Organo-catalyzed enantioselective synthesis of some β-silyl γ-alkyl γ-butyrolactones as intermediates for natural products

Article abstract of DOI:10.1016/j.tetasy.2011.10.013

The enantioselective synthesis of some β-silyl γ-alkyl γ-butyrolactones has been achieved by an organo-catalyzed Michael addition of enolizable aldehydes onto a silylmethylene malonate followed by a silicon-facilitated Bayer-Villiger oxidation of the β-silyl aldehyde adducts as the key step. γ-Alkyl γ-butenolides were obtained from the β-silyl γ-alkyl γ-butyrolactones by Fleming-Tamao oxidation of the silyl group to a hydroxy group and subsequent elimination. These butenolides are the advanced intermediates of some natural products such as (+)-γ-caprolactone, (+)-methylenolactocine, and (-)-quercus lactone.

Full text of DOI:10.1016/j.tetasy.2011.10.013

Tetrahedron: Asymmetry 22 (2011) 1895–1900
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Tetrahedron: Asymmetry
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Organo-catalyzed enantioselective synthesis of some b-silyl c-alkyl
c-butyrolactones as intermediates for natural products
⇑
Raghunath Chowdhury, Sunil K. Ghosh
Bio-Organic Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The enantioselective synthesis of some b-silyl
c-alkyl c-butyrolactones has been achieved by an
Received 6 October 2011
Accepted 26 October 2011
Available online 16 November 2011
organo-catalyzed Michael addition of enolizable aldehydes onto a silylmethylene malonate followed by
a silicon-facilitated Bayer–Villiger oxidation of the b-silyl aldehyde adducts as the key step. -Alkyl
-butenolides were obtained from the b-silyl -alkyl -butyrolactones by Fleming–Tamao oxidation of
the silyl group to a hydroxy group and subsequent elimination. These butenolides are the advanced inter-
c
c
c
c
mediates of some natural products such as (+)-
lactone.
c-caprolactone, (+)-methylenolactocine, and (ꢀ)-quercus
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
(Scheme 1).27–29 Herein, we report enantioselective syntheses of
some b-silyl -alkyl -butyrolactones via an organo-catalyzed
Michael addition of enolizable aldehydes onto silylmethylene
c
c
Chiral c-substituted c-butyrolactones are abundant in nature.
They are also valuable intermediates for the synthesis of a large
variety of molecules containing acyclic and cyclic systems includ-
ing antibiotics, pheromones, plant growth regulators, antifungal
agents, and flavor components.1–3 A few interesting examples, such
malonate 10 and their conversion to c-alkyl c-butenolides via a
silicon-facilitated30 Bayer–Villiger oxidation and Fleming–Tamao
oxidation31,32 as the key steps.
as avenaciolide 1, c-dodecanolactone 2, c-caprolactone 3, protoli-
chesterinic acid 4, methylenolactocine 5, rocellaric acid 6, quercus
2. Results and discussion
lactone 7, and blastmycinone 8 are shown in Figure 1. b-Hydroxy
We have recently established that the direct Michael addition of
enolizable aldehydes to dimethyl(phenyl)silylmethylene malonate
10 could be catalyzed by (S)-diphenylprolinol trimethylsilyl ether
17/acetic acid combination.27 The optimized conditions required
1 equiv of silylmethylene malonate 10, 10 equiv of an aldehyde, a
combination of 15 mol % each of (S)-diphenylprolinol trimethyl-
silyl ether 17 and acetic acid as the catalyst system and dichloro-
methane as the solvent at room temperature for 4 days. Thus,
under these optimized n-butanal, n-hexanal and n-heptanal condi-
tions gave b-silyl aldehyde adducts 11a, 11b, and 11c in very good
yield, diastereoselectivity, and enantioselectivity (Scheme 2).
The diastereoisomeric mixture of aldehydes 11a–c was
subjected to a b-silicon-facilitated Bayer–Villiger oxidation using
3-chloroperoxybenzoic acid in dichloromethane, resulting in an
inseparable mixture of diastereoisomeric formates 18a–c in very
good yield (Scheme 3). In each case, the isomeric formate mixture
was then hydrolyzed with KOH in methanol and the resulting
hydroxy dicarboxylic acid upon heating at 100 °C underwent
decarboxylation and concomitant lactonization leading directly
to the desired major lactones 19a–c in very good yield after
chromatographic purification. The minor diastereoisomeric prod-
uct also was eliminated during this purification step. The
dimethyl(phenyl)silyl group in 19a–c was then converted into a
c
-alkyl
additional features in addition to their occurrences as natural
product such as 8. They can easily be converted into -substituted
-butenolides 9,4,5 well known intermediates for functionalized
butyrolactone and other molecule syntheses.4–9
The syntheses of chiral -substituted -butyrolactones and
c-butyrolactones are a class of molecules, which have
c
c
c
c
butenolides have been an ongoing challenge for synthetic
chemists. Although a large number of methods for the preparation
of optically active
c
c-alkyl c-butyrolactones and c-substituted
-butenolides have been reported in the literature,10–25 substrate
generality, stereochemical purities, and high yields are yet to be
achieved. Recently, we have reported a highly enantioselective
organocatalytic Michael addition of enolizable aldehydes and
methyl ketones to a silylmethylene malonate 1026 leading to
highly functionalized b-silyl aldehydes 1127 and b-silyl ketones
12 (Scheme 1).28,29 These adducts can be easily transformed into
medium-sized rings leading to skeletal and stereochemical
diversities of complex structures, patterned after d-valerolactones
of types 13 and 14, piperidines 15, and pyrrolidines 16
⇑
Corresponding author. Tel.: +91 22 25595012; fax: +91 22 25505151.
E-mail address: ghsunil@barc.gov.in (S.K. Ghosh).
0957-4166/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2011.10.013

1896
R. Chowdhury, S. K. Ghosh / Tetrahedron: Asymmetry 22 (2011) 1895–1900
O
HOOC
O
H
O
O
H
n-C8H17
O
O
n-C13H27
R
O
O
1
R = n-C8H17; 2
R = n-C13H27; 4
3
5
R = C5H11;
R = C2H5;
O
O
Bu-i
HOOC
Me
C4H9-n
O
O
O
O
O
O
Me
n-C13H27
R
n-Bu
O
O
6
7
8
9
Figure 1. Some c-substituted butyrolactones.
OH
R2
SiMe2Ph
R1
R
R
N
O
O
R1
16
O
O
steps
steps
steps
O
SiMe2Ph
O
SiMe2Ph
13
R
PhMe2Si
CO2Et
CO2Et
R
Me
H
CO2Et
CO2Et
steps
R
R
H
Organo-
catalyst
Organo-
catalyst
SiMe2Ph
OH
CO2Et
R
CO2Et
12
10
11
OH
N
R1
R
O
14
O
15
Scheme 1. Application of aldehyde and ketone adducts of 10 in heterocycle synthesis.
Ph
Ph
OTMS
N
H
17
SiMe2Ph
O
PhMe2Si
CO2Et
CO2Et
(15 mol%)
O
CO2Et
+
H
R
AcOH (15 mol%)
CH2Cl2, 28 οC
4 days
H
R
CO2Et
10
11
Product
% yield
79
dr
% ee of major
isomer
R = -C2H5; 11a
86/14
98
R = -C4H9; 11b
R = -C5H11; 11c
73
75
84/16
81/19
>99
98
Scheme 2. The addition of unmodified aldehydes to silylmethylene malonate 10.
hydroxy group following Fleming–Tamao31,32 oxidation using
potassium bromide and peracetic acid with retention of configura-
tion, leading to hydroxy lactones 20a–c. Butenolides 9a–c were
then prepared from these hydroxy lactones 20a–c by the treatment
with MsCl and NEt3 at 0 °C.6
the alkyl group in 9a was also assigned from the 1H and 13C chem-
ical shift values, and comparing the specific rotation value
{½a 2D8
ꢁ
¼ ꢀ92 (c 1.46, MeOH); lit.33
½
a 2D0
ꢁ
¼ ꢀ94 (c 1.05, CH2Cl2)}.
(ꢀ)-Quercus lactone 7 has been obtained using butenolide 9b as
the key intermediate.4 The absolute configuration of 9b was con-
firmed by comparing the physical and spectroscopic data with
Butenolides 9a–c are well known intermediates for the synthe-
sis of many naturally occurring
lide 9a has already been converted33 into the natural product,
(+)- -caprolactone 3 (Scheme 4). The absolute configuration of
c
-lactones. For example, buteno-
the literature values {½a D28
ꢁ
¼ ꢀ101:9 (c 2.16, CHCl3); lit.34
½
a 2D5
ꢁ
¼ ꢀ101 (c 1.2, CHCl3)}. The natural product (+)-methylenolac-
c
tocine 5 has been synthesized from the butenolide 9c in three steps

R. Chowdhury, S. K. Ghosh / Tetrahedron: Asymmetry 22 (2011) 1895–1900
1897
1. KOH,H2O-MeOH
O
2.H3O+
O
SiMe2Ph
CO2Et
m-CPBA
CH2Cl2
SiMe2Ph
CO2Et
3.100 οC
H
O
H
R
CO2Et
R
CO2Et
R = -C2H5; 11a
11b
R = -C2H5; 18a 76%
R = -C4H9; 18b 74%
R = -C5H11; 18c 72%
R = -C4H9;
R = -C5H11; 11c
HO
PhMe2Si
MsCl, Et3N
KBr, AcOOH
O
R
O
O
R
O
O
R
O
20a 60%
20b 58%
9a 75%
R = -C2H5;
R = -C2H5;
R = -C2H5; 19a 65%
9b 77%
R = -C4H9;
R = -C5H11
R = -C4H9;
R = -C5H11
R = -C4H9; 19b 60%
R = -C5H11; 19c 64%
20c 62%
; 9c 76%
;
Scheme 3. Preparation of chiral c-alkyl butenolides.
Ref. 12
literature.35 Diphenylprolinol was commercially available and its
TMS-ether 17 was prepared according to the literature.36
O
O
O
C2H5
C2H5
O
O
O
Solvent removal was carried out using a rotary evaporator con-
nected to a dry ice condenser. TLC (0.5 mm) was carried out using
home made silica plates with a fluorescence indicator. Column
chromatography was performed on silica gel (230–400 mesh). 1H
and 13C NMR spectra were recorded in a 200 MHz (1H: 200 MHz,
13C: 50 MHz) or 500 MHz (1H: 500 MHz, 13C: 125 MHz) or
700 MHz (1H: 700 MHz, 13C: 175 MHz) spectrometers. 1H and 13C
shifts are given in ppm, d scale and are measured relative to inter-
nal CHCl3 and CDCl3 as standards, respectively. Chemical shifts are
reported in ppm (d); multiplicities are indicated by s (singlet), d
(doublet), t (triplet), q (quartet), quint (pentet), m (multiplet) and
br (broad). Coupling constants, J, are reported in Hertz. High reso-
lution mass spectra were recorded at 60–70 eV on a Waters Micro-
mass Q-TOF spectrometer (ESI, Ar). Optical rotations were
measured in a JASCO DIP 360 polarimeter. Infrared spectra (IR)
were recorded on a JASCO FT IR spectrophotometer in NaCl cells
or in KBr disks. Peaks are reported in cmꢀ1. Enantiomeric excess
(ee) determinations were carried out by HPLC instrument fitted
with a chiralpak AD–H/OD–H column and UV detector with k fixed
at 254 nm.
9a
9b
(+)-caprolactone 3
Ref.4
C4H9
O
C4H9
O
(-)-quercus lactone 7
HO2C
Ref. 5
O
C5H11
O
O
C5H11
O
9c
Scheme 4. Formal synthesis of some
(+)-methyleno lactocine 5
c
-butyrolactone natural products.
(Scheme 4).5 The absolute configuration of 9c was also confirmed
by comparing the 1H and 13C chemical shift values as well as the
specific rotation value {½a D28
ꢁ
¼ ꢀ93 (c 2.53, CHCl3); lit.5
½
a 2D5
ꢁ
¼ ꢀ90:1 (c 1.76, CHCl3)}.
4.1. Michael addition of aldehydes to 10 using organocatalyst 17
and AcOH additive
3. Conclusion
In conclusion, we have achieved the enantioselective synthesis
of some b-silyl -alkyl -butyrolactones via an organo-catalyzed
Michael addition of enolizable aldehydes onto a silylmethylene
malonate and their conversion into -alkyl -butenolides, potent
intermediates for -alkyl -butyrolactones natural products, via a
silicon-facilitated Bayer–Villiger oxidation and Fleming–Tamao
oxidation as the key steps. These -alkyl -butenolides are the ad-
vanced intermediates of some natural products, such as (+)- -cap-
General procedure I: The respective aldehyde (5 mmol, 10 equiv)
was added to a stirred mixture of silylmethylene malonate 10
(153 mg, 0.5 mmol, 1 equiv), pyrrolidine 17 (25 mg, 0.075 mmol,
c
c
c
c
0.15 equiv), and acetic acid (4 lL, 0.075 mmol, 0.15 equiv) in
c
c
dichloromethane (1 mL) at 0 °C. After 4 days at 28 °C, the reaction
mixture was diluted with water and extracted with EtOAc/hexane
(1/1). The organic extract was washed with brine, dried (MgSO4)
and evaporated. The residue was purified by column chromatogra-
phy on silica using hexane/EtOAc (95/5) as eluent to give 11a–c
(73–79%).
c
c
c
rolactone 3, (+)-methylenolactocine 5, and (ꢀ)-quercus lactone 7.
4. Experimental
4.1.1. Ethyl (3R,4S)-3-dimethylphenylsilyl-2-ethoxycarbonyl-4-
formylhexanoate 11a
Prepared from silylmethylene malonate 10 and n-butanal
according to General procedure I. Yield: 149 mg, 79%. The diastereo-
meric ratio was determined from 1H NMR spectra; crude (syn/
HPLC grade acetone, NMP, DMF, toluene, THF, methanol were
used as received. Butanal, hexanal, and heptanal were commer-
cially available, and were distilled prior to use. Silylmethylene mal-
onate 10 was prepared following a procedure reported in the

1898
R. Chowdhury, S. K. Ghosh / Tetrahedron: Asymmetry 22 (2011) 1895–1900
anti = 86/14), after purification (syn/anti = 86/14). Careful chroma-
tography of a small portion of a sample gave syn-11a (>95% de,
NMR). Data for syn-11a: ee = 98%. The enantiomeric excess of
syn-11a was determined by HPLC using Daicel OD–H column
(k = 254 nm, hexane/i-PrOH = 99.7:0.3, 0.6 mL/min), tR = 23.58 min
(major), tR = 52.15 min (minor). 1H NMR (200 MHz, CDCl3): d 0.34
(s, 3H), 0.42 (s, 3H), 0.79 (t, J = 7.4 Hz, 3H), 1.17–1.27 (m, 6H),
1.35–1.72 (m, 2H), 2.29 (t, J = 5.2 Hz, 1H), 2.33–2.43 (m, 1H), 3.52
(d, J = 5.0 Hz, 1H), 4.01–4.14 (m, 4H), 7.24–7.35 (m, 3H), 7.53–
7.58 (m, 2H), 9.53 (d, J = 2.0 Hz, 1H). 13C NMR (50 MHz, CDCl3): d
ꢀ2.4, ꢀ1.4, 12.4, 13.9 (2C), 21.6, 26.7, 51.4, 53.7, 61.5, 61.6, 127.7
(2C), 129.1, 134.0 (2C), 138.6, 169.6 (2C), 204.1. IR (film): 3071,
2981, 2937, 2877, 1745, 1725, 1462, 1427, 1252, 1110, 909,
820 cmꢀ1. HRMS (ESI) calcd for C20H31O5Si [M+H]+: 379.1941;
found: 379.1935.
was brought to room temperature and stirred under those condi-
tions for 4 h. The reaction mixture was quenched with aqueous so-
dium metabisulfite solution and extracted with dichloromethane.
The combined organic extract was washed with NaHCO3 solution
followed by water and brine, dried over MgSO4 and evaporated un-
der reduced pressure. The residue was purified by column chroma-
tography on silica using hexane/EtOAc (95/5) as eluent to give the
desired formate esters 18a–c (72–76%).
4.2.1. (2R,3S)-1,1-Di(ethoxycarbonyl)-2-dimethyl(phenyl)-
silylpentan-3-yl formate 18a
Prepared from aldehyde 11a according to General procedure II.
Yield: 298 mg, 76% as an oil. The diastereomeric ratio was
determined from 1H NMR spectra; crude (syn/anti = 86/14), after
purification (syn/anti = 92/8). Careful chromatography of a small
portion of sample gave syn-18a. ½a D25
ꢁ
¼ þ12:5 (c 3.7, CHCl3). 1H
4.1.2. Ethyl (3R,4S)-3-dimethylphenylsilyl-2-ethoxycarbonyl-4-
formyloctanoate 11b
NMR (200 MHz, CDCl3): d 0.33 (s, 3H), 0.44 (s, 3H), 0.67 (t,
J = 7.3 Hz, 3H), 1.20–1.28 (m, 6H), 1.35–1.67 (m, 2H), 2.25 (q,
J = 3.6 Hz, 1H), 3.65 (d, J = 3.6 Hz , 1H), 4.00–4.21 (m, 4H), 5.12–
5.19 (m, 1H), 7.32–7.35 (m, 3H), 7.64–7.59 (m, 2H), 7.96 (s, 1H).
13C NMR (50 MHz, CDCl3): d ꢀ3.5, ꢀ1.6, 9.3, 13.8, 13.9, 27.1, 30.6,
50.2, 61.2, 61.5, 74.9, 127.7 (2C), 129.0, 134.0 (2C), 138.7, 160.4,
169.7, 170.0. IR (film): 3070, 3047, 2956, 2932, 2872, 1747, 1729,
Prepared from silylmethylene malonate 10 and n-hexanal
according to General procedure I. Yield: 148 mg, 73%. The diastereo-
meric ratio was determined from 1H NMR spectra; crude (syn/
anti = 84/16), after purification (syn/anti = 84/16). Careful chroma-
tography of a small portion of sample gave syn-11b (>95% de,
NMR). Data for syn-11b: ee = 99%. The enantiomeric excess of
syn-11b was determined by HPLC using Daicel AD–H column
(k = 254 nm, hexane/i-PrOH = 99.7:0.3, 0.5 mL/min), tR = 34.56 min
(major), tR = 37.36 min (minor). 1H NMR (200 MHz, CDCl3): d 0.35
(s, 3H), 0.42 (s, 3H), 0.78 (t, J = 6.2 Hz, 3H), 1.12–1.39 (m, 12H),
2.27 (t, J = 5.2 Hz, 1H), 2.37–2.51 (m, 1H), 3.53 (d, J = 5.0 Hz, 1H),
4.01–4.17 (m, 4H), 7.32–7.35 (m, 3H), 7.53–7.58 (m, 2H), 9.52 (d,
J = 2.0 Hz,1H). 13C NMR (50 MHz, CDCl3): d ꢀ2.5, ꢀ1.4, 13.8, 13.9
(2C), 22.4, 26.9, 28.2, 29.8, 51.3, 51.8, 61.4, 61.6, 127.7 (2C),
129.0, 134.0 (2C), 138.7, 169.6 (2C), 204.2. IR (film): 3070, 3048,
2958, 2872, 2721, 1745, 1726, 1465, 1427, 1251, 1110, 912,
820 cmꢀ1. HRMS (ESI) calcd for C22H35O5Si [M+H]+: 407.2254;
found: 407.2236.
1373, 1178, 1110, 1033, 820 cmꢀ1
.
4.2.2. (2R,3S)-1,1-Di(ethoxycarbonyl)-2-dimethyl(phenyl)-
silylheptan-3-yl formate 18b
Prepared from aldehyde 11b according to General procedure II.
Yield: 312 mg, 74% as an oil. The diastereomeric ratio was deter-
mined from 1H NMR spectra; crude (syn/anti = 84/16), after purifi-
cation (syn/anti = 93/7). Careful chromatography of a small portion
of sample gave syn-18b. ½a D25
ꢁ
¼ þ12:8 (c 1.64, CHCl3). 1H NMR
(200 MHz, CDCl3): d 0.33 (s, 3H), 0.44 (s, 3H), 0.71 (t, J = 6.6 Hz,
3H), 0.96–1.07 (m, 4H), 1.20–1.28 (m, 6H), 1.35–1.67 (m, 2H),
2.24 (q, J = 3.6 Hz, 1H), 3.65 (d, J = 3.6 Hz, 1H), 4.00–4.21 (m, 4H),
5.12–5.19 (m, 1H), 7.32–7.35 (m, 3H), 7.64–7.59 (m, 2H), 7.94 (s,
1H). 13C NMR (50 MHz, CDCl3): d ꢀ3.6, ꢀ1.5, 13.7, 13.9, 14.0,
22.1, 27.0, 31.0, 33.9, 50.2, 61.2, 61.5, 73.8, 127.8 (2C), 129.0,
134.0 (2C), 138.8, 160.3, 169.7, 169.9. IR (film): 3070, 3047, 2958,
4.1.3. Ethyl (3R,4S)-3-dimethylphenylsilyl-2-ethoxycarbonyl-4-
formylnonanoate 11c
Prepared from silylmethylene malonate 10 and n-heptanal
according to General procedure I. Yield: 157 mg, 75%. The diastereo-
meric ratio was determined from 1H NMR spectra; crude (syn/
anti = 81/19), after purification (syn/anti = 81/19). Careful chroma-
tography of a small portion of sample gave syn-11c (>95% de,
NMR). Data for syn-11c: ee = 97.8%. The enantiomeric excess of
syn-11c was determined by HPLC using Daicel AD–H column
(k = 254 nm, hexane/i-PrOH = 99.6:0.4, 0.6 mL/min), tR = 18.63 min
(major), tR = 24.48 min (minor). 1H NMR (200 MHz, CDCl3): d 0.34
(s, 3H), 0.42 (s, 3H), 0.80 (t, J = 6.2 Hz, 3H), 1.10–1.57 (m, 14H),
2.66 (t, J = 5.2 Hz,1H), 2.42–2.47 (m, 1H), 3.53 (d, J = 5.2 Hz, 1H),
4.01–4.17 (m, 4H), 7.31–7.37 (m, 3H), 7.52–7.58 (m, 2H), 9.51 (d,
J = 2.2 Hz, 1H). 13C NMR (50 MHz, CDCl3): d ꢀ2.4, ꢀ1.4, 13.9 (3C),
22.3, 26.9, 27.4, 28.5, 31.5, 51.3, 51.8, 61.4, 61.6, 127.8 (2C),
129.0, 134.0 (2C), 138.7, 169.7 (2C), 204.2. IR (film): 3070, 3048,
2957, 2930, 2858, 1745, 1727, 1465, 1427, 1250, 1152, 1110,
2934, 2873, 1748, 1729, 1373, 1178, 1111, 1033, 820 cmꢀ1
.
4.2.3. (2R,3S)-1,1-Di(ethoxycarbonyl)-2-dimethyl(phenyl)-
silyloctan-3-yl formate 18c
Prepared from aldehyde 11c according to General procedure II.
Yield: 314 mg, 72% as an oil. The diastereomeric ratio was deter-
mined from 1H NMR spectra; crude (syn/anti = 81/19), after purifi-
cation (syn/anti = 94/6). Careful chromatography of a small portion
of sample gave syn-18c. ½a D23
ꢁ
¼ þ9:7 (c 1.85, CHCl3). 1H NMR
(200 MHz, CDCl3): d 0.33 (s, 3H), 0.44 (s, 3H), 0.76 (t, J = 6.8 Hz,
3H), 0.94–1.20 (m, 6H), 1.22–1.35 (m, 6H), 1.39–1.57 (m, 2H),
2.23 (q, J = 3.6 Hz, 1H), 3.60 (d, J = 3.6 Hz, 1H), 3.98–4.21 (m, 4H),
5.16–5.25 (m, 1H), 7.32–7.35 (m, 3H), 7.54–7.58 (m, 2H), 7.94 (s,
1H). 13C NMR (50 MHz, CDCl3): d ꢀ3.6, ꢀ1.5, 13.7, 13.8, 13.9,
22.3, 24.5, 30.9, 31.2, 34.0, 50.2, 61.2, 61.5, 73.8, 127.7 (2C),
129.0, 134.0 (2C), 138.8, 160.2, 169.7, 169.9. IR (film): 3070,
3047, 2955, 2930, 2871, 1746, 1730, 1372, 1176, 1111, 1033,
.
1029, 819 cmꢀ1 HRMS (ESI) calcd for C23H37O5Si [M+H]+:
421.2410; found: 421.2415.
821 cmꢀ1
.
4.2. Bayer–Villiger oxidation of aldehydes 11a–c
4.3. Synthesis of butyrolactones from formates 18a–c
General procedure II: A solution of 3-chloroperoxybenzoic acid
(ꢂ70%) (375 mg, 1.5 mmol, 1.5 equiv) in dichloromethane
(10 mL) was pre-dried over anhydrous MgSO4 and added to a stir-
red mixture of the respective aldehydes 11a–c (1 mmol, 1 equiv)
and disodium hydrogen phosphate dihydrate (356 mg, 2 mmol,
2 equiv) in dichloromethane (7 mL) at 0 °C. The reaction mixture
General procedure III: Potassium hydroxide (280 mg, 5 mmol,
5 equiv) was added to a stirred solution of the formyl esters 18a–
c (1 mmol) in methanol (7 mL) at room temperature. After 12 h,
the solvent was evaporated under reduced pressure and the resi-
due was diluted with water (2 mL), acidified with dilute HCl and
extracted with ethyl acetate. The organic extract was dried over

R. Chowdhury, S. K. Ghosh / Tetrahedron: Asymmetry 22 (2011) 1895–1900
1899
Na2SO4 and evaporated under reduced pressure. The residue was
heated at 110 °C under a nitrogen atmosphere for 5 h, cooled to
room temperature and purified by column chromatography on
silica using hexane/EtOAc (95/5) as an eluent to give the desired
butyrolactones 19a–c (60–65%) as a single diastereoisomer.
2872, 2862, 1770, 1190, 1053, 987, 757 cmꢀ1. HRMS (ESI) calcd
for C6H11O3 [M+H]+: 131.0663; found: 131.0710.
4.4.2. (4S,5R)-5-Butyl-4-hydroxy-4,5-dihydrofuran-2(3H)-one
20b
Prepared from silylated lactone 19b according to General proce-
4.3.1. (4S,5R)-4-Dimethyl(phenyl)silyl-5-ethyl-4,5-dihydro-
furan-2(3H)-one 19a
dure IV. Yield 93 mg, 58%. ½a D24
ꢁ
¼ þ35:1 (c 0.94, CHCl3). 1H NMR
(700 MHz, CDCl3): d 0.93 (t, J = 6.3 Hz, 3H), 1.38–1.42 (m, 3H),
1.46–1.49 (m, 1H), 1.60–1.68 (m, 2H), 2.50–2.53 (m, 1H), 2.83
(dd, J = 6.3, 18.2 Hz, 1H), 3.0 (br, 1H), 4.28–4.3 (m, 1H), 4.36–4.37
(m, 1H). 13C NMR (175 MHz, CDCl3): d 13.8, 22.3, 27.3, 32.7, 37.7,
71.5, 88.0, 175.6. IR (film): 3738, 3435, 2959, 2934, 2873, 2863,
1771, 1189, 1052, 987, 757 cmꢀ1. HRMS (ESI) calcd for C8H15O3
[M+H]+: 159.1021; found: 159.1028.
Prepared from formate 18a according to General procedure III.
Yield: 160 mg, 65% as an oil. ½a D25
ꢁ
¼ þ31:8 (c 0.66, CHCl3). 1H
NMR (200 MHz, CDCl3): d 0.35 (s, 6H), 0.94 (t, J = 7.3 Hz, 3H),
1.46–1.69 (m, 3H), 2.28–2.62 (m, 2H), 4.23–4.33 (m, 1H),
7.34–7.48 (m, 5H). 13C NMR (50 MHz, CDCl3): d ꢀ4.8, ꢀ4.5, 9.8,
28.3, 29.0, 31.8, 84.6, 128.1 (2C), 129.7, 133.5 (2C), 135.4, 176.9.
IR (film): 3019, 2957, 2930, 2871, 1774, 1426, 1372, 1176, 1111,
821 cmꢀ1
.
HRMS (ESI) calcd for C14H20NaO2Si [M+Na]+:
4.4.3. (4S,5R)-5-Pentyl-4-hydroxy-4,5-dihydrofuran-2(3H)-one
20c
271.1128; found: 271.1130.
Prepared from silylated lactone 19c according to General proce-
4.3.2. (4S,5R)-4-Dimethyl(phenyl)silyl-5-butyl-4,5-dihydro-
furan-2(3H)-one 19b
dure IV. Yield 107 mg, 62%. ½a D26
ꢁ
¼ þ36:0 (c 2.0, CHCl3). 1H NMR
(500 MHz, CDCl3): d 0.87 (t, J = 6.3 Hz, 3H), 1.29–1.45 (m, 6H),
1.54–1.62 (m, 2H), 2.47 (dd, J = 3.5, 18.0 Hz, 1H), 2.79 (dd, J = 6.5,
18.0 Hz, 1H), 3.36 (br, 1H), 4.20–4.30 (m, 1H), 4.30–4.40 (m, 1H),
13C NMR (125 MHz, CDCl3): d 13.8, 22.4, 24.8, 31.4, 32.9, 37.6,
71.4, 88.3, 175.9. IR (film): 3737, 3434, 2960, 2936, 2873, 2860,
1770, 1190, 1052, 985, 758 cmꢀ1. HRMS (ESI) calcd for C9H17O3
[M+H]+: 173.1133; found: 173.1194.
Prepared from formate 18b according to General procedure III.
Yield: 165 mg, 60% as an oil. ½a D25
ꢁ
¼ þ49:0 (c 1.51, CHCl3). 1H
NMR (200 MHz, CDCl3): d 0.36 (s, 6H), 0.83 (t, J = 7.0 Hz, 3H),
1.17–1.31 (m, 3H), 1.36–1.52 (m, 3H), 1.62–1.72 (m, 1H), 2.27–
2.61 (m, 2H), 4.27–4.38 (m, 1H), 7.31–7.48 (m, 5H). 13C NMR
(50 MHz, CDCl3): d ꢀ4.8, ꢀ4.5, 13.7, 22.2, 27.7, 29.0, 31.8, 35.8,
83.5, 128.1 (2C), 129.8, 133.5 (2C), 135.5, 176.9. IR (film): 3019,
2957, 2932, 2859, 1774, 1427, 1254, 1210, 1112, 836, 758 cmꢀ1
.
4.5. Synthesis of
20a–c
c-butenolides from b-hydroxy butyrolactones
HRMS (ESI) calcd for C16H24NaO2Si [M+Na]+: 299.1443; found:
299.1449.
General procedure V: Methanesulfonyl chloride (0.05 mL,
0.65 mmol) was added to a stirred solution of the hydroxylactone
20a–c (0.6 mmol) and triethylamine (0.17 mL, 1.2 mmol) in dichlo-
romethane (4 mL) at 0 °C. After 1 h, the reaction mixture was
quenched with saturated ammonium chloride solution. The reac-
tion mixture was extracted with dichloromethane and the extract
was evaporated to give the crude butenolide which was purified by
column chromatography to give pure 9a–c (75–77%).
4.3.3. (4S,5R)-4-Dimethyl(phenyl)silyl-5-pentyl-4,5-dihydro-
furan-2(3H)-one 19c
Prepared from formate 18c according to General procedure III.
Yield: 185 mg, 64% as an oil. ½a D25
ꢁ
¼ þ45:1 (c 0.82, CHCl3). 1H
NMR (200 MHz, CDCl3): d 0.36 (s, 6H), 0.84 (t, J = 6.5 Hz, 3H),
1.13–1.32 (m, 5H), 1.37–151 (m, 3H), 1.62–1.72 (m, 1H), 2.27–
2.62 (m, 2H), 4.27–4.37 (m, 1H), 7.36–7.48 (m, 5H).13C NMR
(50 MHz, CDCl3): d ꢀ4.8, ꢀ4.4, 13.8, 22.3, 25.3, 29.0, 31.3, 36.1,
83.6, 128.2 (2C), 129.8, 133.7 (2C), 135.5, 177.0. IR (film): 3019,
4.5.1. (R)-5-Ethyl-2(5H)-furanone 9a
2956, 2933, 2859, 1773, 1428, 1254, 1210, 1111, 836, 757 cmꢀ1
.
Prepared from hydroxy lactone 20a according to General proce-
HRMS (ESI) calcd for C17H26NaO2Si [M+Na]+: 313.1600; found:
313.1598.
dure V. Yield: 51 mg, 75% as oil. ½a D24
ꢁ
¼ ꢀ91:8 (c 1.46, MeOH) lit.32
½
a 2D3
ꢁ
¼ ꢀ94 (c 1.46, CH2Cl2). 1H NMR (200 MHz, CDCl3): d 0.98 (t,
J = 7.4 Hz, 3H), 1.59–1.89 (m, 2H), 4.95–5.01 (m, 1H), 6.09 (dd,
J = 5.7 Hz, J = 1.9 Hz, 1H), 7.43 (dd, J = 5.7 Hz, J = 1.3 Hz, 1H). 13C
NMR (50 MHz, CDCl3): d 8.9, 26.3, 84.2, 121.8, 155.8, 173.0. IR
(film): 3018, 2957, 2931, 2860, 1754, 1600, 1465, 1334, 1163,
4.4. Synthesis of b-hydroxy c-butyrolactones from b-silyl
lactones 19a–c
General procedure IV: Potassium bromide (143 mg, 1.2 mmol,
1.2 equiv) was added to a stirred solution of lactones 19a–c
(1 mmol) in freshly prepared peracetic acid (6 mL of a 35% solution
in acetic acid) at 0 °C followed by the addition of H2O2 (30%,
0.15 mL). The reaction mixture was allowed to return to room
temperature and stirred for 24 h. The solvent was removed under
reduced pressure and the residue was dissolved in dichlorometh-
ane. The organic phase was dried (Na2SO4) and evaporated under
reduced pressure to give the crude hydroxyl lactones 20a–c
(58–62%).
1096, 1024, 819 and 756 cmꢀ1
.
4.5.2. (R)-5-Buthyl-2(5H)-furanone 9b
Prepared from hydroxy lactone 20b according to General proce-
dure V. Yield: 64 mg, 77% as oil. ½a D24
ꢁ
¼ ꢀ101:8 (c 2.16, CHCl3) lit.34
½
a 2D4
ꢁ
¼ ꢀ101:8 (CHCl3). 1H NMR (200 MHz, CDCl3): d 0.89 (t,
J = 6.9 Hz, 3H), 1.25–1.51 (m, 4H), 1.55–1.85 (m, 2H), 4.98–5.05
(m, 1H), 6.08 (dd, J = 5.7 Hz, J = 1.9 Hz, 1H), 7.44 (dd, J = 5.8 Hz,
J = 1.2 Hz, 1H). 13C NMR (50 MHz, CDCl3): d 13.7, 22.3, 27.0, 32.8,
83.4, 121.5, 156.2, 173.0. IR (film): 3019, 2959, 2933, 2863, 1755,
1600,1466, 1335, 1164, 1097, 1024, 819 and 754 cmꢀ1
.
4.4.1. (4S,5R)-5-Ethyl-4-hydroxy-4,5-dihydrofuran-2(3H)-one
20a
4.5.3. (R)-5-Pentyl-2(5H)-furanone 9c
Prepared from silylated lactone 19a according to General proce-
Prepared from hydroxy lactone 20c according to General proce-
dure IV. Yield 78 mg, 60%. ½a D29
ꢁ
¼ þ40:0 (c 0.8, CHCl3). 1H NMR
dure V. Yield: 70 mg, 76% as oil. ½a D24
ꢁ
¼ ꢀ93:3 (c 2.53, CHCl3) lit.5
(500 MHz, CDCl3): d 1.02 (t, J = 7.2 Hz, 3H), 1.59–1.70 (m, 2H),
2.51 (dd, J = 3.0, 18.0 Hz, 1H), 2.81 (dd, J = 6.2, 18.2 Hz, 1H), 2.97
(br, 1H), 4.28–4.30 (m, 2H). 13C NMR (125 MHz, CDCl3): d 9.5,
26.0, 37.7, 71.2, 89.2, 175.6. IR (film): 3736, 3435, 2960, 2934,
½
a 2D5
ꢁ
¼ ꢀ90:1 (c 1.76, CHCl3). 1H NMR (200 MHz, CDCl3): d 0.85 (t,
J = 6.5 Hz, 3H), 1.16–1.48 (m, 7H), 1.53–1.83 (m, 2H), 4.96–5.04
(m, 1H), 6.06 (dd, J = 5.6 Hz, J = 1.9 Hz, 1H), 7.43 (dd, J = 5.7 Hz,
J = 1.3 Hz, 1H). 13C NMR (50 MHz, CDCl3): d 13.8, 22.3, 24.6, 31.4,

1900
R. Chowdhury, S. K. Ghosh / Tetrahedron: Asymmetry 22 (2011) 1895–1900
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