Stereoselective synthesis of the fully functionalized HIJ-ring framework of ciguatoxin

Article abstract of DOI:10.1055/s-2004-817769

An efficient convergent synthetic route to construct the HIJ-ring system of ciguatoxin was achieved via stereo controlled eight-membered ring formation by using acetylene cobalt complex and subsequent six-membered ring formation through intramolecular 1,4-addition reaction.

Full text of DOI:10.1055/s-2004-817769

LETTER
603
Stereoselective Synthesis of the Fully Functionalized HIJ-ring Framework of
Ciguatoxin
Stereoselective
a
S
ynthesis
o
k
f
the Fully F
a
unctionaliz
y
ed HIJ-ring
F
u
ramework
o
k
f
Ciguatoxini Baba, Shigeyuki Takai, Naotaka Sawada, Minoru Isobe*
Laboratory of Organic Chemistry, School of Bioagricultural Sciences, Nagoya University
Fax +81(52)7894111; E-mail: isobem@agr.nagoya-u.ac.jp
Received 18 December 2003
The retrosynthetic analysis for the HIJ-ring system is
Abstract: An efficient convergent synthetic route to construct the
HIJ-ring system of ciguatoxin was achieved via stereo controlled
eight-membered ring formation by using acetylene cobalt complex
and subsequent six-membered ring formation through intramolecu-
lar 1,4-addition reaction.
illustrated in Scheme 1. The HIJ-ring system 1, represent-
ing C30-C46 portion of CTX, consists of trans-fused tri-
cyclic 6/8/6-membered ether ring skeleton, which carries
two asymmetric methyl groups. The C57-methyl group in
compound 1 was envisioned to arise from the ketone of
compound 2. The candidate reaction for elaborating the
fully functionalized H-ring is the intramolecular 1,4-addi-
tion of compound 3. The eight-membered ring in 3 would
be prepared via acetylene cobalt complex 4. Opening of
the eight-membered ring I in 4 gives compound 5, which
would in turn arise from a Sonogashira coupling reaction
of acetylene 6 and vinyltriflate 7 between C38 and C39
bond.
Key words: alkyne cobalt complexes, reductive decomplexation,
medium sized ring closure reaction, intramolecular 1,4-addition re-
action, ciguatoxin.
Ciguatera fish poisoning is one of the most important hu-
man poisoning caused by the ingestion of ciguatoxic fish-
es.1 Ciguatoxin (CTX, Figure 1), one of the principal
toxin of the poisoning, has attracted considerable attention
from the scientists as a consequence of their architectural
complexity and potent biological activity.2–4 Recently,
Hirama’s group reported the first total synthesis of
CTX3C, a member of the CTX family.5 We also have de-
veloped valid methodologies for the construction of medi-
um-sized ether rings via cobalt mediated cyclization
during the course of our studies toward the synthesis of
CTX.6,7 Herein we report the advanced divergent synthe-
sis of the fully functionalized HIJ-ring framework. Cen-
tral to this venture is the stereocontrolled eight-membered
ring formation by using acetylene cobalt complex8 and
subsequent six-membered ring formation via stereoselec-
tive intramolecular 1,4-addition reaction.
The construction of the vinyltriflate 7 began with the com-
pound 8, an intermediate of the J-ring vinylsulfone in our
synthesis of right end of CTX (Scheme 2).6 Firstly, the
protective groups in 8 were manipulated to provide 9,
which was transformed to lactone 10 via acetolysis, hy-
drolysis and oxidation of the anomeric position. Addition
of allylmagnesium bromide to lactone 10, followed by
Kishi’s silane reduction,9 provided hydropyran system 11
as an exclusive diastereomer. The terminal olefin of 11
was converted into methylketone through Wacker oxida-
tion.10 Removal of the benzyl group from 11, followed by
protection with ethoxyethyl group, gave compound 12,
which was converted into corresponding vinyltriflate by
57
Me
39
Me
H
H
OH
H
O
H
O
H
56
Me
I
J
K
HO
O
O
M
55
ciguatoxin (CTX)
O
L
O
H
H
31
H
H
G
H
O
OH
H
H
O
H
Me Me
H
H
H
H
H
H
O
F
O
E
57
C
D
B
A
O
H
Me
1
H
39
H
H
H
H
46
O
O
O
HO
H
OH
OR
H
H
OH
J
I
56
Me
O
OR
O
RO
NC
H
H
H
RO
30
1
Figure 1
SYNLETT 2004, No. 4, pp 0603–0608
0
9.
0
3.
2
0
0
4
Advanced online publication: 10.02.2004
DOI: 10.1055/s-2004-817769; Art ID: U30203ST
© Georg Thieme Verlag Stuttgart · New York

604
T. Baba et al.
LETTER
57
O
H
Me
H
H
H
H
H
H
H
H
46
O
O
OR
OR
H
OR
J
I
H
J
I
O
Me
O
O
RO
NC
OR
Me
O
H
RO
H
H
H
1
2
RO
H
NC
30
RO
O
H
H
H
H
O
O
OR
OR
Co2(CO)6
OR
OR
J
I
J
I
OH
Me
O
O
O
H
H
HO
NC
O
H
H
H
H
Me
H
3
4
OR
RO
NC
Co2(CO)6
H
O
39
H
H
H
H
46
38
O
H
H
H
NC
OR
H
O
O
30
O
+
TfO
OR
OR
J
Me
O
NC
HO
OR
HO
OH OH
H
Me
OH
OH
5
6
7
Scheme 1 Retrosynthetic analysis of the HIJ-ring fragment 1
treatment with LDA and PhNTf2 under kinetically con- stereochemistry between H36 and H42, in 60% isolated
trolled condition. Finally, removal of the ethoxyethyl yield. At this point, the stereochemistry was exclusively
group provided the vinyltriflate 7a and its isomer 7b.11
controlled in accordance with thermodynamic stability of
the product. The moderate yield of this reaction was main-
ly due to the instability of acetonide moiety under the
acidic reaction condition. Although the hydrolysate of
acetonide moiety, was potentially useful, only the major
target product was carried forward at this time. With the
requisite bicyclic compound 15 available, we turned our
attention to transform the cobaltcomplex of enyne system
to an endocyclic Michael acceptor to form adjacent six-
membered H-ring. The exocyclic olefin of 15 was found
to be cleaved smoothly by Lemieux–Johnson’s oxidation
reaction to afford ketone 16.
The construction of the other requisite subsegment 6 re-
quired two steps from the aldehyde 13 (Scheme 3).6d The
aldehyde 13 was treated with lithium TMS-acetylide, and
then desilylated with TBAF to give the acetylene 6.12
The coupling of vinyltriflate 7a and acetylene 6 proceeded
with high efficiency to furnish enyne 14, which could be
readily converted into corresponding acetylene cobalt
complex by simply mixing with Co2(CO)8 in CH2Cl2
(Scheme 4). Treatment of this cobalt complex with
BF3·OEt2 at 0 °C resulted in its total consumption within
10 minutes and afforded the bicyclic system 15 having syn
H
H
H
H
H
H
H
H
H
MeO
PivO
O
MeO
BnO
O
O
O
a
b
c
O
OMe
OMe
OMe
OMe
O
BnO
H
H
8
9
10
H
H
H
H
O
OMe
H
H
H
H
H
TfO
O
O
d
e
OMe
OMe
OMe
OMe
HO
OMe
O
7a
7b
BnO
EEO
H
H
H
H
H
O
OMe
OMe
TfO
11
12
HO
H
H
Scheme 2 Synthesis of vinyltriflate 7. Reagents and conditions: a) i) NaOMe, MeOH; ii) NaH, BnBr, TBAI, DMF; iii) Amberlyst 15E,
MeOH; iv) t-BuOK, MeI, THF, 87% in 4 steps; b) i) H2SO4, Ac2O, 0 °C; ii) HCl, DME, H2O, 60 °C; iii) Ac2O, DMSO, 68% in 3 steps; c)
i) CH2=CHCH2MgBr, THF; ii) Et3SiH, BF3·OEt2, CH3CN, 64% in 2 steps; d) i) O2, PdCl2, CuCl, DMF, H2O; ii) 10% Pd/C, H2, EtOH; iii) EVE,
PPTS, CH2Cl2, 73% in 3 steps; e) LDA, THF, –78 °C, then PhNTf2, r.t.: ii) CSA, MeOH, 78% in 2 steps (7a:7b > 10:1).
Synlett 2004, No. 4, 603–608 © Thieme Stuttgart · New York

LETTER
Stereoselective Synthesis of the Fully Functionalized HIJ-ring Framework of Ciguatoxin
605
H
H
H
O
ref. 6c
O
O
O
O
AcO
AcO
a, b
NC
Me
NC
Me
CHO
H
OAc
OTES
OH OH
13
6
Scheme 3 Synthesis of acetylene 6. Reagents and condtions: a) Trimethylsilylacetylene, n-BuLi, THF; b) TBAF, THF, 99% in 2 steps.
Reductive decomplexation of 16 to the corresponding Having accomplished the assembly of the tricyclic inter-
endocyclic olefin under a conventional method, such as n- mediate 20 from two subsegments, the stereocontrolled
Bu3SnH in toluene13a,b or NaH2PO2·H2O in 2-methoxy- introduction of the methyl group to I ring was investigated
ethanol,13c was unsuccessful due to the further lability of (Scheme 5). After the free secondary alcohol was protect-
generated a,b-unsaturated ketone under these reductive ed as the triisopropylsilyl (TIPS) ether, 2-(trimethylsilyl)-
conditions. On the other hand, hydrosilylation in the pres- ethoxymethyl (SEM) protected hydroxymethyl anion was
ence of excess amount of bis(trimethylsilyl)acetylene added to the carbonyl group as C1-unit to afford the SEM
(BTMSA) proceeded successfully in regioselective man- ether 22.17 Removal of the SEM group under acidic con-
ner to provide vinylsilane 17.13a Subsequent protection of dition and subsequent treatment with thiocarbonyldiimi-
the secondary alcohol with benzoyl group afforded 18 in dazole delivered the cyclicthiocarbonate 24.
good yield. As a consequence of our early investigations
The oxygen atom attached to C39 position was selectively
of this process of hydrosilylation, BTMSA was deter-
removed under the radical reduction condition to provide
mined to be a notably efficacious trapping reagent of ac-
the primary alcohol 25 as a mixture of the isomer at C39
tive cobalt complex species, capable of reducing a,b-
unsaturated ketones,14 liberated from the substrate.15 Re-
moval of the triethylsilyl group was performed by treat-
ment of 18 with HF·pyridine in acetonitrile to afford 19.
Upon treatment of the desilylated endocyclic enone 19
with BF3·OEt2, the H-ring cyclization took place with at-
tendant loss of acetonide group to afford the target tricy-
clic compound 20 having syn stereochemistry between
CH3-56 and H-37, as a major product.16
position in the ratio of 4:1.18 The primary alcohol was pro-
tected as the acetate for the verification of the stereochem-
istry through NOE experiments. Then, we found the C39
configuration of the major product was unfortunately
unfavorable probably due to the difference of the steric
hindrance between both sides of the tertiary radical sp2
center, as shown in Scheme 5.
H
H
H
H
H
H
H
H
O
O
O
O
NC
Me
a
O
OMe
OMe
OMe
OMe
+
TfO
O
NC
HO
HO
14
OH OH
Me
OH
O
OH
6
7a
O
H
H
H
H
H
H
O
OMe
OMe
OMe
Co2(CO)6
c
Co2(CO)6
b
d
O
H
OMe
O
O
O
H
O
H42
H36
O
Me
16
Me
15
OH
OH
NC
NOE
NC
NOE
O
O
O
R1
H
H
H
H
H
56
O
H
O
H
37
g
O
HO Me
O
O
OMe
OMe
OMe
O
H
H
H
NC
H
OMe
Me
R2O
NC
BzO
H
20
17 : R1 = SiEt3, R2 = H
18 : R1 = SiEt3, R2 = Bz
19 : R1 = H, R2 = Bz
e
f
Scheme 4 Construction of the HIJ-ring tricyclic framework 20. Reagents and conditions: a) Pd(PPh3)4, CuI, n-PrNH2, toluene, 99%; b) i)
Co2(CO)8, CH2Cl2, 87%; ii) BF3·OEt2, CH2Cl2, 60%; c) OsO4, NaIO4, THF, H2O, 73%; d) Et3SiH, BTMSA, ClCH2CH2Cl, 82%; e) BzCl, py-
ridine, CH2Cl2, DMAP, 100%; f) HF·pyridine, CH3CN; g) BF3·OEt2, CH2Cl2, 62% in 2 steps.
Synlett 2004, No. 4, 603–608 © Thieme Stuttgart · New York

606
T. Baba et al.
LETTER
S
OR
OH
O
O
H
O
H
H
H
H
H
O
H
H
TIPSO
NC
d
Me
b
H
RO Me
O
O
33
O
TIPSO
NC
Me
H
O
O
OMe
O
32
O
OMe
OMe
H
NC
H
OMe
O
OMe
H
H
H
H
BzO
BzO
H
H
c
H
BzO
OMe
H
H
22 : R = SEM
23 : R = H
20 : R = H
21 : R = TIPS
a
24
H
OR
H
NOE
NOE
Me
R
H
OAc
BzO
*
H
H
H
H
39
*
TIPSO
Me
H
H
H
O
39
OR
H
O
e
H
TBSO
O
O
Me
H
H
O
H
O
37
41
NC
O
OMe
OMe
H
NC
H
H
H
O
OMe
OMe
H
BzO
H
H
H
H
BzO
MeO
H
H
O
25 : R = H
26 : R = Ac
f
H
major
OMe
Scheme 5 Homologation of the I-ring methyl group (1). Reagents and conditions: a) TIPSOTf, pyridine, DMF, 0 °C to r.t., 2 d, 93%; b)
n-Bu3SnCH2OSEM, n-BuLi, THF, –78 °C, 75 min, 83%; c) CSA, MeOH, r.t., 6 h; d) 1,1¢-thiocarbonyldiimidazole, toluene, 85 °C, overnight;
e) n-Bu3SnH, AIBN, toluene, 95 °C, 5 min, 74% in 3 steps (major:minor = 4:1); f) Ac2O, pyridine, r.t., 3.5 h, quant.
Viewed at the steric circumstances around C39 position, While the fully functionalized HIJ-ring framework 29 was
we anticipated the desired orientation of the functional constructed from two subsegments in a convergent and
group attached to C39 position would be derived through stereo controlled manner, homologation of the methyl
the process of protonation–deprotonation equilibrium at group in I ring required 9 synthetic steps from the ketone
the C39 position under thermodynamically controlled 21. An important finding of this study is the requested
condition. Then, after the oxidation of the primary alcohol configuration of C39 was successfully provided through
25, the aldehyde 26 was treated under the basic, keto-enol the epimerization of the aldehyde 26. To facilitate the lat-
equilibration, condition (Scheme 6).
ter part of the synthesis, more efficient derivatization
method of the aldehyde was examined with structurally
close compound 30 (Scheme 7). Several useful methods
for accomplishing such homologation have been reported,
but we found the modified Darzens type reaction based on
chloro(trimethylsilyl)methyllithium was the optimum
The result met our expectation. Specifically, the ratio of
the C39-isomers converged upon undesired 26a:desired
26b = 1:8.5. Finally, reduction of the aldehyde 26 and
subsequent radical deoxygenation via the imidazolethio-
carbamate 28 gave the target compound 29.19
OH
X
Y
39
H
H
56
Me
H
H
a
TIPSO
NC
*
b
Me
H
O
TIPSO
NC
O
H
O
O
O
OMe
OMe
O
OMe
OMe
H
H
H
H
BzO
H
H
BzO
H
H
26a : X = H, Y = CHO
26b : X = CHO, Y = H
25
OH
R
57
H
H
H
H
TIPSO
NC
TIPSO
NC
Me
Me
O
H
H
O
O
c
O
O
O
OMe
OMe
OMe
OMe
H
H
H
H H
BzO
BzO
H
H
H
27
28 : R = OC(=S)Im
29 : R = H
d
Scheme 6 Homologation of the I-ring methyl group (2). Reagents and conditions: a) IBX, DMSO, r.t., 20 h, 99% (26a:26b = 4:3); b) DBU,
THF, 0 °C to r.t., 1 h, quant. (26a:26b = 1:8.5); c) NaBH(OAc)3, CH3CN, HOAc, –10 °C to 0 °C, 5 h, 93%; d) 1,1¢-thiocarbonyldiimidazole,
toluene, 85 °C, 7.5 h; e) n-Bu3SnH, AIBN, toluene, 95 °C, 5 min, 80% in 2 steps.
Synlett 2004, No. 4, 603–608 © Thieme Stuttgart · New York

LETTER
Stereoselective Synthesis of the Fully Functionalized HIJ-ring Framework of Ciguatoxin
607
TMS
H
O
O
O
O
H
H
H
H
H
39
a, b
c
TIPSO
NC
TIPSO
NC
Me
Me
H
O
O
H
H
O
O
O
OMe
O
OMe
H
H
H
H
H
H
BzO
BzO
H
30
32
31
Scheme 7 Homologation of the aldehyde via the epoxysilane. Reagents and conditions: a) sec-BuLi, TMSCH2Cl, CeCl3, TMEDA, THF,
–78 °C, 30 min; b) DBU, THF, r.t., 3 h; c) TfOH, THF, H2O, 79% in 3 steps (C39a:C39b>10:1).
condition for this particular system.20 The carbonyl group
(4) For the bioactivity of CTXs, see: (a) Lombert, A.; Bidard,
J.-N.; Lazdunski, M. FEBS Lett. 1987, 219, 355. (b) Lewis,
R. J.; Sellin, M.; Poli, M. A.; Norton, R. S.; Macleod, J. K.;
Sheil, M. M. Toxicon 1991, 29, 1115. (c)Dechraoui, M.-Y.;
Naar, J.; Pauillac, S.; Legrand, A.-M. Toxicon 1999, 37,
in 30 was transformed to the epoxysilane 31 via a chloro-
hydrin by treating with in situ generated chloro(trimethyl-
silyl)methylcerium and subsequent treatment with DBU.
The epoxysilane 31 was successfully converted into the
125. (d) Anger, T.; Madge, D.-J.; Mulla, M.; Riddall, D. J.
aldehyde 32 under the acidic condition. The present pro-
cedure requires only 3 steps to form the aldehyde having
preferable stereochemistry (>10:1) from the ketone, while
6 steps were employed in the previous method.
Med. Chem. 2001, 44, 115. (e) Lin, Y.-Y.; Risk, M.; Ray, S.
M.; Engen, D. V.; Clardy, J.; Golik, J.; James, J. C.;
Nakanishi, K. J. Am. Chem. Soc. 1981, 103, 6773.
(f) Shimizu, Y.; Chou, H.-N.; Bando, H.; Duyne, G. V.;
Clardy, J. C. J. Am. Chem. Soc. 1986, 108, 514.
In conclusion, we have achieved to establish an efficient
synthetic method for the construction of fully functional-
ized HIJ-ring framework based on the convergent strate-
gy. It proceeds with high stereochemical control at all
positions including thermodynamically driven adjustment
of syn-selective eight-membered I-ring cyclization and
six-membered H-ring formation via intramolecular 1,4-
addition reaction. Further studies toward the synthesis of
the right part of CTX along this line are now in progress.
(5) (a) Hirama, M.; Oishi, T.; Uehara, H.; Inoue, M.; Maruyama,
M.; Oguri, H.; Satake, M. Science 2001, 294, 1904.
(b) Inoue, M.; Uehara, H.; Maruyama, M.; Hirama, M. Org.
Lett. 2002, 4, 4551. (c) Tatami, A.; Inoue, M.; Uehara, H.;
Hirama, M. Tetrahedron Lett. 2003, 44, 5229.
(6) For recent synthetic studies of ciguatoxin in our laboratory,
see: (a) Saeeng, R.; Isobe, M. Heterocycles 2001, 54, 789.
(b) Kira, K.; Hamajima, A.; Isobe, M. Tetrahedron 2002, 58,
1875. (c) Takai, S.; Sawada, N.; Isobe, M. J. Org. Chem.
2003, 68, 3225. (d) Baba, T.; Huang, G.; Isobe, M.
Tetrahedron 2003, 59, 6851; and references therein.
(7) For a review of the Nicholas reaction, see: Teobald, B. J.
Tetrahedron 2002, 58, 4133.
Acknowledgment
(8) For construction of medium sized ether rings via acetylene
cobalt complexes in a highly stereoselective syn-trans
orientation, see: (a) Isobe, M.; Yenjai, C.; Tanaka, S. Synlett
1994, 11, 916. (b) Yenjai, C.; Isobe, M. Tetrahedron 1998,
54, 2509. (c) Isobe, M.; Hosokawa, S.; Kira, K. Chem. Lett.
1996, 473. (d) Isobe, M.; Nishizawa, R.; Hosokawa, S.;
Nishikawa, T. Chem. Commun. 1998, 2665.
This work was supported in part by the Grant of the 21st Century
COE program from the Ministry of Education, Sports, Science and
Technology (MEXT). We are grateful to Mr. Kitamura (analytical
laboratory in this school) for elemental analysis.
References
(9) Lewis, M. D.; Cha, J. K.; Kishi, Y. J. Am. Chem. Soc. 1982,
104, 4976.
(1) For reviews, see: (a) Gillespie, N. C.; Lewis, R. J.; Pearn, J.;
Bourke, A. T. C.; Helms, M. J.; Bourke, J. B.; Shields, W. J.
Ned. J. Aust. 1986, 145, 584. (b) Yasumoto, T.; Murata, M.
Chem. Rev. 1993, 93, 1897. (c) Scheuer, P. J. Tetrahedron
1994, 50, 3. (d) Yasumoto, T. Chem. Rec. 2001, 1, 228.
(e) Lewis, R. J. Toxicon 2001, 39, 97.
(2) For the origin of CTXs, see: Yasumoto, T.; Nakajima, R.;
Bagnis, R.; Adachi, R. Nippon Suisan Gakkaishi 1977, 43,
1021.
(3) For the characterization of CTXs, see: (a) Scheuer, P. J.;
Takahashi, W.; Tsutsumi, J.; Yoshida, T. Science 1967, 155,
1267. (b) Tachibana, K. Ph.D. Thesis; University of Hawaii:
Hawaii, 1980. (c) Murata, M.; Legrand, A. M.; Ishibashi, Y.;
Yasumoto, T. J. Am. Chem. Soc. 1989, 111, 8929.
(d) Murata, M.; Legrand, A. M.; Yasumoto, T. Tetrahedron
Lett. 1989, 30, 3793. (e) Murata, M.; Legrand, A. M.;
Ishibashi, Y.; Fukui, M.; Yasumoto, T. J. Am. Chem. Soc.
1990, 112, 4380. (f) Murata, M.; Legrand, A. M.; Scheuer,
P. J.; Yasumoto, T. Tetrahedron Lett. 1992, 33, 525.
(g) Satake, M.; Morohashi, A.; Oguri, H.; Oishi, T.; Hirama,
M.; Harada, N.; Yasumoto, T. J. Am. Chem. Soc. 1997, 119,
11325.
(10) Smidt, J.; Hafner, W.; Jira, R.; Sieber, R.; Sedlmeier, J.;
Sabel, A. Angew. Chem., Int. Ed. Engl. 1962, 1, 80.
(11) Physical data for 7a. 1H NMR (400 MHz, CDCl3): d = 1.39
(1 H, q, J = 11.0 Hz, H-43a), 1.84 (1 H, br, -OH), 2.58 (1 H,
dd, J = 15.5, 9.0 Hz, H-40a), 2.61 (1 H, dt, J = 11.0, 4.0 Hz,
H-43b), 2.92 (1 H, dd, J = 15.5, 2.0 Hz, H-40b), 3.25–3.45
(4 H, m, H-41, H-42, H-44, H-45), 3.38 (3 H, s, -OCH3),
3.39 (3 H, s, -OCH3), 3.56 (1 H, dd, J = 10.5, 4.0 Hz, H-46a),
3.64 (1 H, dd, J = 10.5, 1.5 Hz, H-46b). HRMS (FAB) calcd
for C12H20F3O7S+ [M + H]+: 365.0882. Found: 365.0872.
(12) Physical data for 6. 1H NMR (300 MHz, CDCl3): d = 1.10,
1.11 (3 H, s, -CH3), 1.37, 1.38 [3 H, s, -C(CH3)2], 1.46 [3 H,
s, -C(CH3)2], 1.78–1.90 (total 1 H, m, H-35a), 1.95, 2.07
(total 1 H, ddd, J = 14.5, 5.0, 2.5 Hz and J = 14.5, 4.0, 2.0
Hz, H-35b), 2.50–2.61 (total 2 H, m, H-36, acetylene), 2.78,
2.84 (total 1 H, dd, J = 17.0, 3.5 Hz and J = 17.5, 3.0 Hz, H-
31), 3.03, 3.22 (total 1 H, br-s, -OH), 3.82, 4.10 (total 1 H,
dd, J = 10.0, 2.0 Hz and J = 10.0, 2.5 Hz, H-34), 4.22, 4.29
(total 1 H, dd, J = 9.5, 3.0 Hz and J = 9.0, 3.5 Hz, H-32),
4.64, 4.75 (total 1 H, m, H-36). Anal. Calcd for C13H19NO4:
C, 61.64; H, 7.56; N, 5.53. Found: C, 61.65; H, 7.51; N, 5.43.
Synlett 2004, No. 4, 603–608 © Thieme Stuttgart · New York

608
T. Baba et al.
LETTER
(13) For reductive decomplexation reaction into cis-olefins or
vinylsilanes, see: (a) Hosokawa, S.; Isobe, M. Tetrahedron
Lett. 1998, 39, 2609. (b) Shibuya, S.; Isobe, M. Tetrahedron
1998, 54, 6677. (c) Takai, S.; Ploypradith, P.; Hamajima,
A.; Kira, K.; Isobe, M. Synlett 2002, 588.
aromatic), 7.96–8.00 (2 H, m, aromatic). HRMS (FAB)
calcd for C27H35NNaO9+ [M + Na]+: 540.2210. Found:
540.2180.
(17) Fernandes-Megia, E.; Lay, S. V. Synlett 2000, 455.
(18) Redlich, H.; Sudau, W.; Paulsen, H. Tetrahedron 1985, 41,
4253.
(14) Lee, H.-Y.; An, M. Tetrahedron Lett. 2003, 44, 2775.
(15) (a) Kira, K.; Tanda, H.; Hamajima, A.; Baba, T.; Takai, S.;
Isobe, M. Tetrahedron 2002, 58, 6485. (b) Absence of
BTMSA leads to further reduction of unsaturated ketone
product to corresponding saturated carbonyl compound.
(16) Physical data for 20. 1H NMR (400 MHz, CDCl3) d = 1.34
(3 H, s, H-56), 1.40 (1 H, q, J = 11.5 Hz, H-43a), 1.93 (1 H,
q, J = 11.5 Hz, H-35a), 2.50 (1 H, dt, J = 11.5, 5.0 Hz, H-
35b), 2.53 (1 H, ddd, J = 11.5, 4.5, 4.0 Hz, H43b), 2.60 (1 H,
dd, J = 17.0, 4.0 Hz, H-31a), 2.62 (1 H, dd, J = 17.0, 8.0 Hz,
H-31b), 2.69 (1 H, ddd, J = 11.0, 4.0, 2.0 Hz, H-38a), 2.79–
2.89 (3 H, m, H-38b, H-40a, H-40b), 3.21 (1 H, d, J = 8.0
Hz, -OH), 3.20–3.26 (2 H, m, H-44, H-45), 3.32 (1 H, ddd,
J = 11.5, 9.5, 4.5 Hz, H-42), 3.34 (3 H, s, -OCH3), 3.38 (3 H,
s, -OCH3), 3.43 (1 H, ddd, J = 11.5, 9.5, 5.0 Hz, H-36), 3.48
(1 H, ddd, J = 10.5, 9.5, 4.5 Hz, H-41), 3.53 (1 H, dd,
J = 10.5, 4.0 Hz, H-46b), 3.61 (1 H, dd, J = 10.5, 1.5 Hz, H-
46b), 3.74 (1 H, td, J = 8.0, 4.0 Hz, H-32), 3.75 (1 H, ddd,
J = 10.5, 9.5, 4.0 Hz, H-37), 5.40 (1 H, dd, J = 12.0, 5.0 Hz,
H-34), 7.45–7.52 (2 H, m, aromatic), 7.60–7.64 (1 H, m,
(19) Physical data for 29. 1H NMR (400 MHz, CDCl3) d = 0.89–
1.06 {21 H, m, -Si[CH(CH3)2]3}, 1.07 (3 H, d, J = 7.0 Hz,
CH3-57), 1.33 (1 H, m, H-43a), 1.45–1.71 (2 H, m, H-38a,
H-40a), 1.47 (3/2 H, s, H-56), 1.49 (3/2 H, s, H-56*), 1.72–
1.80 (1 H, m, H-35a), 1.82–2.09 (3 H, m, H-38b, H-39, H-
40b), 2.48–2.57 (3 H, m, H-31a, H-35b, H-43b), 2.82 (1/2 H,
dd, J = 16.5, 5.5 Hz, H-31b), 2.89 (1/2 H, dd, J = 16.5, 5.5
Hz, H-31b*), 3.10–3.66 (6 H, m, H-36, H-37, H-41, H-42,
H-44, H-45), 3.35 (3 H, s, -OCH3) 3.40 (3 H, s, -OCH3), 3.49
(1 H, dd, J = 10.5, 5.5 Hz, H-46a), 3.63 (1 H, dd, J = 10.5,
2.0 Hz, H-46b), 3.97 (1/2 H, t, J = 5.5 Hz, H-32), 4.05 (1/2
H, dd, J = 5.5, 4.5 Hz, H-32*), 5.15 (1 H, dd, J = 11.5, 4.5
Hz, H-34), 7.44–7.49 (2 H, m, aromatic), 7.58–7.62 (1 H, m,
aromatic), 7.99–7.02 (2 H, m, aromatic). The fractional
integral values result from the existence of a rotational
isomer at C32-C33 bond. HRMS (FAB) calcd for
C37H59O8NNaSi+ [M + Na]+: 696.3907. Found: 696.3917.
(20) Burford, C.; Cooke, F.; Ehlinger, E.; Magnus, P. J. Am.
Chem. Soc. 1977, 99, 4536.
Synlett 2004, No. 4, 603–608 © Thieme Stuttgart · New York