
give compound 4 in a highly diastereoselective manner
(96% yield, diastereomeric ratio = 15:1). Iodoetherifica-
In conclusion, the formal synthesis of platensimycin (1)
was realized. For the enantioselective synthesis of key in-
termediate 3, nine steps were required from p-anisalde-
hyde and the total yield obtained was 46% (after removal
of undesired diastereomer). In particular, a total 61% yield
was attained from compound 8, which was the Stobbe
condensation adduct in the first step. The present route
represents a stereoselective and atom-economical synthe-
Synthesis 2011, No. 10, 1532–1536 © Thieme Stuttgart · New York

1534
Y. Ueda et al.
PAPER
13C NMR (75 MHz, CDCl3): d = 34.6, 36.8, 42.9, 52.0, 55.2, 114.0,
sis for the tetracyclic core of platensimycin that employs
less expensive reagents and avoids the use of protecting
groups.
129.9, 130.0, 158.5, 174.5, 177.4.
HRMS-ESI: m/z calcd for C13H16O5 + Na (M + Na)+: 275.0919;
found: 275.0895.
All reactions were carried out under an argon atmosphere. Unless
otherwise noted, materials were obtained from commercial suppli-
ers and used without further purification. 1H and 13C NMR spectra
were measured on a Bruker AV-300 spectrometer and the chemical
shifts are given in ppm using CHCl3 (7.26 ppm) in CDCl3 and
CH3OH (3.34 ppm) in CD3OD for 1H NMR and CDCl3 (77.0 ppm)
and CD3OD (49.8 ppm) for 13C NMR as an internal standard, re-
spectively. IR spectra were taken with a Perkin-Elmer Paragon
1000 FT-IR and only noteworthy absorptions were listed. Mass
spectra were measured on a Micromass LCT spectrometer.
(S)-Methyl (6-Methoxy-4-oxo-1,2,3,4-tetrahydronaphthalen-2-
yl)carboxylate (9)
A mixture of compound 6 (50 mg, 0.2 mmol) and polyphosphoric
acid (600 mg) was stirred with a mechanical stirrer at 50 °C for 1 h.
H2O (5 mL) was added to the reaction mixture and extracted with
EtOAc (2 × 30 mL). The combined organic extracts were washed
with aq NaHCO3 (20 mL), H2O (20 mL), and brine (20 mL). The
organic layer was dried (MgSO4) and concentrated in vacuo. The
residue was purified by column chromatography on silica gel (n-
hexane–EtOAc, 2:1) to give the known compound 96,7 as colorless
crystals (38.5 mg, 0.16 mmol, 83%) with 98% ee (ee was deter-
mined using chiral column OJ-H, n-hexane–i-PrOH, 97:3);
[a]D23 +47.7 (c 0.44, CHCl3); mp 76–78 °C (n-hexane–CHCl3).
(E)-3-(Methoxycarbonyl)-4-(4-methoxyphenyl)but-3-enoic
Acid (8)
To a solution of t-BuOK (7.22 g, 51.5 mmol) in anhyd t-BuOH (40
mL) was added a solution of p-anisaldehyde (7; 5.84 g, 42.9 mmol)
and dimethyl succinate (7.51 g, 6.7 mL, 51.5 mmol) in anhyd t-
BuOH (15 mL) at 100 °C for 30 min under an argon atmosphere,
and the resulting mixture was refluxed for 30 min. The reaction
mixture was cooled to r.t., quenched with concd HCl (5 mL), and
concentrated in vacuo. Ice-water was added to the residue and the
mixture was extracted with Et2O (2 × 200 mL). The combined or-
ganic extracts were washed with H2O (80 mL), and extracted with
sat. aq NaHCO3 (2 × 100 mL). The aqueous layer was acidified with
concd HCl, and the mixture was extracted with Et2O (2 × 200 mL).
The combined organic extracts were washed with brine (50 mL),
dried (MgSO4), and concentrated in vacuo. The residue was purified
by column chromatography on silica gel (n-hexane–EtOAc–
AcOH, 200:100:3) to give the known compound 86,7 as colorless
crystals (7.78 g, 31.1 mmol, 73%); mp 117–118 °C (n-hexane–
CHCl3).
IR (KBr): 2926, 1734, 1679, 1608, 1497, 1438 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.76–2.87 (m, 1 H), 2.87–2.98 (m,
1 H), 3.09–3.24 (m, 3 H), 3.72 (s, 3 H), 3.84 (s, 3 H), 7.09 (dd,
J = 2.8, 8.4 Hz, 1 H), 7.19 (d, J = 8.4 Hz, 1 H), 7.51 (d, J = 2.8 Hz,
1 H).
13C NMR (75 MHz, CDCl3): d = 31.2, 40.2, 40.5, 52.2, 55.4, 109.0,
122.2, 130.0, 132.6, 134.0, 158.6, 173.6, 195.8.
HRMS-ESI: m/z calcd for C13H15O4 (M + H)+: 235.0970; found:
235.0983.
Anal. Calcd for C13H14O4: C, 66.66; H, 6.02. Found: C, 66.79; H,
6.11.
(S)-Methyl (6-Hydroxy-4-oxo-1,2,3,4-tetrahydronaphthalen-2-
yl)carboxylate (10)
HBr (2.0 mL, 48% in H2O) was added to compound 9 (100 mg, 0.43
mmol) at 90 °C. After stirring at 90 °C for 2 h, MeOH (2.0 mL) was
added to the mixture. The reaction mixture was cooled to r.t. and
H2O (10 mL) was added to the mixture. MeOH was removed in vac-
uo and the residue was filtered and the crystals were washed with
H2O (10 mL). The crystals were dried under vacuum to give 10
(89.5 mg, 0.41 mmol, 95%); [a]D23 +52.7 (c 1.0, DMSO); mp 76–
78 °C (MeOH).
IR (KBr): 2938, 1706, 1639, 1607, 1511, 1436 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.62 (s, 2 H), 3.83 (s, 3 H), 3.84
(s, 3 H), 6.94 (d, J = 8.5 Hz, 2 H), 7.35 (d, J = 8.5 Hz, 2 H), 7.87 (s,
1 H).
13C NMR (75 MHz, CDCl3): d = 33.6, 52.4, 55.3, 114.2, 122.9,
127.1, 131.0, 142.4, 160.4, 168.3, 177.1.
HRMS-ESI: m/z calcd for C13H14O5 + Na (M + Na)+: 273.0739;
found: 273.0726.
IR (KBr): 3186, 1720, 1654, 1618, 1579, 1497, 1429, 1356 cm–1.
1H NMR (300 MHz, CD3OD): d = 2.81–2.88 (m, 2 H), 3.07–3.30
(m, 3 H), 3.70 (s, 3 H), 7.02 (dd, J = 2.7, 8.3 Hz, 1 H), 7.20 (d,
J = 8.3 Hz, 1 H), 7.36 (d, J = 2.7 Hz, 1 H).
Anal. Calcd for C13H14O5: C, 62.39; H, 5.64. Found: C, 62.54; H,
5.71.
13C NMR (75 MHz, CD3OD): d = 30.2, 39.4, 39.5, 50.6, 110.9,
(S)-3-(Methoxycarbonyl)-4-(4-methoxyphenyl)butanoic Acid
(6)
121.1, 129.3, 131.9, 132.3, 155.7, 173.4, 196.4.
HRMS-ESI: m/z calcd for C12H12O4 (M + H)+: 221.0814; found:
221.0806.
Under an argon atmosphere, a mixture of Rh(cod)2BF4 (16.2 mg,
40.0 mmol) and (R,R)-Et-DuPhos (14.5 mg, 42.3 mmol) in CH2Cl2
(2 mL) was stirred at r.t. for 30 min. To the mixture was added com-
pound 8 (1.00 g, 4.00 mmol) in one portion. The hydrogenation ap-
paratus was purged three times with H2 and filled with H2 to 150 psi.
After stirring for 24 h at r.t., the mixture was concentrated in vacuo.
The residue was purified by column chromatography on silica gel
(n-hexane–EtOAc, 1:1) to give the known compound 68 as a color-
less oil (1.01 g, 4.00 mmol, ~100%) with 98% ee (ee was deter-
mined after converting of 6 into methyl ester, and by using chiral
column OD-H, n-hexane–i-PrOH, 95:5); [a]D23 –33.9 (c 0.21,
CHCl3).
Anal. Calcd for C12H12O4: C, 65.45; H, 5.49. Found: C, 65.53; H,
5.56.
(S)-3-(Dimethylhydroxymethyl)-7-hydroxy-1-tetralone (5)
To a solution of keto ester 10 (400 mg, 1.81 mmol) in anhyd THF
(20 mL) was slowly added a solution of LHMDS (3.40 mL, 3.63
mmol, 1.07 M in hexane) at –78 °C under an argon atmosphere. Af-
ter stirring at –78 °C for 30 min, a solution of MeLi (9.1 mL, 9.1
mmol, 1.0 M in Et2O) was added to the mixture at the same temper-
ature. The mixture was stirred at –78 °C for 30 min. The mixture
was warmed to r.t. and aq 1 M HCl (20 mL) was added to the mix-
ture. The resulting mixture was extracted with EtOAc (2 × 40 mL)
and the combined organic extracts were washed with brine (20 mL).
The organic layer was dried (MgSO4), filtered, and concentrated in
vacuo. The residue was purified by column chromatography on sil-
IR (film): 3235, 2954, 1732, 1713, 1613, 1514, 1440 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.43 (dd, J = 4.7, 17.2 Hz, 1 H),
2.63–2.78 (m, 2 H), 2.92–3.13 (m, 2 H), 3.67 (s, 3 H), 3.77 (s, 3 H),
6.82 (d, J = 8.6 Hz, 2 H), 7.06 (d, J = 8.6 Hz, 2 H).
Synthesis 2011, No. 10, 1532–1536 © Thieme Stuttgart · New York

PAPER
Synthesis of the Tetracyclic Core of Platensimycin
1535
ica gel (n-hexane–EtOAc, 1:2) to give 5 as colorless crystals (398.2
mg, 1.81 mmol, ~100%) with 96% ee (ee was determined using
chiral column AS-H, n-hexane–i-PrOH, 90:10); [a]D23 +27.5 (c
0.95, MeOH); mp 175–177 °C (n-hexane–EtOAc).
(1S,9S,10R)-4-Hydroxy-10-iodomethyl-10-methyl-11-oxatricy-
clo[7.2.1.02,7]dodeca-2,4,6-triene (14)
To a mixture of 4 (20 mg, 0.0979 mmol) and solid NaHCO3 (82.3
mg, 0.979 mmol) in MeCN (1 mL) was added I2 (49.7 mg, 0.196
mmol) at r.t. under an argon atmosphere in the dark. After stirring
for 2 h at r.t., the mixture was treated with aq NaHSO3 (5 mL) and
extracted with EtOAc (2 × 20 mL). The combined organic extracts
were washed with brine (10 mL), dried (MgSO4), filtered, and con-
centrated in vacuo. The residue was purified by column chromatog-
raphy on silica gel (n-hexane–EtOAc, 2:1) to give 14 as an
amorphous powder (30.7 mg, 0.0931 mmol, 95% yield, diastereo-
meric ratio = 9:1). Both diastereomers were separated by HPLC on
silica gel (n-hexane–EtOAc, 2:1).
IR (KBr): 3448, 3234, 2978, 1664, 1616, 1572, 1498 cm–1.
1H NMR (300 MHz, CD3OD): d = 1.28 (s, 3 H), 1.29 (s, 3 H), 2.13
(tdd, J = 3.6, 12.2, 13.6 Hz, 1 H), 2.43 (dd, J = 13.7, 16.4 Hz, 1 H),
2.69–2.87 (m, 2 H), 3.02 (td, J = 2.7, 15.6 Hz, 1 H), 7.01 (dd,
J = 2.7, 8.3 Hz, 1 H), 7.21 (d, J = 8.3 Hz, 1 H), 7.34 (d, J = 2.7 Hz,
1 H).
13C NMR (75 MHz, CD3OD): d = 24.7, 25.1, 29.4, 39.6, 46.0, 70.2,
110.7, 121.0 129.5, 132.0, 135.0, 155.3, 199.4.
HRMS-ESI: m/z calcd for C13H16O3 + Na (M + Na)+: 243.0997;
found: 243.1015.
Major Isomer
[a]D23 +140.8 (c 0.8, CHCl3).
Anal. Calcd for C13H16O3: C, 70.89; H, 7.32. Found: C, 70.69; H,
7.28.
IR (KBr): 3370, 3078, 2921, 1611, 1508, 1450 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.56 (s, 3 H), 2.10 (d, J = 11.3 Hz,
1 H), 2.51–2.70 (m, 2 H), 3.01 (dd, J = 4.1, 17.5 Hz, 1 H), 3.13 (d,
J = 9.8 Hz, 1 H), 3.21 (d, J = 17.5 Hz, 1 H), 3.30 (d, J = 9.8 Hz, 1
H), 4.80 (d, J = 5.1 Hz, 1 H), 6.60 (d, J = 2.6 Hz, 1 H), 6.75 (dd,
J = 2.6, 8.2 Hz, 1 H), 6.93 (br s, 1 H), 7.00 (d, J = 8.2 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 13.8, 28.0, 31.3, 35.3, 41.8, 78.5,
84.4, 114.3, 115.9, 125.2, 130.0, 140.6, 154.5.
(S)-7-Hydroxy-3-(1-methylethenyl)-1-tetralone (13)
To a solution of 5 (100 mg, 0.45 mmol) in anhyd THF (5.0 mL) was
added Burgess reagent9 (162.3 mg, 0.68 mmol) at r.t. under an argon
atmosphere. After stirring for 2 h at r.t., H2O (20 mL) was added to
the mixture and the resulting mixture was extracted with EtOAc
(2 × 40 mL). The combined organic extracts were washed with
brine (20 mL), dried (MgSO4), filtered, and concentrated in vacuo.
The residue was purified by column chromatography on silica gel
(n-hexane–EtOAc, 3:1) to give 13 as an amorphous powder (88.7
mg, 0.44 mmol, 97%); [a]D23 +25.8 (c 5.60, CHCl3).
HRMS-ESI: m/z calcd for C13H16IO2 (M + H)+: 331.0195; found:
331.0192.
Minor Isomer
IR (KBr): 3421, 2924, 1671, 1610, 1500, 1450 cm–1.
IR (film): 3325, 2952, 1619, 1404, 1455 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.81 (s, 3 H), 2.55 (dd, J = 13.7,
17.4 Hz, 1 H), 2.72–3.04 (m, 4 H), 4.82 (s, 1 H), 4.85 (br s, 1 H),
7.03 (dd, J = 2.8, 8.3 Hz, 1 H), 7.17 (d, J = 8.3 Hz, 1 H), 7.52 (d,
J = 2.7 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 20.6, 34.1, 42.4, 43.9, 110.8, 112.6,
122.1, 130.3, 132.7, 135.9, 146.6, 155.0, 199.5.
1H NMR (300 MHz, CDCl3): d = 1.41 (s, 3 H), 2.02 (d, J = 11.8 Hz,
1 H), 2.44 (td, J = 5.5, 11.8 Hz, 1 H), 2.82–3.11 (m, 3 H), 3.22 (d,
J = 9.9 Hz, 1 H), 3.33 (d, J = 9.9 Hz, 1 H), 4.76 (d, J = 5.2 Hz, 1 H),
5.40 (br s, 1 H), 6.52 (d, J = 2.6 Hz, 1 H), 6.71 (dd, J = 2.6, 8.2 Hz,
1 H), 6.97 (d, J = 8.2 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 17.0, 23.6, 32.2, 34.7, 40.3, 78.4,
83.7, 114.1, 115.5, 125.7, 129.9, 140.7, 153.8.
HRMS-ESI: m/z calcd for C13H15O2 (M + H)+: 203.1072; found:
203.1084.
HRMS-ESI: m/z calcd for C13H16IO2 (M + H)+: 331.0195; found:
331.0175.
Anal. Calcd for C13H14O2: C, 77.20; H, 6.98. Found: C, 77.04; H,
6.90.
(1S,7S,9S,10S)-10-Methyl-11-oxa-4-oxo-tetracyc-
lo[7.2.1.17,10.02.7]trideca-2(3),5-diene (3)
(1S,3S)-1,7-Dihydroxy-3-(1-methylethenyl)-1,2,3,4-tetrahydro-
naphthalene (4)
To a stirred solution of 14 (50 mg, 0.151 mmol) in t-BuOH (1.5 mL)
was added t-BuOK (85.0 mg, 0.757 mmol) at r.t. under an argon at-
mosphere. The resulting mixture was refluxed overnight. The reac-
tion mixture was cooled to r.t., aq NaHCO3 (10 mL) was added, and
the resulting mixture was extracted with EtOAc (2 × 30 mL). The
combined organic extracts were washed with brine (10 mL), dried
(MgSO4), filtered, and concentrated in vacuo. The residue was pu-
rified by column chromatography on silica gel (n-hexane–
EtOAc, 1:1) to give 34h as a colorless oil (30.0 mg, 0.148 mmol,
98%); [a]D23 +32.5 (c 1.2, CHCl3) {Lit.4h [a]D23 +33.7 (c 1.25,
CHCl3)}.
To a solution of 13 (172.0 mg, 0.85 mmol) in MeOH (8.5 mL) was
slowly added solution of NaBH4 (32.2 mg, 0.85 mmol) in MeOH
(0.9 mL) at –10 °C under an argon atmosphere. After stirring for 1
h at –10 °C, the mixture was concentrated in vacuo. The residue was
purified by column chromatography on silica gel (n-hexane–
EtOAc, 1:1) to give diol 4 as an amorphous powder (167.4 mg, 0.82
mmol, 96% yield, diastereomeric ratio = 15:1); [a]D23 +105.8 (c
0.65, EtOH).
IR (KBr): 3256, 2948, 1616, 1506, 1458 cm–1.
1H NMR (300 MHz, CD3OD): d = 1.59 (dt, J = 11.0, 12.2 Hz, 1 H),
1.83 (s, 3 H), 2.25 (tdd, J = 2.1, 5.9, 12.0 Hz, 1 H), 2.40 (br dt,
J = 4.2, 11.3 Hz, 1 H), 2.62 (dd, J = 11.7, 15.6 Hz, 1 H), 2.76 (ddd,
J = 1.5, 4.9, 15.6 Hz, 1 H), 4.75 (dd, J = 5.9, 10.9 Hz, 1 H), 4.80 (br
s, 1 H), 4.83 (br s, 1 H), 6.63 (dd, J = 2.4, 8.3 Hz, 1 H), 6.91 (d,
J = 8.3 Hz, 1 H), 7.03 (d, J = 2.4 Hz, 1 H).
13C NMR (75 MHz, CD3OD): d = 18.7, 33.6, 37.8, 40.2, 68.7, 107.6,
112.0, 113.5, 126.3, 128.4, 139.8, 148.3, 154.6.
HRMS-ESI: m/z calcd for C13H16O2 + Na (M + Na)+: 227.1048;
found: 227.1058.
IR (film): 2966, 1662, 1630, 1148 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.45–1.55 (m, 4 H), 1.76 (d,
J = 11.3 Hz, 1 H), 1.92 (dd, J = 3.2, 11.2 Hz, 1 H), 1.98 (d, J = 11.2
Hz, 1 H), 2.11–2.27 (m, 2 H), 2.58 (t, J = 6.2 Hz, 1 H), 4.69 (d,
J = 4.4 Hz, 1 H), 6.10 (d, J = 1.8 Hz, 1 H), 6.30 (dd, J = 1.8, 10.0
Hz, 1 H), 6.65 (d, J = 10.0 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 22.2, 42.5, 44.4, 48.6, 49.9, 54.8,
80.0, 87.1, 121.8, 130.0, 150.9, 160.4, 187.0.
HRMS-ESI: m/z calcd for C13H15O2 (M + H)+: 203.1072; found:
203.1082.
Synthesis 2011, No. 10, 1532–1536 © Thieme Stuttgart · New York

1536
Y. Ueda et al.
PAPER
46, 8074. (h) Lalic, G.; Corey, E. J. Org. Lett. 2007, 9, 4921.
(i) Heretsch, P.; Giannis, A. Synthesis 2007, 2614.
Acknowledgment
This work was supported by a Grant-in-Aid for Scientific Research
from the Ministry of Education, Culture, Sports, Science, and Tech-
nology, Japan.
(j) Nicolaou, K. C.; Pappo, D.; Tsang, K. Y.; Gibe, R.; Chen,
D. Y.-K. Angew. Chem. Int. Ed. 2008, 47, 944. (k) Kim, C.
H.; Jang, K. P.; Choi, S. Y.; Chung, Y. K.; Lee, E. Angew.
Chem. Int. Ed. 2008, 47, 4009. (l) Matsuo, J.; Takeuchi, K.;
Ishibashi, H. Org. Lett. 2008, 10, 4049. (m) Ghosh, A. K.;
Xi, K. J. Org. Chem. 2009, 74, 1163. (n) Nicolaou, K. C.;
Li, A.; Ellery, S. P.; Edmonds, D. J. Angew. Chem. Int. Ed.
2009, 48, 6293. (o) Yun, S. Y.; Zheng, J.-C.; Lee, D. J. Am.
Chem. Soc. 2009, 131, 8413. (p) McGrath, N. A.; Bartlett,
E. S.; Sittihan, S.; Njardarson, J. T. Angew. Chem. Int. Ed.
2009, 48, 8543. (q) Nicolaou, K. C.; Li, A.; Edmonds, D. J.;
Tria, G. S.; Ellery, S. P. J. Am. Chem. Soc. 2009, 131,
16905. (r) Tiefenbacher, K.; Tröndlin, L.; Mulzer, J.; Pfaltz,
A. Tetrahedron 2010, 66, 6508. (s) Xing, S.; Pan, W.; Liu,
C.; Ren, J.; Wang, Z. Angew. Chem. Int. Ed. 2010, 49, 3215.
(t) Eey, S. T.-C.; Lear, M. J. Org. Lett. 2010, 12, 5510.
(u) Magnus, P.; Rivera, H.; Lynch, V. Org. Lett. 2010, 12,
5677. (v) Beaulieu, M.-A.; Sabot, C.; Achache, N.; Guérard,
K. C.; Canesi, S. Chem. Eur. J. 2010, 16, 11224. (w) Hirai,
S.; Nakada, M. Tetrahedron 2011, 67, 518.
References
(1) Wang, J.; Soisson, S. M.; Young, K.; Shoop, W.; Kodali, S.;
Galgoci, A.; Painter, R.; Parthasarathy, G.; Tang, Y. S.;
Cummings, R.; Ha, S.; Dorso, K.; Motyl, M.; Jayasuriya, H.;
Ondeyka, J.; Herath, K.; Zhang, C.; Hernandez, L.; Allocco,
J.; Basilio, A.; Tormo, J. R.; Genilloud, O.; Vicente, F.;
Pelaez, F.; Colwell, L.; Lee, S. H.; Michael, B.; Felcetto, T.;
Gill, C.; Silver, L. L.; Hermes, J. D.; Bartizal, K.; Barrett, J.;
Schmatz, D.; Becker, J. W.; Cully, D.; Singh, S. B. Nature
2006, 441, 358.
(2) Singh, S. B.; Jayasuriya, H.; Ondeyka, J. G.; Herath, K. B.;
Zhang, C.; Zink, D. L.; Tsou, N. N.; Ball, R. G.; Basilio, A.;
Genilloud, O.; Diez, M. T.; Vicente, F.; Pelaez, F.; Young,
K.; Wang, J. J. Am. Chem. Soc. 2006, 128, 11916.
(3) Nicolaou, K. C.; Li, A.; Edmonds, D. J. Angew. Chem. Int.
Ed. 2006, 45, 7086.
(4) (a) Nicolaou, K. C.; Edmonds, D. J.; Li, A.; Tria, G. S.
Angew. Chem. Int. Ed. 2007, 46, 3942. (b) Zou, Y.; Chen,
C.-H.; Taylor, C. D.; Foxman, B. M.; Snider, B. B. Org. Lett.
2007, 9, 1825. (c) Kaliappan, K. P.; Ravikumar, V. Org.
Lett. 2007, 9, 2417. (d) Nicolaou, K. C.; Tang, Y.; Wang, J.
Chem. Commun. 2007, 1922. (e) Li, P.; Payette, J. N.;
Yamamoto, H. J. Am. Chem. Soc. 2007, 129, 9534.
(f) Ghosh, A. K.; Xi, K. Org. Lett. 2007, 9, 4013.
(5) For reviews on the synthetic approaches to platensimycin,
see: (a) Tiefenbacher, K.; Mulzer, J. Angew. Chem. Int. Ed.
2008, 47, 2548. (b) Harsh, P.; O’Doherty, G. A. Chemtracts
2009, 22, 31. (c) Palanichamy, K.; Kaliappan, K. P. Chem.
Asian J. 2010, 5, 668. (d) Lu, X.; You, Q. Curr. Med. Chem.
2010, 17, 1139.
(6) Caro, Y.; Torrado, M.; Masaguer, C. F.; Raviña, E.
Tetrahedron: Asymmetry 2003, 14, 3689.
(7) Kometani, T.; Shiotani, S. J. Med. Chem. 1978, 21, 1105.
(8) Tang, W.; Liu, D.; Zhang, X. Org. Lett. 2003, 5, 205.
(9) Burgess, E. M. J. Org. Chem. 1973, 38, 26.
(g) Tiefenbacher, K.; Mulzer, J. Angew. Chem. Int. Ed. 2007,
Synthesis 2011, No. 10, 1532–1536 © Thieme Stuttgart · New York