Stereoselective synthesis of tarchonanthuslactone via the Prins cyclisation

Article abstract of DOI:10.1016/j.tet.2007.01.019

The stereoselective total synthesis of tarchonanthuslactone, a polyketide natural product, has been achieved. The synthesis exploits the high stereochemical control in the Prins cyclisation along with ring closing metathesis (RCM) as a key step.

Full text of DOI:10.1016/j.tet.2007.01.019

Tetrahedron 63 (2007) 2689–2694
Stereoselective synthesis of tarchonanthuslactone via
the Prins cyclisation
*
J. S. Yadav, N. Niranjan Kumar, M. Sridhar Reddy and A. R. Prasad
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad-500 007, Andhra Pradesh, India
Received 1 September 2006; revised 29 December 2006; accepted 11 January 2007
Available online 14 January 2007
Abstract—The stereoselective total synthesis of tarchonanthuslactone, a polyketide natural product, has been achieved. The synthesis
exploits the high stereochemical control in the Prins cyclisation along with ring closing metathesis (RCM) as a key step.
Ó 2007 Published by Elsevier Ltd.
1. Introduction
activity, there have been several approaches reported for
the synthesis of tarchonanthuslactone.7 In this paper, we
describe a stereoselective synthesis of tarchonanthuslactone
via Prins cyclisation.
Many polyketide natural products possessing syn- and anti-
1,3-diols1 along with 5,6-pyrone units exhibit various
biological activities like plant growth inhibition as well as
antifeedant, antifungal, antibacterial and antitumour proper-
ties.2,3 Due to this wide spectrum of biological properties,
several synthetic approaches have been reported for their
synthesis.4 Some such natural products are strictifolione
1,5a passifloricin A 2,5b pironetin 35c and cryptocarya diace-
tate 45d (Fig. 1). A representative example of this class is
tarchonanthuslactone 5, an a,b-unsaturated d-lactone, iso-
lated by Bohlmann from the leaves of a tree called Tarcho-
nanthus trilobus in 1979.6 Its absolute configuration was
later established by Nakata et al. by asymmetric synthesis.7k
Hsu et al. revealed that tarchonanthuslactone lowers plasma
glucose in diabetic rats.8 Owing to this interesting biological
The Prins cyclisation has been emerged as a powerful syn-
thetic tool for the construction of multisubstituted tetra-
hydropyran system9 and has been utilised in the synthesis of
several natural products.10 We have recently explored the
utility of Prins cyclisation in the synthesis of various poly-
ketide intermediates and applied it in the synthesis of some
natural products.11 As a part of this ongoing programme,
we investigated the synthesis of tarchonanthuslactone.
In our retrosynthetic analysis (Fig. 2), we envisioned that the
target molecule could be achieved from 14 through ring
closing metathesis (RCM) and esterification with relevant
O
O
O
O
OH OH
O
OH OH
OMe OH
O
( )14
OH
strictifolione 1
passifloricin A 2
pironetin 3
O
O
O
HO
HO
O
O
O
OAc OAc
(-)-tarchonanthuslactone 5
Cryptocarya diacetate 4
Figure 1.
Keywords: 5,6-Pyrones; Prins cyclisation; Ring closing metathesis.
* Corresponding author. Tel.: +91 40 27193030; fax: +91 40 27160512; e-mail: yadavpub@iict.res.in
0040–4020/$ - see front matter Ó 2007 Published by Elsevier Ltd.
doi:10.1016/j.tet.2007.01.019

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J. S. Yadav et al. / Tetrahedron 63 (2007) 2689–2694
O
OH
MOMO
OH
MOMO
O
Et
Et
5
O
7
14
6
crotonaldehyde
Prins cyclisation
OH
9
Figure 2.
aromatic fragment. Compound 14 was viewed to obtain from
6 via Mitsunobu inversion. It was proposed to obtain the 1,3-
diol 6 from 7 via allylic cleavage and in turn 7 would be
obtained via Prins cyclisation of homoallylic alcohol 9 and
crotonaldehyde.
as its MOM ether 12 and cleavage of the TBS group in the
presence of TBAF afforded alcohol 6. Alcohol 6 when sub-
jected to standard Mitsunobu inversion conditions (DEAD,
PPh3, p-nitrobenzoic acid in THF then K2CO3 in MeOH)15
yielded 13 with required syn-1,3-diol system. Alcohol 13
was then transformed into its acrylic ester 14 and subjected
to RCM in the presence of Grubbs’ G216a,b to furnish 15.
Of note was the failure of the RCM reaction with Grubbs’
G116c catalyst; the failure of which may be attributed to
the presence of an internal double bond. Deprotection of
MOM ether 15 using TFA in CH2Cl2 (1:5) provided the
corresponding alcohol 16, which on esterification with
acid 177h in the presence of DCC and DMAP yielded ester
15. Deprotection of the TBS groups in 18 using TBAF in
THF furnished the target molecule 5, which in all respects
was identical to the reported natural product.7h
2. Results and discussion
The synthesis of tarchonanthuslactone is described in
Scheme 1. Cu mediated opening12 of epoxide in (R)-propyl-
ene oxide 8 (obtained via Jacobson’s HKR methodology)13
with vinyl magnesium bromide yielded homoallylic alcohol
9.14 The Prins cyclisation of 9 with crotonaldehyde in
presence of TFA followed by hydrolysis of the resulting tri-
fluoroacetate yielded tetrahydropyran 7 in 70% yield. TBS
protection of 7 with TBSCl, DMAP and imidazole provided
the corresponding TBS ether 10, which when treated with
Na in liquid ammonia underwent clean allylic cleavage to
furnish 1,3-diol 11 in 90% yield. Diol 11 after protecting
3. Conclusion
In conclusion, we proved the versatility of the Prins cyclisa-
tion in natural product synthesis by achieving the total syn-
thesis of tarchonanthuslactone 5. Further applications of the
Prins cyclisation in the synthesis of natural products are in
progress and will be disclosed in due course.
OR
OH
OTBS
11
a
d
b
Et
O
OH
9
O
8
7, R = H
c
10, R= TBS
4. Experimental
4.1. General
MOMO
f
OR
MOMO
OH
e
g
h
Et
Et
12, R = TBS
6, R = H
13
O
Commercial reagents were used without further purification.
All solvents were purified by standard techniques. Infrared
(IR) spectra were recorded on a Perkin–Elmer 683 spectro-
meter. Optical rotations were obtained on Jasco Dip 360
digital polarimeter. NMR spectra were recorded in CDCl3
solvent on a Varian Gemini 200, Bruker 300 or Varian Unity
400 NMR spectrometers. Chemical shifts (d) are quoted in
parts per million and are referenced to tetramethylsilane
(TMS) as an internal standard. Coupling constants (J) are
quoted in hertz. Column chromatographic separations were
carried out on silica gel (60–120 mesh) and flash chromato-
graphic separations were carried out using 230–400 mesh
size silica gel. Mass spectra were obtained on Finnegan
MAT 1020B or micro mass VG 70-70H spectrometer oper-
ating at 70 eV using a direct inlet system.
O
O
OR
MOMO
O
k
i
Et
TBSO
COOH
14
15, R = MOM
16, R = H
17
j
TBSO
O
O
TBSO
TBSO
O
O
l
5
18
Scheme 1. Reagents and conditions: (a) CH2]CHMgBr, CuBr, THF,
ꢀ78 ꢁC to ꢀ40 ꢁC, 6 h, 80%; (b) crotonaldehyde, TFA, CH2Cl2, rt, 4 h,
then K2CO3, MeOH, rt, 1 h, 70%; (c) TBSCl, imidazole, DMAP, CH2Cl2,
0 ꢁC–rt, 4 h, 92%; (d) Na, liquid NH3, THF, ꢀ33 ꢁC, 45 min, 90%; (e)
MOMCl, DIPEA, DMAP, CH2Cl2, 0 ꢁC–rt, 4 h, 92%; (f) TBAF, THF,
0 ꢁC–rt, 4 h, 94%; (g) p-NO2CH2CO2H, DEAD, Ph3P, THF, 0 ꢁC–rt,
30 min, then K2CO3, MeOH, rt, 4 h, 75%; (h) acryloyl chloride, TEA,
DMAP, CH2Cl2, 0 ꢁC–rt, 1 h, 84%; (i) Grubbs’ G2 catalyst, CH2Cl2, rt,
12 h, 60%; (j) TFA/CH2Cl2 (1:5), 0 ꢁC–rt, 2 h, 85%; (k) 17, DCC, DMAP,
5 h, 0 ꢁC–rt, 83% and (l) TBAF, benzoic acid, THF, rt, 1 h, 82%.
4.1.1. (R)-4-Penten-2-ol 9. To a solution of magnesium
(6.7 g, 275 mmol) in dry THF (220 mL) at room temperature

J. S. Yadav et al. / Tetrahedron 63 (2007) 2689–2694
2691
were sequentially added 1,2-dibromoethane (0.6 mL,
6.85 mmol) and freshly prepared vinyl bromide (19.6 mL,
chromatography (3% EtOAc/hexane) afforded TBS ether
10 (3.34 g, 92%) as a colourless oil. Rf ¼0.7 (SiO2, 10%
EtOAc in hexane); [a]D25 +2.32 (c 2.0, CHCl3); IR (Neat):
275 mmol) in
a dropwise manner. CuCN (617 mg,
1
6.85 mmol) was added after allowing the reaction mixture
to stir for 0.5 h. Then the mixture was cooled to ꢀ78 ꢁC
and propylene oxide 8 (8.0 g, 137 mmol) in THF (30 mL)
was added and the mixture warmed to ꢀ40 ꢁC. After stirring
the mixture for 4 h at ꢀ40 ꢁC, saturated NH4Cl solution
(100 mL) was added and the mixture extracted with EtOAc
(2ꢂ30 mL). The combined organic layers were washed with
brine (50 mL), dried over Na2SO4 and concentrated under
reduced pressure. Purification by column chromatography
(12% EtOAc/hexane) afforded 9 (9.48 g, 80%) as a colour-
less liquid. Rf ¼0.45 (SiO2, 20% EtOAc in hexane); [a]D20
+10.2 (c 2.5, Et2O) (lit.:14 10.86 (c 3.2, Et2O)); IR (Neat):
n¼2933, 2856, 1635, 1078, 772 cmꢀ1; H NMR (CDCl3,
300 MHz): d 5.64 (dt, 1H, J¼15.6, 6.2 Hz), 5.44 (dd, 1H,
J¼15.6, 6.2 Hz), 3.82–3.58 (m, 2H), 3.51–3.28 (m, 1H),
1.87–1.62 (m, 5H), 1.29–1.05 (m, 5H), 0.86 (s, 9H), 0.03
(s, 6H); 13C NMR (CDCl3, 75.467 MHz): d 131.7, 127.3,
76.2, 71.5, 68.7, 43.2, 41.4, 25.8, 21.8, 18.0, 17.7, ꢀ4.5;
MS (ESI): m/z 293 (M+Na)+, 271 (M+H)+. Anal. Calcd for
C15H30O2Si (270.48): C, 66.61; H, 11.18%. Found: C,
66.27; H, 11.09%.
4.1.4. (E/Z,2R,4R)-2-(Hydroxy)non-6-en-4-yloxy(tert-
butyl)dimethylsilane 11. To a solution of sodium (1.53 g,
66 mmol) in liquid NH3 (15 mL) was added TBS ether 10
(1.8 g, 6.6 mmol) in dry THF (8 mL). The mixture was
stirred for 45 min at ꢀ33 ꢁC and then solid NH4Cl (3.56 g,
66 mmol) was added after cooling the mixture to ꢀ78 ꢁC.
NH3 was allowed to evaporate and the residual mixture
was taken up in ethyl acetate (20 mL) and washed with water
(8 mL), brine (8 mL) and dried over anhydrous Na2SO4.
Evaporation of the solvent and chromatography (20%
EtOAc/hexane) of the crude afforded 11 (1.38 g, 90% yield)
as a colourless liquid. Rf ¼0.2 (SiO2, 25% EtOAc in hexane);
IR (Neat): n¼3445, 2929, 2856, 1633, 1064, 834 cmꢀ1; 1H
NMR (CDCl3, 300 MHz): d 5.53–5.20 (m, 2H), 4.20–4.02
(m, 1H), 3.99–3.85 (m, 1H), 2.11–1.89 (m, 2H), 1.67–1.46
(m, 4H), 1.30–1.10 (m, 5H), 0.99–0.87 (m, 12H), 0.09 (s,
3H), 0.07 (s, 3H); 13C NMR (CDCl3, 75.467 MHz):
d 135.0, 131.0, 125.0, 124.4, 71.8, 67.7, 67.5, 64.4, 44.2,
37.5, 28.6, 25.7, 25.6, 23.8, 22.8, 17.9, 17.8, ꢀ4.5, ꢀ4.8,
ꢀ5.0; MS (LSI): m/z 295.2 (M+Na)+, 273.1 (M+H)+.
Anal. Calcd for C15H32O2Si (272.50): C, 66.12; H,
11.84%. Found: C, 65.38; H, 11.53%.
n¼3447, 2924, 1635, 759 cmꢀ1
;
1H NMR (CDCl3,
300 MHz): d 5.84–5.56 (m, 1H), 5.10–4.91 (m, 2H), 3.83–
3.67 (m, 1H), 2.73–2.33 (br s, 1H), 2.11 (t, 2H, J¼6.7 Hz),
1.08 (d, 3H, J¼5.9 Hz); 13C NMR (CDCl3, 75.467 MHz):
d 134.7, 117.3, 66.7, 43.4, 22.4; MS (ESI): m/z 87 (M+H)+.
4.1.2. (2R,4S,6R)-Tetrahydro-2-methyl-6-[(E)-prop-1-
enyl]-2H-pyran-4-ol 7. Trifluoroacetic acid (53.7 mL,
697 mmol) was added slowly to a solution of the homo-
allylic alcohol 9 (2.0 g, 23 mmol) and crotonaldehyde
(4.88 g, 69 mmol) in CH2Cl2 (90 mL) at room temperature
under a nitrogen atmosphere. The reaction mixture was
stirred for 4 h and then saturated aqueous sodium hydrogen
carbonate solution (100 mL) was added and the pH was
adjusted to >7 by the addition of triethylamine. The layers
were then separated and the aqueous layer was extracted
with CH2Cl2 (4ꢂ40 mL) and the organic layers were com-
bined, dried and the solvent was removed under reduced
pressure. The residue was dissolved in methanol (30 mL)
and stirred with potassium carbonate (6.4 g, 46 mmol) for
1 h. After removing MeOH under reduced pressure, water
(30 mL) was added. The mixture was extracted with di-
chloromethane (3ꢂ30 mL) and the combined organic layers
were dried (MgSO4) and the solvent was removed under
reduced pressure. Column chromatography (15% EtOAc/
hexane) afforded pure product 7 (3.89 g, 70% yield) as a
colourless liquid. Rf ¼0.15 (SiO2, 20% EtOAc in hexane);
[a]2D5 +8.78 (c 2.25, CHCl3); IR (Neat): n¼3441, 2924,
4.1.5. (E/Z,2R,4R)-2-(Methoxymethoxy)non-6-en-4-
yloxy(tert-butyl)dimethylsilane 12. To alcohol 11 (1.5 g,
5.5 mmol) in anhydrous CH2Cl2 (12 mL) at 0 ꢁC were added
diisopropylethylamine (2.13 g, 16.5 mmol), catalyticDMAP
(8 mg) and MOMCl (0.88 g, 11.0 mmol) successively and
the mixturewas stirred for 4 h atroom temperature, quenched
by adding water (8 mL) and extracted with CH2Cl2
(3ꢂ8 mL). The organic extracts were washed with brine
(8 mL), dried over anhydrous Na2SO4 and concentrated
under vacuum to remove the solvent and the crude residue
was purified by column chromatography (6% EtOAc/
hexane) to afford the MOM ether 12 (1.6 g, 92%) as colour-
less oil. Rf ¼0.4 (SiO2, 10% EtOAc in hexane); IR (Neat):
2853, 1636, 760 cmꢀ1 1H NMR (CDCl3, 300 MHz):
;
d 5.64 (dt, 1H, J¼15.4, 6.2 Hz), 5.48 (dd, 1H, J¼15.4,
6.2 Hz), 3.82–3.67 (m, 2H), 3.52–3.38 (m, 1H), 1.96–1.87
(m, 2H), 1.71 (d, 3H, J¼6.2 Hz), 1.39 (br s, 1H), 1.26–
1.04 (m, 5H); 13C NMR (CDCl3, 75.467 MHz): d 131.4,
127.4, 76.0, 71.4, 67.8, 42.6, 40.8, 21.6, 17.6; MS (ESI):
m/z 157 (M+H)+. Anal. Calcd for C9H16O2 (156.22): C,
69.20; H, 10.32%. Found: C, 68.91; H, 9.98%.
1
n¼2930, 2857, 1635, 1042, 769 cmꢀ1; H NMR (CDCl3,
300 MHz): d 5.52–5.29 (m, 2H), 4.66–4.55 (m, 2H), 4.00–
3.57 (m, 2H), 3.34 (s, 1.5H), 3.33 (s, 1.5H), 2.09–1.96 (m,
2H), 1.67–1.41 (m, 4H), 1.18–1.12 (m, 3H), 1.01–0.82 (m,
12H), 0.04 (s, 6H); 13C NMR (CDCl3, 75.467 MHz):
d 131.2, 130.9, 125.0, 124.7, 96.0, 95.4, 75.5, 71.4, 69.1,
65.8, 55.5, 55.2, 43.2, 41.2, 37.7, 35.2, 28.1, 27.8, 25.8,
24.5, 17.8, 13.7, 10.9, ꢀ3.9, ꢀ4.1, ꢀ4.5; MS (LSI): m/z
339.2 (M+Na)+. Anal. Calcd for C17H36O3Si (316.55): C,
64.50; H, 11.46%. Found: C, 64.14; H, 11.24%.
4.1.3. (2R,4S,6R)-Tetrahydro-2-methyl-6-[(E)-prop-1-
enyl-2H-pyran-4-yloxy](tert-butyl)-dimethylsilane 10.
To a solution of 7 (2.10 g, 13.4 mmol) in dry CH2Cl2
(30 mL) were added catalytic DMAP (10 mg) and imidazole
(1.37 g, 20.0 mmol) in one portion followed by TBSCl
(2.43 mg, 16.0 mmol) in three portions at 0 ꢁC. The reaction
mixture was stirred for 4 h and slowly warmed to room
temperature. It was then quenched by the addition of
saturated NH4Cl solution (15 mL), diluted with CH2Cl2
(30 mL), washed with brine (15 mL), dried (Na2SO4) and
concentrated in vacuo. Purification of the crude by column
4.1.6. (E/Z,2R,4R)-2-(Methoxymethoxy)non-6-en-4-ol 6.
To an ice cold solution of 12 (1.5 g, 4.70 mmol) in dry
THF (10 mL) was added TBAF (5.67 mL, 1 M in THF,

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J. S. Yadav et al. / Tetrahedron 63 (2007) 2689–2694
5.64 mmol). After 15 min of stirring, reaction mixture was
brought to room temperature and stirred for another 4 h.
The reaction mixture was cooled to 0 ꢁC and quenched
with saturated NH4Cl solution (5 mL), extracted with ethyl
acetate (2ꢂ20 mL), dried over anhydrous Na2SO4 and con-
centrated in vacuo. The residue was purified by column chro-
matography (25% EtOAc/hexane) to afford the alcohol 6
(902 mg, 94% yield) as a colourless liquid. Rf ¼0.4 (SiO2,
40% EtOAc in hexane); IR (Neat): n¼3447, 2926, 1736,
130.6, 128.9, 125.5, 125.2, 124.2, 95.5, 94.8, 74.2, 71.3,
70.4, 55.5, 55.2, 41.4, 40.6, 37.5, 34.2, 28.1, 25.6, 20.3,
20.0, 17.7, 13.6; MS (ESI): m/z 279 (M+Na)+. Anal. Calcd
for C14H24O4 (256.34): C, 65.60; H, 9.44%. Found: C,
65.33; H, 9.27%.
4.1.9. (S)-5,6-Dihydro-6-[(R)-2-(methoxymethoxy)pro-
pyl]pyran-2-one 15. Grubbs’ G2 catalyst (66.3 mg,
5 mol %) was dissolved in 10 mL of degassed CH2Cl2 and
was added dropwise to a solution of the acrylic ester 14
(400 mg, 1.56 mmol) in 40 mL of degassed CH2Cl2. The
reaction mixture was stirred at room temperature for 12 h
by which time all of the starting material was consumed
(TLC). The solvent was removed under vacuum and the
crude product was purified by silica gel column chromato-
graphy (20% EtOAc/hexane) to obtain 15 (187 mg, 60%
yield) as a colourless oil. Rf ¼0.3 (SiO2, 30% EtOAc in
hexane); [a]2D5 ꢀ6.5 (c 0.5, CHCl3); IR (Neat): n¼2925,
1
1638, 1036 cmꢀ1; H NMR (CDCl3, 300 MHz): d 5.54–
5.26 (m, 2H), 4.75–4.56 (m, 2H), 4.14–3.67 (m, 2H), 3.40
(s, 1.5H), 3.39 (s, 1.5H), 2.35–1.93 (m, 2H), 1.66–1.36 (m,
4H), 1.26–1.12 (m, 3H), 1.04–0.89 (m, 3H); 13C NMR
(CDCl3, 75.467 MHz): d 130.5, 125.2, 124.3, 124.0, 96.1,
95.3, 75.6, 71.3, 71.1, 67.4, 63.9, 55.6, 55.4, 42.8, 40.8,
37.9, 34.6, 28.3, 25.5, 20.5, 20.3, 17.7; MS (LSI): m/z
225.1 (M+Na)+. Anal. Calcd for C11H22O3 (202.29): C,
65.31; H, 10.96%. Found: C, 65.45; H, 10.73%.
2853, 1718, 1648, 1247, 1033 cmꢀ1 1H NMR (CDCl3,
;
4.1.7. (E/Z,2R,4S)-2-(Methoxymethoxy)non-6-en-4-ol 13.
To a stirred mixture of 6 (1.1 g, 5.4 mmol), triphenylphos-
phine (4.56 g, 17.4 mmol) and p-nitrobenzoic acid (1.18 g,
7.0 mmol) in dry THF (20 mL) at 0 ꢁC was added diethyl-
azodicarboxylate (3.03 g, 17.4 mmol) via a syringe. The re-
action mixturewas then stirred for 0.5 h at room temperature,
diluted with water (10 mL) and extracted with ethyl acetate
(2ꢂ15 mL). After removing the solvent, the crude residue
was dissolved in MeOH (10 mL) and K2CO3 was added
(1.5 g, 10.8 mmol). After stirring the mixture for 4 h at
room temperature, it was diluted with water (15 mL) and ex-
tracted with CH2Cl2 (3ꢂ10 mL). Removal of solvent under
reduced pressure followed by flash chromatography (25%
EtOAc/hexane) afforded 13 (825 mg, 75% yield) as a colour-
less liquid. Rf ¼0.4 (40% EtOAc in hexane); IR (Neat):
300 MHz): d 6.85 (ddd, 1H, J¼9.8, 5.2, 3.0 Hz), 6.01 (dt,
1H, J¼9.8, 1.5 Hz), 4.64 (d, 1H, J¼6.7 Hz), 4.63–4.53 (m,
2H), 3.97–3.84 (m, 1H), 3.33 (s, 3H), 2.42–2.28 (m, 1H),
2.19–2.07 (m, 1H), 1.80–1.55 (m, 2H), 1.25 (d, 3H,
J¼6.5 Hz); 13C NMR (CDCl3, 75.467 MHz): d 164.1,
144.8, 121.5, 96.1, 75.2, 69.7, 55.4, 41.8, 29.4, 20.1; MS
(ESI): m/z 223.1 (M+Na)+, 201.0 (M+H)+. Anal. Calcd for
C10H16O4 (200.23): C, 59.99; H, 8.05%. Found: C, 59.62;
H, 7.81%.
4.1.10. [5(S),7(R)]-7-Hydroxy-5-(oct-2-enolide) 16. Com-
pound 15 (200 mg, 1.0 mmol) dissolved in CH2Cl2
(1.8 mL) and then TFA (456 mg, 4 mmol) was added drop-
wise at room temperature. After stirring the mixture at the
same temperature for 2 h, the reaction mixture was quenched
with saturated NaHCO3 solution (8 mL) and extracted with
CH2Cl2 (2ꢂ8 mL). The combined organic extracts were
washed with brine (8 mL), concentrated in vacuo and the
residue subjected to column chromatography (20% EtOAc/
hexane) to afford alcohol 16 (132 mg, 85% yield) as a colour-
less oil. Rf ¼0.3 (SiO2, 30% EtOAc in hexane); [a]2D5 ꢀ111
(c l, CHCl3); IR (Neat): n¼3422, 2925, 2855, 1712, 1387,
1
n¼3445, 2962, 2932, 1608, 1100, 1037 cmꢀ1; H NMR
(CDCl3, 300 MHz): d 5.59–5.19 (m, 2H), 4.83–4.53 (m,
2H), 4.05–3.64 (m, 2H), 3.38 (s, 1.5H), 3.37 (s, 1.5H), 3.06
(br s, 1H), 2.37–1.94 (m, 3H), 1.80–1.41 (m, 3H), 1.30–
0.85 (m, 6H); 13C NMR (CDCl3, 75.467 MHz): d 134.1,
130.5, 124.7, 123.9, 95.1, 94.4, 73.4, 73.0, 67.1, 55.7, 55.5,
44.1, 43.2, 40.7, 37.6, 28.4, 25.5, 23.4, 20.6, 20.2, 17.7;
MS (LSI): m/z 225.1 (M+Na)+. Anal. Calcd for C11H22O3
(202.29): C, 65.31; H, 10.96%. Found: C, 65.08; H, 10.61%.
1253, 1117, 1049 cmꢀ1 1H NMR (CDCl3, 300 MHz):
;
d 6.9 (ddd, J¼10.0, 8.5, 4.0 Hz), 6.0 (dt, 1H, J¼10.0,
2.0 Hz), 4.82–4.53 (m, 1H), 4.35–4.00 (m, 1H), 2.28–2.49
(m, 2H), 2.10–1.45 (m, 2H), 1.24 (d, 3H, J¼6.0 Hz); 13C
NMR (CDCl3, 75.467 MHz): d 164.2, 145.5, 121.2, 76.8,
65.2, 43.3, 29.8, 23.7; MS (ESI): m/z 157 (M+H)+. Anal.
Calcd for C8H12O3 (156.18): C, 61.52; H, 7.74%. Found:
C, 61.29; H, 7.43%.
4.1.8. (E/Z,2R,4S)-2-(Methoxymethoxy)non-6-en-4-yl-
acrylate 14. The alcohol 13 (600 mg, 2.97 mmol) was dis-
solved in 10 mL of CH2Cl2 and to the solution was added
sequentially catalytic DMAP (5 mg), acryloyl chloride
(403 mg, 4.45 mmol) and Et3N (0.54 mL, 5.94 mmol) at
0 ꢁC. After stirring the reaction mixture for 1 h at room
temperature, diluted with water (10 mL) and extracted
with CH2Cl2 (2ꢂ10 mL). The combined organic extracts
were washed with brine (10 mL) and concentrated in vacuo.
The residue was purified by column chromatography (4%
EtOAc/hexane) to afford 14 (638 mg, 84% yield) as a colour-
less liquid. Rf ¼0.6 (SiO2, 10% EtOAc in hexane); IR (Neat):
4.1.11. 30,40-Bis(tert-butyldimethylsilyloxy)hydrocin-
namic acid 17. To a stirred solution of 30,40-dihydroxy-
hydrocinnamic acid (900 mg, 2.2 mmol) in dry DMF
(10 mL) were added imidazole (1.34 g, 19.8 mmol) and
tert-butyldimethylsilyl chloride (1.49 g, 10 mmol). After
48 h at room temperature, the mixture was diluted with ether
(40 mL) and water (10 mL). The mixture was stirred until
a clear phase-separation appeared and then extracted with
ether (4ꢂ40 mL). The combined organic layers were washed
with saturated NH4Cl (3ꢂ100 mL) and brine (2ꢂ100 mL),
dried (Na2SO4) and concentrated under reduced pressure.
Silica gel column chromatography (15% EtOAc/hexane)
of the residue gave the acid 17 as a white solid (846 mg,
1
n¼2930, 1637, 1405, 1197, 1038 cmꢀ1; H NMR (CDCl3,
300 MHz): d 6.37 (dd, 1H, J¼18.7, 1.5 Hz), 6.14–6.02 (m,
1H), 5.83–5.77 (m, 1H), 5.55–5.27 (m, 2H), 4.66–4.52 (m,
3H), 3.73–3.53 (m, 1H), 3.36 (s, 1.5H), 3.35 (s, 1.5H),
2.33–2.15 (m, 1H), 2.11–1.84 (m, 2H), 1.70–1.50 (m, 3H),
1.36–1.15 (m, 4.5H), 1.01–0.93 (m, 1.5H); 13C NMR
(CDCl3, 75.467 MHz): d 165.5, 135.8, 135.3, 134.7, 134.0,

J. S. Yadav et al. / Tetrahedron 63 (2007) 2689–2694
2693
94% yield). Mp 87–88 ꢁC; Rf ¼0.2 (SiO2, 20% EtOAc in
Acknowledgements
hexane); IR (Neat): n¼3060, 2840, 1710, 1600, 1575,
1
1500, 1450 cmꢀ1; H NMR (CDCl3, 300 MHz): d 6.74 (d,
N.N.K. thanks UGC and M.S.R. thanks CSIR, New Delhi for
the award of fellowship.
1H, J¼8.0 Hz), 6.67 (d, 1H, J¼2 Hz), 6.63 (dd, 1H,
J¼8.0, 2.0 Hz), 2.84 (t, 2H, J¼7.5 Hz), 2.62 (t, 2H,
J¼7.5 Hz), 0.98 (s, 18H), 0.18 (s, 12H); 13C NMR
(CDCl3, 75.467 MHz): d 179.6, 146.7, 145.3, 133.3, 121.1,
121.0, 35.9, 29.9, 25.9, 18.4, ꢀ4.1; MS (ESI): m/z 428.6
(M+NH4)+. Anal. Calcd for C21H38O4Si2 (410.69): C,
61.42; H, 9.33%. Found: C, 61.04; H, 8.95%.
Supplementary data
Supplementary data associated with this article can be found
in the online version, at doi:10.1016/j.tet.2007.01.019.
4.1.12. [5(S),7(R)]-7-[S-(Oct-2-enolide)30,40-tris(tert-
butyldimethylsilyloxy)]dihydrocinnamate 18. To a solu-
tion of alcohol 16 (106 mg, 0.68 mmol) in CH2Cl2 (20 mL)
were added acid 17 (308 mg, 0.75 mmol) and DCC
(155 mg, 0.75 mmol) at room temperature. DMAP (41 mg,
0.34 mmol) was then added and stirring continued for
15 h. Filtration of the reaction mixture, evaporation of the
solvent and column chromatography (15% EtOAc/hexane)
of the resulting crude afforded ester 18 (312 mg, 83% yield)
as a colourless oil. Rf ¼0.2 (SiO2, 20% EtOAc in hexane);
[a]2D5 ꢀ44 (c l, CHCI3); IR (Neat): n¼2960, 2860, 1740,
References and notes
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1690, 1600, 1575, 1500, 1450 cmꢀ1 1H NMR (CDCl3,
;
300 MHz): d 6.80 (ddd, 1H, J¼10, 5.5, 3.0 Hz), 6.68 (d,
1H, J¼8.0 Hz), 6.63 (d, 1H, J¼2.0 Hz), 6.58 (dd, 1H,
J¼8.0, 2.0 Hz), 5.96 (ddd, 1H, J¼10, 2.0, 1.0 Hz), 5.07
(ddq, 1H, J¼8.0, 6.5, 6.0 Hz), 4.39 (m, 1H), 2.78 (t, 2H,
J¼7.5 Hz), 2.52 (t, 2H, J¼7.5 Hz), 2.40–2.21 (m, 2H),
1.94 (m, 2H), 1.22 (d, 3H, J¼6 Hz), 0.95 (s, 12H), 0.94 (s,
3H), 0.16 (s, 12H), 0.14 (s, 3H); 13C NMR (CDCl3,
75.467 MHz): d 172.3, 163.8, 146.5, 145.1, 144.7, 133.3,
121.17, 121.02, 120.97, 120.76, 74.8, 67.0, 40.7, 36.1,
30.1, 29.0, 25.8, 20.2, 18.3, ꢀ4.2; MS (ESI): m/z 549
(M+H)+. Anal. Calcd for C29H48O6Si2 (548.86): C, 63.46;
H, 8.81%. Found: C, 62.51; H, 8.57%.
4.1.13. Tarchonanthuslactone 5. A solution of compound
18 (272 mg, 0.49 mmol) in THF (20 mL) was treated with
benzoic acid (180 mg, 0.15 mmol) and with a 1.1 M solution
of TBAF in THF (4.5 mL, 5 mmol) and then stirred at room
temperature for 1 h. The solvent was evaporated and AcOEt
(20 mL) and water (20 mL) were added to the residue. The
aqueous layer was saturated with sodium chloride and
extracted with AcOEt (4ꢂ30 mL). The combined organic
layers were washed with water (2ꢂ50 mL) and brine
(2ꢂ50 mL), dried (Na2SO4) and the solvent evaporated.
The crude product was purified by column chromatography
(ether) to give tarchonanthuslactone 5 (130 mg, 82% yield)
as a white solid. Mp 89–90 ꢁC (lit.:7h 89–90 ꢁC); Rf ¼0.32
(ether); [a]2D5 ꢀ81 (c 0.35, CHCl3) (lit.:7h ꢀ83 (c 0.4,
CHCl3)); IR (Neat): n¼3341, 2925, 2853, 1715, 1606,
1522, 1445 cmꢀ1
;
1H NMR (CDCl3, 300 MHz): d 6.80
8. Hsu, F. L.; Chen, Y. C.; Cheng, J. T. Planta Med. 2000, 66,
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(ddd, 1H, J¼10.0, 6.0, 3.0 Hz), 6.73 (d, 1H, J¼8.0 Hz),
6.7 (d, 1H, J¼2.0 Hz), 6.53 (br s, 2H), 6.53 (dd, 1H,
J¼8.0, 2.0 Hz), 5.96 (ddd, 1H, J¼10.0, 2.0, 1.0 Hz), 5.04
(qdd, 1H, J¼8.0, 7.0, 6.5 Hz), 4.21 (dddd, 1H, J¼11.0,
6.5, 4.5, 6.0 Hz), 2.79 (t, 2H, J¼7.0 Hz), 2.57 (t, 2H,
J¼7.0 Hz), 2.34–2.13 (m, 2H), 1.89 (m, 2H), 1.21 (d, 3H,
J¼6.5 Hz); 13C NMR (CDCl3, 75.467 MHz): d 173.0,
165.3, 146.0, 144.0, 142.4, 132.4, 120.5, 120.1, 115.2,
75.2, 67.2, 40.5, 36.0, 30.1, 28.8, 20.2. MS (ESI): m/z 321
(M+H)+. Anal. Calcd for C17H20O6 (320.33): C, 63.74; H,
6.29%. Found: C, 63.37; H, 6.08%.
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