An efficient total synthesis of (+)-goniodiol

Article abstract of DOI:10.1055/s-0030-1259431

An efficient total synthesis of (+)-goniodiol was illustrated by using Carreira alkynylation and Sharpless asymmetric dihydroxylation as key steps. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0030-1259431

PAPER
821
An Efficient Total Synthesis of (+)-Goniodiol
Total
S
ynthesis of
o
(+)-Goniodi
w
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500007, India
Fax +91(40)27160512; E-mail: gowravaramsr@yahoo.com; E-mail: sabitha@iict.res.in
Received 29 November 2010; revised 10 December 2010
Because of its unique and intriguing structure as well as
antitumor activities, much efforts have been centered on
the development of methodology for the synthesis of this
molecule.6,7 The majority of these syntheses utilize either
chiral pool starting materials or enzymatic resolutions or
longer reaction sequences.
Abstract: An efficient total synthesis of (+)-goniodiol was illustrat-
ed by using Carreira alkynylation and Sharpless asymmetric dihy-
droxylation as key steps.
Key words: styryl lactones, goniodiol, Carreira alkynylation,
Sharpless asymmetric dihydroxylation
In continuation of our interest in the synthesis of bioactive
lactones,8 we herein report a convenient synthesis of (+)-
goniodiol (1) by utilizing Carreira alkynylation and
Sharpless dihydroxylation reactions.
Styryl lactones are a series of natural products, exhibiting
moderate to significant biological activity including anti-
tumor and antifungal properties, as well as antibiotic po-
tential.1 Up to now, more than twenty styryl lactones have
been isolated from plants and fungi.2 (+)-Goniodiol (1)
(Figure 1), an oxygenated 6-dihydrostyryl-5,6-dihydro-2-
pyrone, was isolated from the leaves and twigs of Gonio-
thalamus sesquipedalis (Annonaceae)2c and the stem bark
of Thai Goniothalamus giganteus.2d Goniodiol exhibited
potent selective cytotoxicity against human lung carcino-
ma cell lines A-549,3 HL-60 cells,4 and P-388 murine leu-
kemia cells.5
In our retrosynthetic analysis (Scheme 1), we envisaged
that the target molecule 1 could be prepared through acid-
catalyzed cyclization of compound 2, which was obtained
from syn-diol 3. Compound 3 can be prepared from allylic
alcohol 4, which in turn could be easily derived from benz-
aldehyde 5 and the protected homopropargylic alcohol 6.
The synthesis of (+)-goniodiol (1) (Scheme 2) com-
menced with the Carreira alkynylation reaction of benzal-
dehyde 5 with p-methoxybenzyl ether of homoprop-
argylic alcohol 6 in the presence of (+)-N-methylephed-
rine, zinc triflate, and triethylamine9 to afford the chiral
propargylic alcohol 7 in 88% yield with high enantiose-
lectivity. On the other hand, compound 7 can be prepared
by an alternative route by the following reaction manipu-
lations. Accordingly, benzaldehyde 5 was treated with
PMB ether of homopropargylic alcohol 6 in presence of
LHMDS to afford compound 8, which on oxidition10 with
IBX in DMSO–CH2Cl2 afforded the corresponding ke-
O
OH
O
OH
Figure 1 Structure of (+)-goniodiol (1)
OP
O
OP OH
OPMB
OH
CO2Me
1
O
2 P = MOM
3 P = MOM
OH
CHO
OPMB
+
OPMB
5
6
4
Scheme 1 Retrosynthetic analysis of (+)-goniodiol (1)
SYNTHESIS 2011, No. 5, pp 0821–0825
x
x
.
x
x
.2
0
1
1
Advanced online publication: 31.01.2011
DOI: 10.1055/s-0030-1259431; Art ID: Z29910SS
© Georg Thieme Verlag Stuttgart · New York

822
G. Sabitha et al.
PAPER
tone 9. Now, ketone 9 on asymmetric reduction11 with
(R)-(Me)-CBS [(R)-2-methyl-CBS-oxazaborolidine] cat-
alyst in the presence of BH3·SMe2 gave the chiral propar-
gylic alcohol 7 in 66% yield with excellent ee (Scheme 2).
OP
a
OPMB
c
7
4 P = H
b
OH
10 P = MOM
CHO
OP
O
a
+
OP OH
OPMB
OPMB
OR
d
OPMB
7
6
5
O
OH
b
3 P = MOM
d
11 P = MOM, R = PMB
12 P = MOM, R = H
e
O
OH
OP
O
c
f
CO2Me
g
OPMB
OPMB
(+)-goniodiol (1)
O
8
9
2 P = MOM
Scheme 2 Reagents and conditions: a) (+)-N-methylephedrine,
Zn(OTf)2, Et3N, 6, 2 h; then 5, 1 h, r.t., 88% (90% ee); b) 6, LHMDS,
THF, 0 °C, 1 h, 5, –78 to 25 °C, 2 h, 90%; c) IBX, DMSO, CH2Cl2,
0–25 °C, 92% d) (R)-(Me)-CBS, BH3·SMe2, THF, –20 °C, 1 h, 66%
(99% ee).
Scheme 3 Reagents and conditions: a) LiAlH4, THF, 0–25 °C, 3 h,
90%; b) MOM-Cl, DIPEA, CH2Cl2, 0–25 °C, 3 h, 96%; c) AD-mix-
b, methanesulfonamide, t-BuOH–H2O (1:1), 0 °C, 10 h, 90%; d) 2-
methoxypropene, CSA, CH2Cl2, 0 °C, 10 min, 99%; e) H2, 10% Pd/C,
EtOAc–EtOH (1:1), 6 h, 25 °C, 96%; f) i. DMP, NaHCO3, CH2Cl2,
0 °C, 30 min; ii) MeO2CCH2P(O)(OCH2CF3)2, NaH, THF, 18-
Crown-6, –78 °C, 1 h, 82%; g) p-TsOH, EtOH, 50 °C, overnight,
84%.
Compound 7 was reduced12 with LiAlH4 in THF to fur-
nish the E-allylic alcohol 4. The secondary hydroxy group
of compound 4 was protected as its MOM ether13 10 by
treating with MOM-Cl in the presence of Hünig’s base in
92% yield. Compound 10 was then converted to syn-diol
3 by employing Sharpless asymmetric dihydroxylation
conditions.14 Thus, compound 10 was treated with AD-
mix-b in t-BuOH–H2O (1:1) to afford diol 3 as a single
isomer in 90% yield, whereas on oxidative osmylation,
compound 10 gave the desired compound 3 in 4:1 dr (94%
yield). Subsequent acetonide protection15 of hydroxy
groups followed by the deprotection of PMB group16 with
H2 over Pd/C furnished 12 in 96% yield (Scheme 3).
syringe or cannula. Evaporation of solvents was performed at re-
duced pressure on a Büchi rotary evaporator. 1H and 13C NMR spec-
tra of samples in CDCl3 were recorded on Varian FT-400MHz and
Bruker UXNMR FT-300 MHz (Avance) spectrometers. Chemical
shifts are reported in d relative to TMS (d = 0.0) as an internal stan-
dard. Mass spectra were recorded E1 conditions at 70 eV on ES-
MSD (Agilent technologies) spectrometers. Column chromatogra-
phy was performed on silica gel (60–120 mesh) supplied by Acme
Chemical Co., India. TLC was performed on Merck 60 F-254 silica
gel plates. Optical rotations were measured with Jasco DIP-370 Po-
larimeter.
Oxidation17 of alcohol 12 to its corresponding aldehyde
and subsequent chain elongation18 with Still–Gennari re-
agent furnished the Z-isomer 2 in 82% yield along with
traces of E-isomer. Compound 2 on treating with catalytic
amount of PTSA in EtOH at 50 °C afforded the target
molecule 1 by tandem deprotection and in situ cyclization
process. Spectral and analytical data of compound 1 were
in agreement with the natural product.3
5-[(4-Methoxybenzyl)oxy]-1-phenylpent-2-yn-1-ol (8)
To a stirred solution of 6 (2.68 g, 14.13 mmol) in anhyd THF (15
mL) was added LHMDS (1 M solution in heptane, 23.5 mL, 23.55
mmol) at 0 °C under N2 atmosphere. The reaction mixture was
stirred at the same temperature for 1 h and cooled to –78 °C. Then
5 (1.0 g, 9.42 mmol) was added slowly via a syringe and the mixture
was allowed to warm to 25 °C. After completion of the reaction (as
indicated by TLC), the mixture was quenched with sat. aq NH4Cl
(10 mL) and diluted with EtOAc (20 mL). The mixture was extract-
ed with EtOAc (2 × 10 mL), and the combined organic layers were
washed with brine (2 × 20 mL) and H2O (2 × 20 mL), and dried
(Na2SO4). Concentration under vacuum gave the crude product,
which was purified by column chromatography using 20% EtOAc
in hexanes to afford 8 as a pale yellow oil; yield: 2.51 g (90%).
In summary, the total synthesis of (+)-goniodiol (1), a cy-
totoxic styryl lactone was accomplished in a stereocon-
trolled manner by the creation of chiral centers via
Carreira alkynylation or CBS-reduction and Sharpless
asymmetric dihydroxylation reactions in good overall
yield.
1H NMR (300 MHz, CDCl3): d = 7.49 (d, J = 7.0 Hz, 2 H), 7.35–
7.27 (m, 3 H), 7.20 (d, J = 8.6 Hz, 2 H), 6.80 (d, J = 8.6 Hz, 2 H),
5.38 (d, J = 5.8 Hz, 1 H), 4.45 (s, 2 H), 3.79 (s, 3 H), 3.55 (t, J = 6.5
Hz, 2 H), 2.55 (dt, J = 6.6, 2.2 Hz, 2 H).
Reactions were conducted under N2 in anhyd solvents such as
CH2Cl2, THF, and EtOAc. All reactions were monitored by TLC
(silica-coated plates and visualizing under UV light). Hexanes used
refer to the fraction boiling in the range of 60 to 80 °C. Yields refer
to chromatographically and spectroscopically (1H and 13C NMR)
homogeneous material. Air sensitive reagents were transferred by
ESMS: m/z = 319 [M + Na]+.
5-[(4-Methoxybenzyl)oxy]-1-phenylpent-2-yn-1-one (9)
To an ice-cold solution of IBX (0.9 g, 3.24 mmol) in DMSO (2.0
mL), was added a solution of 8 (0.8 g, 2.70 mmol) in anhyd CH2Cl2
Synthesis 2011, No. 5, 821–825 © Thieme Stuttgart · New York

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Total Synthesis of (+)-Goniodiol
823
(5 mL) and the reaction mixture was stirred at 25 °C for 3 h. The
mixture was diluted with CH2Cl2 (20 mL), filtered through a Celite
pad, and the pad was washed with CH2Cl2 (3 × 10 mL). The com-
bined filtrates were washed with H2O (2 × 10 mL), dried (Na2SO4),
and concentrated under reduced pressure. The resultant residue was
purified by column chromatography using 12% EtOAc in hexanes
to afford ketone 9 as a pale yellow oil; yield: 0.73 g (92%).
1H NMR (300 MHz, CDCl3): d = 7.32–7.28 (m, 5 H), 7.17 (d,
J = 8.6 Hz, 2 H), 6.80 (d, J = 8.6 Hz, 2 H), 5.73–5.68 (m, 2 H), 5.11
(dd, J = 4.9, 2.0 Hz, 1 H), 4.39 (s, 2 H), 3.79 (s, 3 H), 3.45 (t, J = 6.6
Hz, 2 H), 2.37–2.30 (m, 2 H).
ESMS: m/z = 321 [M + Na]+.
1-Methoxy-4-{[(E,5S)-5-(methoxymethoxy)-5-phenylpent-3-
enyl]oxymethyl}benzene (10)
IR (neat): 2927, 2863, 2237, 1643, 1256, 1095 cm–1.
To a stirred solution of compound 4 (0.3 g, 1.00 mmol) in CH2Cl2
(10 mL) at 0 °C under N2 atmosphere was added i-Pr2NEt (Hünig’s
base) (0.51 mL, 3.02 mmol), and after 5 min MOMCl (0.13 mL,
1.50 mmol) was added dropwise. After stirring for 3 h at 25 °C, the
reaction mixture was diluted with CH2Cl2 (20 mL). The combined
organic layers were washed with sat. aq NH4Cl (2 × 5 mL), brine
(2 × 5 mL) and H2O (1 × 5 mL), and dried (Na2SO4). The solvent
was removed under vacuum and the residue was purified on a silica
gel column using 10% EtOAc in hexanes to afford the pure com-
pound 10 as a pale yellow liquid; yield: 0.33 g (96%); [a]D25 +0.3 (c
1.5, CHCl3).
1H NMR (300 MHz, CDCl3): d = 8.10 (dd, J = 7.1, 1.3 Hz, 2 H),
7.55 (tt, J = 7.3, 1.3 Hz, 1 H), 7.41 (t, J = 7.1 Hz, 2 H), 7.23 (d,
J = 8.5 Hz, 2 H), 6.82 (d, J = 8.5 Hz, 2 H), 4.49 (s, 2 H), 3.78 (s, 3
H), 3.67 (t, J = 6.8 Hz, 2 H), 2.75 (t, J = 6.8 Hz, 2 H).
ESMS: m/z = 317 [M + Na]+.
(1S)-5-[(4-Methoxybenzyl)oxy]-1-phenylpent-2-yn-1-ol (7)
Procedure A: A 1 M solution of (R)-(Me)-CBS in toluene (0.40 mL,
0.40 mmol) under static atmosphere of N2 was dissolved in anhyd
THF (5 mL). To this solution was added BH3·SMe2 (0.20 mL, 2.04
mmol) and the mixture was cooled to –20 °C. Prochiral ketone 9
(0.6 g, 2.04 mmol), either neat or concentrated solution in THF, was
added via a syringe and the mixture was stirred at –20 °C for 1 h.
The reaction was quenched with MeOH (0.5 mL) at the same tem-
perature, then allowed to warm to 25 °C. The solvent was removed
under reduced pressure and the residue was purified by column
chromatography using 15% EtOAc in hexanes to afford the pure al-
cohol 7 as a pale yellow oil; yield: 0.40 g (66%, 99% ee).
IR (neat): 3029, 2938, 2864, 1606 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.26–7.24 (m, 5 H), 7.12 (d,
J = 8.3 Hz, 2 H), 6.75 (d, J = 8.3 Hz, 2 H), 5.73–5.49 (m, 2 H), 4.96
(d, J = 6.8 Hz, 1 H), 4.63 (d, J = 6.8 Hz, 1 H), 4.48 (d, J = 6.8 Hz, 1
H), 4.34 (s, 2 H), 3.74 (s, 3 H), 3.41 (t, J = 6.8 Hz, 2 H), 3.30 (s, 3
H), 2.34–2.26 (m, 2 H).
ESMS: m/z = 365 [M + Na]+.
Procedure B: (+)-N-Methylephedrine (0.25 g, 1.41 mmol) and
Zn(OTf)2 (0.51 g, 1.41 mmol) were dried at 120 °C under vacuum,
then flushed with N2 gas for 15 min. To the mixture was added Et3N
(0.2 mL, 1.41 mmol), PMB ether of homopropargyl alcohol 6
(0.26 g, 1.41 mmol), either neat or at very high concentration in tol-
uene, and the resultant mixture was stirred for 2 h. Then benzalde-
hyde 5 (0.1 g, 0.94 mmol) was added dropwise slowly. The reaction
mixture was stirred for 1 h, quenched with aq NH4Cl (10 mL), and
diluted with Et2O (30 mL). The layers were separated and the aque-
ous layer was extracted with Et2O (3 × 10 mL). The combined or-
ganic layers were dried (Na2SO4) and concentrated under vacuum.
The residue was purified by silica gel column chromatography us-
ing 15% EtOAc in hexanes to afford the propargyl alcohol 7; yield:
0.53 g (88%, 90% ee) as a pale yellow oil; [a]D25 +5.3 (c 2.0,
CHCl3).
(1R,2S,3R)-5-[(4-Methoxybenzyl)oxy]-1-(methoxymethoxy)-1-
phenylpentane-2,3-diol (3)
A 50 mL round-bottomed flask, equipped with a magnetic stirrer, is
charged with t-BuOH (6 mL), H2O (6 mL), 1.79 g of AD-mix-b
(1.28 mmol), and MeSO2NH2 (125 mg, 1.17 mmol). The mixture
was stirred at 25 °C until both phases were clear and then cooled to
0 °C, whereupon the inorganic salts partially precipitated. Then ole-
fin 10 (400 mg, 1.17 mmol) was added at once, and the heteroge-
neous slurry was stirred vigorously at 0 °C until TLC revealed the
absence of the starting olefin (10 h). The reaction was quenched at
0 °C by the addition of Na2SO3 (500 mg) and then warmed to 25 °C
and stirred for 30–60 min. The mixture was extracted several times
with CH2Cl2, the combined organic layers were washed with aq 2 N
KOH (5 mL), and dried (MgSO4). Removal of the solvent gave the
crude compound, which on purification by flash chromatography
(silica gel, 50% EtOAc in hexanes) afforded the pure diol 3 as a pale
yellow oil; yield: 0.39 g (90%); [a]D25 –86.0 (c 1.0, CHCl3).
IR (neat): 3418, 3029, 2921, 2864, 2233, 1249, 1093 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.49 (d, J = 7.3 Hz, 2 H), 7.35–
7.27 (m, 3 H), 7.20 (d, J = 8.8 Hz, 2 H), 6.80 (d, J = 8.8 Hz, 2 H),
5.38 (d, J = 5.8 Hz, 1 H), 4.45 (s, 2 H), 3.79 (s, 3 H), 3.55 (t, J = 6.6
Hz, 2 H), 2.55 (dt, J = 6.6, 2.2 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 159.0, 141.0, 129.8, 129.2, 128.3,
128.0, 126.5, 113.7, 83.8, 81.2, 72.4, 67.7, 64.4, 55.1, 20.1.
IR (neat): 3451, 2930, 1611, 1247, 1097 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.35–7.31 (m, 5 H), 7.16 (d,
J = 8.3 Hz, 2 H), 6.81 (d, J = 8.3 Hz, 2 H), 4.67 (d, J = 6.8 Hz, 1 H),
4.53 (ABq, J = 6.8 Hz, 2 H), 4.40 (s, 2 H), 4.41–4.05 (m, 2 H), 3.79
(s, 3 H), 3.60 (t, J = 5.2 Hz, 2 H), 3.54–3.48 (m, 1 H), 3.34 (s, 3 H),
2.99 (d, J = 4.5 Hz, 1 H), 2.47 (d, J = 6.8 Hz, 1 H), 2.00–1.82 (m, 1
H), 1.79–1.67 (m, 1 H).
ESMS: m/z = 319 [M + Na]+.
(1S,2E)-5-[(4-Methoxybenzyl)oxy]-1-phenylpent-2-en-1-ol (4)
To a stirred suspension of LiAlH4 (0.10 g, 2.13 mmol) in THF (5
mL) at 0 °C was added dropwise a solution of compound 7 (0.5 g,
1.77 mmol) in THF (15 mL). The reaction mixture was allowed to
attain 25 °C and stirred for 4 h. It was then cooled to 0 °C, diluted
with Et2O (30 mL), and quenched by dropwise addition of sat. aq
NH4Cl (2 mL). The solid material was filtered and washed thor-
oughly with hot EtOAc for several times. The combined organic
layers were washed with H2O (15 mL) and brine (10 mL), and dried
(Na2SO4). The organic layer was concentrated under reduced pres-
sure and the residue was purified by column chromatography using
15% EtOAc in hexanes to afford compound 4 as a colorless liquid;
yield: 0.45 g (90%); [a]D25 –5.7 (c 1.0, CHCl3).
13C NMR (75 MHz, CDCl3): d = 159.1, 138.8, 130.0, 129.2, 128.3,
128.0, 127.6, 113.7, 94.6, 79.0, 76.0, 72.8, 68.3, 67.4, 55.2, 33.6.
ESMS: m/z = 399 [M + Na]+.
(4R,5R)-4-{2-[(4-Methoxybenzyl)oxy]ethyl}-5-[(R)-(methoxy-
methoxy)(phenyl)methyl]-2,2-dimethyl-1,3-dioxolane (11)
Catalytic amount of CSA was added to a stirred solution of diol 3
(1.1 g, 2.90 mmol) and 2-methoxypropene (0.42 g, 4.40 mmol) in
CH2Cl2 (10 mL) at 0 °C and the reaction mixture was allowed to stir
for 10 min. The mixture was quenched with Et3N (0.2 mL) and the
solvent was removed under vacuum. The crude product was puri-
fied by column chromatography using 5% EtOAc in hexanes to af-
IR (neat): 2928, 2858, 1464, 1104, 1040, 838, 777 cm–1.
Synthesis 2011, No. 5, 821–825 © Thieme Stuttgart · New York

824
G. Sabitha et al.
PAPER
ford the pure product 11 as a colorless oil; yield: 1.20 g (99%);
[a]D25 –63.5 (c 1.0, CHCl3).
IR (neat): 2928, 2846, 1248, 1029 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.31–7.26 (m, 5 H), 7.20 (d,
J = 9.0 Hz, 2 H), 6.81 (d, J = 9.0 Hz, 2 H), 4.64 (d, J = 6.0 Hz, 1 H),
4.50 (s, 2 H), 4.39 (s, 2 H), 4.08 (dt, J = 8.3, 3.0 Hz, 1 H), 3.85 (dt,
J = 7.5, 6.0 Hz, 1 H), 3.79 (s, 3 H), 3.55–3.50 (m, 2 H), 3.30 (s, 3
H), 1.90–1.79 (m, 1 H), 1.75–1.62 (m, 1 H), 1.32 (s, 3 H), 1.26 (s, 3
H).
ESMS: m/z = 373 [M + Na]+.
(6R)-6-[(1R,2R)-1,2-Dihydroxy-2-phenylethyl]-5,6-dihydro-2H-
pyran-2-one [(+)-Goniodiol, 1]
Catalytic amount of PTSA was added to a solution of compound 2
(0.3 g, 0.85 mmol) in EtOH (10 mL). The reaction mixture was
stirred overnight at 50 °C. After completion of the reaction, the mix-
ture was quenched with sat. aq NaHCO3 (0.2 mL), and the solvent
was removed under vacuum. The crude residue was purified to af-
ford the target molecule 1; yield: 0.17 g (84%); [a]D25 +72.8 (c 1.0,
CHCl3).
LCMS: m/z = 439 [M + Na]+.
IR (neat): 3405, 2923, 2853, 1706 cm–1.
2-{(4R,5R)-5-[(R)-(Methoxymethoxy)(phenyl)methyl]-2,2-di-
methyl-1,3-dioxolan-4-yl}ethan-1-ol (12)
1H NMR (400 MHz, CDCl3): d = 7.41–7.33 (m, 5 H), 6.90 (ddd,
J = 9.5, 6.5, 2.2 Hz, 1 H), 5.98 (dd, J = 9.5, 2.9 Hz, 1 H), 4.93 (d,
J = 6.5 Hz, 1 H), 4.74 (td, J = 13.1, 2.9 Hz, 1 H), 3.71–3.66 (m, 1
H), 2.84–2.74 (m, 1 H), 2.39–2.27 (m, 1 H), 2.18–2.09 (m, 1 H),
2.06–1.97 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 163.3, 145.8, 140.0, 128.7, 128.3,
126.5, 120.8, 75.1, 73.8, 29.7.
Catalytic amount of 10% Pd/C was added to a solution of compound
11 (0.6 g, 1.44 mmol) in EtOAc (2 mL) and EtOH (2 mL) and the
mixture was stirred for 6 h at 25 °C under H2 atm. After completion
of the reaction, the reaction mixture was filtered through a Celite
pad and washed with EtOAc (2 × 10 mL). The solvent was removed
under vacuum and the crude product was subjected to flash column
chromatography (eluent: 35% EtOAc in hexanes) to furnish the
pure alcohol 12; yield 0.40 g (96%).
ESMS: m/z = 257 [M + Na]+.
IR (neat): 3446, 2932, 1030, 703 cm–1.
Acknowledgment
1H NMR (300 MHz, CDCl3): d = 7.35–7.28 (m, 5 H), 4.68 (d,
J = 6.0 Hz, 1 H), 4.53 (ABq, J = 6.7 Hz, 2 H), 4.21–4.13 (m, 1 H),
3.89 (dd, J = 7.5, 6.0 Hz, 1 H), 3.71 (t, J = 4.5 Hz, 2 H), 3.34 (s, 3
H), 2.26 (br s, 1 H), 1.72–1.64 (m, 2 H), 1.35 (s, 3 H), 1.34 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 137.6, 128.4, 128.2, 127.8, 109.0,
94.2, 83.5, 77.6, 60.2, 60.1, 56.9, 36.4, 27.3, 26.9.
M.B. thanks CSIR, New Delhi for the award of a fellowship.
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ESMS: m/z = 319 [M + Na]+.
Methyl (Z)-4-{(4R,5R)-5-[(R)-(Methoxymethoxy)(phenyl)meth-
yl]-2,2-dimethyl-1,3-dioxolan-4-yl}but-2-enoate (2)
Dess–Martin periodinane (515 mg, 1.21 mmol) was added to a
stirred solution of primary alcohol 12 (300 mg, 1.01 mmol) and
NaHCO3 (127 mg, 1.52 mmol) in CH2Cl2 (15 mL) at 0 °C and the
reaction mixture was stirred for 30 min. After completion of the re-
action, the mixture was diluted with CH2Cl2 (15 mL). The combined
organic layers were washed with H2O (15 mL), dried (Na2SO4), and
concentrated under reduced pressure. The crude product was sub-
jected to cis-olefination without further purification. Thus, a solu-
tion of bis(trifluoromethanephosphono) acetate (354 mg, 1.11
mmol) in THF (5 mL) was added to a suspension of NaH (29 mg,
1.21 mmol) and a catalytic amount of 18-Crown-6 in THF (5 mL)
at 0 °C. The mixture was stirred for 30 min, then it was cooled to
–78 °C and treated with a solution of crude aldehyde obtained as
above in THF (5 mL). After completion of the reaction, the excess
NaH was quenched by the dropwise addition of aq NH4Cl (10 mL)
and extracted with Et2O (2 × 10 mL). The combined organic layers
were washed with H2O (10 mL), dried (Na2SO4), and concentrated
under vacuum. The residue was purified by column chromatogra-
phy using 5% EtOAc in hexanes to furnish the pure cis-olefin 2;
yield: 0.5 g (82%).
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IR (neat): 2924, 2853, 1722, 1646, 1024, 703 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.33–7.29 (m, 5 H), 6.31 (td,
J = 12.3, 6.8 Hz, 1 H), 5.82 (td, J = 11.3, 2.2 Hz, 1 H), 4.65 (d,
J = 6.0 Hz, 1 H), 4.53 (ABq, J = 6.8 Hz, 2 H), 4.02 (dt, J = 7.5, 3.7
Hz, 1 H), 3.88 (dd, J = 7.5, 6.0 Hz, 1 H), 3.69 (s, 3 H), 3.33 (s, 3 H),
3.03–2.92 (m, 1 H), 2.88–2.77 (m, 1 H), 1.35 (s, 3 H), 1.28 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 166.5, 145.3, 137.6, 128.2, 128.1,
128.0, 120.9, 109.2, 94.2, 82.9, 77.6, 74.4, 55.8, 51.0, 32.8, 27.3,
26.8.
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