Enantioselective synthesis of the tricyclic core of GKK1032, novel antibiotic anti-tumor agents, by employing an intramolecular Diels-Alder cycloaddition strategy

Article abstract of DOI:10.1055/s-2005-869843

An efficient and enantioselective synthesis of a decahydrofluorene nucleus, the tricyclic core (ABC-ring system) of GKK1032s, novel antimicrobial and anti-tumor agents, was achieved using a highly diastereoselective intramolecular Diels-Alder (IMDA) react

Full text of DOI:10.1055/s-2005-869843

LETTER
1539
Enantioselective Synthesis of the Tricyclic Core of GKK1032, Novel
Antibiotic Anti-Tumor Agents, by Employing an Intramolecular Diels–Alder
Cycloaddition Strategy
E
nantioselective Synth
o
e
sis of the
T
ricyclic
C
i
ore of
t
G
K
K
1
e
032 ru Asano,a Munenori Inoue,*a,b Tadashi Katoh*c
a
b
c
Department of Electronic Chemistry, Tokyo Institute of Technology, Nagatsuta, Yokohama 226-8502, Japan
Sagami Chemical Research Center, 2743-1 Hayakawa, Ayase, Kanagawa 252-1193, Japan
Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
Fax +81(22)2752013; E-mail: katoh@tohoku-pharm.ac.jp
Received 4 April 2005
Me
H
Me
H
1
Abstract: An efficient and enantioselective synthesis of a deca-
hydrofluorene nucleus, the tricyclic core (ABC-ring system) of
GKK1032s, novel antimicrobial and anti-tumor agents, was
achieved using a highly diastereoselective intramolecular Diels–
Alder (IMDA) reaction. The substrate for the IMDA reaction was
synthesized through intermolecular Diels–Alder reaction of
Kitahara–Danishefsky’s diene and an enone derived from enulose
to construct the functionalized C-ring. CuCl-promoted Stille cou-
pling of a vinyl iodide and a vinylstannane installed the requisite
triene side chain.
Me
5
Me
Me
Me
Me
O
Me
O
A
9
A
6
3
14
C
B
C
B
15
NH
O
NH
OR
13
H
H
11
O
O
H
H
O
O
Me
Me
3 : GKK1032B
1 : GKK1032A1 ( R = Me )
2 : GKK1032A2 ( R = H )
Me
Key words: Diels–Alder reaction, Stille coupling, natural product
synthesis, GKK1032s, antimicrobial agents, anti-tumor agents
H
Me
O
Me
A
C
B
X
Y
NH
OH
H
O
H
In 2001, GKK1032A1 (1), A2 (2), and B (3) were isolated
by the Kyowa Hakko research group from the culture
broth of Penicillium sp. GKK1032 (Figure 1).1 In addition
to displaying antimicrobial activity against Bacillus
subtilis No.10707, these compounds exhibit anti-tumor
activity against the human cervical cancer-derived HeLa
S3 cells. Just one year later, Omura et al. also reported the
isolation of FO-7711CD6 from the culture broth of
Penicillium sp., whose planar structure was incidentally
identical to that of GKK1032A2 (2).2 Subsequently, He et
al. disclosed the isolation of pyrrocidines A (4) and B (5)
from the fermentation broth of a fungus, LL-Cyan426, and
their structures were assigned as the analogues of
GKK1032s.3 These natural products have novel and quite
unique structural features that include a common deca-
hydrofluorene nucleus (ABC-ring) incorporated with an
unusual 12- or 13-membered macrocycle, through
ethereal and carbonyl linkages.
O
Me
4 : pyrrocidine A ( X,Y = C=CH )
5 : pyrrocidine B ( X,Y = CH–CH2 )
Figure 1 Structures of GKK1032A1 (1), A2 (2), B (3) and
pyrrocidines A (4), B (5).
total synthesis of GKK1032s (1–3) in enantiomerically
pure form. possible biosynthetic pathway to
A
GKK1032A2 (2) was recently reported by Oikawa;4 how-
ever, to the best of our knowledge, synthetic studies of
GKK1032s and pyrrocidines have not appeared in the lit-
erature to date. Herein, we report our preliminary results
concerning an efficient and enantioselective synthesis of
decahydrofluorene nucleus 6, which represents the first
entry to the tricyclic core (ABC-ring) of GKK1032s.5
Our synthetic plan for the target molecule 6 is outlined in
Scheme 1. The most crucial step in this scheme is envi-
sioned to be an intramolecular Diels–Alder (IMDA) reac-
tion of the tetraene 7 via an endo-transition state 7A to
construct the requisite tricyclic core while controlling the
stereogenic centers at C3, C6, C14, and C15 in 6
(7→[7A]→6). The precursor 7 would be prepared directly
by Stille-coupling of the vinyl iodide 8 and the vinyl-
stannane 9. The intermediate 8 should be accessed from
the methyl acetylene 10 via hydrometallation/iodination
and Wittig reaction. The intermediate 10 could in turn be
derived through an intermolecular Diels–Alder reaction
between Kitahara–Danishefsky’s diene 116 and the
known enulose derivative 12.7
The gross structure and stereochemistry of GKK1032s
were assigned based on exhaustive spectroscopic studies
and the relative stereochemistry of 3 was determined by
X-ray crystallographic analysis, while their absolute con-
figurations have not been revealed.
The interesting biological properties and unique structural
features, as well as the unknown absolute stereochemis-
try, prompted us to undertake a project directed toward the
SYNLETT 2005, No. 10, pp 1539–1542
1
7
.0
6
.2
0
0
5
Advanced online publication: 12.05.2005
DOI: 10.1055/s-2005-869843; Art ID: U09705ST
© Georg Thieme Verlag Stuttgart · New York

1540
M. Asano et al.
LETTER
O
O
Me
OMe
Me
Me
SR
Me
O
Me
H
H
H
Me
Me
H
H
Me
a
A
14
6
RS
3
+
C
B
CO2Me
O
S
HO
O
15
O
CO2Me
TMSO
H
H
Me
O
H
S
Me
H
OH
11
12
13
7A
6
Me
OMe
H
O
Me
Me
OMe
H
Me
b, c
H
Me
Me
O
I
Bu3Sn
Me
AcO
Me
O
9
Me
O
H
H
Me
H
H
S
OAc
S
CO2Me
CO2Me
NOEs
Me
14
S
S
H
H
OH
O
OH
O
Me
Me
7
8
Me
f, g
d
13
MeO
MeO
Me
X
O
OMe
Me
O
Me
H
H
O
Me
O
+
10
15 : X = O
16 : X = (OMe)2
MeO
e
O
O
TMSO
MeO
H
O
O
Scheme 2 Synthesis of the key intermediate 10. Reagents and con-
ditions: (a) toluene, 150 °C, 72 h, 60%; (b) p-TsOH, MeOH, reflux, 2
h, 77%; (c) Ac2O, pyridine, r.t., 5 h, 94%; (d) H2, 10% Pd/C, EtOAc,
r.t., 12 h, 89%; (e) PPTS, MeOH, 0 °C, 2.5 h, 75%; (f) KN(SiMe3)2,
THF; PhNTf2, –78 °C, 2 h, 84%; (g) LDA, THF; MeI, 0 °C, 1 h, 73%.
12
10
11
Scheme 1 Retrosynthetic analysis for the tricyclic core 6 (ABC-ring
system) of GKK1032s.
We initially pursued the synthesis of acetylene 10 as
shown in Scheme 2. The intermolecular Diels–Alder
reaction between Kitahara–Danishefsky’s diene 116 and
the known enone 12,7 readily prepared from D-mannitol,
provided the cyclohexenone 138 in 60% yield as the sole
isolated product. The stereostructure of 13 was proven by
NOE studies of the bicyclic enone 14 derived from 13 by
acid-catalyzed transacetalization followed by acetylation
of the resulting alcohol. In this Diels–Alder reaction, the
preferential approach of diene 11 to dienophile 12 took
place from the opposite side of the bulky acetonide func-
tion, as previously reported by Ortuño et al.,9 affording 13
as the sole isomer. Hydrogenation of the olefinic double
bond in 13 followed by regioselective dimetylacetal for-
mation of the resulting cyclohexanone 15 provided the
dimethyl acetal 16 in 67% yield for the two steps. Com-
pound 16 was further converted to the methyl acetylene
10 through a two-step sequence involving vinyl triflate
formation10 (84% yield) and base-induced elimination/
methylation (73% yield).
then allowed to react with iodine to furnish the desired vi-
nyl iodide 17 in 84% yield. In the next stage, introduction
of an a,b-unsaturated ester moiety, which would serve as
a dienophile in the designed key IMDA reaction, was per-
formed. Thus, deprotection of the acetonide function in 17
by acid treatment led to the formation of the 5-membered
acetal 18 in 82% yield. Swern oxidation of 18 followed
by Wittig reaction of the resulting aldehyde 19 afforded
the corresponding a,b-unsaturated ester 20 in 69% yield
for the two steps. Finally, compound 20 was transformed
to the requisite intermediate 8 in 98% yield via trans-
acetalization by exposure to 1,3-propanedithiol in the
presence of BF3·Et2O.
Me
Me
I
Me
Me
I
a, b
c
10
MeO
MeO
MeO
H
X
O
O
H
O
Having obtained the key intermediate 10, we next carried
out the synthesis of the vinyl iodide 8 as shown in
Scheme 3. Conversion of 10 to the corresponding vinyl
iodide 17 under standard conditions, radical-mediated
hydrostannylation/iodination (Bu3SnH/AIBN; I2),11
Pd(0)-catalyzed hydrostannylation/iodination [Bu3SnH/
18 : X = CH2OH
19 : X = CHO
17
d
Me
Me
I
Me
Me
I
f
e
S
CO2Me
MeO
H
Pd(PPh3)4;
I2],12
or
hydrozirconation/iodination
O
S
H
(Cp2ZrHCl; I2),13 gave a poor yield of the product 17. Af-
ter several experiments, to our delight, we found that the
use of Semmelhack’s conditions14 proved the most suc-
cessful. Thus, treatment of 10 with a mixture of n-
Bu3SnH, Pd(OAc)2, and PCy3 in hexane at room temper-
ature provided the corresponding (E)-vinyl stannane
(58% yield) with complete regioselectivity, which was
OH
CO2Me
20
8
Scheme 3 Synthesis of the key intermediate 8. Reagents and condi-
tions: (a) n-Bu3SnH, Pd(OAc)2, PCy3, hexane, r.t., 12 h, 58%; (b) I2,
CH2Cl2, 0 °C, 30 min, 84%; (c) PPTS, MeOH, reflux, 2 h, 82%; (d)
(COCl)2, DMSO, CH2Cl2, –78 °C; Et3N, 0 °C, 30 min; (e)
Ph3P=CHCO2Me, toluene, r.t., 12 h, 69% (2 steps); (f) HS(CH2)3SH,
BF3·Et2O, CH2Cl2, –40 °C, 1 h, 98%.
Synlett 2005, No. 10, 1539–1542 © Thieme Stuttgart · New York

LETTER
Enantioselective Synthesis of the Tricyclic Core of GKK1032
1541
With the key intermediate 8 in hand, as shown in
Scheme 4, we next investigated the model studies for the
construction of the tricyclic core structure 22, which lacks
a methyl substituent at the C3-position in the A-ring; the
sequence involves Stille coupling of the vinyl iodide 8
with the known vinylstannane 2115 and subsequent key
IMDA reaction of the product 20. Since Corey et al. re-
ported that Stille coupling was dramatically accelerated
by the presence of CuCl,16 we decided to employ the
modified method of Corey et al. [Pd(PPh3)4, CuCl/LiCl,
DMF–THF, r.t., 12 h], which led to the formation of the
desired tetraene 20 (23% yield) and an unexpected cyclo-
addition product 22 (23% yield) as the sole diastereomer.
NOE experiments of the cycloadduct 22 revealed that the
newly generated stereochemistry at the C3-, C6-, C14-,
and C15-positions was fully matched with that of
GKK1032s. The formation of 22 under the mild Stille
coupling conditions is particularly intriguing, and this
phenomenon must be attributed to the structural nature
inherent in the tetraene 20.17 Conversion of 20 to 22 (80%
yield) was readily achieved by refluxing a solution of 20
in toluene.
Me
Me
Me
Me
CO2Me
a
8
Bu3Sn
+
S
9
S
H
OH
7
R’S
H
R
H
Me
H
Me
H
Me
6
R’S
Me
b
14
A
6
HO
3
14
15
Me
H
C
B
S
Me
15
3
CO2Me
H
H
H
H
S
H
NOEs
OH
H
6
R = CO2Me
Scheme 5 Synthesis of the tricyclic core 6 of GKK1032s. Reagents
and conditions: (a) Pd(PPh3)4 (10 mol%), CuCl/LiCl, DMF–THF, r.t.,
12 h, 60%; (b) BHT, toluene, 120 °C, 24 h, 70%.
Scheme 5, which proved that the relative stereochemistry
within 6 was fully identical with that of GKK1032s. The
remarkable stereochemical outcome observed in the
IMDA reaction can be rationalized by the predominant
endo-transition state 7A as depicted in Scheme 1.
Me
Me
In summary, we have succeeded in developing a facile
synthetic route to the decahydrofluorene 6 via a highly
diastereoselective IMDA reaction (7→[7A]→6), which is
the first entry to a common tricylic core structure (ABC-
ring system) of the GKK1032 family (1–3). The IMDA
precursor 7 was efficiently synthesized by a method
featuring stereoselective intermolecular Diels–Alder re-
action of the siloxydiene 11 and the enone 12 to construct
the functionalized C-ring (11 + 12→13) and Cu(I)-accel-
erated Stille coupling of the vinyl iodide 8 and the vinyl-
stannane 9 to install the requisite triene moiety (8 + 9→7).
Further investigation toward the total synthesis of
GKK1032s (1–3) and pyrrocidines (4, 5) is now in
progress and will be reported in due course.
a
Bu3Sn
+
+
8
S
CO2Me
21
S
H
OH
20
R’S
Me
H
H
H
H
Me
H
6
Me
R’S
A
14
15
6
14
3
HO
15
C
B
S
H
H
R
Me
3
CO2Me
H
H
H
H
S
H
OH
22
NOEs
H
R = CO2Me
Scheme 4 Synthesis of the tricyclic model compound 22. Reagents
and conditions: (a) Pd(PPh3)4 (10 mol%), CuCl/LiCl, DMF–THF, r.t.,
12 h, 23% for 20 and 23% for 22.
Acknowledgment
We are grateful to Dr. T. Mori (Tokyo Institute of Technology) for
his assistance in MS spectra measurements.
Encouraged by these successful results, we finally con-
ducted the synthesis of the targeted compound 6, the tri-
cyclic core of GKK1032s, as shown in Scheme 5. Thus,
Stille coupling of the vinyl iodide 8 and the vinylstannane
918 was carried out under the same conditions described
for the model studies to furnish the desired tetraene 719 in
60% yield. In this reaction, contrary to the model studies,
no cycloadducts were isolated from the reaction mixture;
therefore, the key IMDA reaction was executed by heat-
ing a solution of 7 in toluene in a sealed tube with a cata-
lytic amount of 2,6-di-tert-butyl-4-methylphenol (BHT)
for 24 hours, giving rise to a 70% yield of decahydrofluo-
rene 620 as the isolated diasteromer.21 The stereostructure
of 6 was also confirmed by NOE experiments as shown in
References
(1) (a) Koizumi, F.; Hasegawa, A.; Ando, K.; Ogawa, T.; Hara,
M. Jpn. Kokai Tokyo Koho; JP 2001247574, 2001.
(b) Hasegawa, A.; Koizumi, F.; Takahashi, Y.; Ando, K.;
Ogawa, T.; Hara, M.; Yoshida, M. 43rd Tennen Yuki
Kagobutu Touronnkai Koen Yoshishu; Osaka Japan, 2001,
467.
(2) Omura, S.; Komiyama, K.; Hayashi, M.; Masuma, R.;
Fukami, A. Jpn. Kokai Tokkyo Koho; JP 2002255969, 2002.
(3) He, H.; Yang, H. Y.; Bigelis, R.; Solum, E. H.; Greenstein,
M.; Carter, G. T. Tetrahedron Lett. 2002, 43, 1633.
(4) Oikawa, H. J. Org. Chem. 2003, 68, 3552.
Synlett 2005, No. 10, 1539–1542 © Thieme Stuttgart · New York

1542
M. Asano et al.
LETTER
(17) Detailed discussions on this IMDA reaction will be
(5) Quite recently, three other synthetic studies of GKK1032s
and pyrrocidines were independently presented by
Kuwajima’s group, Tadano’s group, and Uchiro’s group:
(a) Arai, N.; Kuwajima, I. The 85th Annual Spring Meeting
of the Chemical Society of Japan, Yokohama Japan 2005,
Abstract 2, 872. (b) Kurosaka, J.; Sinkawa, T.; Miyazaki,
Y.; Munakata, R.; Takao, K.; Tadano, K. The 85th Annual
Spring Meeting of the Chemical Society of Japan, Yokohama
Japan 2005, Abstract 2, 874. (c) Hasegawa, D.; Sakuma,
Y.; Takagi, Y.; Uchiro, T. The 125th Annual Meeting of the
Pharmaceutical Society of Japan, Tokyo Japan 2005,
Abstract 4, 71.
(6) (a) Danishefsky, S.; Kitahara, T. J. Am. Chem. Soc. 1974, 96,
7807. (b) Danishefsky, S.; Kitahara, T.; Schuda, P. F. Org.
Synth., Coll. Vol. 7 1990, 312.
(7) (a) Izquierdo Cubero, I.; Portal Olea, M. D.; Garcia Poza, D.
Carbohydr. Res. 1985, 138, 135. (b) Schmid, C. R.; Bryant,
J. D.; Dowlatzedah, M.; Phillips, J. L.; Prather, D. E.;
Schantz, R. D.; Sear, N. L.; Vianco, C. S. J. Org. Chem.
1991, 56, 4056.
presented in a full account.
(18) The vinylstannane 9 was prepared from the known
compound i: (a) Scarlato, G. R.; DeMattei, J. A.; Chong, L.
S.; Ogawa, A. K.; Lin, M. R.; Armstrong, R. W. J. Org.
Chem. 1996, 61, 6139. (b) Baker, R.; Castro, J. L. J. Chem.
Soc., Perkin Trans. 1 1990, 47; via a two-step sequence of
reactions as shown in Scheme 6.
1) MnO2, CH2Cl2
Me
Me
r.t., 12 h
Bu3Sn
OH
Bu3Sn
2) CH3P+Ph3Br–, n-BuLi
THF, r.t., 2 h
i
9
( 51%, 2 steps )
Scheme 6
(19) Data for 7: Colorless viscous oil, [a]D20 +18.2 (c 0.23,
CHCl3). IR (neat): 607, 648, 731, 779, 897, 908, 985, 1043,
1097, 1167, 1194, 1240, 1273, 1373, 1435, 1655, 1722,
2860, 2933, 2947, 2979, 3463 cm–1. 1H NMR (500 MHz,
CDCl3): d = 1.31 (s, 3 H), 1.41–1.48 (m, 1 H), 1.50 (d,
J = 4.8 Hz, 1 H), 1.83–2.04 (m, 4 H), 1.87 (d, J = 1.0 Hz, 3
H), 1.92 (d, J = 1.0 Hz, 3 H), 2.06–2.19 (m, 3 H), 2.24–2.30
(m, 1 H), 2.61–2.76 (m, 2 H), 2.81–2.98 (m, 2 H), 3.74 (s, 3
H), 4.59–4.65 (m, 1 H), 5.03 (d, J = 10.7 Hz, 1 H), 5.17 (d,
J = 17.4 Hz, 1 H), 5.26 (br s, 1 H), 5.88 (br s, 1 H), 6.04 (dd,
J = 1.9, 15.6 Hz, 1 H), 6.37 (dd, J = 10.7, 17.4 Hz, 1 H), 6.94
(dd, J = 4.1, 15.6 Hz, 1 H). 13C NMR (125 MHz, CDCl3):
d = 13.3, 18.7, 21.0, 25.8, 26.0, 26.3, 32.0, 33.6, 34.6, 40.0,
44.5, 50.2, 51.7, 71.4, 112.2, 119.8, 133.1, 133.6, 137.7,
140.2, 142.0, 151.2, 166.8. HR-EIMS: m/z calcd for
C23H34O3S2 (M+): 422.1949; found: 422.1954.
(8) Data for 13: Pale yellow oil [a]D20 –55.7 (c 0.24, CHCl3). IR
(neat): 631, 733, 787, 852, 906, 920, 968, 1057, 1084, 1211,
1242, 1358, 1371, 1419, 1456, 1680, 1709, 1736, 2937, 2985
cm–1. 1H NMR (500 MHz, CDCl3): d = 1.30 (s, 3 H), 1.36 (s,
3 H), 1.38 (s, 3 H), 2.25 (s, 3 H), 2.49 (dd, J = 4.5, 17.1 Hz,
1 H), 2.60 (dd, J = 11.1, 17.1 Hz, 1 H), 2.71 (ddd, J = 2.7,
4.5, 11.1 Hz, 1 H), 3.36 (dd, J = 7.6, 8.2 Hz, 1 H), 4.01 (dd,
J = 6.7, 8.2 Hz, 1 H), 4.07–4.15 (m, 1 H), 6.07 (d, J = 10.2
Hz, 1 H), 6.66 (d, J = 10.2 Hz, 1 H). 13C NMR (125 MHz,
CDCl3): d = 17.6, 25.0, 25.8, 26.2, 34.3, 40.1, 53.4, 67.6,
74.3, 109.4, 129.0, 150.1, 198.0, 208.1. HR-FABMS: m/z
calcd for C14H21O4 [(M + H)+]: 253.1440; found: 253.1448.
(9) Ortuño, R. M.; Ibarzo, J.; d’Angelo, J.; Dumas, F.; Alvarez-
Larena, A.; Piniella, J. F. Tetrahedron: Asymmetry 1996, 7,
127.
(10) Hendrickson, J. B.; Bergeron, R. Tetrahedron Lett. 1973, 14,
4607.
(11) (a) Corey, E. J.; Wollenberg, R. H. J. Am. Chem. Soc. 1974,
96, 5581. (b) Chen, S.-M. L.; Schaub, R. E.; Grudzinskas, C.
V. J. Org. Chem. 1978, 43, 3450.
(12) (a) Ichinose, Y.; Oda, H.; Oshima, K.; Utimoto, K. Bull.
Chem. Soc. Jpn. 1987, 60, 3468. (b) Smith, N. D.; Mancuso,
J.; Lautens, M. Chem. Rev. 2000, 100, 3257.
(20) Data for 6: White solid, mp 161–166 °C, [a]D20 +65.7 (c
0.45, CHCl3). IR (neat): 607, 621, 688, 783, 804, 852, 908,
995, 1047, 1159, 1223, 1259, 1331, 1375, 1435, 1716, 2875,
2931, 3500 cm–1. 1H NMR (500 MHz, CDCl3): d = 0.79 (s,
3 H), 1.28 (s, 3 H), 1.42–1.53 (m, 1 H), 1.69–1.83 (m, 3 H),
1.75 (s, 3 H), 1.89–2.00 (m, 3 H), 2.00–2.10 (m, 2 H), 2.11–
2.18 (m, 1 H), 2.33 (dt, J = 8.3, 12.0 Hz, 1 H), 2.52 (dt,
J = 13.4, 2.2 Hz, 1 H), 2.61 (d, J = 12.0 Hz, 1 H), 2.65–2.75
(m, 1 H), 2.77–2.87 (m, 2 H), 2.95–3.03 (m, 1 H), 3.68 (s, 3
H), 3.93–3.99 (m, 1 H), 4.85 (s, 1 H), 4.98 (dd, J = 1.5, 17.2
Hz, 1 H), 5.05, (dd, J = 1.5, 10.4 Hz, 1 H), 5.69 (dd, J = 10.4,
17.2 Hz, 1 H). 13C NMR (125 MHz, CDCl3): d = 13.3, 21.2,
25.9, 26.1, 26.4, 26.7, 34.5, 35.0, 35.3, 41.3, 42.4, 44.0, 50.3,
51.3, 52.3, 54.4, 55.5, 72.7, 114.5, 131.3, 135.4, 142.8,
174.8. HR-EIMS: m/z calcd for C23H34O3S2 (M+): 422.1949;
found 422.1950.
(13) Hart, D. W.; Blackburn, T. F.; Schwartz, J. J. Am. Chem.
Soc. 1975, 97, 679.
(14) Semmelhack, M. F.; Hooley, R. J. Tetrahedron Lett. 2003,
44, 5737.
(15) Gómez, A. M.; López, J. C.; Fraser-Reid, B. Synthesis 1993,
943.
(16) Han, X.; Stoltz, B. M.; Corey, E. J. J. Am. Chem. Soc. 1999,
121, 7600.
(21) In this IMDA reaction, a small amount (<10% yield) of
unidentified products was generated along with the desired
decahydrofluorene 6.
Synlett 2005, No. 10, 1539–1542 © Thieme Stuttgart · New York