Total synthesis of sapinofuranone A from d-ribose

Article abstract of DOI:10.1016/j.tet.2012.05.012

The total synthesis of sapinofuranone A has been achieved starting from naturally occurring carbohydrate d-ribose via a short and high yielding route. The key transformations include Wittig olefination, Ohira-Bestmann reaction, Sonogashira coupling. Finally acetonide deprotection and subsequent lactonization using catalytic amount of hydrochloric acid completed the total synthesis of sapinofuranone A.

Full text of DOI:10.1016/j.tet.2012.05.012

Tetrahedron 68 (2012) 5829e5832
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Total synthesis of sapinofuranone A from -ribose
D
*
Lingaiah Nagarapu , Shuklachary Karnakanti, Rajashaker Bantu
Organic Chemistry Division-II, Indian Institute of Chemical Technology (CSIR), Tarnaka, Hyderabad 500607, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The total synthesis of sapinofuranone
A has been achieved starting from naturally occurring
Received 15 March 2012
Received in revised form 30 April 2012
Accepted 3 May 2012
carbohydrate
D-ribose via a short and high yielding route. The key transformations include Wittig
olefination, OhiraeBestmann reaction, Sonogashira coupling. Finally acetonide deprotection and
subsequent lactonization using catalytic amount of hydrochloric acid completed the total synthesis of
sapinofuranone A.
Available online 11 May 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Wittig olefination
OhiraeBestmann reaction
Sonogashira coupling
1. Introduction
lactonization. While in turn the diene 12 could be derived from 8 by
IBX oxidation followed by OhiraeBestmann reaction by the for-
During recent years, butanolide and the corresponding
g
-lac-
mation of triple bond and Sonogashira coupling and selective re-
duction of triple bond by Zn catalyst. Compound 8 can be obtained
from 6 by Wittig olefination and reduction of conjugated double
bond by NiCl2$6H2O and NaBH4. Compound 6 could be derived
tone motifs containing natural products are attaining significant
interest due to their potent biological properties.1 5-Substituted
dihydrofuranones, named sapinofuranone A and B (1 and 2), were
isolated from liquid cultures of Sphaeropsis sapinea, a phytopatho-
genic fungus causing a wide range of disease symptoms on conifers
(Fig. 1).
from the commercially available
As shown in Scheme 2, the synthesis of the key intermediate 9
starting from the commercially available -ribose 4 was treated
D-ribose 4 (Scheme 1).
D
This butanolide natural product, sapinofuranone A, was isolated
by Antonio Evidente and co-workers in 1999 from liquid cultures of
a phytopathogenic fungus, S. sapinea.2 A new strategy to extend the
application of the J-based configuration and an application to
sapinofuranone A was demonstrated by Gomez-Paloma and co-
workers in 2002.3 Intrigued by the biological properties of these 5-
substituted dihyrofuranone, we got interested in the total synthesis
of sapinofuranone A. In continuation to our work on the total
synthesis of furanoside building blocks containing natural prod-
ucts4 herein, we report the stereoselective total synthesis of a nat-
with catalytic amount of H2SO4 and acetone, which resulted in 2,3-
acetonide 5 in quantitative yields. Sequential reduction with NaBH4
followed by oxidative cleavage of the diol with NaIO4 provided al-
dehyde 6. The aldehyde was subjected to Wittig olefination using
O
O
O
OH
O
O
ural product sapinofuranone
A in a stereoselective fashion
O
OH
involving easily accessible starting materials. To date, only one re-
port on the synthesis of sapinofuranone A (1) exists.5
SapinofuranoneA(1)
OH
2. Results and discussion
gama-methylbutenolide
The retro-synthetic analysis of compound 1 is shown in Scheme
1. It was envisioned that sapinofuranone A (1) could be synthesized
from 12 by one-pot acetonide deprotection and simple
O
O
O
O
OH
SapinofuranoneB(2)
OH
SapinofuranoneB(2a)
* Corresponding author. Tel.: þ91 40 27191509/10/11; fax: þ91 40 27193382;
e-mail address: lnagarapuiict@yahoo.com (L. Nagarapu).
Fig. 1. Sapinofuranone A, sapinofuranone B, and related compounds.
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.05.012

5830
L. Nagarapu et al. / Tetrahedron 68 (2012) 5829e5832
O
O
O
O
OEt
i
OMe
OMe
OMe
ii
O
O
O
O
O
O
9
11
12
10
iii
O
O
O
iv
OH
O
O
Sapinofuranone A (1)
Scheme 3. Reagents and conditions: (i) CH3COC]N2PO(OMe)2/K2CO3, MeOH, rt, 3 h;
(ii) BrCH]CHCH3, [Pd(Ph3P)2Cl2], CuI, Et3N (dry), 6H; (iii) Zn (Cu/Ag), MeOH reflux,
12 h; (iv) cat.HCl/THF, rt, 6 h.
In another approach, we obtained the following diastereomeric
mixture. Toward the end, the compound 9 was subjected to Wittig
olefination to furnish 12, as expected, was non-stereoselective and
led to a mixture of nearly 7/3 of diastereomers cis 12: trans 12a
(Scheme 4). While the two diastereomers were inseparable and the
mixture was treated with catalytic amount of HCl, which yielded
inseparable diastereomeric mixture of sapinofuranone A (1). We
could not find a suitable method to separate the diastereomeric
mixture. We concluded that the synthetic route involving Wittig
olefination of the compound 9 to target molecule sapinofuranone A
(1) could not evade the above mentioned synthetic dead end.
Scheme 1. Retro synthesis of sapinofuranone A.
O
O
O
OH
OH
HO
OEt
HO
a
b
c
D-Ribose
O
O
O
O
O
O
O
4
6
5
7
d
O
O
O
OMe
OEt
HO
OEt
f
e
O
O
O
O
O
O
O
9
O
10
8
O
OEt
v
g
OEt
O
O
O
O
vi
O
O
OH
O
O
OMe
OMe
O
O
9
i
h
O
O
cis 1 trans 1a, 70:30
OH
O
O
cis 12 trans 12a, 60:40
11
Scheme 4. Reagents and conditions: (v) CH3CH]CHCH2PPh3Br, LiHMDS, THF, ꢁ78 ꢀC,
Sapinofuranone A (1)
12
4 h; (vi) cat.HCl/THF, rt, 6 h.
Scheme 2. Reagents and conditions: (a) cat.H2SO4/acetone, 4 h; (b)(i) NaBH4/MeOH,
0
ꢀC, 2H, (ii) NaIO4, tBuOH/H2O (3/2), 12 h; (c) Ph3PCHCO2Et/cat.PhCOOH, CH2Cl2,
reflux, 12 h; (d) NaBH4, NiCl2$6H2O, MeOH, 0 ꢀC to rt, 3 h; (e) IBX, DMSO, rt, 3 h; (f)
CH3COC]N2PO(OMe)2/K2CO3, MeOH, rt, 3 h; (g) BrCH]CHCH3, [Pd(Ph3P)2Cl2], CuI,
piperidine, DMF, 70 ꢀC, 4H; (h) Zn (Cu/Ag), MeOH reflux, 12 h; (i) cat.HCl/THF, rt, 6 h.
3. Conclusion
In summary, we have synthesized sapinofuranone A via a short
(eightsteps), highyielding route (18%overallyieldfrom commercially
available D-ribose). The key transformations involved in the synthesis
are Sonogashira coupling; one-pot tandem acetonide deprotection
and subsequent dihydrofuranone ring formation. Our approach to the
syntheses of 8 and 9 are promisingly applicable for the syntheses of
ylide to yield the fragment 7 with a yield of 89%. The conjugated
double bond was reduced with catalytic amount of NiCl2$6H2O and
NaBH4 to give the compound 8 with 94.9% yield. Compound 8 ox-
idized with IBX in DMSO at room temperature afforded the key
intermediate 9. Compound 9 was characterized from 1H NMR
other butanolide natural products of g-lactone motifs.
spectrum by the appearance of aldehydic proton (1H) at
d 9.67 as
doublet (d, 1H, J¼2.44 Hz). It was also characterized by 13C NMR
spectrum by the appearance of aldehydic carbonyl carbon at
4. Experimental section
4.1. General information
d
201.8. The mass spectrum exhibited the mass value of m/z 253
(MþNa)þ was in agreement with the structure. This synthetic
method is regarded as the best procedure from the viewpoint of the
number of steps and the overall yields and large-scale preparation
conditions and has a great potential to be utilized extensively in the
synthesis of the sapinofuranones.
All reactions requiring anhydrous conditions were performed in
oven-dried glassware under argon. Nuclear Magnetic Resonance (1H
and 13C NMR) spectra were recorded on Varian Gemini 200, 400 or
Bruker WH 300 MHz spectrometers, using tetramethylsilane (TMS)
as the internal standard. Chemical shifts were expressed in (ppm)
down field from TMS. IR spectra were recorded on PerkineElmer
model 683 or 1310 spectrometers with sodium chloride optics or KBr
pellets. EI Mass spectra were recoded on a VG Micromass-7070 Hz
70 eV using a direct inlet system. ESI MS were recorded on Thermo
Finnigan LCQ ion trap mass spectrometer equipped with an electron
spray ionization. High Resolution Mass spectra were recoded on Q
STAR mass spectrometer (Applied Biosystems USA) at 5 or 7 K res-
olution using polyethylene glycol as an internal reference com-
pound. Optical rotations were recorded on JASCO DIP 370 digital
polarimeter. All reactions were monitored by thin layer
With the key intermediate 9 in hand, we focused the synthesis
of 1 (Scheme 3). Aldehyde 9 subjected to one-carbon homologation
using OhiraeBestmann reagent afforded the alkyne 10 in 75% yield.
Alkyne 10 was subjected to Sonogashira coupling with trans-1-
bromo-1-propene using Cu2I2, Pd(Ph3P)2Cl2, and triethylamine to
afford the desired product 11. The compound 11 was reduced using
activated Zn6 affording the diene 12 as a single isomer, which on
treatment with catalytic amount of HCl in THF underwent one-pot
acetonide deprotection and lactonization to afford the target mol-
ecule sapinofuranone A in 79% yield. The 1H NMR and 13C NMR
spectral data of our synthetic compound were in good agreement
with the data previously reported in literature.2

L. Nagarapu et al. / Tetrahedron 68 (2012) 5829e5832
5831
chromatography (TLC) employing 0.25 mm silica gel plates (60F-
254, E-Merck). Column chromatography was performed using Acme
silica gel (60e120 mesh). Visualization of the spots onTLC plates was
achieved either by exposure to UV light, iodine vapor and by dipping
the plates in phosphomolybdic acideceric (IV) sulfateesulfuric acid
solution (PMA solution) and heating the plates at 120 ꢀC.
13C NMR (300 MHz, CDCl3):
d
14.2, 25.2, 27.6, 60.6, 61.8, 75.9, 78.2,
109.5, 123.0, 142.0, 165.8. MS (ESI): m/z 253 (MþNa)þ. HRMS: calcd
for C8H14O5Na: 253.10464. Found 253.10406.
4.1.4. Ethyl 3-((4R,5S)-5-(hydroxymethyl)-2,2-dimethyl-1,3-
dioxolan-4-yl)propanoate (8). To a stirred solution of conjugated
alkene 7 (8.2 g, 35.6 mmol) in MeOH (100 mL), NiCl4$6H2O (1.7 g,
7.13 mmol) was added at 0 ꢀC. The resulting mixture was stirred at
4.1.1. (3aR,6R,6aR)-6-(Hydroxymethyl)-2,2-dimethyltetrahydrofuro
[3,4-d][1,3]dioxol-4-ol (5). To a stirred solution of
D-ribose (4)
0
ꢀC for 10 min and NaBH4 (2.7 g, 71.3 mmol) was added in small
(10.0 g, 66.6 mmol) in acetone (100 mL), concd H2SO4 (0.3 mL) was
added drop wise at room temperature. And the resulting reaction
mixture was stirred at room temperature for 2 h, until TLC showed
complete conversion of the starting material. The reaction mixture
was neutralized by addition of solid NaHCO3 and filtered to remove
inorganic solid. The filtrate was concentrated under reduced pres-
sure to give colorless syrup. The residue was purified by silica gel
column chromatography using hexane and ethyl acetate (30%) as
the eluent to afford 5 as colorless syrup (11.7 g, 92.4%); Rf 0.4 (50%
portions. The reaction mixture was stirred for another 3 h and
quenched with water. The whole reaction mixture was concen-
trated to get the residue, which was extracted with EtOAc. The
organic extract was washed with brine and dried over anhydrous
Na2SO4, and evaporated. The crude reaction mixture was purified
by silica gel column chromatography using EtOAc/hexane (25%) as
an eluent to provide the corresponding saturated ester compound 8
(7.8 g, 94.9%) as a clear oil. Rf 0.5 (50% EtOAc/hexane); ½a D28
þ21.3 (c
ꢂ
2.1, CHCl3); IR (KBr, neat): 1041, 1163, 1250, 1372, 1732, 2934, 2985,
EtOAc/hexane); ½a D28
ꢂ
ꢁ36.7 (c 1.1, acetone); IR (KBr, neat): 869,
3472; 1H NMR (300 MHz, CDCl3):
d
1.26 (3H, t, J¼7.17 Hz, CH3CH2),
1068, 1211, 1376, 1458, 1635, 2940, 2986, 3408; 1H NMR (300 MHz,
1.32 (3H, s, CH3),1.43 (3H, s, CH3),1.77e1.85 (2H, m, CH2), 2.31e2.55
(2H, m, CH2), 3.60e3.63 (2H, m, CH2OH), 4.08e4.17 (4H, m, 2CH,
CDCl3):
d 1.32 (3H, s, CH3), 1.49 (3H, s, CH3), 3.74 (2H, s, CH2OH), 4.41
(1H, s, CHCH2), 4.59 (1H, d, J¼6.04 Hz, CH), 4.84 (1H, d, J¼5.66 Hz,
CH2CH3); 13C NMR (300 MHz, CDCl3):
d 14.1, 24.5, 25.3, 28.0, 31.0,
CH), 5.42 (1H, s, CHOH); 13C NMR (300 MHz, CDCl3):
d
24.5, 26.2,
60.4, 61.4, 75.9, 77.7, 108.2, 173.1; MS (ESI): m/z 255 (MþNa)þ;
63.3, 81.5, 86.5, 87.5, 102.5, 112.0; MS (ESI): m/z 213 (MþNa)þ;
HRMS: calcd for C8H14O5Na: 255.12029. Found 255.12007.
HRMS: calcd for C8H14O5Na: 213.07334. Found 213.07304.
4.1.5. Ethyl
3-((4R,5R)-5-formyl-2,2-dimethyl-1,3-dioxolan-4-yl)
4.1.2. (3aS,6aS)-2,2-Dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-ol
propanoate (9). To a stirred solution of IBX (4.1 g, 15.0 mmol) in dry
DMSO (10 mL), a solution of compound 8 (2.5 g, 10.7 mmol) in THF
(60 mL) was added drop wise at room temperature. The resulting
reaction mixture was stirred for 3 h until TLC showed complete
conversion of the starting material. The reaction mixture was
quenched by addition of cold water (15 mL) and diluted with
diethyl ether (50 mL). Organic layer was separated and washed
with satd NaHCO3 (2ꢃ10 mL), dried (Na2SO4), and concentrated
under reduced pressure to obtain the title compound 9 (2.28 g,
92.3%) as a thick syrup, which was used further without purifica-
tion. Rf 0.8 (50% EtOAc/hexane); IR (KBr, neat): 1074, 1272, 1373,
(6). To a stirred solution of
D-ribose monoacetonide 5 (11.0 g,
57.8 mmol) in dry methanol (70 mL), NaBH4 (3.29 g, 86.8 mmol) was
added in small portions at 0 ꢀC. And the resulting reaction mixture
was stirred at room temperature for 1 h until TLC showed complete
conversion of starting material. Then the solvent was distilled off
t
under reduced pressure, and then BuOH/H2O (90/60 mL), NaIO4
(49.5 g, 231.5 mmol) were added in small portions at room tem-
perature. And the resulting reaction mixture was stirred at room
temperature for 12 h until TLC showed complete conversion of
stirring material. The reaction mixture was diluted with CH2Cl2
(200 mL) and neutralized by the addition of solid NaHCO3 and fil-
tered to remove inorganic solid. The filtrate was extracted into
CH2Cl2 (2ꢃ50 mL), dried (Na2SO4), and concentrated under reduced
pressure to obtain a residue, which was chromatographed [SiO2,
60e120 mesh, hexane/ethyl acetate, 75/25] to obtain the title
1454, 1732, 2931; 1H NMR (500 MHz, CDCl3):
d 1.25 (3H, t,
J¼7.32 Hz, CH3), 1.40 (3H, s, CH3), 1.57 (3H, s, CH3), 1.99e2.13 (2H, m,
CH2), 2.39e2.55 (2H, m, CH2), 4.14 (2H, q, J¼7.32,14.64 Hz, CH2CH3),
4.29e4.33 (1H, m, CH), 4.36e4.41 (1H, m, CH), 9.67 (1H, d,
J¼2.44 Hz, CHO); 13C NMR (300 MHz, CDCl3):
d 14.1, 19.1, 25.2, 27.6,
compound 6 (7.3 g, 78.9%) as an oil. Rf 0.4 (30%EtOAc/hexane); ½a D28
ꢂ
30.9, 60.5, 71.7, 81.7, 110.6, 172.5, 201.8. MS (ESI): m/z 253 (MþNa)þ.
ꢁ76.1 (c 1.3, CHCl3); IR (KBr, neat): 1067,1210,1375,1459,1633, 2925,
HRMS: calcd for C8H14O5Na: 253.10464. Found 253.10493.
3433; 1H NMR (300 MHz, CDCl3):
d 1.29 (3H, s, CH3),1.44 (3H, s, CH3),
3.91e4.06 (2H, m, CH2), 4.51 (1H, d, J¼5.66 Hz, CH), 4.77e4.81 (1H,
4.1.6. Methyl 3-((4R,5S)-5-ethynyl-2,2-dimethyl-1,3-dioxolan-4-yl)
propanoate (10). To a stirred solution of K2CO3 (2.4 g, 17.4 mmol)
and dimethyl-1-diazo-2-oxopropylphosphonate (1.8 g, 9.56 mmol)
in dry MeOH (15 mL), aldehyde 9 (2.0 g, 8.7 mmol) dissolved in dry
MeOH (5 mL) was added drop wise at room temperature. The
resulting mixture was stirred for 4 h until TLC showed complete
conversion of the starting material. The reaction mixture was fil-
tered to remove inorganic solid, and the filtrate was concentrated
under reduced pressure to obtain alkyne compound 10 (1.38 g,
dd, J¼3.39, 5.66 Hz, CH), 5.35 (1H, s, CHOH); 13C NMR (300 MHz,
CDCl3):
d 24.5, 26.0, 71.6, 79.8, 85.0, 101.5, 112.1; MS (EI): m/z 183
(MþNa)þ; HRMS: calcd for C8H14O5Na: 183.04957. Found 183.04913.
4.1.3. Ethyl3-((4R,5S)-5-(hydroxymethyl)-2,2-dimethyl-1,3-dioxolan-
4-yl)acrylate (7). To a solution of compound 6 (7.1 g, 44.3 mmol) in
CH2Cl2 (80 mL), ethoxycarbonylmethylene triphenylphosphonate
(21.6 g, 62.1 mmol), and benzoic acid (0.3 g) were added at room
temperature. The resulting reaction mixture was refluxed at ꢀC for
18 h until TLC showed complete conversion of the starting material.
The reaction mixture was allowed to come to room temperature
and concentrated under reduced pressure to obtain a residue,
which was chromatographed [SiO2, 60e120 mesh, hexane/ethyl
acetate, 80/10] to obtain the title compound 7 (9.0 g, 89.0%) as
75.0%) as pale yellow oil. Rf 0.7 (30% EtOAc/hexane); ½a D28
ꢁ17.1 (c
ꢂ
1.1, CHCl3); IR (KBr, neat): 863, 1064, 1226, 1371, 1738, 2934, 2987,
3272; 1H NMR (300 MHz, CDCl3):
d 1.33 (3H, s, CH3), 1.52 (3H, s,
CH3), 2.01e2.13 (2H, m, CH2), 2.45e2.54 (3H, m, CH2, CH), 3.69 (3H,
s, CH3), 4.10e4.17 (1H, m, CH), 4.77 (1H, dd, J¼2.26, 5.66 Hz, CH); 13
C
NMR (300 MHz, CDCl3): d 25.8, 26.2, 27.6, 30.3, 51.6, 68.7, 76.0, 76.5,
analytically pure low melting solid. Rf 0.5 (30%EtOAc/hexane); ½a D28
ꢂ
79.4, 109.8, 173.4; MS (ESI): m/z 235 (MþNa)þ; HRMS: calcd for
ꢁ139 (c 1.1, CHCl3); IR (KBr, neat): 1049, 1163, 1216, 1372, 1720,
C8H14O5Na: 235.09408. Found 235.09374.
2932, 2985, 3483; 1H NMR (300 MHz, CDCl3):
d 1.30 (3H, t,
J¼7.16 Hz, CH3CH2), 1.38 (3H, s, CH3), 1.51 (3H, s, CH3), 4.11e4.24
(4H, m, 2ꢃ CH2), 4.29e4.36 (1H, m, CH), 4.74e4.81 (1H, m, CH), 6.08
(1H, dd, J¼1.51, 15.48 Hz, CH), 6.86 (1H, dd, J¼5.66, 15.86 Hz, CH);
4.1.7. Methyl-3-((4R,5S)-2,2-dimethyl-5-((E)-pent-3-en-1-ynyl)-1,3-
dioxolan-4-yl)propanoate (11). To a stirred solution of Pd(PPh3)2Cl2
(264 mg, 0.377 mmol) and CuI (229 mg, 1.20 mmol) in piperidine

5832
L. Nagarapu et al. / Tetrahedron 68 (2012) 5829e5832
were added solutions of trans-1-bromopropene (958 mg,
7.92 mmol) in piperidine and acetylene compound 10 (800 mg,
3.77 mmol) in DMF under argon atmosphere. The resultant mixture
was stirred for 10 min at room temperature and then heated to
70 ꢀC for 5 h. The reaction mixture was filtered through Celite and
filtrate was concentrated under reduced pressure to obtain a resi-
due, which was chromatographed [SiO2, 60e120 mesh, hexane/
ethyl acetate, 80/10] to obtain the title compound 11 (670 mg,
room temperature for 12 h, until the TLC showed complete con-
version of the starting material. The reaction mixture was neu-
tralized by addition of solid NaHCO3 and filtered to remove
inorganic solid. The filtrate was concentrated under reduced pres-
sure to obtain a residue, which was chromatographed [SiO2,
60e120 mesh, hexane/ethyl acetate, 80/10] to obtain the title
compound 1 (118 mg, 78.6%) as a colorless oil. Rf 0.3 (EtOAc/hexane,
50/50); ½a 2D8
ꢂ
þ66.1 (c 1.1, CHCl3), [lit.2 ½a D28
þ65.2 (c 1.3, CHCl3)]; IR
ꢂ
70.5%) as a pale yellow liquid. Rf 0.5 (10% EtOAc/hexane); ½a D28
ꢂ
ꢁ21.1
(KBr, neat): 1054, 1469, 1621, 1713, 2922, 3435; 1H NMR (300 MHz,
(c 1.0, CHCl3); IR (KBr, neat): 1072, 1166, 1225, 1370, 1738, 2930; 1H
CDCl3):
d
1.81 (3H, ddd, J¼1.51, 3.06, 6.79 Hz, CH3), 2.13e2.38 (2H,
NMR (300 MHz, CDCl3):
d
1.33 (3H, s, CH3), 1.51 (3H, s, CH3), 1.78
m, CH2), 2.45e2.70 (2H, m, CH2), 4.54 (1H, dt, J¼3.02, 6.79, 10.57 Hz,
CH), 4.89 (1H, dd, J¼2.26, 8.68 Hz, CH), 5.21 (1H, t, J¼7.93 Hz, CH),
5.78e5.90 (1H, m, CH), 6.12e6.35 (2H, m, 2ꢃ CH); 13C NMR
(3H, d, J¼6.99 Hz, CH3), 1.99e2.07 (2H, m, CH2), 2.42e2.55 (2H,m,
CH2), 3.68 (3H, s, CH3), 4.08e4.16 (1H, m, CH), 4.88 (1H, d,
J¼4.99 Hz, CH), 5.51 (1H, d, J¼15.99 Hz, CH), 6.14e6.22 (1H, m, CH);
(300 MHz, CDCl3):
d 18.3, 21.2, 28.5, 68.4, 82.3, 123.8, 126.0, 132.9,
13C NMR (300 MHz, CDCl3):
d
18.6, 25.9, 26.5, 27.8, 30.3, 51.6, 69.4,
133.6, 177.5; MS (ESI): m/z 205 (MþNa)þ; HRMS: calcd for
76.9, 82.5, 86.6, 109.4, 109.9, 140.7, 173.5; MS (ESI): m/z 275
(MþNa)þ; HRMS: calcd for C8H14O5Na: 275.12538. Found
275.12516.
C8H14O5Na: 205.08357. Found 205.08383.
Acknowledgements
4.1.8. Methyl-3-((4R,5S)-2,2-dimethyl-5-((1Z,3E)-penta-1,3-dienyl-
1)-1,3-dioxolan-4-yl) propanoate (12). To a suspension of activated
Zn (1.25 g), alkyne 11 (500 mg, 1.98 mmol) in MeOH (20 mL) was
added drop wise at room temperature. The resulting reaction
mixture was heated for 60 ꢀC and stirred for 12 h until the TLC
showed complete conversion of the starting material. The reaction
mixture was filtered to remove the inorganic solid, and filtrate was
concentrated under reduced pressure and diluted with ethyl ace-
tate (15 mL). The organic layer was washed with water and dried
over Na2SO4, and concentrated under reduced pressure to obtain
a residue, which was chromatographed [SiO2, 60e120 mesh, hex-
ane/ethyl acetate, 80/10] to obtain the title compound 12 (377 mg,
Authors thank the Director, Dr. J. S. Yadav, and Head, Organic
Chemistry Division-II, IICT for their support. S.C.K. thanks CSIR, New
Delhi for research fellowship.
Supplementary data
Copies of 1H and 13C NMR spectra for all new compounds.
Supplementary data related to this article can be found online at
doi:10.1016/j.tet.2012.05.012.
References and notes
74.9%) as a light yellow liquid. Rf 0.6 (EtOAc/hexane, 20/80); ½a D28
ꢂ
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þ17.6 (c 1.0, CHCl3); IR (KBr, neat): 1071, 1164, 1273, 1378, 1736,
2925; 1H NMR (300 MHz, CDCl3):
d 1.37 (3H, s, CH3), 1.47 (3H, s,
CH3), 1.79 (3H, dd, J¼1.13, 6.79 Hz, CH3), 1.99e2.12 (2H, m, CH2),
2.28e2.54 (2H, m, CH2), 3.67 (3H, s, CH3), 4.12e4.20 (1H, m, CH),
5.05 (1H, dd, J¼5.28, 8.67 Hz, CH), 5.30 (1H, t, J¼9.44, 10.57 Hz, CH),
5.73e5.80 (1H, m, CH), 6.15 (1H, t, J¼10.57,11.33 Hz, CH), 6.30 (1H, t,
J¼12.46, 15.48 Hz, CH); 13C NMR (300 MHz, CDCl3):
d 19.1, 25.6,
26.0, 27.6, 28.2, 51.5, 71.7, 74.1, 108.1, 123.3, 126.0, 128.7, 130.8, 173.7;
MS (ESI): m/z 277 (MþNa)þ; HRMS: calcd for C8H14O5Na:
277.14103. Found 277.14066.
4.1.9. (R)-5-((S,2Z,4E)-1-Hydroxyhexa-2,4-dienyl)dihydrofuran-
2(3H)-one (1). To
a stirred solution of ester 12 (210 mg,
5. Rodrigo, J. M.; Zhao, Y.; Hoveyda, H. A.; Snapper, M. L. Org. Lett. 2011, 13,
3778e3781.
6. Boland, W.; Schroer, N.; Sieler, C. Helv. Chem. Acta 1987, 70, 1025e1040.
0.826 mmol) in THF (25 mL), catalytic amount of concd HCl was
added at 0 ꢀC. And the resulting reaction mixture was stirred at