Methyl (5R)-5-hydroxy-3-methylidenedecanoate as a promising building block in asymmetric syntheses of bioactive natural compounds

Article abstract of DOI:10.1134/S107042801307004X

Simple and efficient asymmetric syntheses of several lactones with the use of methyl (5R)-5-hydroxy-3-methylidenedecanoate as a polyfunctional building block are described.

Full text of DOI:10.1134/S107042801307004X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 7, pp. 979–985. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © I.V. Mineeva, 2013, published in Zhurnal Organicheskoi Khimii, 2013, Vol. 49, No. 7, pp. 995–1001.
Methyl (5R)-5-Hydroxy-3-Methylidenedecanoate
as a Promising Building Block in Asymmetric Syntheses
of Bioactive Natural Compounds
I. V. Mineeva
Belarusian State University, pr. Nezavisimosti 4, Minsk, 220030 Belarus
e-mail: i.mineyeva@yandex.ru
Received November 17, 2012
Abstract—Simple and efficient asymmetric syntheses of several lactones with the use of methyl (5R)-5-hy-
droxy-3-methylidenedecanoate as a polyfunctional building block are described.
DOI: 10.1134/S107042801307004X
Previously unknown methyl (5R)-5-hydroxy-3-
methylidenedecanoate (I), which is readily available
from methyl-3-(tributylstannylmethyl)but-3-enoate (II)
via asymmetric allylation [1] according to Scheme 1, is
a representative of the β-methylidene-δ-hydroxy car-
boxylic acid ester series. There are only a few data on
the use of the latter in organic synthesis [2]. Examples
are syntheses of (+)-dactylolide [3], isotretinoin [4],
and epothilones Β and D [5]. Stannane II can be
prepared in turn on a gram scale from cyclopropyl
methanesulfonate III according to the procedure devel-
oped previously by our research team [4].
dihydropyranone IV which was reduced at 0°C to
saturated lactone V with high yield and diastereoselec-
tivity (10:1). A convenient procedure was developed
for the two-step transformation of lactone IV into
dyhydropyran X via reduction with LiAlH4 and sub-
sequent cyclization of intermediate diol in the presence
of zinc chloride [12]. Dihydropyran X and structurally
related compounds are often used as intermediate
products in organic synthesis [13, 15].
A sequence of simple transformations including
osonolysis of I, lactonization, and elimination of
hydroxy group afforded (R)-massoia lactone (VI) [16–
22] which is an important component of Cryptocarya
massoia bark oil [23] used in food and perfume
industries [24]. Persistent interest in the synthesis of
massoia lactone (VI) is determined by wide occurrence
of α,β-unsaturated δ-lactones in nature and their
diverse biological activity which is promising from the
viewpoint of medical practice [25–27].
The present study extends the scope of application
of β-methylidene-δ-hydroxy ester I and its structural
analogs in stereoselective syntheses of various lactones
which may be useful, e.g., in the preparation of insect
pheromones and many other natural compounds.
A methodology is also proposed to obtain various
compounds with both retention and removal of the
methylidene fragment in compound Ι and its deriv-
atives.
By addition of a lithium cuprate reagent massoia
lactone (VI) can be converted into compound VII
[28, 29] which is epimeric to lactone V. Unsaturated
lactone VI was oxidized with hydrogen peroxide in
alkaline medium to obtain epoxy derivative VIII
which can be converted into (+)-(3R,5R)-3-hydroxy-
1,5-decanolide (IX) [30] produced by Cephalosporium
(5R)-5-Hydroxy-3-methylidenedecanoate (I) was
converted into lactones IV–IX (Scheme 2) as prom-
ising intermediate products in the synthesis of com-
pounds with more complex structure [6–11]. Treatment
of ester I with sodium carbonate in methanol gave
Scheme 1.
(1) MgBr2, Et2O, CHCl3
(2) Bu3SnCl, Zn, THF, NH4Cl
C5H11CHO, (R)-BINOL
Ti(OPr-i)4, CH2Cl2
O
OMs
O
CH2
OH
CH2
O
SnBu3
MeO
MeO
C5H11
OMe
III
II, 42%
I, 80%
979

MINEEVA
980
Scheme 2.
O
NaBH4, NiCl2·6H2O
H3BO3, THF–H2O
O
O
C5H11
Me
Me
V, 78%
Na2CO3, MeOH
O
C5H11
Me
(1) LiAlH4, Et2O
(2) ZnCl2, ClCH2CH2Cl
O
IV, 94%
C5H11
X, 77%
I
O
MeLi, CuI, (MeO)3P
O
(1) O3, MeOH
(2) NaBH4
O
C5H11
Me
(3) TsOH, CH2Cl2
(4) MsCl, Et3N, CH2Cl2
VII
O
O
O
C5H11
VI, 78%
H2O2, NaOH
MeOH
Ph2Se2, NaBH4
AcOH–i-PrOH
O
O
O
C5H11
VIII, 80%
C5H11
OH
IX
recifei. Structure IX is identical to the lactone fragment
present in mevinolin and compactin and is responsible
for inhibition of cholesterol-induced accumulation of
fat (hypocholesterolemic activity) [31–37].
catalyzed lactonization. The hydroxy group in I was
protected by silylation with tert-butyldimethylsilyl
chloride, and the subsequent ozonolysis of ester XIII
afforded protected keto ester XIV (Scheme 3). Silylat-
ed δ-hydroxy-β-keto esters have found application in
the synthesis of many biologically active compounds,
such as goniothalamin [44], antifungal agent (6S)-5,6-
dihydro-6-[(2R)-2-hydroxy-6-phenylhexyl]-2H-pyran-
2-one [45], parasorbic acid and colletodiol [46],
lactone analogs of compactin and mevinolin [47, 48],
and many others [49, 50].
(R)-δ-Decalactone (XI) (Scheme 3) was found in
cashew apple product from cashew tree, Anacardium
occidentale L., and in Polianthes Tuberosal Amaryl-
lidaceae flowers [36, 38–43]; it is responsible for their
sweet mild fruit odor; it is used as additive in the man-
ufacture of cheese, butter, and other food. (R)-δ-Deca-
lactone (XI) may be prepared in two steps [44] via
reduction of keto lactone XII which was synthesized in
turn in this work by ozonolysis of ester I, followed by
reductive treatment of the reaction mixture and base-
Compound I was also converted into tetrahydro-
pyranyl ether XV (Scheme 4). Ozonolysis of XV,
followed by reductive treatment of the reaction mix-
Scheme 3.
O
O
(1) O3, CH2Cl2
(2) PPh3
(1) AcCl, pyridine, CH2Cl2
(3) Na2CO3, MeOH
(2) H2–Pd/C, EtOAc
O
O
C5H11
O
C5H11
XII, 87%
XI
I
t-BuMe2SiCl, imidazole
CH2Cl2
(1) O3, CH2Cl2
(2) PPh3
OTBS CH2
O
OTBS O
O
C5H11
OMe
C5H11
OMe
XIII, 88%
XIV, 91%
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 7 2013

METHYL (5R)-5-HYDROXY-3-METHYLIDENEDECANOATE
981
Scheme 4.
(1) O3, CH2Cl2
(2) NaBH4, MeOH
PPTS, CH2Cl2
I
+
O
O
O
O
O
O
OH
O
O
C5H11
OMe
C5H11
OMe
O
XV, 89%
XVI, 75%
(1) MsCl, Et3N, CHCl3
(2) PPTS, MeOH
(1) NaBH4, NiCl2·6H2O, H3BO3, MeOH–H2O
(2) TsOH, CH2Cl2
OH
O
O
C5H11
OMe
C5H11
XI, 82%
XVII, 90%
HO
O
O
C5H11
O
C5H11
[51]
[17]
IX
XVII
O
OH
XVIII
ture, gave intermediate hydroxy ester XVΙ which was
subjected to dehydration and deprotection to produce
α,β-unsaturated δ-hydroxy ester XVΙI as a mixture of
E and Z isomers at a ratio of 100:3. δ-Hydroxy ester
XVΙI may be used to prepare verbalactone (XVΙII)
exhibiting a strong antibacterial activity against three
strains of Gram-positive (Staphylococcus aureus,
Staphylococcus epidermidis) and five strains of Gram-
negative bacteria (Salmonella enteritidis) [34, 37].
(+)-(3R,5R)-3-Hydroxy-1,5-decanolide (IX) can also
be obtained from XVII [51]. (R)-δ-Decalactone (XI)
was synthesized by reduction of XVΙI and subsequent
lactonization.
tions were measured on an SM-3 polarimeter (scale
division value 0.05°) at room temperature. Individual
compounds were isolated by chromatography on silica
gel (70–230 mesh). All solvents were dried according
to standard procedures and distilled prior to use.
(6R)-4-Methyl-6-pentyl-5,6-dihydro-2H-pyran-2-
one (IV). Sodium carbonate, 0.8 g (7.5 mmol), was
added at room temperature to a solution of 0.64 g
(3 mmol) of unsaturated hydroxy ester I in 20 ml of
methanol, and the mixture was stirred for 2 h, treated
with water (30 ml), and extracted with diethyl ether
(3×20 ml). The combined extracts were dried over
MgSO4 and evaporated under reduced pressure, and
the residue was subjected to chromatography on silica
gel using petroleum ether–ethyl acetate (20:1) as
eluent. Yield 0.51 g (94%), [α]D = –24.1° (c = 0.4,
To conclude, the results of the present study offered
simple and convenient schemes for the synthesis of
nine natural lactones, including (R)-massoia lactone,
(+)-(3R,5R)-3-hydroxy-1,5-decanolide, (R)-δ-decalac-
tone, and verbalactone, starting from a single com-
pound, readily accessible methyl (5R)-5-hydroxy-3-
methylidenedecanoate (I).
1
CHCl3). IR spectrum, ν, cm–1: 1729, 1246. H NMR
spectrum, δ, ppm: 0.83 t (3H, CH3CH2, J = 7.2 Hz),
1.20–1.49 m [6H, CH3(CH2)3CH2], 1.52–1.61 m and
1.68–1.76 m (1H each, 6-CH2), 1.92 s (3H, 4-CH3),
2.14 d.d (1H, 5-H, J = 17.9, 4.1 Hz), 2.26 d.d (1H,
5-H, J = 17.9, 10.5 Hz), 4.27–4.34 m (1H, 6-H),
5.73 br.s (1H, 3-H). 13C NMR spectrum, δC, ppm: 13.9
(CH3), 22.5 (CH3), 22.9 (CH2), 24.5 (CH2), 31.5 (CH2),
34.7 (CH2), 34.8 (CH2), 77.3 (CH), 116.5 (CH), 157.0
(C3), 165.4 (C2). Found, %: C 72.51; H 9.91. C11H18O2.
Calculated, %: C 72.49; H 9.95.
EXPERIMENTAL
1
The H and 13C NMR spectra were recorded from
solutions in chloroform-d on a Bruker AC 400 spec-
trometer at 400 and 100 MHz, respectively. The IR
spectra were measured from solutions in carbon tetra-
chloride on a Bruker Vertex 70 spectrometer. The
melting points were determined in capillaries on
an Apotec melting point apparatus. The optical rota-
(4S,6R)-4-Methyl-6-pentyltetrahydro-2H-pyran-
2-one (V). Lactone IV, 0.46 g (2.5 mmol), was
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 7 2013

MINEEVA
982
dispersed in a mixture of 12 ml of THF and 12 ml of
water, the resulting emulsion was cooled to 0°C, 0.65 g
(2.8 mmol) of NiCl2·6H2O and 0.59 g (10 mmol) of
H3BO3 were added, and 0.21 g (5.5 mmol) of NaBH4
was added in portions under stirring over a period of
15 min (foaming!). The mixture was stirred for 1 h on
cooling, 5 g of sodium chloride was added at room
temperature, and the mixture was extracted with
diethyl ether (3×10 ml). The extracts were combined
and dried over Na2SO4, the solvent was distilled off
under reduced pressure, and the product was isolated
by chromatography on silica gel using petroleum
ether–ethyl acetate (25:1) as eluent. Yield 0.45 g
(98%), [α]D = –42.3° (c = 1.4, CHCl3). IR spectrum, ν,
Na2SO4, the solvent was removed under reduced pres-
sure, and the residue was subjected to chromatography
using petroleum ether–ethyl acetate (20:1) as eluent.
Yield 0.61 g (78%). The spectral parameters and
optical rotation of the product were consistent with
those given in [21].
(3R,4R,6R)-3,4-Epoxy-6-pentyltetrahydro-2H-
pyran-2-one (VIII). Unsaturated lactone VI, 0.34 g
(2 mmol), was dissolved in 15 ml of methanol, 0.7 ml
(6.7 mmol) of 30% aqueous hydrogen peroxide and
0.2 ml (1.2 mmol) of a 6 M aqueous solution of
sodium hydroxide were added at room temperature,
and the mixture was stirred for 30 min, diluted with
30 ml of water, and extracted with diethyl ether (3×
10 ml), The extracts were combined and dried over
MgSO4, the solvent was distilled off under reduced
pressure, and the residue was subjected to chromatog-
raphy on silica gel using petroleum ether–ethyl acetate
(15:1) as eluent. Yield 0.29 g (80%), [α]D = +81.0°
(c = 0.9, CHCl3). IR spectrum, ν, cm–1: 1737, 1265,
1
cm–1: 1742, 1458, 1379, 1238, 1097. H NMR spec-
trum, δ, ppm: 0.84 t (3H, CH3CH2, J = 7.2 Hz), 0.99 d
(3H, 4-CH3, J = 6.1 Hz), 1.11–1.20 m (1H, 4-H), 1.20–
1.48 m [6H, CH3(CH2)3], 1.49–1.58 m and 1.60–
1.70 m (1H each, 6-CH2), 1.84–1.90 m (1H, 5-H),
1.94–2.03 m (2H, 3-H, 5-H), 2.59–2.67 m (1H, 3-H),
13
1
4.20–4.26 m (1H, 6-H). C NMR spectrum, δC, ppm:
1034, 1016. H NMR spectrum, δ, ppm: 0.88 t (3H,
13.9 (CH3), 21.5 (CH3), 22.4 (CH2), 24.7 (CH2), 26.6
(CH), 31.6 (CH2), 35.9 (CH2), 36.8 (CH2), 38.0 (CH2),
80.5 (CH), 171.56 (C=O). Found, %: C 71.74;
H 10.91. C11H20O2. Calculated, %: C 71.70; H 10.94.
CH3CH2, J = 6.9 Hz), 1.19–1.78 m [6H, CH3(CH2)3],
2.16–2.37 m (4H, 5-H, 6-CH2), 3.45 s and 3.72 s (1H
each, 3-H, 4-H), 4.26–4.34 m (1H, 6-H). 13C NMR
spectrum, δC, ppm: 14.1 (CH3), 22.7 (CH2), 24.8
(CH2), 31.9 (CH2), 36.6 (CH2), 37.6 (CH2), 57.6 (CH),
58.5 (CH), 73.9 (CH), 166.9 (C=O). Found, %:
C 65.23; H 8.70. C10H16O3. Calculated, %: C 65.19;
H 8.75.
(6R)-6-Pentyl-5,6-dihydro-2H-pyran-2-one (VI,
massoia lactone). A solution of 1 g (4.7 mmol) of
ester I in 25 ml of methanol was cooled to –78°C,
an ozone–oxygen mixture was passed through the
solution over a period of 1 h until the mixture turned
persistently blue, and oxygen was then passed to
remove excess ozone. Sodium tetrahydridoborate,
0.90 g (23.5 mmol), was added in portions under vig-
orous stirring, and the mixture was allowed to warm up
to room temperature, treated with a saturated aqueous
solution of ammonium chloride (50 ml), and extracted
with methylene chloride (3×35 ml). The combined
extracts were washed with a saturated aqueous solution
of sodium hydrogen carbonate (50 ml) and dried over
MgSO4, the solvent was distilled off under reduced
pressure, the residue was dissolved in 15 ml of methy-
lene chloride, and 0.1 g (0.6 mmol) of p-toluenesul-
fonic acid dihydrate was added at room temperature.
After 12 h, 2 ml (14.4 mmol) of triethylamine and
0.3 ml (4.5 mmol) of methanesulfonyl chloride in 1 ml
of methylene chloride were added, and the mixture
was stirred for 2 h and treated with a saturated aqueous
solution of sodium hydrogen carbonate (25 ml). The
organic phase was separated, the aqueous phase was
extracted with chloroform (3 ×10 ml), the extracts
were combined with the organic phase and dried over
(2R)-4-Methyl-2-pentyl-3,6-dihydro-2H-pyran
(X). A solution of 2.55 g (14 mmol) of unsaturated
lactone IV in 30 ml of anhydrous diethyl ether was
added under stirring at 0°C to a suspension of 0.26 g
(7 mmol) of LiAlH4 in 15 ml of anhydrous diethyl
ether, and the mixture was stirred for 1 h at that tem-
perature. The mixture was treated with 5% sulfuric
acid (10 ml), the organic phase was separated, the
aqueous phase was extracted with diethyl ether (3×
15 ml), the extracts were combined with the organic
phase and dried over MgSO4, the solvent was removed
under reduced pressure, the residue was dissolved in
50 ml of dichloroethane, 2.24 g (16.8 mmol) of
calcined zinc(II) chloride was added to the solution,
and the mixture was heated for 2 h under reflux. The
mixture was then treated with a saturated aqueous
solution of NaHCO3 (100 ml), the organic phase was
separated, the aqueous phase was extracted with
methylene chloride (3×20 ml), the extracts were com-
bined with the organic phase and dried over MgSO4,
the solvent was removed under reduced pressure, and
the product was isolated by chromatography on silica
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METHYL (5R)-5-HYDROXY-3-METHYLIDENEDECANOATE
983
gel using petroleum ether–ethyl acetate (100:1) as
eluent. Yield 1.81 g (77%), [α]D = –12.0° (c = 1.9,
CHCl3). IR spectrum, ν, cm–1: 1466, 1381, 1140, 1113.
1H NMR spectrum, δ, ppm: 0.87 t (3H, CH3CH2, J =
6.9 Hz), 1.23–1.33 m (5H) and 1.40–1.47 m (2H)
[CH3(CH2)4], 1.52–1.60 m (1H, 6-CH2), 1.68 s (3H,
4-CH3), 1.78–1.84 m and 1.88–1.97 m (1H each, 5-H),
3.40–3.46 m (1H, 6-H), 4.12 br.s (2H, 2-H), 5.40 br.s
phase was separated, the aqueous phase was extracted
with methylene chloride (3×5 ml), the extracts were
combined with the organic phase and dried over
MgSO4, the solvent was distilled off under reduced
pressure, and the residue was subjected to chromatog-
raphy using petroleum ether–ethyl acetate (80:1) as
eluent. Yield 0.58 g (88%), [α]D = –40.0° (c = 0.9,
CHCl3). IR spectrum, ν, cm–1: 1743, 1258, 1158, 1094.
1H NMR spectrum, δ, ppm: 0.02 s and 0.04 s (3H each,
Me2Si), 0.86–0.92 m (12H, t-BuSi, CH3CH2), 1.22–
1.45 m [6H, CH3(CH2)3], 2.24–2.27 m (2H, 3-CH2),
3.07 d and 3.12 d (1H each, 2-H, J = 15.1 Hz),
3.68 br.s (3H, CH3O), 3.74–3.82 m (1H, 2′-H),
4.95 br.s (2H, CH2=). 13C NMR spectrum, δC, ppm:
–4.5 (SiCH3), 14.0 (CH3), 18.1 (C), 22.6 (CH2), 24.9
(CH2), 25.9 [(CH3)3C], 32.0 (CH2), 36.8 (CH2), 42.1
(CH2), 43.6 (CH2), 51.7 (OCH3), 71.0 (CH), 116.5
(C4), 139.7 (C3), 171.9 (C=O). Found, %: C 65.84;
H 11.01. C18H36O3Si. Calculated, %: C 65.80; H 11.04.
13
(1H, 3-H). C NMR spectrum, δC, ppm: 14.06 (CH3),
22.60 (CH2), 22.99 (CH3), 25.44 (CH2), 31.81 (CH2),
35.93 (CH2), 35.97 (CH2), 65.88 (CH2), 73.78 (C6),
119.73 (C3), 131.84 (C4). Found, %: C 78.55; H 11.94.
C11H20O. Calculated, %: C 78.51; H 11.98.
(6R)-6-Pentyltetrahydro-2H-pyran-2,4-dione
(XII). A solution of 0.86 g (4 mmol) of compound I in
25 ml of methylene chloride was cooled to –78°C,
an ozone–oxygen mixture was passed through the
solution over a period of 1 h until it turned persistently
blue, and oxygen was then passed to remove excess
ozone. Triphenylphosphine, 1.05 g (8.9 mmol), was
added in portions under vigorous stirring, and the mix-
ture was allowed to warm up to room temperature over
a period of 3 h. The solvent was removed under
reduced pressure, the residue was dissolved in 25 ml of
methanol, 1.07 g (10.0 mmol) of sodium carbonate
was added to the solution, and the mixture was stirred
for 8 h, treated with water (50 ml), and extracted with
chloroform (3×20 ml). The combined extracts were
dried over MgSO4, the solvent was distilled off under
reduced pressure, and the product was isolated by
chromatography on silica gel using petroleum ether–
ethyl acetate (3:1) as eluent. Yield 0.64 g (87%),
mp 86–88°C, [α]D = –42.0° (c = 0.9, CHCl3). IR spec-
Methyl (5R)-5-[tert-butyl(dimethyl)silyloxy]-3-
oxodecanoate (XIV) was synthesized as described
above for compound XII. Yield 91%, [α]D = +4.0° (c =
1.4, CHCl3). IR spectrum, ν, cm–1: 1753, 1720, 1255,
1
1072. H NMR spectrum, δ, ppm: 0.02 s and 0.06 s
(3H each, Me2Si), 0.86 br.s (9H, t-BuSi), 0.88 t (3H,
CH3CH2, J = 6.6 Hz), 1.22–1.34 m (6H, CH3(CH2)3],
1.41–1.49 m (2H, 6-H), 2.59 d.d (1H, 4-H, J = 15.2,
4.9 Hz), 2.69 d.d (1H, 4-H, J = 15.2, 6.9 Hz), 3.47 d
and 3.51 d (1H each, 2-H, J = 15.7 Hz), 3.73 br.s (3H,
CH3O), 4.13–4.20 m (1H, 5-H). 13C NMR spectrum,
δC, ppm: –4.6 (Me2Si), 14.1 (CH3), 18.5 (C), 22.6
(CH2), 26.1 [(CH3)3C], 27.3 (CH2), 30.9 (CH2), 37.5
(CH2), 49.1 (CH2), 51.4 (CH2), 52.3 (OCH3), 66.8
(CH), 167.4 (C=O), 171.9 (C=O). Found, %: C 61.80;
H 10.33. C17H34O4Si. Calculated, %: C 61.77; H 10.37.
1
trum, ν cm–1: 1740, 1730, 1264. H NMR spectrum, δ,
ppm: 0.90 t (3H, CH3, J = 6.9 Hz), 1.25–1.50 m [6H,
CH3(CH2)3], 1.65–1.73 m and 1.79–1.88 m (1H each,
6-CH2), 2.47 d.d (1H, 5-H, J = 18.2, 11.4 Hz), 2.71 d.d
(1H, 5-H, J = 18.2, 2.6 Hz), 3.43 d and 3.57 d (1H
each, 3-H, J = 18.9 Hz), 4.59–4.66 m (1H, 6-H).
13C NMR spectrum, δC, ppm: 13.9 (CH3), 22.5 (CH2),
24.4 (CH2), 31.3 (CH2), 34.5 (CH2), 43.5 (CH2), 47.0
(CH2), 75.6 (C6), 170.4 (C2), 200.3 (C4). Found, %:
C 65.24; H 8.66. C10H16O3. Calculated, %: C 65.19;
H 8.75.
Methyl 3-[(2R)-2-(tetrahydro-2H-pyran-2-yl-
oxy)heptyl]but-3-enoate (XV). Ester I, 0.64 g
(3 mmol), was dissolved in 4 ml of anhydrous methy-
lene chloride, 0.32 g (3.7 mmol) of dihydropyran and
a catalytic amount of pyridinium p-toluenesulfonate
(PPTS) were added, and the mixture was kept for 12 h
at room temperature. The mixture was washed with
a saturated aqueous solution of NaHCO3 (100 ml) and
dried over MgSO4, the solvent was removed under
reduced pressure, and the residue was subjected to
chromatography using petroleum ether–ethyl acetate
(100:1) as eluent. Yield 0.80 g (89%). IR spectrum, ν,
Methyl 3-{(2R)-2-[tert-butyl(dimethyl)silyloxy]-
heptyl}but-3-enoate (XIII). Ester I, 0.43 g (2 mmol),
was dissolved in 10 ml of anhydrous methylene
chloride, 0.3 g (3.5 mmol) of imidazole and 0.45 g
(3 mmol) of tert-butyl(chloro)dimethylsilane were
added, and the mixture was stirred for 12 h. The
mixture was treated with water (30 ml), the organic
1
cm–1: 1741, 1165, 1024. H NMR spectrum, δ, ppm:
0.86 t and 0.87 t (1.5H each, CH3CH2, J = 6.9 Hz),
1.22–1.36 m (6H, CH2, pyran), 1.41–1.66 m [6H,
CH3(CH2)3], 1.67–1.89 m (2H, 3′-H), 2.29–2.31 m and
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MINEEVA
984
2.36–2.41 m (1H each, 1′-H), 3.05–3.22 m (2H, 2-H),
3.68 br.s (3H, CH3O), 3.73–3.79 m (1H, OCH2), 3.83–
3.93 m (2H, OCH2, 2′-H), 4.63–4.67 m (1H, OCHO),
4.93–5.00 m (2H, =CH2). 13C NMR spectrum, δC,
ppm: 14.03, 14.05, 19.7, 19.8, 22.6, 24.7, 25.3, 25.4,
25.5, 25.9, 30.7, 31.0, 31.9, 32.0, 33.3, 35.0, 40.2,
41.5, 41.8, 42.0, 51.7, 51.8, 62.6, 62.9, 75.0, 76.7,
94.6, 96.1, 116.3, 116.6, 139.6, 140.0, 171.9, 172.1.
Found, %: C 68.46; H 10.09. C17H30O4. Calculated, %:
C 68.42; H 10.13.
by chromatography using petroleum ether–ethyl
acetate (45:1) as eluent. Yield 0.67 g (90%), [α]D =
–5.4° (c = 2.3, CHCl3). IR spectrum, ν, cm–1: 3440,
1
1726, 1326, 1272, 1170, 1126, 1042. H NMR spec-
trum, δ, ppm: 0.88 t (3H, CH3CH2, J = 6.9 Hz), 1.25–
1.49 m [8H, CH3(CH2)4], 1.61 br.s (1H, OH), 2.28–
2.44 m (2H, 4-H), 3.71–3.76 m (1H, 5-H), 3.73 br.s
(3H, CH3O), 5.90 d (1H, 2-H, J = 15.8 Hz), 6.99 d.d.d
13
(1H, 3-H, J = 15.8, 7.9, 7.9 Hz). C NMR spectrum,
δC, ppm: 14.0 (CH3), 22.6 (CH2), 25.3 (CH2), 31.7
(CH2), 37.1 (CH2), 40.2 (CH2), 51.5 (CH3), 70.6 (CH),
123.4 (CH), 145.6 (CH), 166.7 (C=O). Found, %:
C 66.01; H 10.03. C11H20O3. Calculated, %: C 65.97;
H 10.07.
Methyl (3R,5R)-3-hydroxy-5-(tetrahydro-2H-
pyran-2-yloxy)decanoate (XVI). A solution of 1.49 g
(5 mmol) of ester XV in 25 ml of methanol was cooled
to –78°C, an ozone–oxygen mixture was passed there-
through over a period of 1 h (until persistent blue
color), and oxygen was then passed to remove excess
ozone. Sodium tetrahydridoborate, 0.58 g (15 mmol),
was added in portions under vigorous stirring, and the
mixture was allowed to warm up to room temperature,
treated with a saturated solution of ammonium chlo-
ride (50 ml), and extracted with methylene chloride
(3×25 ml). The combined extracts were dried over
MgSO4, the solvent was removed under reduced pres-
sure, and the residue was purified by chromatography
using petroleum ether–ethyl acetate (25:1) as eluent.
Yield 1.13 g (75%). IR spectrum, ν, cm–1: 3462, 1739,
(6R)-6-Pentyltetrahydro-2H-pyran-2-one (XI).
An emulsion of 0.2 g (1 mmol) of unsaturated ester
XVII in a mixture of 2.5 ml of methanol and 2.5 ml of
water was cooled to 0°C, 0.26 g (1.1 mmol) of
NiCl2 ·6H2O and 0.12 g (2 mmol) of H3BO3 were
added, and 0.08 g (2.2 mmol) of NaBH4 was then
added in portions over a period of 5 min under stirring.
The mixture was stirred for 0.5 h on cooling, 1 g of
sodium chloride was added at room temperature, and
the mixture was extracted with diethyl ether (4×5 ml).
The combined extracts were dried over Na2SO4, the
solvent was distilled off under reduced pressure, the
residue was dissolved in 4 ml of methylene chloride,
50 mg (0.3 mmol) of p-toluenesulfonic acid dihydrate
was added, and the mixture was stirred for 12 h (until
the reaction was complete). A few drops of triethyl-
amine were added, the mixture was evaporated, and
the residue was subjected to chromatography using
petroleum ether–ethyl acetate (25:1) as eluent. Yield
0.14 g (82%). The spectral parameters and optical
rotation of the product were in agreement with those
given in [35].
1
1200, 1165, 1076, 1024. H NMR spectrum, δ, ppm:
0.80–0.84 m (3H, CH3CH2), 1.17–1.35 m (16H, CH2),
2.25–2.51 m (2H, 2-H), 3.36–3.45 m (1H, OCH2),
3.73–3.91 m (2H, OCH2, 5-H), 3.63 br.s and 3.64 br.s
(1.5H each, CH3O), 4.04–4.32 m (2H, 3-H, OH), 4.51–
4.53 m and 4.62–4.66 m (0.5H each, OCHO). Found,
%: C 63.60; H 9.97. C16H30O5. Calculated, %: C 63.55;
H 10.00.
Methyl (2E,5R)-5-hydroxydec-2-enoate (XVII).
A solution of 1.13 g (3.7 mmol) of hydroxy ester XVI
in 25 ml of anhydrous chloroform was cooled to 0°C,
1.1 ml (9.5 mmol) of triethylamine and 0.4 ml
(5.5 mmol) of methanesulfonyl chloride in 3 ml of
chloroform were added under stirring, and the mixture
was stirred for 2 h and treated with a saturated aqueous
solution of NaHCO3 (25 ml). The organic phase was
separated, the aqueous phase was extracted with
chloroform (3×15 ml), the extracts were combined
with the organic phase and dried over MgSO4, and the
solvent was distilled off under reduced pressure. The
residue was dissolved in 25 ml of methanol, 0.1 g
(0.4 mmol) of PPTS was added, and the mixture was
heated for 1 h under reflux. A few drops of triethyl-
amine were then added, the solvent was removed
under reduced pressure, and the residue was purified
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