Novel concise ring closure leading to bridged ten-membered ring compounds

Article abstract of DOI:10.1039/a901392j

An unusual TBAF-mediated intramolecular cyclisation of diallylsilane derivatives 3 and 12 provided bicyclo[6.2.2]-dodecanes 5 and 13 in good yields.

Full text of DOI:10.1039/a901392j

Novel concise ring closure leading to bridged ten-membered ring compounds
Hiroshi Fujishima, Hiroshi Takeshita, Masahiro Toyota and Masataka Ihara*
Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, Sendai, 980–8578, Japan.
E–mail: mihara@mail.pharm.tohoku.ac.jp
Received (in Cambridge, UK) 19th February 1999, Accepted 12th April 1999
An unusual TBAF-mediated intramolecular cyclisation of
diallylsilane derivatives 3 and 12 provided bicyclo[6.2.2]-
dodecanes 5 and 13 in good yields.
i
TMS
The taxol derivatives have attracted the attention of synthetic
chemists due to their novel mode of action and the complexity
of their structures.1 So far, several groups have achieved the
total synthesis of taxol2 and numerous synthetic methods have
OH
OH
1
2
ii
R1
O
O
OH
TMS
O
CHO
H
3
Ph
N
O
D
C
B
A
O
iii
Ph
O
H
OAc
HO
O
OH
R2
Taxol R1 = Ac, R2 = Bz
Taxotere R1 = H, R2 = Boc
H
been developed for the construction of the key bicyclic (BC
ring) system. However, assembly of the eight-membered ring
(B ring) needs multiple steps owing to its highly oxygenated
structural features and, therefore, the establishment of a novel
and concise route is highly desirable. In order to achieve an
efficient construction of the B ring framework, we have been
studying various intramolecular cyclisations.3 In particular,
cyclisation reactions employing allylsilanes4,5 attracted our
attention. During our investigations, we found that an unusual
cyclisation took place when the diallylsilanes 3 and 12 were
treated with TBAF, leading to the formation of the bridged ten-
membered ring compounds 5 and 13, respectively. Herein we
describe the outcome of this novel TBAF-promoted cyclisation
and the structural determination of the cyclised products.
The synthesis of substrate 3 is summarized in Scheme 1. The
alcohol 13a was treated with BuLi and TMSCl in the presence of
TMEDA to give the C- and O-silylated product, which was
reacted with 2 M H2SO4 to furnish the diallylsilane 2 as a
mixture of diastereoisomers (diastereoselection 3:1). Oxidation
of 2 with a catalytic amount of tetrapropylammonium perruthe-
nate (TPAP) and NMO6 in CH2Cl2 afforded the desired
aldehyde 3.
OH
OH
4
5
Scheme 1 Reagents and conditions: i, BuLi, TMSCI, TMEDA, THF, 0 °C,
then 2 M H2SO4 (93%); ii, 20 mol% TPAP, NMO, 4 Å molecular sieves,
CH2Cl2, rt (71%); iii, see Table 1.
was suggested by the absence of absorptions due to the
conjugated diene in the UV spectrum.
The cyclisation of the substituted material 12 was next
investigated under the same conditions as above. The assembly
of 12 is depicted in Scheme 2. The coupling reaction of the
aldehyde 69 and the vinyl iodide 710 with 2.2 equiv. of ButLi
afforded the alcohol 8 in 84% yield. Methylation of 8 followed
by desilylation of 9 gave the alcohol 10. Upon treatment of 10
as above, the diallylsilanes 11 were obtained as a mixture of
diastereoisomers (diastereoselection 13:1). Oxidation of 11
with TPAP as above afforded the aldehyde 12, which was
converted into the bridged ten-membered ring products 1311 as
a 14:1 mixture of two diastereoisomers with 1.1 equiv. of
TBAF at room temperature in 66% yield.
The structure of the product 13 was determined by X-ray
First of all, 3 was subjected to the Hosomi–Sakurai reaction4
in the presence of Lewis acids,7 that is, the solution of material
in solvent was treated with 1.1–3.0 equiv. of Lewis acid.
Contrary to our expectations, reactions with TiCl4 or BF3·OEt2
did not provide the cyclised compound 4, but brought about
rapid decomposition of 3 (Table 1; entries 1 and 2); with LiBF4
and HF·Py, compound 3 was recovered (entries 3 and 4).
However, the a-carbon of the allylsilane moiety of 3 added as a
nucleophile to the aldehyde in the presence of TBAF yielding
the bicyclic products 58 in fair to good yield (entries 5–8). It is
important to note that this reaction proceeds with a catalytic
amount of TBAF (0.05 equiv.) at room temperature for 1 h to
afford 5 in 47% yield (entry 5). Moreover, the addition of 4 Å
molecular sieves gave the best result and 4 was obtained in 79%
yield (entry 7). The ten-membered structure (the so-called
dihydro[6]paracyclophane) of 5, obtained as a single isomer,
analysis (Fig. 1), after its conversion into the ketone 1412
Table 1 Reactions of 3 with various Lewis acids or TBAF
Entry Reagent (equiv.)
Solvent
T/°C
t/h
Yield(%)a
1
2
3
4
5
6
7
8
TiCl4 (1.1)
BF3·OEt2 (1.5)
LiBF4 (1.1)
HF·Py (1.1)
TBAFb (0.05)
TBAFb (1.0)
TBAFb,c (3.0)
TBAFb,c (3.0)
b
CH2Cl2
CH2Cl2
THF
THF
THF
THF
THF
MeCN
278
1.0
4.0
7.0
7.0
1.0
0.7
0.3
1.0
0
0
0
278 ? 0
0 ? rt
0 ? rt
0
rt
rt
rt
rt
47
44
79
38
a Isolated yield. 1.0 M THF solution was used. 4 Å molecular sieves
c
were added.
Chem. Commun., 1999, 893–894
893

TBDPSO
CHO
R1O
i–iii
6
7
OR2
I
8 R1 = H, R2 = TBDPS
9 R1 = Me, R2 = TBDPS
10 R1 = Me, R2 = H
MeO
vi
iv,v
TMS
R
Fig. 1 Molecular structure of 14.
11 R = CH2OH
12 R = CHO
3 (a) M. Ihara, S. Suzuki, Y. Tokunaga, H. Takeshita and K. Fukumoto,
Chem. Commun., 1996, 1801; (b) M. Ihara, S. Suzuki, Y. Tokunaga and
K. Fukumoto, J. Chem. Soc., Perkin Trans. 1, 1995, 2881.
4 A. Hosomi and H. Sakurai, Tetrahedron Lett., 1976, 1295.
5 G. Majetich, D. Lowery and V. Khetani, Tetrahedron Lett., 1990, 31,
51.
MeO
MeO
vii
H
6 S. V. Ley, J. Norman, W. P. Griffith and S. P Marsden, Synthesis, 1994,
639.
H
OH
O
7 EtAlCl2, AlCl3, SnCl4 and TBDMSOTf were also investigated in these
reactions, however, neither 4 nor 5 was obtained.
14
13
Scheme 2 Reagents and conditions: i, But Li, THF, 278 °C (84%); ii, MeI,
NaH, DMF, 0 °C ? rt (96%); iii, TBAF, THF, rt (94%); iv, BuLi, TMSCI,
TMEDA, THF, 0 °C, then 10% KHSO4 (94%); v, 20 mol% TPAP, NMO,
4 Å molecular sieves, CH2Cl2, rt (77%), vi, TBAF, THF, rt (66%); vii, 20
mol% TPAP, NMO, 4 Å molecular sieves, CH2Cl2, rt (95%).
8 Selected data for 5: dH(300 MHz, CDCl3) 1.17 (s, 3H), 1.35–1.59 (m,
4H), 1.84–1.99 (m, 2H), 2.90–3.01 (m, 1H), 3.11 (dt, J 4.8, 3.2, 1H),
3.79 (dd, J 8.8, 3.2, 1H), 5.25 (ddd, J 11.6, 9.2, 7.6, 1H), 5.31 (d, J 11.6
Hz), 5.71 (ddd, J 9.6, 5.2, 1.6 Hz), 5.81 (dd, J 9.6, 1.6 Hz), 5.83–5.92 (m,
2H); dC (75 MHz, CDCl3) 137.3, 137.2, 136.0, 128.7, 126.0, 123.8,
77.6, 44.5, 40.0, 31.1, 29.6, 25.9, 25.6.
9 D. D. Sternbach and C. L. Ensinger, J. Org. Chem., 1990, 55, 2725.
10 D. Seyferth, J. K. Heeren, G. Singh, S. O. Grim and W. B. Hughes, J.
Organomet. Chem., 1966, 5, 267; G. Stork and K. Zhao, Tetrahedron
Lett., 1989, 30, 2173.
obtained as a single stereoisomer. It is well documented by
Birch that cyclopentadienyl anions react in the middle posi-
tion.13
11 Selected data for 13: dH(300 MHz, CDCl3): 0.79 (s, 3H), 0.93–0.99 (m,
4H), 1.21 (s, 3H), 1.40–1.60 (br s, 1H), 1.98 (dd, J 15.0, 8.8 Hz),
3.08–3.13 (m, 1H), 3.20 and 3.25 (each s, 2.8H and 0.2H), 3.99 (dd, J
8.8, 2.2 Hz), 4.67 (dd, J 9.2, 1.1 Hz), 5.09 (dd, J 12.5, 9.2 Hz), 5.52 (dd,
J 12.5, 1.1 Hz), 5.70–5.90 (m, 4H); m/z 230 (M+ 2 18).
12 Crystal data for 14: C16H22O2, plates, mp 34–35 °C, triclinic, P1, a =
7.641(1), b = 15.890(3), c = 6.3477(9) Å, a = 96.66(1), b =
109.31(1), g = 99.48(1)°, V = 705.3(2) Å3, Z = 2, m = 0.75 cm21, Dc
= 1.169 g cm–3, F000 = 272, T = 150 K, R, Rw = 0.039, 0.038 for
2302 absorption–corrected reflections with I > 3.10 s (I). CCDC
182/1220. see http://www.rsc.org/suppdata/cc/1999/893/ for crystallo-
graphic files in .cif format.
In summary, the Hosomi–Sakurai type reaction of 3 and 12
possessing the diallylsilane moiety afforded the bicyclic
compounds 5 and 13 under mild conditions. We thank Dr C.
Kabuto, Instrumental Analysis Center, Faculty of Science,
Tohoku University, for the X-ray analysis of 14.
Notes and references
1 For review: G. I. George, T. T. Chen, I. Ojima and D. M. Vyas, Taxane
Anticancer Agents, American Cancer Society, San Diego. 1995.
2 For a recent total synthesis: K. Morihara, R. Hara, S. Kawahara, T.
Nishimori, N. Nakamura, H. Kusama and I. Kuwajima, J. Am. Chem.
Soc., 1998, 120, 12980 and references therein.
13 A. D. Birch, A. L. Hinde and L. Radom, J. Am. Chem. Soc., 1981, 103,
284 and references therein.
Communication 9/01392J
894
Chem. Commun., 1999, 893–894