Synthesis of [m,7,n]-tricycles via platinum-catalyzed cyclization of conjugated enynals with a pendant alkene

Article abstract of DOI:10.1055/s-2007-986635

Conjugated enynals anchored to cycloalkenes, in the presence of platinum catalysts, were cyclized to the corresponding [m,7,n]-tricarbocycles, which are valuable skeletons in biologically active natural products like taxoids. Georg Thieme Verlag Stuttgart

Full text of DOI:10.1055/s-2007-986635

LETTER
2337
Synthesis of [m,7,n]-Tricycles via Platinum-Catalyzed Cyclization of
Conjugated Enynals with a Pendant Alkene
S
C
ynthesis of [m,7
h
,n]-Tricycle
a
f
romCon
n
ga ls Ho Oh,* Joong Hyun Ryu, Ho Ik Lee
Department of Chemistry, Hanyang University, Sungdong-Gu, Seoul 133-791, Korea
Fax +82(2)22990762; E-mail: changho@hanyang.ac.kr
Received 8 July 2007
OAc OAc
BzO
Abstract: Conjugated enynals anchored to cycloalkenes, in the
presence of platinum catalysts, were cyclized to the corresponding
AcO
O
OH
[
m,7,n]-tricarbocycles, which are valuable skeletons in biologically
BzHN
Ph
O
OH
active natural products like taxoids.
HO
H
R
O
H
O
Key words: platinum, enynal, catalyst, cyclization, tetracycle
OH OBz
OH
OH
OAc
HO
brevifoliol (R = H)
taxol
taxuspinanane B (R = OAc)
OH
The promising anticancer activity of taxol and related
compounds has attracted considerable attention from
organic and medicinal chemists toward the development
of efficient synthetic methods for taxoids and more active
analogues (Figure 1).1
R
O
OH
Conjugated enynals may serve as versatile substrates for
dichotenone A (R = Me)
dichotenone B (R = CH2OAc)
[
m,7,n]-tricyclic skeletons via metal-catalyzed reactions.
In fact, conjugated enynals with certain alkynophilic
metal cations are known to form metal–pyrylium inter-
mediates which undergo cycloaddition with a pendent
Figure 1
2
unsaturated bond. Recently, we reported [3+2] cyclo-
postulate their powerful catalytic activities toward
enynals to form reactive pyrylium intermediates which
could undergo cycloaddition via either [4+2] or [3+2]
route. Herein we wish to report Pt-catalyzed synthesis of
addition of Rh-carbenoid dipolar carbonyl ylides derived
from enynals with a pendant double bond. Yamamoto
and co-workers reported a gold-catalyzed benzannulation
of o-alkynylbenzaldehydes with alkynes involving a
3
[
m,7,n]-tricyclic skeletons having an oxygen bridge in the
[
4+2] cycloaddition of Au-pyrylium intermediates with
seven-membered ring from conjugated enynals with a
pendent double bond (Scheme 2).
dienophiles such as alkynes and enol ethers at high
4
temperature. In this context, we reported Au-catalyzed
In order to exploit this transformation, we first prepared a
cyclization of diynals 1 to dihydrobenzo[f]azulen-4(1H)-
ones 2 via [3+2] cycloaddition and Pt-catalyzed cycliza-
tion to 2,3-dihydrophenanthren-4(1H)-ones 3 via [4+2]
7
substrate 4a by known procedures. At first, cyclization of
enynal 4a was attempted with AuBr , AuCl, and
3
5
AuCl(PPh ), but the substrate 4a was dimerized within an
cycloaddition (Scheme 1).
3
hour. Thus we changed catalysts from gold compounds to
less reactive platinum compounds (Table 1).
Continuing our interest in cycloisomerization involving
Huisgen-type [3+2] cycloadditions, we have paid atten-
tion to metal–pyrylium intermediates derived from an
AuBr3 in 1,2-dichloroethane (DCE) and toluene
completely converted 4a within one hour at room tem-
perature and 0 °C, respectively, but afforded a complex
dimeric compound, the structure of which is still under
6
aliphatic anchor. Similar to gold, platinum is alkyno-
philic and prone to form Pt–carbene complexes. Combin-
ing properties associated with platinum cations, we could
O
O
a
b
E
E
O
E
3
1
E
2
E
E = COOEt
E
Scheme 1 Reagent and conditions: (a) PtCl or PtCl (3 mol%), DCE, 80 °C, 3 h, 3 (40–43%); (b) AuBr (3 mol%), DCE, r.t., 8 h, 2 (80%).
2
4
3
SYNLETT 2007, No. 15, pp 2337–2342
1
7
.0
9
.2
0
0
7
Advanced online publication: 28.08.2007
DOI: 10.1055/s-2007-986635; Art ID: U06507ST
Georg Thieme Verlag Stuttgart · New York
©

2
338
C. H. Oh et al.
LETTER
CHO
"
Pt(II)"
[4+2]
O+
–
E
E
E
E
E
4a
E
A1 Pt(II)
7a
O
E = COOEt
[
3+2]
H
O
O
E
E
5a
E
6a
O
E
Scheme 2
Table 1 Metal-Catalyzed Reactions of Enynal 4a
Entry
Catalysts (5 mol%)
AuBr3
Solvent
DCE
Temp (°C), time (h)
r.t., 1
Product (%yield)
dimer (89)
1
2
3
4
5
6
7
8
9
AuBr3
toluene
CH Cl
0, 1
dimer (82)
AuCl
r.t., 0.5
r.t., 1
dimer (71)
2
2
2
AuCl(PPh3)
PtCl2
CH Cl
dimer (79)
2
toluene
toluene
DCE
110, 48
100, 12
80, 12
5a (30), 6a (12)
5a (47), 6a (11)
5a (44), 6a (38)
dec.
PtCl (PPh )
2
3 2
PtCl (PPh )
2
3 2
PtCl (PPh )
DMF
100, 12
100, 12
2
3 2
PtCl (PPh )
dioxane
5a (86)
2
3 2
Table 2 Pt-Catalyzed Cyclizations of Enynals 410
CHO
H
5
mol% PtCl2(PPh3)2
,4-dioxane
O
+
1
O
4
5
7
Entry
Substrates
Temp (°C), time (h)
100, 2
Products
5b
Yields (%)
1
2
3
4
5
6
7
8
9
4b
4c
4d
4e
4f
78
72
65
77
66
80
86
64
–
100, 24
100, 4
5c
5d
100, 4
5e
120, 15
100, 2
7f
4g
4h
4i
5g
100, 2
5h
100, 15
100, 1
5i
4j
5j
10
4k
100, 24
5k
–
8
characterization (entries 1 and 2). AuCl and AuCl(PPh3) the major product along with 6a (entries 5 and 6). The
also afforded the same dimeric product (entries 3 and 4). present reaction in DCE was a little better in terms of the
Pt(+2) is isoelectronic with Au(+3). Both PtCl and combined yield (82%) of 5a and 6a, but DMF as solvent
2
PtCl (PPh ) catalyzed cycloisomerization of 4a to 5a as did not work (entries 7 and 8). It is noteworthy that the
2
3 2
Synlett 2007, No. 15, 2337–2342 © Thieme Stuttgart · New York

LETTER
Synthesis of [m,7,n]-Tricycles from Conjugated Enynals
2339
product 6a could be formed with a trace of water present afforded 5b, 5c, and 5d in 78%, 72% and 65% yields,
in the reaction solvents. 1,4-Dioxane turned out to be the respectively. As the ring size increased from five to seven,
1
best among the solvents we tested, where H NMR of the the reactions required longer time to complete. The enynal
crude reaction mixture indicated the exclusive formation 4c with a methyl substituent on the olefinic position
of 5a (entry 8). Structure of the product 5a was fully char- required much longer reaction time but afforded the
1
13
acterized by 1D and 2D NMR studies. H NMR,
C
expected product 5c in 72% yield.
NMR, DEPT, COSY, and HMQC spectra of 5a revealed
the proposed structure. The proton connections of 5a were
further confirmed by 1D TOCSY data. HMBC data
showed the overall skeleton by long-range coupling and
NOE studies confirmed its relative stereochemistry based
The substrate 4e, a homologue of 4b, was an important
substrate since it afforded a different type of ring skeleton.
The reaction proceeded well to give [5,7,6]-carbocycle 5e
in 77% yield. Sterically bulky substrate 4f, however,
underwent cyclization in a different mode, via [4+2], to
afford the [6,6,6]-tricyclic product 7f in 66% yield after
deprotection of the TBS group. Nitrogen-tethered sub-
strates 4g, 4h, and 4i were converted more readily in the
same way. Six- and five-membered enynals 4g and 4h
gave the corresponding [6,7,5]- and [5,7,5]-tricycles 5g
9
on the proximity among protons. With this initial
success, we examined the scope of this reaction toward
various enynals (Table 2, Figure 2). Overall, the present
cyclizations turned out to be quite general as long as the
structural blocking was not severe. Five- and seven-
membered enynals 4b, 4c, and 4d under our conditions
CHO
CHO
O
O
E
E
E
NTs
4b
E
E
5b
5c
NTs
NTs
5g
5h
E
4
g
CHO
CHO
O
O
O
O
E
NTs
NTs
O
4c
4h
4i
E
CHO
CHO
CHO
O
E
E
NTs
O
5i
4d
E
5d
E
CHO
O
E
E
E
5
e
4j
5j
4e
E
CHO
CHO
O
E
E
5k
4k
E
E
4f
7f
O
OH
OTBS
Figure 2
O
O
O
4
5
O
6
Pt(II)
H
Pt(0) + 2H+
Pt(II) + H2
H+
O+
O
O
HO
HPt(II)
Pt(I)
A1
Pt(I)
B2
C2
H+
–
X (or any base)
H
O+
–
[
3+2]
O
O
H2O
Pt(II)
A2
H2O
Pt(II)
B1
Pt(II)
C1
Scheme 3
Synlett 2007, No. 15, 2337–2342 © Thieme Stuttgart · New York

2
340
C. H. Oh et al.
LETTER
K.; Frost, T. M.; Bats, J. W. Catal. Today 2002, 72, 19.
and 5h in 80% and 86% yields, respectively. The methyl
substituent on the olefinic position of 4i again did not
affect the present reaction leading to 5i. Enynals with an
oxygen linker (4j) and an internal olefin (4j), unfortunate-
ly, did not proceed to the corresponding products. It is
noteworthy that the key skeletons of [m,7,n]-tricycles
fused with an oxygen bridge are found in many biologi-
cally active natural products such as barbatusol, pisiterin,
(
(
d) Dankwardt, J. W. Tetrahedron Lett. 2001, 42, 4237.
e) Hildebrandt, D.; Hüggenberg, W.; Kanthak, M.; Plöger,
T.; Müller, I. M.; Dyker, G. Chem. Commun. 2006, 2260.
f) Kusama, H.; Iwasawa, N. Chem. Lett. 2006, 1082.
(
(
5) (a) Kim, N.; Kim, Y. M.; Park, W.; Sung, D.; Gupta, A. K.;
Oh, C. H. Org. Lett. 2005, 7, 5289. (b) Gupta, A. K.; Rhim,
C. Y.; Oh, C. H.; Mane, R. S.; Han, S.-H. Green Chem. 2006,
8, 25.
1
1
(6) (a) Huisgen, R. Angew. Chem. Int. Ed. 1968, 7, 321.
b) Hamberger, H.; Huisgen, R. J. Chem. Soc. D. 1971, 19,
190.
(7) For preparation of 2-bromocycloalkenecarboxaldehydes
using PBr /DMF, see: (a) Mal, S. K.; Ray, D.; Ray, J. K.
faveline, and xochitlone; therefore this study would
have a high potential in synthetic organic chemistry.
(
1
Mechanistically, the proposed intermediate A1 is stabi-
lized by a resonance form A2 (Scheme 3). The intermedi-
ate A2 would undergo [3+2] cycloaddition to platinum-
carbene B1. Any basic species could deprotonate from B1
to form B2 followed by protolysis to give the product 5.
In the presence of water, however, B1 is expected to form
3
Tetrahedron Lett. 2004, 45, 277. (b) Harvey, R. G.; Pataki,
J.; Cortez, C.; Raddo, P. D.; Yang, C. J. Org. Chem. 1991,
56, 1210. (c) For Sonogashira coupling of enynes with
bromocycloalkenecarboxaldehydes, see: Buszek, K. R.;
Jeong, Y. Synth. Commun. 1994, 24, 2461. (d) For a review
of the Sonogashira reaction, see: Rossi, R.; Carpita, A.;
Bellina, F. Org. Prep. Proced. Int. 1995, 27, 129.
C2, which would be further transformed to 6 with releas-
ing either Pt(II)-H or Pt(0)-2H . Formation of 7f can be
+
2
understood via the intramolecular [4+2] cycloaddition of
(8) For Pt- and Au-catalyzed enyne cyclizations, see:
(a) Nevado, C.; Cárdenas, D. J.; Echavarren, A. M. Chem.
Eur. J. 2003, 9, 2627. (b) Mamane, V.; Gress, T.; Krause,
H.; Fürstner, A. J. Am. Chem. Soc. 2004, 126, 8654.
(c) Chatani, N.; Furukawa, N.; Sakurai, H.; Murai, S.
Organometallics 1996, 15, 901. (d) Fürstner, A.; Davies, P.
W.; Gress, T. J. Am. Chem. Soc. 2005, 127, 8244.
A1 followed by the base-promoted fragmentation.4a,5a
In conclusion, conjugated enynals 4 anchored to cyclo-
alkenes were successfully cyclized to the corresponding
fused tetracyclic compounds 5, which would be valuable
skeletons in many complex natural products. This trans-
formation is highly selective, atom-economical, and an
environmentally benign technique. Synthetic applications
to natural products and further exploration by using other
transition metal catalysts are currently underway.
(
9) The structure of product 5a was fully characterized by 1D
1
13
and 2D NMR studies. H NMR, C NMR, DEPT, COSY,
and HMQC spectra of 5a revealed the proposed structure.
The proton connections of 5a were further confirmed by 1D
TOCSY data. HMBC data showed the overall skeleton by
long-range coupling and NOE studies confirmed its relative
a
stereochemistry based on the proximity of H at C-12 with
Acknowledgment
both H-11 and H-13 as shown in Table 3.
We would like to thank the Center of Molecular Design and Syn-
thesis (CMDS, KOSEF) and BK21 for financial support.
Table 3
NOE
H
O
Hβ
References and Notes
NOE
Hα
H
1
13
1
4
2
3
12
(
1) (a) Wani, M. C.; Taylor, H. L.; Wall, M. E.; Coggon, P.;
11
10
McPhall, A. T. J. Am. Chem. Soc. 1971, 93, 2325.
5
COOEt
4
6
7
(b) Kingston, D. G. I.; Yuan, H.; Jagtap, P. G.; Samala, L.
9
8
COOEt
The Chemistry of Organic Natural Products, Vol. 84; Herz,
W.; Kirby, G. W.; Moore, R. E.; Steglich, W.; Tamm, C.,
Eds.; Springer-Verlag: New York, 2002. (c) Baloglu, E.;
Kingston, D. G. I. J. Nat. Prod. 1999, 62, 1448.
1
13C NMR,
C# d H NMR, COSY, TOCSY
d
HMBC
DEPT, HMQC (H → C#)
(
2) (a) Nicolaou, K. C.; Skokotas, G.; Furaya, S.; Suemune, H.;
Nicolaou, D. C. Angew. Chem. 1990, 102, 1066. (b) Asao,
N.; Sato, K.; Menggenbateer; Yamamoto, Y. J. Org. Chem.
1
2
3
4
5
6
7
8
5.49 (td, J = 1.6, 4.0 Hz)
2.07 (m, 2 H)
121.53 (CH)
25.31 (CH
2, 13, 14
1, 3, 4
)
2
2005, 70, 3682. (c) Dyker, G.; Hildebrandt, D. J. Org.
1.70 (m, 1 H), 1.56 (m, 1 H)
2.24 (m, 2 H)
22.76 (CH2)
4, 2, 1, 5
Chem. 2005, 70, 6093. (d) Luo, Y.; Herndon, J. W.
Organometallics 2005, 24, 3099. (e) Padwa, A.; Krumpe,
K. E.; Gareau, Y.; Chiacchio, U. J. Org. Chem. 1991, 56,
29.16 (CH2) 2, 5, 6, 14
133.06
2523. (f) Padwa, A.; Krumpe, K. E.; Zhi, L. Tetrahedron
Lett. 1989, 30, 2633.
(
3) (a) Shin, S.; Gupta, A. K.; Rhim, C. Y.; Oh, C. H. Chem.
Commun. 2005, 4429. For recent benzannulation of
enynals, see: (b) Ohe, K.; Miki, K.; Yokoi, T.; Nishino, F.;
Uemura, S. Organometallics 2000, 19, 5525. (c) Ohe, K.;
Yokoi, T.; Miki, K.; Nishino, F.; Uemura, S. J. Am. Chem.
Soc. 2002, 124, 526.
5.72 (s)
127.12 (CH)
90.82
11, 7, 5, 4
2.66 (d, J = 14.4 Hz),
42.14 (CH2) 9, 6, 7,
–
2
.51(d, J = 14.4 Hz)
COO
(
4) (a) Asao, N.; Aikawa, H.; Yamamoto, Y. J. Am. Chem. Soc.
9
62.77
2004, 126, 7458. (b) Hashmi, A. S. K.; Frost, T. M.; Bats, J.
W. J. Am. Chem. Soc. 2000, 122, 11553. (c) Hashmi, A. S.
Synlett 2007, No. 15, 2337–2342 © Thieme Stuttgart · New York

LETTER
Synthesis of [m,7,n]-Tricycles from Conjugated Enynals
2341
Table 3 (continued)
(ddd, J = 0.8, 8.8, 12.0 Hz, 1 H), 1.25 (t, J = 7.2 Hz, 3 H),
1
3
1
.24 (t, J = 7.2 Hz, 3 H). C NMR (100 MHz, CDCl ): d =
3
NOE
176.38, 171.20, 145.59, 144.45, 126.36, 120.74, 90.23,
H
Hβ
NOE
80.15, 62.39, 61.56, 61.33, 52.37, 42.03, 41.08, 40.98,
31.36, 26.39, 14.02, 14.00. IR (NaCl): 1741, 1670, 1593
Hα
H
1
4
13
1
4
2
3
12
11
–
1
O
10
9
cm . HRMS: m/z calcd for C H NaO : 355.1521; found:
19 24 5
5
COOEt
355.1517.
7
6
1
5
c: H NMR (400 MHz, CDCl ): d = 5.62 (d, J = 2.0 Hz, 1
8
3
COOEt
H), 5.54 (d, J = 1.2 Hz, 1 H), 4.84 (d, J = 7.2 Hz, 1 H), 4.10–
4.28 (m, 4 H), 2.82 (dd, J = 10.8, 13.6 Hz, 2 H), 2.45–2.55
1
13C NMR,
DEPT, HMQC (H → C#)
C# d H NMR, COSY, TOCSY
d
HMBC
(
m, 6 H), 1.97 (d, J = 14.0 Hz, 1 H), 1.55 (dd, J = 1.4, 12.2
Hz, 1 H), 1.24 (t, J = 7.2 Hz, 3 H), 1.23 (t, J = 7.2 Hz, 3 H),
1
3
1
0
2.31 (dd, J = 7.6, 13.6 Hz),
.28 (dd, J = 4.4, 13.6 Hz)
41.09 (CH2) 8, 9, 11,
1.09 (s, 3 H). C NMR (100 MHz, CDCl ): d = 172.54,
3
–
2
COO
171.56, 146.59, 144.99, 126.22, 117.86, 91.62, 74.80, 61.57,
6
1.35, 59.97, 57.70, 49.49, 49.16, 40.76, 31.31, 26.42,
1
1
1
2
2.67 (ddd, J = 4.4, 7.2, 8.8 Hz)
52.59 (CH)
7, 10, 12
–1
25.94, 13.98 (2 ꢀ C). IR (NaCl): 1740, 1675, 1595 cm .
HRMS: m/z calcd for C H NaO : 369.1678; found:
2
0
26
5
2.13 (ddd, J = 3.4, 7.2, 12.4 Hz), 40.82 (CH2) 14
369.1674.
1.89 (ddd, J = 0.8, 8.8, 12.4 Hz)
1
5d: H NMR (400 MHz, CDCl ): d = 5.80 (s, 1 H), 5.48 (dd,
3
J = 5.2, 6.0 Hz, 1 H), 4.66 (d, J = 7.2 Hz, 1 H), 4.10–4.26 (m,
H), 2.65 (d, J = 14.4 Hz, 1 H), 2.64 (ddd, J = 3.0, 8.4, 16.4
Hz, 1 H), 2.49 (d, J = 14.4 Hz, 1 H), 2.35 (m, 2 H), 2.17–2.31
m, 4 H), 2.10 (ddd, J = 3.2, 7.6, 12.4 Hz, 1 H), 1.85 (ddd,
J = 0.8, 8.4, 12.4 Hz, 1 H), 1.61–1.75 (m, 4 H), 1.24 (t, J =
1
1
3
4
4.70 (d, J = 7.6 Hz)
81.18 (CH)
137.79
11, 7, 1, 5
4
(
(
10) General Experimental Procedure for Cyclization: In a
new 5 mL test tube, enynals 4a–i (0.3 mmol), PtCl (PPh )
3 2
13
7.2 Hz, 3 H), 1.23 (t, J = 7.2 Hz, 3 H). C NMR (100 MHz,
2
CDCl ): d = 172.30, 171.16, 139.96, 137.25, 130.01, 125.71,
3
(5 mol%), and anhyd 1,4-dioxane (0.5 mL) were charged at
9
4
1
3
5
0.27, 83.11, 62.46, 61.57, 61.35, 52.46, 41.65, 40.68,
0
°C and the reaction mixture was kept under an argon
0.52, 34.16, 27.62, 26.46, 25.89, 14.02, 14.00. IR (NaCl):
atmosphere. The resulting mixture was stirred for 1–24 h in
a preheated oil-bath (100 °C) with periodic monitoring of the
reaction (TLC). Upon completion, the solvent was removed
under vacuum and the crude product was subjected to flash
column chromatography to afford the pure products 5a–e
and 5g–i. In the case of substrate 4f, the reaction mixture was
cooled to 0 °C and treated with a 1.0 M TBAF solution in
THF (1.0 mmol). Extractive work-up and flash
–1
731, 1448 cm . HRMS: m/z calcd for C H NaO :
2
1
28
5
83.1834; found: 383.1833.
1
e: H NMR (400 MHz, CDCl ): d = 5.58 (s, 1 H), 5.42 (dd,
3
J = 0.8, 2.0 Hz, 1 H), 4.85 (dd, J = 4.4, 5.6 Hz, 1 H), 4.30 (dq,
J = 7.2, 12.0 Hz, 1 H), 4.19 (dq, J = 7.2, 14.4 Hz, 1 H), 4.15
(
2
dq, J = 7.2, 14.4 Hz, 1 H), 4.08 (dq, J = 7.2, 12.0 Hz, 1 H),
.78 (dd, J = 2.0, 15.2 Hz, 1 H), 2.37–2.53 (m, 4 H), 2.31 (dq,
J = 1.6, 13.6 Hz, 1 H), 2.21 (d, J = 15.2 Hz, 1 H), 2.07 (m, 1
chromatography gave the desilylated 7f in 66% yield.
H), 1.80 (m, 2 H), 1.65 (m, 2 H), 1.47 (m, 1 H), 1.23 (t, J =
1
5
a: H NMR (500 MHz, CDCl ): d = 5.72 (s, 1 H), 5.49 (td,
13
3
7
.2 Hz, 3 H), 1.22 (t, J = 7.2 Hz, 3 H). C NMR (100 MHz,
J = 1.6, 4.0 Hz, 1 H), 4.70 (d, J = 7.6 Hz, 1 H), 4.09–4.25 (m,
H), 2.67 (ddd, J = 4.4, 7.2, 8.8 Hz, 1 H), 2.66 (d, J = 14.4
CDCl ): d = 172.81, 170.86, 145.55, 144.20, 124.17, 122.90,
3
4
7
3
1
3
7
8.65, 72.91, 61.48, 60.96, 51.88, 43.90, 40.08, 36.03,
Hz, 1 H), 2.51 (d, J = 14.4 Hz, 1 H), 2.31 (dd, J = 7.6, 13.6
Hz, 1 H), 2.28 (dd, J = 4.4, 13.6 Hz, 1 H), 2.24 (m, 2 H), 2.13
1.23, 29.46, 28.08, 26.53, 14.00, 13.95. IR (NaCl): 1737,
–1
670, 1599 cm . HRMS: m/z calcd for C H NaO :
2
0
26
5
(
ddd, J = 3.4, 7.2, 12.4 Hz, 1 H), 2.07 (m, 2 H), 1.89 (ddd,
69.1678; found: 369.1680.
J = 0.8, 8.8, 12.4 Hz, 1 H), 1.70 (m, 1 H), 1.56 (m, 1 H), 1.25
1
f: H NMR (400 MHz, CDCl ): d = 5.52 (s, 1 H), 5.43 (d,
1
3
3
(
t, J = 7.2 Hz, 3 H), 1.24 (t, J = 7.2 Hz, 3 H). C NMR (125
J = 4.4 Hz, 1 H), 4.16 (d, J = 5.6 Hz, 1 H), 3.26 (d, J = 4.8
Hz, 1 H), 2.75 (dq, J = 2.4, 12.0 Hz, 1 H), 2.05–2.34 (m,
MHz, CDCl ): d = 172.27, 171.15, 137.79, 133.06, 127.12,
3
1
4
1
3
6
21.53, 90.82, 81.18, 62.77, 61.57, 61.35, 52.59, 42.14,
1.09, 40.82, 29.16, 25.31, 22.76, 14.03, 14.00. IR (NaCl):
739, 1673, 1598 cm . HRMS: m/z calcd for C H NaO :
7
1
H), 1.86 (m, 1 H), 1.68–1.77 (m, 2 H), 1.55–1.64 (m, 1 H),
13
.22 (s, 3 H), 0.83 (s, 3 H). C NMR (100 MHz, CDCl ):
–
1
3
2
0
26
5
d = 213.13, 134.61, 130.00, 122.96, 121.56, 80.57, 53.80,
69.1678; found: 369.1683.
4
4.42, 36.95, 33.12, 32.97, 31.35, 29.48, 26.09, 25.37,
1
a: H NMR (400 MHz, CDCl ): d = 4.52 (d, J = 6.4 Hz, 1
–1
3
23.01. IR (NaCl): 3465, 1753, 1663 cm . HRMS: m/z calcd
H), 4.13–4.27 (m, 4 H), 3.15 (d, J = 14.4 Hz, 1 H), 2.59 (m,
for C H NaO : 269.1517; found: 269.1520.
1
6
22
2
1
1
2
1
1
H), 2.56 (d, J = 14.4 Hz, 1 H), 2.43 (dd, J = 4.8, 13.6 Hz,
H), 2.38 (dd, J = 9.6, 13.6 Hz, 1 H), 2.17–2.31 (m, 2 H),
.14 (ddd, J = 5.2, 6.8, 12.4 Hz, 1 H), 2.02–2.11 (m, 2 H),
.99 (dd, J = 9.2, 12.4 Hz, 1 H), 1.67–1.81 (m, 2 H), 1.40–
.55 (m, 2 H), 1.27 (t, J = 7.2 Hz, 3 H), 1.24 (t, J = 7.2 Hz, 3
1
5
g: H NMR (400 MHz, CDCl ): d = 7.70 (d, J = 8.0 Hz, 2
3
H), 7.31 (d, J = 8.0 Hz, 2 H), 5.57 (s, 1 H), 5.51 (dd, J = 0.8,
.4 Hz, 1 H), 4.65 (d, J = 8.8 Hz, 1 H), 3.69 (dd, J = 7.6, 8.0
Hz, 1 H), 3.51 (s, 2 H), 3.50 (m, 1 H), 2.70–2.83 (m, 2 H),
4
2.43 (s, 3 H), 2.23 (m, 2 H), 2.08 (m, 2 H), 1.98 (ddd, J = 1.6,
1
3
H). C NMR (100 MHz, CDCl ): d = 195.06, 171.37,
3
7
.2, 12.8 Hz, 1 H), 1.77 (ddd, J = 1.2, 8.0, 12.8 Hz, 1 H), 1.68
1
4
1
71.25, 159.49, 129.00, 96.80, 80.08, 62.42, 61.94, 61.73,
4.92, 39.49, 37.36, 36.93, 26.97, 21.81, 21.72, 21.03,
4.28, 14.22. IR (NaCl): 1739, 1678, 1636 cm . HRMS:
13
(
m, 1 H). C NMR (100 MHz, CDCl ): d = 147.37, 143.21,
3
142.00, 129.64, 127.62, 123.43, 122.19, 118.67, 89.17,
–
1
8
0.82, 55.14, 54.34, 52.12, 36.89, 28.80, 24.94, 21.55. IR
m/z calcd for C H NaO : 385.1627; found: 385.1625.
–1
2
0
26
6
(NaCl): 1598, 1472 cm . HRMS: m/z calcd for
1
5
b: H NMR (400 MHz, CDCl ): d = 5.73 (d, J = 1.2 Hz, 1
3
C H NNaSO S: 380.1296; found: 380.1294.
2
0
23
3
H), 5.63 (d, J = 2.0 Hz, 1 H), 4.99 (d, J = 8.4 Hz, 1 H), 4.10–
1
5
h: H NMR (400 MHz, CDCl ): d = 7.72 (d, J = 8.4 Hz, 2
3
4.26 (m, 4 H), 2.70 (d, J = 14.0 Hz, 1 H), 2.68 (ddd, J = 4.4,
7.2, 8.8 Hz, 1 H), 2.49 (d, J = 14.0 Hz, 1 H), 2.46 (m, 2 H),
2.44 (m, 2 H), 2.33 (dd, J = 7.2, 13.4 Hz, 1 H), 2.26 (dd, J =
9.2, 13.4 Hz, 1 H), 2.16 (ddd, J = 3.6, 7.2, 12.0 Hz, 1 H), 1.95
H), 7.32 (d, J = 8.4 Hz, 2 H), 5.65 (d, J = 1.2 Hz, 1 H), 5.59
dd, J = 1.4, 3.2 Hz, 1 H), 4.97 (d, J = 6.8 Hz, 1 H), 3.68 (dd,
(
J = 7.6, 8.0 Hz, 1 H), 3.50 (ABq, Dd = 13.2 Hz, J = 11.2 Hz,
Synlett 2007, No. 15, 2337–2342 © Thieme Stuttgart · New York

2
342
C. H. Oh et al.
LETTER
2
1
H), 2.79 (ddd, J = 2.4, 8.8, 16.4 Hz, 1 H), 2.75 (dd, J = 9.2,
6.4 Hz, 1 H), 2.40–2.47 (m, 4 H), 2.43 (s, 3 H), 1.99 (ddd,
NMR (100 MHz, CDCl ): d = 147.95, 144.43, 143.26,
133.66, 129.55, 127.48, 126.72, 115.02, 89.95, 75.18, 60.72,
3
J = 2.0, 7.6, 12.8 Hz, 1 H), 1.82 (ddd, J = 1.6, 8.0, 12.8 Hz,
57.91, 54.20, 43.90, 31.26, 26.49, 21.52, 21.01. IR (NaCl):
H). 13C NMR (100 MHz, CDCl ): d = 147.10, 143.82,
1599, 1455 cm . HRMS: m/z calcd for C H NNaSO S:
–1
1
1
8
3
20 23
3
43.47, 133.24, 129.64, 127.66, 127.15, 117.64, 94.45,
8.90, 55.32, 54.60, 52.31, 37.42, 31.36, 26.44, 21.57. IR
380.1296; found: 380.1298.
(11) For isolations, see: (a) Kelecom, A. Tetrahedron 1983, 39,
3603. (b) Yatagai, M.; Takahashi, T. Phytochemistry 1980,
19, 1149. (c) Endo, Y.; Ohta, T.; Nozoe, S. Tetrahedron
Lett. 1991, 32, 3083. (d) Dominguez, X. A.; Sanchez, H. V.;
Espinosa, G. B.; Villarreal, A. M.; Guerra, N. E. Rev.
Latinoam. Quim. 1990, 21, 26. (e) For synthesis, see:
Majetich, G.; Hicks, R.; Zhang, Y.; Tian, X.; Feltman, T. L.;
Fang, J.; Ducan, S. Jr. J. Org. Chem. 1996, 61, 8169.
–
1
(NaCl): 1597, 1457 cm . HRMS: m/z calcd for
C H NNaSO S: 366.1140; found: 366.1144.
1
9
21
3
1
5
i: H NMR (400 MHz, CDCl ): d = 7.71 (d, J = 8.4 Hz, 2
3
H), 7.30 (d, J = 8.4 Hz, 2 H), 5.63 (d, J = 2.0 Hz, 1 H), 5.45
s, 1 H), 4.83 (d, J = 6.8 Hz, 1 H), 3.53 (ABq, Dd = 16.0 Hz,
(
J = 12.0 Hz, 2 H), 3.40 (d, J = 8.8 Hz, 1 H), 3.06 (d, J = 8.8
Hz, 1 H), 2.47 (m, 4 H), 2.42 (s, 3 H), 2.25 (dd, J = 7.6, 12.4
1
3
Hz, 1 H), 1.42 (dd, J = 1.2, 12.8 Hz, 1 H), 1.12 (s, 3 H).
C
Synlett 2007, No. 15, 2337–2342 © Thieme Stuttgart · New York

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