Asymmetric synthesis of the diene unit of methyl sartortuoate via a temperature-sensitive intramolecular Horner-Wadsworth-Emmons (HWE) reaction

Article abstract of DOI:10.1055/s-2007-967970

The asymmetric synthesis of the diene unit of methyl sartortuoate is described. A temperature-sensitive intramolecular Horner-Wadsworth-Emmons reaction was employed for the construction of the 14-membered ring. A Payne rearrangement of an 2,3-epoxy alcoho

Full text of DOI:10.1055/s-2007-967970

LETTER
571
Asymmetric Synthesis of the Diene Unit of Methyl Sartortuoate via a
Temperature-Sensitive Intramolecular Horner–Wadsworth–Emmons (HWE)
Reaction
A
symmetric Synth
e
esis of the
D
q
iene Unit
o
u
f
Methyl Sar
a
tortuoate n Yao, Yuan Gao, Peng Liu, Bingfeng Sun, Xingxiang Xu*
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, P. R. of China
Fax +86(21)64166128; E-mail: xuxx@mail.sioc.ac.cn
Received 15 November 2006
Abstract: The asymmetric synthesis of the diene unit of methyl
sartortuoate is described. A temperature-sensitive intramolecular
Horner–Wadsworth–Emmons reaction was employed for the con-
struction of the 14-membered ring. A Payne rearrangement of an
2,3-epoxy alcohol was utilized for the installation of the hydroxyl
group at the C14 position of the diene unit.
O
O
O
O
O
COOMe
COOMe
OH
OH
O
O
H
O
H
O
Key words: asymmetric synthesis, methyl sartortuoate, diene unit,
HWE reaction, Payne rearrangement
H
H
H
OH
HO
methyl sartortuoate (1)
methyl isosartortuoate (2)
O
Methyl sartortuoate (1) and methyl isosartortuoate (2),
two representative members of the structurally novel class
of biscembranoids, were isolated from the marine Sarco-
phyton tortuosum tixierduriant by Su et al. (Figure 1).1,2
The relative configurations of 1 and 2 were elucidated by
extensive NMR studies and their absolute stereochemistry
was supported by X-ray analysis.1 A preliminary bioassay
proved that both of them displayed inhibitory effects
against mice S180 and cytotoxic activities towards KB
cells.1 Biogenetically, 1 and 2 are proposed to be formed
by a biosynthetic Diels–Alder reaction of two cem-
brenanes as the precursors. Although none of such precur-
sors of 1 and 2 have been isolated, the hypothesis is
supported by the isolation of methyl sarcoate (4),2b a di-
enophile unit of methyl sarcophytoate (3).2a While the po-
tential bioactivity and the intriguing structural features as
well as the interesting biogenetic possibility have aroused
some synthetic interest, the total synthesis of these bis-
cembranoids has not been reported to date. Nakata et al.
has reported the elegant asymmetric synthesis of both the
diene unit and the dienophile unit (i.e. 4) of 3.3 Previously,
we reported the asymmetric synthesis of the dienophile
unit of 1 and 2, and in this communication we describe the
asymmetric synthesis of the diene unit (i.e. 5) of 1.4
O
O
H
H
COOMe
O
O
COOMe
O
H
HO
O
HO
methyl sarcophytoate (3)
methyl sarcoate (4)
Figure 1 Selected biscembranoids 1–3 and methyl sarcoate (4)
1
Diels–Alder
OMOM
OMOM
O
O
HO
OH OH
OMOM
OMOM
OAc
6
5
OMOM
OMOM
O
O
O
EtOOC
OMOM
OH
OMOM
8
Our initial retrosynthetic analysis of 5 is outlined in
Scheme 1. We envisaged that the triene moiety of 5 could
be derived from a triol 6, which, in turn, would be
achieved by opening of a 2,3-epoxy alcohol 7. An in-
tramolecular HWE reaction of an aldehyde phosphono-
acetate 9 would be employed for the crucial cyclization to
secure the 14-membered ring of 8. Finally, 9 could be
derived from a functionalized tetrahydropyran 10.
7
P(O)(OEt)2
OMOM
OMOM
TBDPSO
EtOOC
O
O
O
H
HO
OMOM
OH
9
10
SYNLETT 2007, No. 4, pp 0571–0574
Advanced online publication: 21.02.2007
0
1.
0
3.
2
0
0
7
Scheme 1 Retrosynthetic analysis of 5
DOI: 10.1055/s-2007-967970; Art ID: W23006ST
© Georg Thieme Verlag Stuttgart · New York

572
H. Yao et al.
LETTER
The synthesis of the required precursor for the HWE reac- cyclization conditions, we investigated the temperature
tion commenced with compound 10, which has been pre- effect. The results in Table 1 demonstrate that the reaction
pared previously in our laboratory (Scheme 2).4d Thus, was temperature dependent. When the reaction was per-
selective tosylation of the primary hydroxyl group of 10, formed at 0 °C (entry 1), the desired product 811 and the
followed by treatment with KCN and protection of the side product 15 were obtained in 1:1 ratio with moderate
tertiary alcohol with MOMCl provide the ether 11.
yield, whereas at 8–24 °C (entries 2–5), 8 became the
major product and was obtained as a single E-isomer12 at
C1–C14. Surprisingly, when the reaction was performed
at 30 °C, only the side product 15 was formed in this reac-
tion (entry 6).
OMOM
OMOM
TBDPSO
TBDPSO
O
a–c
O
HO
NC
OH
OMOM
Table 1 Optimization of the Intramolecular HWE Reactiona
10
11
P(O)(OEt)2
d,e
OMOM
OMOM
EtOOC
EtOOC
O
O
OMOM
O
OMOM
O
TBDPSO
HO
AcO
0–30 °C
O
f, g
O
OMOM
H
H
HO
9
15
+
OMOM
OMOM
13
12
OMOM
O
1
h,i
EtOOC
14
OMOM
P(O)(OEt)2
8
P(O)(OEt)2
AcO
OMOM
OMOM
EtOOC
EtOOC
O
Entry
Temp (°C) Yield (%)
Yield (%)
15/8
O
j, k
O
H
of 15b
of 8b
OMOM
OMOM
1
2
3
4
5
6
0
8
22
22
25
33
46
37
0
1:1
14
9
20
1:1.3
1:2.2
0:1
Scheme 2 Reagents and conditions: (a) TsCl, Et3N, r.t., 95%; (b)
KCN, EtOH–H2O, 70 °C, 91%; (c) MOMCl, DIPEA, KI, CH2Cl2,
96%; (d) DIBAL-H, toluene, –78 °C, then HCl (1 M), 0 °C; (e)
NaBH4, MeOH, 0 °C, 73% for two steps; (f) Ac2O, Et3N, CH2Cl2, r.t.,
96%; (g) TBAF, THF, r.t., 95%; (h) triphosgene, Et3N, CH2Cl2, 0 °C;
(i) EtO2CCH2PO(OEt)2, NaH, DMSO, 0 °C to r.t.; (j) K2CO3, EtOH,
r.t., 82% for three steps; (k) Dess–Martin periodiane, CH2Cl2, r.t.,
92%.
16
20
24
30
15
tracec
10
1:3.7
1:0
50
a Reactions were carried out in DME (0.003 M of 9) using NaH (3.0
equiv) and 18-crown-6 (5 equiv) for 8 h.
b Isolated yield.
Reduction of 11 with DIBAL-H, hydrolysis with 1 N HCl
and further reduction with NaBH4 afforded alcohol 12.
Acylation of the primary alcohol of 12 with Ac2O and
subsequent removal of the TBDPS group yielded the
allylic alcohol 13. Conversion of the hydroxyl group of 13
to the corresponding chloride followed by nucleophilic
displacement with EtO2CCH2PO(OEt)2 afforded 14.
Saponification of the acetyl group of 14 and oxidation of
the resulting alcohol by Dess–Martin periodinane5 afford-
ed the desired aldehyde 9.
c Monitored by TLC.
Upon successful macrocyclization, we focused on the in-
troducing the hydroxyl group at C14 and constructing the
conjugated triene moiety (Scheme 3). Allylic alcohol 16,
which was obtained from the reduction of ester 8 with
DIBAL-H, was epoxidized using Sharpless asymmetric
epoxidation to get the epoxy alcohol 7.13 Initial attempts
to open the epoxide of 7 to introduce 14-OH group utiliz-
ing Sharpless method14 only afforded unreacted starting
material. On the other hand, Payne rearrangement15 of 7
followed by the in situ opening of the equilibrating 1,2-ep-
oxide 17 with 0.5 M of NaOH in t-BuOH at 75 °C smooth-
ly gave the triol 6 as a single isomer in 80% yield. Then,
acylation of 6 with Ac2O in pyridine, followed by elimi-
With precursor 9 in hand, we then constructed the 14-
membered ring using a HWE reaction.6 We examined
different reaction conditions and found that several typi-
cal conditions such as K2CO3–18-crown-6–toluene,7
NaHMDS–THF8 and LiHMDS–THF8 gave a very com-
plicated product mixture. When we tried the reaction
using DBU–LiCl–MeCN,9 9 was transformed into an un-
desirable side product 1510 in 50% yield. The elimination
of MOMO group under basic conditions produced
MOMOH, which served as a carbon atom source for the
intermolecular HWE reaction. Finally, the macrocycliza-
tion was successfully realized when we treated 9 with
NaH and 18-crown-6 in DME. To optimize the macro-
16
nation of tertiary alcohol using SOCl2 provided a con-
jugated diene 2017 in 78% yield. X-ray analysis of this
product confirmed the configurations of all stereocenters
(Figure 2). To the best of our knowledge, this is the first
example utilizing Payne rearrangement to introduce the
hydroxyl group at 14-position of cembranoids. The elim-
Synlett 2007, No. 4, 571–574 © Thieme Stuttgart · New York

LETTER
Asymmetric Synthesis of the Diene Unit of Methyl Sartortuoate
573
ination of the tertiary alcohol of 19 gave 20 and unconju-
gated diene 20a in a 5:1 ratio. Compounds 20 and 20a
could be separated by standard chromatographic methods.
The acetyl group of 20 was then removed with K2CO3 in
EtOH at 0 °C and the resulting alcohol was oxidized with
Dess–Martin oxidation to afford aldehyde 21. Treatment
of 21 with MeMgBr, followed by oxidation yielded ke-
tone 22.18 Due to the poor reactivity of the unsaturated ke-
tone, methylenation of 22 failed under several conditions,
such as Lombardo’s conditions,19 Takai’s conditions20
and Petasis’s conditions.21 Fortunately, treatment of 22
with MeMgBr, followed by dehydration using MsCl and
Et3N smoothly afforded the desired triene unit 5.22
OMOM
O
HO
a
8
OMOM
16
b
OMOM
Figure 2 X-ray crystal structure of 20
OMOM
O
HO
O
c
O
O
In summary, the asymmetric synthesis of the diene unit of
1 has been successfully achieved. Key steps were the tem-
perature-sensitive intramolecular HWE reaction for the
construction of the 14-membered ring and Payne rear-
rangement of 2,3-epoxyl alcohol for the installation of the
hydroxyl group at the 14-position of the diene unit. Efforts
towards the total synthesis of 1 by a Diels–Alder reaction
are still in progress.
OMOM
OMOM
17
7
OH
OMOM
OMOM
OMOM
d
HO
HO
HO
O
O
14
AcO
OMOM
OMOM
OAc
e
OH
6
19
Acknowledgment
This work was supported by Chinese Academy of Sciences and the
National Natural Science Foundation of China.
OMOM
2
O
O
AcO
+
AcO
1
OMOM
OAc
OMOM
OAc
References and Notes
20a
20
(1) (a) Su, J.; Long, K.; Peng, T.; Zheng, Q.; Lin, X. Acta Chim.
Sin. 1985, 43, 796. (b) Su, J.; Long, K.; Peng, T.; Zeng, L.;
Zheng, Q.; Lin, X. Sci. Sin., Ser. B (Engl. Ed.) 1988, 31,
1172. (c) Su, J.; Long, K.; Peng, T.; He, C. H.; Clardy, J. J.
Am. Chem. Soc. 1986, 108, 177.
f, g
OMOM
O
O
(2) For other related compounds, see: (a) Kusumi, T.; Igari, M.;
Ishitsuka, M. O.; Itezono, Y.; Nakayama, N.; Kakisawa, H.
J. Org. Chem. 1990, 55, 6286. (b) Leone, P. A.; Bowden, B.
F.; Carrol, A. R.; Coll, J. C.; Meehan, G. V. J. Nat. Prod.
1993, 56, 521. (c) Zeng, L.; Lan, W.; Su, J.; Zhang, G.;
Feng, X.; Liang, Y.; Yang, X. J. Nat. Prod. 2004, 67, 1915.
(d) Feller, M.; Rudi, A.; Berer, N.; Goldberg, I.; Stein, Z.;
Benayahu, Y.; Schleyer, M.; Kashman, Y. J. Nat. Prod.
2004, 67, 1303. (e) Ishitsuka, M. O.; Kusumi, T.; Kakisawa,
H. Tetrahedron Lett. 1991, 32, 2917.
OMOM
21
H
OAc
h, i
OMOM
OMOM
j, k
O
O
O
OMOM
Me OAc
OMOM
Me OAc
22
5
(3) For synthetic studies on biscembranoids by the Nakata’s
group, see: (a) Yasuda, M.; Ide, M.; Matsumoto, Y.; Nakata,
M. Synlett 1997, 899. (b) Yasuda, M.; Ide, M.; Matsumoto,
Y.; Nakata, M. Bull. Chem. Soc. Jpn. 1998, 71, 1417.
(c) Ichige, T.; Kamimura, S.; Mayumi, K.; Sakamoto, Y.;
Terashita, S.; Ohteki, E.; Kanoh, N.; Nakata, M.
Scheme 3 Reagents and conditions: (a) DIBAL-H, Et2O, –78 °C,
95%; (b) tert-butyl hydroperoxide (TBHP), D-(–)-DIPT, CH2Cl2,
–20 °C, 77%; (c) 0.5 M NaOH, t-BuOH, H2O, r.t. to 75 °C, 63%;
(d) Ac2O, pyridine, r.t., 90%; (e) SOCl2, pyridine, CH2Cl2, 0 °C, 78%;
(f) K2CO3, EtOH, 0 °C, 66%; (g) Dess–Martin periodiane, CH2Cl2,
r.t., 53%; (h) MeMgBr, THF, –78 °C; (i) Dess–Martin periodiane,
NaHCO3, CH2Cl2, r.t., 36% for two steps; (j) MeMgBr, THF, –20 °C;
(k) MsCl, Et3N, CH2Cl2, 0 °C to r.t., 33% for two steps.
Tetrahedron Lett. 2005, 46, 1263.
Synlett 2007, No. 4, 571–574 © Thieme Stuttgart · New York

574
H. Yao et al.
LETTER
(4) (a) Chen, X.; Fan, C.; Xu, X. Chin. J. Chem. 2000, 18, 717.
(b) Hong, Z.; Chen, X.; Xu, X. Tetrahedron Lett. 2003, 44,
485. (c) Hong, Z.; Chen, X.; Xu, X. Tetrahedron Lett. 2003,
44, 489. (d) Gao, Y.; Nan, F.; Xu, X. Tetrahedron Lett.
2000, 41, 4811. (e) Liao, X.; Xu, X. Tetrahedron Lett. 2000,
41, 4641. (f) Liu, P.; Liao, X.; Xu, X. Chin. J. Chem. 2003,
21, 811. (g) Liu, P.; Xu, X. Tetrahedron Lett. 2004, 45,
5163.
(5) (a) Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155.
(b) Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1991, 113,
7277.
(6) (a) Marynoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89, 863.
(b) Burri, K. F.; Cardone, R. A.; Chen, W. Y.; Rosen, P. J.
Am. Chem. Soc. 1978, 100, 7069.
(7) (a) Paquette, L. A.; Wang, T. Z.; Philippo, C.; Wang, S. P. J.
Am. Chem. Soc. 1991, 113, 7277. (b) Nicolaou, K. C.; Seitz,
S. P.; Pavia, M. R. J. Am. Chem. Soc. 1982, 104, 2030.
(8) Stock, G.; Nakamura, E. J. Org. Chem. 1979, 44, 4010.
(9) Blanchette, M. A.; Choy, W.; Davis, J. T.; Essenfeld, A. P.;
Masamune, S.; Roush, W. R.; Saka, T. Tetrahedron Lett.
1984, 25, 2183.
(13) Gao, Y.; Klunder, J. M.; Hanson, R. M.; Masamune, H.; Ko,
S. Y.; Sharpless, K. B. J. Am. Chem. Soc. 1987, 109, 5765.
(14) (a) Caron, M.; Sharpless, K. B. J. Org. Chem. 1985, 50,
1557. (b) Chong, J. M.; Sharpless, K. B. J. Org. Chem. 1985,
50, 1560.
(15) Payne, G. B. J. Org. Chem. 1962, 27, 3819.
(16) Trost, B. M.; Madsen, R.; Guile, S. D.; Brown, B. J. Am.
Chem. Soc. 2000, 122, 5947.
(17) (a) Compound 20: white solid; mp 80–81 °C; [a]D20 –234
(c = 0.40, CHCl3). IR (film): 2942, 1740, 1376, 1243, 1092,
1033 cm–1. 1H NMR (300 MHz, CDCl3): d = 6.27 (d, J = 10.5
Hz, 1 H), 6.05 (dd, J = 8.4 Hz, 2 H), 4.22 (d, J = 7.5 Hz, 1
H), 4.83 (d, J = 7.5 Hz, 1 H), 4.71 (d, J = 7.5 Hz, 1 H), 4.65
(d, J = 12.3 Hz, 1 H), 4.37 (d, J = 12.3 Hz, 1 H), 4.92 (d, J =
7.5 Hz, 1 H), 3.97–4.01 (m, 1 H), 3.73 (d, J = 8.4 Hz, 1 H),
3.40 (s, 3 H), 3.32 (s, 3 H), 2.50–2.62 (m, 1 H), 2.15–2.33
(m, 1 H), 2.14–2.15 (m, 8 H), 2.054 (s, 3 H), 2.047 (s, 3 H),
1.74 (s, 3 H), 1.23 (s, 3 H), 1.21 (s, 3 H). 13C NMR (75 MHz,
CDCl3): d = 170.6, 170.1, 139.0, 134.6, 126.0, 118.1, 91.0,
90.8, 82.7, 79.9, 75.2, 69.0, 68.4, 65.2, 55.7, 55.2, 40.4, 39.8,
30.3, 24.6, 21.1 (2 C), 21.0, 20.0, 19.9, 18.3. ESI–MS: m/z =
521.3 [M + Na]+. HRMS (ESI): m/z [M + Na]+ calcd for
C26H42O9: 521.2721; found: 521.2743. (b) The crystallo-
graphic data for 20 has been deposited at the Cambridge
Crystallographic Data Centre with deposition no. CCDC
632316.
(10) Compound 15: colorless oil; [a]D20 +15.8 (c = 0.50, MeOH).
IR (film): 2932, 1717, 1676, 1448, 1184, 1137, 1098, 1037
cm–1. 1H NMR (300 MHz, CDCl3): d = 10.09 (d, J = 7.8 Hz,
1 H), 6.14 (s, 1 H), 6.12 (d, J = 7.8 Hz, 1 H), 5.39 (s, 1 H),
5.22 (t, J = 7.5 Hz, 1 H), 4.77 (d, J = 7.2 Hz, 1 H), 4.72 (d,
J = 7.2 Hz, 1 H), 4.22 (q, J = 7.2 Hz, 2 H), 4.08–4.11 (m, 1
H), 3.62–3.66 (m, 1 H), 3.39 (s, 3 H), 3.01 (d, J = 7.5 Hz, 2
H), 2.19 (s, 3 H), 1.40–2.10 (m, 8 H), 1.64 (s, 3 H), 1.30 (t,
J = 7.2 Hz, 3 H), 1.20 (s, 3 H). 13C NMR (75 MHz, CDCl3):
d = 191.7, 167.3, 161.6, 139.7, 137.2, 126.2, 124.4, 120.8,
90.7, 77.8, 74.8, 72.67, 60.6, 55.5, 36.0, 31.5, 30.1, 26.5,
24.6, 21.0, 16.1, 14.3, 14.2. ESI–MS: m/z = 409.1 [M + H]+,
431.1 [M + Na]+. HRMS (ESI): m/z [M + Na]+ calcd for
C23H36O6: 431.2404; found: 431.2401.
(18) Compound 22: colorless oil; [a]D20 –254 (c = 0.10, CHCl3).
IR (film): 2981, 2945, 2855, 1734, 1673, 1647, 1440, 1376,
1275, 1244, 1033, 910 cm–1. 1H NMR (300 MHz, CDCl3):
d = 6.98 (d, J = 10.2Hz, 1 H), 6.25 (d, J = 11.1 Hz, 1 H), 5.95
(d, J = 10.2 Hz, 1 H), 5.03 (d, J = 7.2 Hz, 1 H), 4.82 (d, J =
7.5 Hz, 1 H), 4.69 (d, J = 7.5 Hz, 1 H), 4.42 (d, J = 7.2 Hz,
1 H), 3.98–4.02 (m, 1 H), 3.70–3.73 (m, 1 H), 3.40 (s, 3 H),
3.33 (s, 3 H), 1.80–2.70 (m, 4 H), 2.27 (s, 3 H), 2.00 (s, 3 H),
1.40–1.80 (m, 6 H), 1.83 (s, 3 H), 1.23 (s, 3 H), 1.20 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 190.2, 170.6, 145.2, 140.7,
131.9, 118.3, 91.1, 91.0, 82.5, 80.1, 75.2, 68.5, 68.4, 55.7,
55.3, 40.2, 39.6, 30.1, 27.5, 24.5, 21.3, 21.0, 20.1, 20.0, 18.8.
ESI–MS: m/z = 491.1 [M + Na+]. HRMS (ESI): m/z [M +
Na]+ calcd for C25H40O8: 491.2615; found: 491.2605.
(19) Lombardo, L. Org. Synth. 1987, 65, 81.
(11) Compound 8: colorless oil; [a]D20 +88.4 (c = 0.49, CHCl3).
IR (film): 2979, 2934, 1707, 1448, 1380, 1222, 1145, 1097,
1037, 919 cm–1. 1H NMR (300 MHz, CDCl3): d = 6.81 (t,
J = 7.2 Hz, 1 H), 5.36 (t, J = 7.5 Hz, 1 H), 4.82 (d, J = 8.1
Hz, 1 H), 4.77 (d, J = 7.5 Hz, 1 H), 4.75 (d, J = 7.5 Hz, 1 H),
4.73 (d, J = 8.1 Hz, 1 H), 4.22 (q, J = 7.2 Hz, 2 H), 3.76–3.80
(m, 1 H), 3.69 (d, J = 5.1 Hz, 1 H), 3.38 (s, 3 H), 3.37 (s,
3 H), 2.70–3.10 (m, 4 H), 2.32–2.40 (m, 1 H), 2.00–2.10 (m,
2 H), 1.80–2.00 (m, 2 H), 1.50–1.70 (m, 3 H), 1.62 (s, 3 H),
1.32 (t, J = 7.2 Hz, 3 H), 1.25 (s, 3 H), 1.19 (s, 3 H). 13C NMR
(75 MHz, CDCl3): d = 168.0, 142.0, 139.1, 127.8, 123.2,
91.4, 90.9, 79.6, 77.4, 76.4, 75.9, 60.0, 55.6, 55.4, 39.7, 38.4,
33.9, 29.5, 27.7, 23.6, 22.7, 21.4, 15.4, 14.3. ESI–MS: m/z =
463.2 [M + Na]+. HRMS (ESI): m/z [M + Na]+ calcd for
C24H40O7: 463.2666; found: 463.2685.
(20) Takai, K.; Kakiuchi, T.; Kataoka, Y.; Utimoto, K. J. Org.
Chem. 1994, 59, 2668.
(21) Petasis, N. A.; Bzowej, E. I. J. Am. Chem. Soc. 1990, 112,
6392.
(22) Compound 5: colorless oil; [a]D20 –176 (c = 0.05, CHCl3).
IR (film): 2925, 2853, 1742, 1458, 1375, 1240, 1144, 1092,
1072, 1034, 910 cm–1. 1H NMR (500 MHz, CDCl3): d =
6.08–6.13 (m, 3 H), 4.96 (d, J = 7.4 Hz, 1 H), 4.93 (s, 1 H),
4.85 (s, 1 H), 4.84 (d, J = 7.3 Hz, 1 H), 5.03 (d, J = 7.3 Hz,
1 H), 4.39 (d, J = 7.4 Hz, 1 H), 4.03 (dd, J = 3.0 Hz, 1 H),
3.69 (d, J = 8.3 Hz, 1 H), 3.40 (s, 3 H), 3.33 (s, 3 H), 1.40–
2.80 (m, 10 H), 1.98 (s, 3 H), 1.88 (s, 3 H), 1.73 (s, 3 H), 1.25
(s, 3 H), 1.21 (s, 3 H). 13C NMR (125 MHz, CDCl3): d =
169.9, 143.5, 137.4, 121.2, 119.0, 113.9, 112.9, 91.1, 91.0,
82.7, 80.2, 75.3, 69.8, 68.3, 55.7, 55.2, 40.3, 39.8, 30.4, 29.7,
24.6, 22.8, 21.5, 21.1, 20.2, 18.4. ESI–MS: m/z = 489.4
[M + Na]+. HRMS (ESI): m/z [M + Na]+ calcd for C26H42O7:
489.2828; found: 489.2823.
(12) The stereochemistry of the conjugated double bond is
assigned from the chemical shift and the coupling constant
data of the vinylic proton, and by analogy with closely
related cyclizations.
Synlett 2007, No. 4, 571–574 © Thieme Stuttgart · New York