Synthesis of dictyopterene A

Article abstract of DOI:10.1055/s-2008-1042918

The total synthesis of dictyopterene A was accomplished via an enantiomerically pure cyclopropylboronic ester building block. Crucial olefination steps were carried out employing the Julia-Kocienski as well as the Wittig reactions. The Matteson homologation was the final key step for the total synthesis. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1042918

LETTER
971
Synthesis of Dictyopterene A
S
E
ynthesis of
D
y
r
ctyopter
w
ene
A
in Hohn, Jiří Paleček, Jörg Pietruszka*
Institut für Bioorganische Chemie, Heinrich-Heine-Universität Düsseldorf im Forschungszentrum Jülich,
Im Stetternicher Forst, Geb. 15.8, 52426 Jülich, Germany
Fax +49(2461)616196; E-mail: j.pietruszka@fz-juelich.de
Received 5 January 2008
via a hydroboration–cyclopropanation–deprotection se-
Abstract: The total synthesis of dictyopterene A was accomplished
via an enantiomerically pure cyclopropylboronic ester building
block. Crucial olefination steps were carried out employing the
7
8
quence. The highly stable esters are ideal boron building
9
blocks for cyclopropane chemistry allowing a variety of
Julia–Kocienski as well as the Wittig reactions. The Matteson ho- transformations in the side chain in the presence of the bo-
mologation was the final key step for the total synthesis.
ron group. Furthermore, the boron moiety can be readily
displaced later in the sequence. For the present investiga-
tions we planned first to extend the hydroxymethyl group
to the hexenyl side chain, before utilizing the boron func-
tionality in a simple Matteson homologation.
Key words: boron, cyclopropanes, natural products, total synthe-
sis, stereoselectivity
Dictyopterenes are unsaturated C hydrocarbons bearing Three different approaches were tested to introduce the
1
1
1
,2
a cyclopropane, and in particular a vinyl- and E-hex- hexenyl group after selective oxidation of alcohol 2 to al-
enyl-substituted ring in the case of dictyopterene A. These dehyde 3 with the Dess–Martin-reagent1 (DMP, 95%;
natural compounds were first isolated by Moore as major Scheme 1).
0,11
components from the odoriferous oil of the Hawaiian sea-
Wittig olefination12 with methyltriphenylphosphonium
bromide in the presence of n-butyl lithium in THF afford-
weeds, genus Dictyopteris in the mixture with two related
2
a
minor cycloheptadienes dictyopterenes C¢ and D¢; the
ed the vinylcyclopropane 4 (85%) which was in a second
1
R,2R configuration being established.3 These com-
13
step subjected to cross-metathesis conditions with 1-
pounds comprise a family of sexual pheromones for the
marine brown algae, exhibiting remarkable activity in-
cluding their sperm attracting physiological ability and
are responsible for the intense ocean smell. Various syn-
theses have been developed; however, only few of the re-
ported procedures afforded the optically pure
N
N
N
N
Mes
Mes
Ph
N
C5H9
N
S
Cl
Cl
2
Ru
O2
Ph
7
4
,5
5
dictyopterenes. Nevertheless, most natural products
were either obtained in a mixture with undesired configu-
PCy3
DMP (1.1. equiv),
CH2Cl2, 24 h, r.t.
a) Ph3PC5H11Br (1 equiv), n-BuLi (1 equiv),
4
a,b,e,f,5
rational isomers
or in dictyopterene composi-
LiBr (6 equiv), THF, Et O, r.t., 20 min
2
4
c,d
tions, hence further chromatographic separations were
necessary. Dictyopterene syntheses leading to racemic
mixtures have also been published.
b) 3 (1 equiv), THF, –78 °C,
warmed to –30 °C, 20 min
O
Ph Ph
O
O
c) n-BuLi (1 equiv), –30 °C, warmed to r.t.
6
O
O
B
d) cooled to –78 °C, after 15 min,
HCl⋅Et2O (1 equiv) added
e) KOt-Bu (1 equiv), warmed to r.t., 1 h
70%; E:Z = 80:20
3
95%
Ph Ph
HO
Ph Ph
O
O
O
O
B
a) Ph3PCH3Br (1.5 equiv),
n-BuLi (1.5 equiv), THF, 0 °C, 1 h
b) 3 (1 equiv), THF, 0 °C, 24 h
1
2
Ph Ph
a) 7 (1.5 equiv),
KHMDS (1.8 equiv),
DME, –60 °C, 5 min
b) 3 (1 equiv), DME,
Figure 1 Structure of the title dictyopterene A (1) and the envisaged
enantiomerically pure cyclopropylboronic ester building block 2
Ph Ph
O
O
O
O
–
60 °C, 10 min
B
93%; E:Z > 99:1
In the present communication we wish to report an alter-
native synthetic approach towards enantiomerically pure
Ph Ph
4
85%
(
–)-(1S,2S)-dictyopterene A (1), relying on the enantio-
Bu
Ph Ph
merically pure cyclopropylboronic ester building block 2
which has been prepared according to our original three-
step procedure from benzyl-protected propargyl alcohol
1
-hexene (15 equiv),
O
O
O
Grubbs II 5 (0.05 equiv),
B
O
CH Cl , 40 °C, 4 d
2
2
6
Ph Ph
9
0%; E:Z = 85:15
SYNLETT 2008, No. 7, pp 0971–0974
Advanced online publication: 17.03.2008
DOI: 10.1055/s-2008-1042918; Art ID: D01008ST
x
x.
x
x.
2
0
0
8
Scheme 1 The crucial E-olefination step: transformation of the west
methylenealcohol side 2 to the E-hexenyl chain 6
©
Georg Thieme Verlag Stuttgart · New York

9
72
E. Hohn et al.
LETTER
hexene using Grubbs catalyst 5. The E-olefin 6 was ob- pleased to find that the selectivity was excellent in all cas-
tained as a 85:15 mixture with undesired Z-isomer.
The Wittig–Schlosser reaction14 was employed for the
es. However, the yield needed to be optimized: Commer-
cially available solutions of the base in toluene always
gave inferior results (20–43%, entries 1–3). When using
neat KHMDS the yields were further increased when tak-
ing more base (up to 1.8 equiv) and decreasing the reac-
tion time (entries 4–7) to an optimum of 10 minutes at
second olefination route in which olefin 6 was synthesized
from the starting aldehyde 3 and amyl-triphenylphospho-
nium bromide in the presence of excess LiBr (6 equiv) in
a one-step procedure. Phenyllithium or n-BuLi was ap-
plied for the generation of the initial betaine and the con-
secutive inversion of the b-oxidoylid to the
thermodynamically more stable threo isomer (Table 1).
Optimization of the Wittig–Schlosser conditions (entries
1
6
–
60 °C (entry 8, 93%). The minor Z-olefin 6 could only
1
be detected by 600 MHz H NMR in traces and it was re-
moved after one recrystallization step from n-pentane.
The third approach obviously constitutes the most effi-
cient method towards the desired vinylcyclopropane 6.
1
–5) afforded E-olefin 6 again as a mixture (80:20) with
the Z-isomer. Best yields (70%) were obtained with n-bu- Deprotection of the boronic ester7,17 6 (Scheme 2) was
tyl lithium (Scheme 1, Table 1, entry 4).
straightforward. It was carried out by treating it with 100
equivalents of KHF in MeOH (80 °C). Quantitative con-
2
Next, we turned our attention to the one-pot Julia–Kocien-
ski method using highly E-selective 1-phenyl-1H-tetra-
zol-5-yl sulfone (7) in the presence of KHMDS or
version was observed and 89% of trifluoroborate 8 was
isolated. The transesterification process7
,11a,18
to the reac-
1
5
tive dioxaborinane 9 was accomplished by the reaction of
NaHMDS as base (Scheme 1, Table 2). We were
trifluoroborate 8 with Me SiCl in the presence of Et N to
3
3
form the labile cyclopropylboronic dichloride, followed
by in situ condensation with 1,3-propanediol. Dioxabori-
Table 1 Optimization of the Wittig–Schlosser Reaction
Entrya Base I
equiv)b
Base II
(equiv)
Olefin 6
E/Z
Yield
(%)
19
nane 9 was obtained after distillation of the crude prod-
c
d
(
11a,20
uct in 90% yield. Following Matteson’s procedure,
treatment with chlormethyllithium and subsequent oxida-
tion with 30% H O /KHCO afforded the volatile primary
alcohol 10 (48%) which was then in the last two steps con-
1
2
3
4
PhLi (2)
PhLi (2)
64:36
59: 41
70: 30
80: 20
67: 33
30
44
53
70
23
2
2
3
PhLi (1)
PhLi (1)
verted into10,11the target molecule 1: Dess–Martin
PhLi (1)
n-BuLi (1)
n-BuLi (1)
n-BuLi (2)
periodinane
was again successfully employed for the
n-BuLi (1)
n-BuLi (1)
oxidation of alcohol 10 and the desired aldehyde 11 was
isolated in very good yield (88%). Finally, Wittig
5
12
reaction of precursor 11 afforded dictyopterene A (1) in
a
Reaction conditions were the same for all experiments (see
81% yield. All spectroscopic data were in full agreement
Scheme 1) only bases were modified.
21
with those previously reported.
b
Base I was employed for the generation of the initial betaine–lithium
In summary, we have developed a novel approach for syn-
complex.
c
21
Base II was employed for the inversion b-oxidoylides.
Olefinic ratio of 6 was determined by H NMR.
thesis of optically pure dictyopterene A. Key to the suc-
d
1
cess was the utilization of highly stable
Table 2 Optimization of the Julia–Kocienski Olefination
Entry
Temp
°C)
Timec
Sulfone 7
(equiv)
Base
Olefin 6
E:Z
Yield
(%)
d
(
1a
2a
3a
4a
5b
6b
7b
–78
–78
–78
–60
–60
–60
–78
–60
15 h
1.2
1.2
1.2
1.2
1.2
1.3
1.3
1.5
KHMDS (1.2 equiv, 0.5 M in toluene)
KHMDS (3 equiv, 0.5 M in toluene)
NaHMDS (1.2 equiv, 1 M in toluene)
KHMDS (1.2 equiv, neat)
>99:1
98:2
20
36
43
46
54
73
71
93
15 h
15 h
97:3
15 h
>99:1
>99:1
>99:1
>99:1
>99:1e
15 h
KHMDS (1.4 equiv, neat)
15 min
1 min
10 min
KHMDS (1.8 equiv, neat)
KHMDS (1.8 equiv, neat)
8a
KHMDS (1.8 equiv, neat)
a
Base was added dropwise over 5 min to a stirred solution of sulfone 7. The resulting yellow-orange solution was stirred for 1 h (in the case of
the experiment according to entry 8 only 5 min) and the aldehyde 3 was added dropwise over 5 min.
Base was added dropwise over 20 min to a stirred mixture of sulfone 7 and aldehyde 3.
b
c
Reactions were in progress for these reported times, i.e. after addition of all components to the reaction mixture, and then quenched with H O.
2
d
e
1
Olefinic ratio of 6 was determined by 300 MHz H NMR.
1
The minor Z-olefin 6 was only detected by 600 MHz H NMR and was readily removed after recrystallization from n-pentane.
Synlett 2008, No. 7, 971–974 © Thieme Stuttgart · New York

LETTER
Synthesis of Dictyopterene A
973
Jaenicke, L. Naturwissenschaften 1985, 72, 97.
C4H9
KHF2 (100 equiv),
MeOH, 80 °C, 5 d
(
j) Hombeck, M.; Pohnert, G.; Boland, W. Chem. Commun.
1999, 243. (k) Boland, W.; Müller, D. G. Tetrahedron Lett.
987, 28, 307. (l) Kajiwara, T.; Hatanaka, A.; Tahala, Y.;
6
BF3K
8
89%
1
Kawai, T.; Ishihara, M.; Tsuneya, T.; Fujimura, T.
Phytochemistry 1989, 28, 636. (m) Kajiwara, T.; Hatanaka,
A.; Kodama, K.; Ochi, S.; Fujimura, T. Phytochemistry
1991, 30, 1805. (n) Wirth, D.; Fischer-Lui, I.; Boland, W.;
Icheln, D.; Runge, T.; König, W. A.; Philips, J.; Clayton, M.
Helv. Chim. Acta 1992, 75, 734. (o) Pohnert, G.; Boland,
W. Tetrahedron 1996, 52, 10073.
a) Me3SiCl (3 equiv), Et3N (3 equiv),
MeCN, r.t., 5 min
b) 1,3-propanediol (0.95 equiv),
r.t., 30 min
a) CH2ICl (1.8 equiv),
t-BuLi (1.8 equiv),
THF, –78 °C to r.t., 4 d
C4H9
O
O
B
(
3) Later, (1S,2S)-dictyopterene B enantiomer was discovered
us a minor component in female gametes and essential oils
of families Scytosiphonaceae, Chordariaceae, Dictyo-
taceae, see ref. 2m.
b) H2O2, NaHCO3,
9
90%
0
°C to r.t., 3 h
1
2
. DMP (1.5 equiv), CH2Cl2,
py (3 equiv), 1 h, r.t.
(4) Optically pure dictyopterene A: (a) Kajiwara, T.; Nakatomi,
C4H9
T.; Sasaki, Y.; Hatanaka, A. Agric. Biol. Chem. 1980, 44,
88 %
2099. (b) Schotten, T.; Boland, W.; Jaenicke, L. Helv. Chim.
1
Acta 1985, 68, 1186. (c) Grandjean, D.; Pale, P.; Chuche, J.
Tetrahedron 1991, 47, 1215. (d) Colobert, F.; Genet, J. P.
Tetrahedron Lett. 1985, 26, 2779. (e) Narjes, F.; Bolte, O.;
Icheln, D.; König, W. A.; Schaumann, E. J. Org. Chem.
1993, 58, 626. (f) Itoh, T.; Inoue, H.; Emoto, S. Bull. Chem.
Soc. Jpn. 2000, 73, 409.
. a) Ph3PCH3Br (3 equiv),
n-BuLi (2.9 equiv),
Et2O, 0 °C, 30 min
b) aldehyde 11, Et2O,
OH
1
0 48%
0
°C, 24 h
8
1%
(
(
5) Optically pure dictyopterene B: Dorch, D.; Kunz, E.;
Scheme 2 Conversion of boronic ester 6 to dictyopterene A (1)
Helmchen, G. Tetrahedron Lett. 1985, 26, 3319; and ref.
4a,b.
6) Selected examples: (a) Yamada, K.; Tan, H.; Hirota, K.
Tetrahedron Lett. 1980, 21, 4873. (b) Ohloff, G.;
Pickenhagen, W. Helv. Chem. Acta 1969, 52, 880.
cyclopropylboronic ester 2 that first enabled a variety of
transformations in the side chain to furnish the hexenyl
derivative 6 and in a second step a Matteson homologa-
tion. Further investigations are in progress to extend the
approach, applying it to different natural product synthe-
sis projects.
(c) Billups, W. E.; Chow, W. Y.; Gross, J. H. J. Chem. Soc.,
Chem. Commun. 1974, 252. (d) Das, K. C.; Weinstein, B.
Tetrahedron Lett. 1969, 40, 3459. (e) Abraham, W. D.;
Cohen, T. J. Am. Chem. Soc. 1991, 113, 2313.
(f) Schneider, M. P.; Goldbach, M. J. Am. Chem. Soc. 1980,
1
02, 6114.
Acknowledgment
(
(
7) Hohn, E.; Pietruszka, J.; Solguda, G. Synlett 2006, 1531.
8) (a) Luithle, J. E. A.; Pietruszka, J. J. Org. Chem. 1999, 64,
We gratefully acknowledge the Deutsche Forschungsgemeinschaft,
the Otto-Röhm-Gedächtnisstiftung, the ‘Landesgraduiertenförde-
rung Baden-Württemberg’ (grant for E.H.), and the DAAD (grant
for J.Pa.) for the generous support of our projects. Donations from
the BASF AG, the Bayer AG, Boehringer Ingelheim KG, the De-
gussa AG, the Novartis AG, and the Wacker AG were greatly ap-
preciated.
8287. (b) Luithle, J. E. A.; Pietruszka, J. Eur. J. Org. Chem.
2000, 2557. (c) Hohn, E.; Pietruszka, J. Adv. Synth. Catal.
2004, 346, 863.
(
9) Thematic issue on cyclopropane chemistry (guest editor: A.
de Meijere): Chem. Rev. 2002, 103, 931-1647.
10) (a) Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155.
(
(
(
(
b) Ireland, R. E.; Liu, L. J. Org. Chem. 1993, 58, 2899.
c) Wavrin, L.; Viala, J. Synthesis 2002, 326.
11) (a) Luithle, J. E. A.; Pietruszka, J. J. Org. Chem. 2000, 65,
194. (b) Garcia, P. G.; Hohn, E.; Pietruszka, J.
J. Organomet. Chem. 2003, 680, 281.
References and Notes
9
(
1) Reviews: (a) Moore, R. E. Acc. Chem. Res. 1977, 10, 40.
b) Jaenicke, L.; Müller, D. G. Fortschr. Chem. Org. Naurst.
973, 30, 61. (c) Moore, R. E. In Marine Natural Products;
Scheuer, P. J., Ed.; Academic Press: New York, 1978, Chap.
(
1
(12) Review: Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89,
863.
(13) (a) Chatterjee, A. K.; Choi, T.-L.; Sanders, D. P.; Grubbs, R.
H. J. Am. Chem. Soc. 2003, 125, 11360. (b) Blackwell, H.
E.; O’Leary, D. J.; Chatterjee, A. K.; Washenfelder, R. A.;
Bussmann, D. A.; Grubbs, R. H. J. Am. Chem. Soc. 2000,
122, 58.
(14) (a) Schlosser, M.; Christmann, K. F. Angew. Chem., Int. Ed.
Engl. 1966, 5, 126. (b) Schlosser, M.; Tuong, H. B.; Schaub,
B. Tetrahedron Lett. 1985, 26, 311.
(15) (a) Reviews: Blakemore, P. R. J. Chem. Soc., Perkin Trans.
1 2002, 2563. (b) Blakemore, P. R.; Kocienski, P. J.;
Morley, A.; Muir, K. J. Chem. Soc., Perkin Trans. 1 1999,
955. (c) Blakemore, P. R.; Cole, W. J.; Kocienski, P. J.;
Morley, A. Synlett 1998, 26. (d) Bellingham, R.; Jarowicki,
K.; Kocienski, P.; Martin, V. Synthesis 1996, 285.
(16) Representative Procedure – Synthesis of E-olefin 6
To a stirred solution of the sulfone 7 (0.08 g, 0.28 mmol, 1.5
2. (d) Jaenicke, L.; Boland, W. Angew. Chem., Int. Ed. Engl.
1
982, 21, 643.
(
2) (a) Moore, R. E.; Pettus, J. A. Jr.; Doty, M. S. Tetrahedron
Lett. 1968, 9, 4787. (b) Pettus, J. A. Jr.; Moore, R. E. J.
Chem. Soc., Chem. Commun. 1970, 1093. (c) Pettus, J. A.
Jr.; Moore, R. E. J. Am. Chem. Soc. 1971, 93, 3087.
(
1
(
d) Moore, R. E.; Pettus, J. A. Jr.; Mistysyn, J. J. Org. Chem.
974, 39, 2201. (e) Moore, R. E. Lloydia 1976, 39, 181.
f) Moore, R. E. Act. Chem. Res. 1977, 10, 40. (g) Müller,
D. G.; Gassmann, G.; Boland, W.; Marnek, F.; Jaenicke, L.
Science 1981, 212, 1040. (h) Müller, D. G.; Clayton, M. N.;
Gassmann, G.; Boland, W.; Marner, F.-J.; Jaenicke, L.
Experientia 1984, 40, 211. (i) Müller, D. G.; Clayton, M.
N.; Gassmann, G.; Boland, W.; Marner, F.-J.; Schotten, T.;
Synlett 2008, No. 7, 971–974 © Thieme Stuttgart · New York

9
74
E. Hohn et al.
LETTER
equiv) in anhyd DME (4 mL) at –60 °C under N was added
13.8 (C-3¢), 21.0 (C-5¢¢), 22.1 (C-4¢¢), 27.2 (C-2¢), 31.8 (C-
3¢¢), 51.7 (CPh OCH ), 77.7 (C-4 and C-5), 83.3
2
dropwise via cannula a solution of KHMDS (0.07 g, 0.34
mmol, 1.8 equiv) in anhyd DME (2 mL) over 5 min. The
yellow-orange solution was stirred for 5 min and the
aldehyde 3 (0.1 g, 0.19 mmol, 1 equiv) in anhyd DME (2
mL) was added dropwise via cannula over 5 min. The
reaction mixture was stirred additional 10 min at –60 °C and
2
3
(CPh OCH ), 127.1, 127.2, 127.4, 127.7, 128.1, 128.3
2
3
(arom. CH), 129.6 (C-1¢¢), 133.5 (C-2¢¢), 141.1, 141.3 (arom.
C
).
ipso
(17) (a) Vedejs, E.; Chapman, R. W.; Fields, S. C.; Lin, S.;
Schrimpf, M. R. J. Org. Chem. 1995, 60, 3020.
(b) Matteson, D. S.; Kim, G. Y. Org. Lett. 2002, 4, 2153.
(c) Kim, B. J.; Matteson, D. S. Angew. Chem. Int. Ed. 2004,
43, 3056.
was then quenched with H O (1 mL). The mixture was
2
stirred vigorously whilst warming to r.t., diluted with Et O
2
(
(
(
4 mL) and H O (4 mL), and finally extracted with Et O
2
2
3 × 4 mL). The combined organic layers were dried
(18) Yuen, A. K. L.; Hutton, C. A. Tetrahedron Lett. 2005, 46,
7899.
MgSO ), filtered, and concentrated under reduced pressure.
4
The crude product 6 was purified by flash column
(19) Published racemate of oxaborinane 9: Markó, I. E.; Giard,
T.; Sumida, S.; Gies, A.-E. Tetrahedron Lett. 2002, 43,
2317.
chromatography (SiO , petroleum ether–EtOAc, 95:5) to
2
afford the E-olefin 6 (0.10 g, 93%) as colorless crystals;
E/Z > 99:1. The minor Z-isomer 6 was only detected by 600
(20) (a) Sadhu, K. M.; Matteson, D. S. Organometallics 1985, 4,
1687. (b) Matteson, D. S. Tetrahedron 1998, 54, 10555.
(c) Pietruszka, J.; Witt, A. J. Chem. Soc., Perkin Trans. 1
2000, 4293.
1
MHz H NMR and was removed by a single recrystallization
from pentane.
2
0
E-Olefin 6: [a]D –79.7 (c 1.0, CHCl ); mp 113 °C. Anal.
3
2
0
Calcd for C H BO (586.57): C, 79.86; H, 7.39. Found: C,
(21) (–)-(1S,2S)-Dictyopterene A (1): [a] –69.3 (c 0.40,
D
22
39
43
4
7
9.91; H, 7.31. MS–FAB (NBA + NaI): m/z (%) = 609 (<5)
CHCl ); ref. 2d: [a] +72 (c 6.74, CHCl ) for the 1R,2R-
3 D 3
+
+
+
+
[M + Na ], 197 (100) [Ph COCH ], 167 (12) [Ph C ], 105
enantiomer. GC-MS (EI, 70 eV): m/z (%) = 150 (100) [M ],
2
3
2
+
+
+
+
(
10) [C H O ], 77 (6) [C H ]. IR (film): 3060, 3024, 2956,
135 (15) [M – CH ], 122 (24) [M – C H ], 121 (60) [M –
7
5
6
5
3 2 4
+
1
2
932, 2833, 1493, 1446, 1421, 1366, 1239, 1184, 1075,
C H ]. H NMR (600 MHz, CDCl ): d = 0.75–0.84 (m, 2 H,
2
5
3
–
1
1
3
1032, 1019, 965, 921, 857 cm . H NMR (600 MHz,
3¢-H), 0.87 (t, J
= 7.0 Hz, 3 H, 6¢¢-H), 1.25–1.35 (m, 4
5
¢¢,6¢¢
3
3
CDCl ): d = –0.53 (ddd, J
= 9.8 Hz, J
= 6.5 Hz,
H, 4¢¢ and 5¢¢-H), 1.36–1.41 (m, 2 H, 1¢-H and 2¢-H), 1.95–
3
1¢,3¢b
1¢,3¢a
3
3
3
2
J
= 5.3 Hz, 1 H, 1¢-H), 0.24 (ddd, J2¢,3a¢= 7.8 Hz,
2.05 (m, 2 H, 3¢¢-H), 4.84 (dd, J = 10.2 Hz, J
= 2.3
= 2.3 Hz, 1
1
¢,2¢
1,2
2a,2b
3
3
3
3
2
J1¢,3¢a = 6.4 Hz, J
J1¢,3¢b = 9.8 Hz, J
= 3.4 Hz, 1 H, 3¢-H ), 0.34 (ddd,
Hz, 1 H, 2-H ), 4.98 (dd, J = 17.2 Hz, J
3¢a,3¢b
a
a
1,2
2a,2b
3
3
3
3
= 6.5 Hz, J
= 3.4 Hz, 1 H, 3¢-Hb),
H, 2-H ), 5.03 (dd, J
H), 5.36 (ddd, J = 10.2 Hz, J = 17.2 Hz, J = 6.7 Hz,
1 H, 1-H), 5.46 (dt, J
= 15.1 Hz, J
= 6.1 Hz, 1 H, 1¢¢-
1¢¢,2¢
3
2¢,3¢b
3¢a, 3¢b
b
1¢¢,2¢¢
3
3
3
0
.91 (t, J5 = 7.2 Hz, 3 H, 6¢¢-H), 1.17–1.27 (m, 1 H, 2¢-H),
¢¢,6¢¢
1,2 1,2 1,1¢
3
3
1.28–1.36 (m, 4 H, 4¢¢-H, 5¢¢-H), 1.95 (m, 2 H, 3¢¢-H), 2.99
= 15.1 Hz, J = 6.9 Hz, 1 H, 2¢¢-
2¢¢,3¢¢
1
¢¢,2¢¢
3
3
13
(s, 6 H, OCH ), 4.79 (dd, J
= 15.1 Hz, J
= 8.5 Hz, 1
= 15.1 Hz,
¢¢,2¢¢
H). C NMR (150 MHz, CDCl ): d = 14.1 (C-6¢¢), 14.8 (C-
3
1¢¢,2¢¢
1¢¢,2¢
3
3
H, 1¢¢-H), 5.25 (s, 2 H, 4-H, 5-H), 5.51 (dt, J
3¢), 22.3 (C-5¢¢), 23.6 (C-2¢), 24.3 (C-1¢), 31.8 (C-4¢¢), 32.2
1
3
J
= 6.9 Hz, 1 H, 2¢¢-H), 7.27–7.34 (m, 20 H, arom. H).
(C-3¢¢), 111.8 (C-2), 129.2 (C-2¢¢), 131.6 (C-1¢¢), 140.9 (C-
2
¢¢,3¢¢
13
C NMR (125 MHz, CDCl ): d = 1.8 (C-1¢), 12.4 (C-6¢¢),
1).
3
Synlett 2008, No. 7, 971–974 © Thieme Stuttgart · New York

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