A simple and efficient synthesis of enantiomeric (3aRS,4RS,6aSR)-4-hydroxy- 3,3a,4,6a-tetrahydro-1H-cyclopenta[c]furan-1-ones

Article abstract of DOI:10.1016/j.tet.2012.05.036

Diastereomeric amides produced via the cleavage of easily available (±)-7,7-dichloro-4-exo-trimethylsilylbicyclo[3.2.0]hept-2-en-6-one by treatment with (+)-α-methylbenzylamine were transformed into bicyclic lactam-aminals, which can easily be separated by column chromatography on SiO₂. The latter products lead to enantiomeric (3a,6a)-4-hydroxy-3, 3a,4,6a-tetrahydro-1H-cyclopenta[c]furan-1-ones after the removal of the chiral auxiliary and epoxidation.

Full text of DOI:10.1016/j.tet.2012.05.036

Tetrahedron 68 (2012) 5754e5758
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A simple and efficient synthesis of enantiomeric (3aRS,4RS,6aSR)-4-hydroxy-
3,3a,4,6a-tetrahydro-1H-cyclopenta[c]furan-1-ones
,
a
b
a
Airat M. Gimazetdinov a , Salavat S. Gataullin , Ivan S. Bushmarinov , Mansur S. Miftakhov
*
a Institute of Organic Chemistry of Ufa Research Centre, Russian Academy of Sciences, Prospect Oktyabrya 71, 450054 Ufa, Russian Federation
b A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilova Str., 28, 119991 Moscow, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
Diastereomeric amides produced via the cleavage of easily available (ꢀ)-7,7-dichloro-4-exo-trime-
-methylbenzylamine were transformed
into bicyclic lactam-aminals, which can easily be separated by column chromatography on SiO2. The
latter products lead to enantiomeric (3a,6a)-4-hydroxy-3,3a,4,6a-tetrahydro-1H-cyclopenta[c]furan-1-
ones after the removal of the chiral auxiliary and epoxidation.
Received 29 February 2012
Received in revised form 23 April 2012
Accepted 8 May 2012
thylsilylbicyclo[3.2.0]hept-2-en-6-one by treatment with (þ)-
a
Available online 14 May 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
(þ)-
Chiral auxiliary
-Lactones
a-Methylbenzylamine
g
Cyclopentene block-synthons
Optical resolution
1. Introduction
O
O
In the synthesis of natural and unnatural biologically active
cyclopentanoids, the preparation of chiral orthogonally function-
alized cyclopentane (cyclopentene) block-synthons is important.1
They are required in the synthesis of monocyclic cyclopentanoids
O
O
(prostaglandins,2
carbanucleosides,3
pheromones,4
cyclo-
HO
(3aS,4S,6aR)-1
HO
(3aR,4R,6aS)-1
pentenone antibiotics5) as well as in approaches to the more
complex bi- and polycyclic compounds containing a fragment of
the cyclopentane ring (Brefeldin A,6 Hitachimycin,7 Didemenones,8
Hybridalactone,9 Retigeranic Acid,10 Quadrone,11 Ginkgolide12).
Fig. 1. Target hydroxylactones (3aR,4R,6aS)-1 and (3aS,4S,6aR)-1.
In this paper, we describe the synthesis of new enantiomeric g-
lactones (3aR,4R,6aS)-1 and (3aS,4S,6aR)-1, which may find various
applications in approaches to a variety of the cyclopentanoids
(Fig. 1).
dichlorocyclobutane ring of 2 by treatment with (þ)-
a-methyl-
benzylamine gave an inseparable mixture of diastereomers 3 and
4. Hydrolysis of the gem-dichloromethyl group in 3 and 4 gave
bicyclic aminals 5 and 6, which were easily separated by column
chromatography on SiO2 (Scheme 1). Each of these bicyclic acetals
was stereochemically pure and did not contain any C3-epimer.
Compounds 5 and 6 were characterized as the less hindered exo-
epimers. Thus, in the 1H NMR spectrum a doublet resonance for
the 3-H at 1.82 ppm appeared with J3,3a¼4.0 Hz, which is char-
acteristic for 5.
2. Results and discussion
As a basic starting compound in the synthesis of compounds 1,
an easily available racemic bicyclic adduct 2 was selected.13 Op-
tical resolution of 2 was carried out using (þ)-
amine by the method previously described by us14 for the
analogue of without the TMS-group. cleavage of the
a-methylbenzyl-
The individual aminals 5 and 6 were transformed into lactones
915 by the consecutive operations of the borohydride reduction and
acidic hydrolysis of amides 7 and 8.
2
A
Treatment of compounds 9 with m-CPBA gave the unstable
endo-epoxides 10. The epoxidation in this case proceeds
* Corresponding author. E-mail address: gimazetdinov@anrb.ru (A.M.
Gimazetdinov).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.05.036

A.M. Gimazetdinov et al. / Tetrahedron 68 (2012) 5754e5758
5755
SiMe3
Me3Si
O
b
a
Ph
+
Cl
H2N
2
Cl
Me3Si
O
O
Me3Si
c
N
Ph
N
H
Ph
b
c
H
+
CHCl2
CHCl2
3
4
Fig. 2. The general view of molecule (3aR,6R,6aS)-9 in crystal. Atoms are represented
by thermal displacement ellipsoids (p¼50%).
Me3Si
Me3Si
O
O
3. Conclusion
N
N
3a
3a
3
3
Ph
Ph
+
We have developed
a convenient route to enantiomeric
H
H
5
OH
d
OH
hydroxylactones (3aR,4R,6aS)-1 and (3aS,4S,6aR)-1 from a common
source. Prepared compounds may find applications as key building
blocks in the design and synthesis of a wide range of biologically
active cyclopentanoids.
6
d
O
Me3Si
O
Me3Si
N
Ph
N
Ph
H
H
4. Experimental
4.1. General
CH2OH
CH2OH
8
7
a) Cl2CHCOCl, NEt3, hexane, 0 0C, 5 h, 70%; b) benzene, rt, 4 h, 92%; c) MeCN:H2O, 4:1,
reflux, 8 h, 93%; d) NaBH4, dioxane:H2O, 5:1, reflux, 5 h, 91-92%.
Solvents were purified and dried by standard procedures before
use. Reagents were generally of the best quality commercial grade
and used without further purification unless otherwise indicated.
All reactions were carried out in oven-dried glassware. Dichlor-
oacetyl chloride was prepared as described in the literature.16
Cyclopentadiene was obtained by thermal cracking of dicyclo-
pentadiene. Trimethylsilylcyclopentadiene was prepared as de-
scribed in the literature.17 TLC was performed using Sorbfil STC-1A
Scheme 1. Optical resolution of (ꢀ)-7,7-dichloro-4-exo-trimethylsilylbicyclo[3.2.0]
hept-2-en-6-one 2..
stereoselectively, due to steric factor.13 Finally, removal of the TMS-
group by the fragmentation of endo-epoxides 10 led to targets
hydroxylactones (3aR,4R,6aS)-1 and (3aS,4S,6aR)-1 (Scheme 2).
The stereochemistry of the stereogenic centers of compounds
(3aR,4R,6aS)-1 and (3aS,4S,6aR)-1 and their precursors was
assigned based on X-ray data for lactone (3aR,6R,6aS)-9. The
structure of (3aR,6R,6aS)-9 was determined by single-crystal XRD
study (see Experimental). The values of Flack parameter of
ꢁ0.07(13) and Hooft parameter of ꢁ0.02(11) identified the absolute
configuration as (3aR,6R,6aS) (Fig. 2).
110 mm layer, silica gel 5-17 precoated foil plates. Column chro-
matography was conducted using 210e280 mesh silica gel. Optical
rotations were measured using the sodium D line at 589 nm on
a PerkineElmer, Model 241MC polarimeter at 20 ꢂC. IR (infrared
spectra) were recorded on a Shimadzu IRPrestige-21 spectrometer
as Nujol mull or as neat thin films on KBr plates (film) and were
reported in reciprocal centimeters (cmꢁ1). 1H and 13C NMR spectra
were obtained using a Bruker AM-300 (300 MHz for 1H and
O
Me3Si
Me3Si
O
O
a
b
c
O
O
O
7
8
O
HO
(3aR,6R,6aS)-9
Me3Si
(1aS,1bR,4aS,5S,5aS)-10
(3aR,4R,6aS)-1
O
Me3Si
O
O
c
a
b
O
O
O
O
HO
(3aS,4S,6aR)-1
(3aS,6S,6aR)-9
(1aR,1bS,4aR,5R,5aR)-10
a) 9N H2SO4:dioxane, 1:5, reflux, 4 h, 89%;b) m-CPBA, NaHCO3, CH2Cl2, from 0 0C to rt, 8h;
c) 9N H2SO4:THF, 1:5, rt, 2 h, 87% (two steps).
Scheme 2. Synthesis of target hydroxylactones 1.

5756
A.M. Gimazetdinov et al. / Tetrahedron 68 (2012) 5754e5758
75.47 MHz for 13C) as solutions in CDCl3 (Aldrich Chemical Com-
pany; spectra grade). Chemical shifts are reported in unitdparts
NaHCO3 (0.75 g, 11.5 mmol) in H2O (5 mL). After being stirred
at room temperature for 0.5 h, the reaction solution was
refluxed for 7.5 h, monitored by TLC (1:3 ethyl acetate/petro-
leum ether), cooled to room temperature, and concentrated
under vacuum. The residue was diluted with water (15 mL) and
extracted with 3ꢃ20 mL ethyl acetate. The combined ethyl
acetate extracts were washed with saturated brine, dried over
anhydrous sodium sulfate, and concentrated under vacuum.
Purification of the products by column chromatography (1:3
d
per million (ppm) downfield from tetramethyl silane (TMS) as the
internal reference. Splitting patterns are designated as s, singlet; br
s, broad singlet; d, doublet, t, triplet; q, quartet; quint., quintet.
Mass spectra were recorded on Shimadzu LCMS QP-2010EV (APCI)
spectrometer. Elemental analyses were carried on an Euro EA 3000
CHNS-analyzer. Melting points were recorded on a Mel-Temp
apparatus.
ethyl acetate/petroleum ether) afforded
5 (0.6 g, 47%) as
4.2. General protocol for ( )-7,7-dichloro-4-exo-
a white crystalline solid and 6 (0.59 g, 46%) as a yellow crys-
trimethylsilylbicyclo[3.2.0]-hept-2-en-6-ones 2
talline solid.
To a flame-dried, nitrogen-purged flask were added hexane
(150 mL), trimethylsilylcyclopentadiene (10.3 g, 0.075 mol) and
dichloroacetyl chloride (15 g, 0.1 mol). Triethylamine (10.2 g,
0.1 mol) in hexane (100 mL) was added via syringe at 0 ꢂC in a pe-
riod of 1.5 h and allowed to stir for 3 h at the same temperature. The
triethylammonium hydrochloride salt was removed by filtration
through a short pad of Celite and washed with hexane (2ꢃ50 mL).
The combined filtrates were concentrated under reduced pressure
and the residue was purified by distillation to furnish 2 (13.1 g, 70%)
as a yellow oil, bp 71e73 ꢂC/0.3 mmHg (lit.13 71e73 ꢂC/0.3 mmHg).
Found: C, 48.19; H, 5.51; Cl, 28.49. C10H14 Cl2OSi requires C, 48.19; H,
4.4.1. (3aR,6R,6aS)-3S-Hydroxy-2-[(1R)-phenylethyl]-6-(trime-
thylsilyl)-3,3a,6,6a-tetrahydrocyclopenta[c]pyrrol-1(2H)-one
(5). Mp¼116e118 ꢂC. Found: C, 68.43; H, 7.77; N, 4.32. C18H25NO2Si
requires C, 68.57; H, 7.93; N, 4.44%; Rf (ethyl acetate/petroleum
ether¼1:3) 0.4; [
a
]
D
20 ꢁ54.6 (c 1.3, CH2Cl2); nmax (Nujol mull) 3250,
2929, 2852, 1651, 1454, 1330, 1274, 1251, 1058, 837, 700 cmꢁ1
;
dH
(300 MHz, CDCl3/TMS) 7.23e7.45 (5H, m, Ph), 5.73e5.77 (1H, m,
CH]CHCHSi(CH3)3), 5.41e5.46 (1H, m, CH]CHCHSi(CH3)3), 5.35
(1H, q, J 7.1 Hz, CHPh), 5.08 (1H, d, J 4.0 Hz, CHOH), 3.04e3.07 (2H,
br s, CHCHOH, CHC]O), 2.36e2.39 (1H, br s, CHSi(CH3)3), 1.82 (1H,
d, J 4.0 Hz, OH), 1.50 (3H, d, J 7.1 Hz, CH3), 0.0 (9H, s, Si(CH3)3); dC
(75 MHz, CDCl3/CHCl3) 177.7, 141.3, 135.2, 128.9, 127.9, 127.3, 124.6,
84.5, 53.3, 50.0, 45.0, 38.8, 16.9, ꢁ3.3; m/z (APCI) 316 (69, MHþ), 298
(100), 194 (27%).
5.62; Cl, 28.63%; nmax (liquid film) 1805, 1674, 1568 cmꢁ1
; dH
(300 MHz, CDCl3/TMS) 5.97e6.00 (1H, m, CH]CHCHSi(CH3)3),
5.63e5.66 (1H, m, CH]CHCHSi(CH3)3), 4.06e4.09 (1H, m,
CHCHCl2), 3.96e3.99 (1H, m, CHC]O), 2.45e2.47 (1H, m,
CHSi(CH3)3), 0.01 (9H, s, Si(CH3)3); dC (75 MHz, CDCl3/CHCl3): 197.8,
139.0, 124.5, 88.7, 60.1, 59.7, 34.7, ꢁ3.5; m/z (APCI) 249 (100, MHþ,
35Cl), 177 (68), 149 (13.3%).
4.4.2. (3aS,6S,6aR)-3R-Hydroxy-2-[(1R)-phenylethyl]-6-(trime-
thylsilyl)-3,3a,6,6a-tetrahydrocyclopenta[c]pyrrol-1(2H)-one
(6). Mp¼134e136 ꢂC. Found: C, 68.31; H, 7.75; N, 4.25. C18H25NO2Si
requires C, 68.57; H, 7.93; N, 4.44%; Rf (ethyl acetate/petroleum
20
4.3. General protocol for 2-(dichloromethyl)-N-[(1R)-1-
phenylethyl]-5-(trimethylsilyl)-cyclopent-3-ene-1-
carboxamides 3 and 4
ether¼1:3) 0.3; [
a
]
ꢁ0.1 (c 1.01, CH2Cl2); nmax (Nujol mull) 3265,
D
2925, 2852, 1649, 1444, 1377, 1271, 1247, 1053, 835, 698 cmꢁ1
; dH
(300 MHz, CDCl3/TMS) 7.23e7.35 (5H, m, Ph), 5.73e5.77 (1H, m,
CH]CHCHSi(CH3)3), 5.37 (1H, q, J 6.9 Hz, CHPh), 5.25e5.30 (1H, m,
CH]CHCHSi(CH3)3), 4.66e4.69 (1H, br s, CHOH), 3.22e3.27 (1H, br
s, OH), 3.05e3.15 (2H, m, CHCHOH, CHC]O), 2.39e2.81 (1H, br s,
CHSi(CH3)3), 1.69 (3H, d, J 7.1 Hz, CH3), 0.04 (9H, s, Si(CH3)3); dC
(75 MHz, CDCl3/CHCl3) 177.6, 140.0, 132.3, 128.4, 127.4, 125.5, 124.7,
85.2, 54.2, 50.0, 44.9, 38.8, 18.7, ꢁ3.3; m/z (APCI) 316 (65, MHþ), 298
(100), 194 (33%).
To a stirred solution of (2.0 g, 8 mmol) 2 in benzene (40 mL) at
room temperature under nitrogen was added dropwise a solution
(þ)-a-methylbenzylamine (ee 99.9%, Aldrich) (1.09 g, 9 mmol) in
benzene (10 mL). The reaction was monitored by TLC (1:5 ethyl
acetate/petroleum ether) and after stirring 4 h at room tempera-
ture the solution was concentrated under reduced pressure, and the
residue was diluted with CH2Cl2 (50 mL) and washed with water,
5% aqueous solution HCl, water and brine, then dried over MgSO4.
Removal of the solvent under reduced pressure afforded an in-
separable 1:1 mixture of the title compounds 3 and 4 (2.73 g, 92%) as
a yellow solid, mp 126e132. Found: C, 58.24; H, 6.62; N, 3.64; Cl,
18.91. C18H25Cl2NOSi requires C, 58.38; H, 6.76; N, 3.78; Cl,19.11%; Rf
(ethyl acetate/petroleum ether¼1:5) 0.7; nmax (Nujol mull) 3332,
4.5. General protocol for (1S,2R,5R)-2-(hydroxymethyl)-N-
[(1R)-1-phenylethyl]-5-(trimethylsilyl)-cyclopent-3-ene-1-
carboxamide 7
To a suspension of sodium borohydride (0.61 g, 16 mmol) in
a water/dioxane mixture (4 mL/20 mL) was added a solution of 5
(1.0 g, 3.2 mmol) in 3 mL of dioxane. The mixture was heated un-
der refluxed for 5 h and monitored by TLC (1:1 ethyl acetate/pe-
troleum ether). The excess hydride was decomposed by the
successive addition of 1 mL of water, 1.5 mL of 15% sodium hy-
droxide, and 3 mL of water; the suspension was filtered. The fil-
trate was extracted with 3ꢃ10 mL methylene chloride. The
combined methylene chloride extracts were washed with satu-
rated brine, dried over anhydrous sodium sulfate, and concen-
trated under vacuum. Purification of the product by column
chromatography (1:1 ethyl acetate/petroleum ether) afforded the
2956, 2852, 1635, 1527, 1249, 840, 756, 698 cmꢁ1
;
dH (300 MHz,
CDCl3/TMS) 7.28e7.41 (5H, m, Ph), 6.20 (0.5H, d, J 9.5 Hz, CHCl2),
6.16 (0.5H, d, 9.3 Hz, CHCl2), 5.89e5.97 (1H, m, CH]
J
CHCHSi(CH3)3), 5.63e5.83 (2H, m, CH]CHCHSi(CH3)3 and NH),
5.13 (1H, quint., J 6.8 Hz, CHPh), 3.48e3.69 (1H, m, CHCHCl2),
2.93e2.99 (1H, m, CHC]O), 2.23e2.35 (1H, m, CHSi(CH3)3), 1.51
(3H, d, J 6.9 Hz, CH3), 0.03e0.08 (9H, m, Si(CH3)3); dC (75 MHz,
CDCl3/CHCl3) 171.9, 143.0, 142.5, 135.3, 129.0, 127.5, 127.4, 126.5,
126.1, 125.9, 125.8, 74.3, 74.1, 61.5, 61.3, 48.9, 48.7, 41.9, 21.3, 21.0,
ꢁ3.1, ꢁ1.9; m/z (APCI) 370 (100, MHþ, 35Cl). Anal. Calcd for
C18H25Cl2NOSi: C, 58.38; H, 6.76; N, 3.78; Cl, 19.11. Found: C, 58.24;
H, 6.62; N, 3.64; Cl, 18.91.
title compound
7 (0.93 g, 92%) as a white crystalline solid,
mp¼107e109 ꢂC. Found: C, 68.03; H, 8.42; N, 4.28. C18H27NO2Si
requires C, 68.14; H, 8.52; N, 4.42%; Rf (ethyl acetate/petroleum
4.4. General protocol for aminals 5 and 6
ether¼1:1) 0.3; [
a
]
20 ꢁ77.8 (c 1.39, CH2Cl2); nmax (Nujol mull) 3292,
D
2955, 2852, 1629, 1525, 1458, 1377, 1247, 1036, 867, 839, 698 cmꢁ1
;
To a stirred solution of 1:1 mixture 3 and 4 (1.5 g, 4 mmol)
in CH3CN (20 mL) at room temperature was added a solution
dH (300 MHz, CDCl3/TMS) 7.19e7.31 (5H, m, Ph), 6.46 (1H, d, J
7.8 Hz, NH), 5.78 (1H, d, J 5.8 Hz, CH]CHCHSi(CH3)3), 5.37e5.44

A.M. Gimazetdinov et al. / Tetrahedron 68 (2012) 5754e5758
5757
(1H, m, CH]CHCHSi(CH3)3), 5.11 (1H, quint., J 6.9 Hz, CHPh),
3.38e3.48 (3H, m, CH2OH), 2.96e3.02 (1H, m, CHCH2OH), 2.9 (1H,
dd, J 7.3, 9.3 Hz, CHC]O), 2.29e2.35 (1H, m, CHSi(CH3)3), 1.47 (3H,
d, J 6.8 Hz, CH3), ꢁ0.1 (9H, s, Si(CH3)3); dC (75 MHz, CDCl3/CHCl3)
174.4, 142.8, 133.3, 128.5, 127.4, 127.3, 126.3, 62.9, 52.6, 49.6, 49.0,
38.9, 21.4, ꢁ3.2; m/z (APCI) 318 (100, MHþ), 300 (27.4), 229 (12.5),
214 (15.7), 197 (61.2%).
ether¼1:5) 0.5; [
a
]
20 þ174.5 (c 1.3, CH2Cl2); nmax (Nujol mull) 3048,
D
2955, 2862, 1755, 1462, 1377, 1251, 1168, 1053, 981, 960, 839,
717 cmꢁ1
; dH (300 MHz, CDCl3/TMS) 5.75e5.84 (1H, m, CH]
CHCHSi(CH3)3), 5.43e5.48 (1H, m, CH]CHCHSi(CH3)3), 4.35 (1H,
ddd, J 4.2, 7.0, 9.0 Hz, CHaHbOC]O), 4.20 (1H, dd, J 3.9, 9.0 Hz,
CHaHbOC]O), 3.44 (1H, t, J 6.9 Hz, CHCH]CH), 2.85 (1H, dd, J 4.1,
8.0 Hz, CHC]O), 2.35e2.40 (1H, br s, CHSi(CH3)3), ꢁ0.01 (s, 9H,
Si(CH3)3); dC (75 MHz, CDCl3/CHCl3) 181.5, 134.9, 126.5, 71.9, 46.6,
43.7, 39.9, ꢁ3.4; m/z (APCI) 197 (MHþ).
4.6. General protocol for (1R,2S,5S)-2-(hydroxymethyl)-N-
[(1R)-1-phenylethyl]-5-(trimethylsilyl)-cyclopent-3-ene-1-
carboxamide 8
4.9. General protocol for (1aS,1bR,4aS,5S,5aS)-10 and
(3aR,4R,6aS)-1
Compound 6 (1.5 g, 4.8 mmol), treated with sodium borohy-
dride as described in the synthesis of 7, afforded the title compound
8 (1.39 g, 91%) as a white crystalline solid, mp¼159e161 ꢂC. Found:
A solution of 1.04 g (6.0 mmol) of m-chloroperoxybenzoic acid
and 0.51 g (6.0 mmol) of NaHCO3 in 10 mL of methylene chloride
was added to a solution of 0.4 g (2.0 mmol) of lactone (3aR,6-
R,6aS)-9 in 10 mL of methylene chloride at 0 ꢂC. After being stir-
red at 0 ꢂC for 2 h, the reaction solution was heated to room
temperature and stirred for 6 h, monitored by TLC (1:1 ethyl ac-
etate/petroleum ether). To a solution was then added 15 mL of
a saturated solution of Na2S2O3 and the mixture stirred for 1 h.
Organic layer was separated and washed with 15 mL of 5%
aqueous solution of NaHCO3. Aqueous layer was extracted with
3ꢃ15 mL methylene chloride, the combined organic extracts dried
over MgSO4 and evaporated under reduced pressure. To the re-
ceived low stable epoxide (1aS,1bR,4aS,5S,5aS)-10 without puri-
fication were added 15 mL tetrahydrofuran, 3 mL 9 N solution of
H2SO4 and the mixture was stirred 2 h at room temperature. The
residue was diluted with water (10 mL) and extracted with
3ꢃ15 mL ethyl acetate. The combined organic extracts were
washed with saturated brine, dried over anhydrous sodium sul-
fate, and concentrated under vacuum. Purification of the products
by column chromatography (3:1 ethyl acetate/petroleum ether)
afforded (3aR,4R,6aS)-1 (0.24 g, 87%) as a transparent viscous oily
liquid.
C, 67.93; H, 8.33; N, 4.35. C18H27NO2Si requires C, 68.14; H, 8.52; N,
20
4.42%; Rf (ethyl acetate/petroleum ether¼1:1) 0.3; [
a
]
D
þ183.5 (c
1.24, CH2Cl2); nmax (Nujol mull) 3263, 2951, 2852, 1637, 1546,
1455, 1377, 1247, 1056, 839, 696 cmꢁ1
dH (300 MHz, CDCl3/
TMS) 7.19e7.30 (5H, m, Ph), 6.22 (1H, d, J 6.4 Hz, NH), 5.75 (1H,
d, 5.5 Hz, CH]CHCHSi(CH3)3), 5.35e5.39 (1H, m, CH]
CHCHSi(CH3)3), 5.10 (1H, quint., J 7.1 Hz, CHPh), 3.50 (1H, dd, J 2.8,
12.1 Hz, CHaHbOH), 3.40 (1H, dd, 5.2, 12.3 Hz, CHaHbOH),
;
J
J
3.10e3.25 (1H, br s, OH), 2.81e2.97 (2H, m, J 9.3 Hz, CHC]O,
CHCH2OH), 2.28e2.33 (1H, m, CHSi(CH3)3), 1.43 (3H, d, J 6.9 Hz,
CH3), ꢁ0.06 (9H, s, Si(CH3)3); dC (75 MHz, CDCl3/CHCl3) 174.5, 142.8,
133.2, 128.4, 127.6, 127.5, 126.2, 62.9, 52.6, 49.9, 48.9, 39.1, 21.2,
ꢁ3.1; m/z (APCI) 318 (100, MHþ), 300 (29.2), 229 (13.8), 214 (14.5),
197 (65.7%).
4.7. General protocol for (3aR,6R,6aS)-9
To a stirred solution of 7 (0.5 g, 1.6 mmol) in dioxane (15 mL) at
room temperature was added a 9 N solution of H2SO4 (3 mL). The
mixture was heated under refluxed for 4 h and monitored by TLC
(1:5 ethyl acetate/petroleum ether), cooled to room temperature,
and concentrated under vacuum. The residue was diluted with
water (5 mL) and extracted with 3ꢃ15 mL ethyl acetate. The com-
bined organic extracts were washed with saturated brine, dried
over anhydrous sodium sulfate, and concentrated under vacuum.
Purification of the products by column chromatography (1:5 ethyl
acetate/petroleum ether) afforded (3aR,6R,6aS)-9 (0.28 g, 89%) as
a white crystalline solid.
4.9.1. (1aS,1bR,4aS,5S,5aS)-5-(Trimethylsilyl)-hexahydro-4H-oxireno
[3,4]-cyclopenta[1,2-c]furan-4-one ((1aS,1bR,4aS,5S,5aS)-10). Viscous
oily liquid; Rf (ethyl acetate/petroleum ether¼3:1) 0.7; dH
(300 MHz, CDCl3/TMS) 4.57 (1H, d, J 9.4 Hz, CHaHbOC]O), 4.43
(1H, dd,
CHOCHCHSi(CH3)3), 3.52 (1H, d, J 2.4 Hz, CHOCHCHSi(CH3)3),
2.70e2.82 (2H, m, 9.6 Hz, CHCH2O, CHC]O), 2.13 (1H, s,
J 6.5, 9.4 Hz, CHaHbOC]O), 3.65 (1H, t, J 2.1 Hz,
J
CHSi(CH3)3), 0.11 (s, 9H, Si(CH3)3); dC (75 MHz, CDCl3/CHCl3) 176.7,
70.1, 68.2, 61.1, 42.5, 40.4, 31.9, ꢁ2.6.
4.7.1. (3aR,6R,6aS)-6-(Trimethylsilyl)-3,3a,6,6a-[3.3.0]oct-6-en-2-
one ((3aR,6R,6aS)-9). Mp¼65e67 ꢂC. Found: C, 61.03; H, 8.10.
C10H16O2Si requires C, 61.22; H, 8.16%; Rf (ethyl acetate/petroleum
4.9.2. (3aR,4R,6aS)-4-Hydroxy-3,3a,4,6a-tetrahydro-1H-cyclopenta
[c]furan-1-one ((3aR,4R,6aS)-1). Found: C, 59.85; H, 5.54. C7H8O3
20
ether¼1:5) 0.5; [
a
]
ꢁ175.1 (c 1.36, CH2Cl2); nmax (Nujol mull)
D
3045, 2954, 2862, 1751, 1447, 1379, 1249, 1145, 1051, 987, 958, 835,
requires C, 59.99; H, 5.75%; Rf (ethyl acetate/petroleum ether¼3:1)
20
715 cmꢁ1
;
dH (300 MHz, CDCl3/TMS) 5.77e5.84 (1H, m, CH]
0.3; [
a
]
þ163.1 (c 1.095, CH2Cl2); nmax (liquid film) 3423, 2976,
D
CHCHSi(CH3)3), 5.44e5.49 (1H, m, CH]CHCHSi(CH3)3), 4.36 (1H,
ddd, J 4.4, 7.1, 9.1 Hz, CHaHbOC]O), 4.19 (1H, dd, J 3.8, 9.2 Hz,
CHaHbOC]O), 3.45 (1H, t, J 6.9 Hz, CHCH]CH), 2.87 (1H, dd, J 4.2,
8.0 Hz, CHC]O), 2.37e2.41 (1H, br s, CHSi(CH3)3), 0.0 (s, 9H,
Si(CH3)3); dC (75 MHz, CDCl3/CHCl3) 181.5, 134.9, 126.5, 71.9, 46.5,
43.7, 39.9, ꢁ3.4; m/z (APCI) 197 (MHþ).
2920, 1759, 1479, 1381, 1188, 1109, 1018, 952 cmꢁ1
; dH (300 MHz,
CDCl3/TMS) 5.91e5.96 (2H, br s, CH]CH), 5.03 (1H, d, J 7.5 Hz,
CHOH), 4.65 (1H, dd, J 5.2, 9.6 Hz, CHaHbOC]O), 4.36 (1H, t, J 9.4 Hz,
CHaHbOC]O), 3.62 (1H, d, J 8.5 Hz, CHC]O), 3.29 (1H, qd, J 5.8,
8.2 Hz, CHCH]CH), 1.91e2.09 (1H, br s, OH); dC (75 MHz, CDCl3/
CHCl3) 177.0, 136.3, 129.2, 67.0, 66.9, 51.2, 41.0; m/z (APCI) 141 (100,
MHþ), 111 (19.6), 83 (13.1%).
4.8. General protocol for (3aS,6S,6aR)-9
4.10. General protocol for (1aR,1bS,4aR,5R,5aR)-10 and
(3aS,4S,6aR)-1
Compound 8 (0.6 g, 1.9 mmol), treated as described in the syn-
thesis of (3aR,6R,6aS)-9, afforded (3aS,6S,6aR)-9 (0.31 g, 89%) as
a white crystalline solid.
Compound (3aS,6S,6aR)-9 (0.6 g, 3.0 mmol), treated as de-
scribed in the synthesis of (1aS,1bR,4aS,5S,5aS)-10 and (3aR,4-
R,6aS)-1, afforded epoxide (1aR,1bS,4aR,5R,5aR)-10 and then
hydroxylactone (3aS,4S,6aR)-1 (0.36 g, 87%) as a transparent vis-
cous oily liquid.
4.8.1. (3aS,6S,6aR)-6-(Trimethylsilyl)-3,3a,6,6a-[3.3.0]oct-6-en-2-
one ((3aS,6S,6aR)-9). Mp¼65e67 ꢂC. Found: C, 61.08; H, 8.02.
C10H16O2Si requires C, 61.22; H, 8.16%; Rf (ethyl acetate/petroleum

5758
A.M. Gimazetdinov et al. / Tetrahedron 68 (2012) 5754e5758
4.10.1. (1aR,1bS,4aR,5R,5aR)-5-(Trimethylsilyl)-hexahydro-4H-oxireno
[3,4]-cyclopenta[1,2-c]furan-4-one ((1aR,1bS,4aR,5R,5aR)-10). Viscous
oily liquid; Rf (ethyl acetate/petroleum ether¼3:1) 0.7; dH
(300 MHz, CDCl3/TMS) 4.54 (1H, d, J 9.4 Hz, CHaHbOC]O), 4.40
Acknowledgements
This study was performed under financial support by the Min-
istry of Education and Science of the Russian Federation (state
contract No14.740.11.0367)
(1H, dd,
J 6.6, 9.6 Hz, CHaHbOC]O), 3.64 (1H, t, J 2.2 Hz,
CHOCHCHSi(CH3)3), 3.50 (1H, d, J 2.8 Hz, CHOCHCHSi(CH3)3),
2.70e2.82 (2H, m, J 8.9 Hz, CHCH2O, CHC]O), 2.09 (1H, s,
CHSi(CH3)3), 0.09 (s, 9H, Si(CH3)3); dC (75 MHz, CDCl3/CHCl3) 176.5,
70.0, 68.1, 61.0, 42.2, 40.4, 32.6, ꢁ2.8.
References and notes
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4.10.2. (3aS,4S,6aR)-4-Hydroxy-3,3a,4,6a-tetrahydro-1H-cyclopenta
[c]furan-1-one ((3aS,4S,6aR)-1). Found: C, 59.82; H, 5.61. C7H8O3
requires C, 59.99; H, 5.75%; Rf (ethyl acetate/petroleum
20
ether¼3:1) 0.3; [
a
]
ꢁ162.5 (c 1.08, CH2Cl2); nmax (liquid film)
D
3423, 2976, 2920, 1759, 1477, 1379, 1186, 1097, 1020, 960 cmꢁ1
; dH
(300 MHz, CDCl3/TMS) 5.91e5.96 (2H, br s, CH]CH), 5.02 (1H, d, J
7.5 Hz, CHOH), 4.62 (1H, dd, J 5.3, 9.7 Hz, CHaHbOC]O), 4.38 (1H,
t, J 9.1 Hz, CHaHbOC]O), 3.61 (1H, d, J 8.5 Hz, CHC]O), 3.29 (1H,
qd, J 5.5, 8.8 Hz, CHCH]CH), 2.20e2.33 (1H, br s, OH); dC (75 MHz,
CDCl3/CHCl3) 176.8, 136.3, 129.2, 67.0, 66.9, 51.2, 41.0; m/z (APCI)
141 (100, MHþ), 111 (21.4), 83 (17.9%).
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4.11. X-ray crystallographic analysis of (3aR,6R,6aS)-9
Single crystals of C10H16O2Si ((3aR,6R,6aS)-9) were grown
from mixture petroleum ether/ethyl acetate. A suitable crystal
was selected and studied on a Bruker SMART 1000 diffractom-
eter. The crystal was kept at 120 K during data collection. Using
Olex2,18 the structure was solved with the XS19 structure solution
program using Direct Methods and refined with the XL20 re-
finement package using Least Squares minimization.
9. Corey, E. J.; De, B. J. Am. Chem. Soc. 1984, 106, 2735.
10. Hudlicky, T.; Fleming, A.; Radesca, L. J. Am. Chem. Soc. 1989, 111, 6691.
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12. Corey, E. J.; Kang, M.-C.; Desai, M. C.; Ghosh, A. K.; Houpis, I. N. J. Am. Chem. Soc.
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13. Fleming, I.; Au-Yeung, B.-W. Tetrahedron 1981, 37, 13.
14. Gimazetdinov, A. M.; Vostrikov, N. S.; Miftakhov, M. S. Tetrahedron: Asymmetry.
4.11.1. Crystal data for (3aR,6R,6aS)-9. C10H16O2Si, M¼196.32, or-
ꢀ
ꢀ
ꢀ
thorhombic, a¼8.175(3) A, b¼10.280(4) A, c¼26.455(8) A, V¼2223.2
2008, 19, 1094.
3
ꢀ
15. Synthesis of racemic mixture of 10 and 11: Au-Yeung, B.-W.; Wang, Y. J. Chem.
Soc., Chem. Commun. 1985, 825.
16. Dahlberg, J. A.; Myrin, L. M. Ann. Occup. Hyg. 1971, 14, 269.
17. Kraihanzel, C. S.; Losee, M. L. J. Am. Chem. Soc. 1968, 90, 4701.
18. Dolomanov, O. V.; Bourhis, L. J.; Gildea, R. J.; Howard, J. A. K.; Puschmann, H. J.
Appl. Crystallogr. 2009, 42, 339.
(13) A , T¼120 K, space group P212121 (no.19), Z¼8,
m
(Mo K
a
)¼0.180,
16,634 reflections measured, 5524 unique (Rint¼0.0997), which
were used in all calculations. The final wR2 was 0.0860 (all data) and
R1 was 0.0474 (>2s(I)). CCDC 865270 contains the supplementary
crystallographic data for this paper. These data can be obtained free
of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
19. Sheldrick, G. M. SHELXS-97, Program for refinement of Crystal Structure. Uni-
€
versity of Gottingen: Germany, 1997.
20. Sheldrick, G. M. Acta Crystallogr. 2008, A64, 112.