Selective cyclopropylcarbinyl rearrangement of tricyclo[5.3.1.0]undecanols induced by pyridinium chlorochromate

Article abstract of DOI:10.1016/S0040-4039(01)02291-2

Tricyclo[5.3.1.0]undecanols were transformed to bicyclo[5.3.1]undecanols in good yield by using pyridinium chlorochromate.

Full text of DOI:10.1016/S0040-4039(01)02291-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 823–827
Selective cyclopropylcarbinyl rearrangement of
tricyclo[5.3.1.0]undecanols induced by pyridinium chlorochromate
Janine Cossy,a,* Samir BouzBouz,a Mohamed Laghgarb and Badia Tabyaouib
aLaboratoire de Chimie Organique associe´ au CNRS, ESPCI, 10 rue Vauquelin 75231 Paris Cedex 05, France
bLaboratoire de Chimie Organique, Universite´ Chouaib Doukkali, Faculte´ des Sciences, 2500 El Jadida, Morocco
Received 12 October 2001; accepted 28 November 2001
Abstract—Tricyclo[5.3.1.0]undecanols were transformed to bicyclo[5.3.1]undecanols in good yield by using pyridinium chlorochro-
mate. © 2002 Elsevier Science Ltd. All rights reserved.
The bicyclo[5.3.1]undecanol ring system is present in
naturally occurring taxanes and particularly in anti-
cancer drugs such as taxol.1
addition of vinylmagnesium bromide (2 equiv., THF,
0°C).11 After thermolysis at 210°C, diol 9 was rear-
ranged to hydroazulenone 1011 which was reduced to
Here, we report an easy access to the synthesis of the
AB ring system of taxol which allows the functionaliza-
tion of the eight- or six-membered ring. Although the
cyclopropylcarbinyl rearrangement of bicyclic systems2–6
has been extensively studied, the cyclopropylcarbinyl
rearrangements of tricyclic systems are rare.7–10 We
investigated cyclopropylcarbinyl rearrangement of tri-
cyclo[5.3.1.0]undecanols of type A and B under oxida-
tive conditions, e.g. with pyridinium chlorochromate
(PCC) and under acidic conditions (10% aqueous HCl
in THF: 1/1).
the corresponding alcohol 11 in 99% yield by using
NaBH4 (1 equiv.) in the presence of CeCl3·7H2O (1
equiv.) in MeOH. The obtained alcohol 11 was then
treated with CH2I2 (6 equiv.) in the presence of Et2Zn
(3 equiv.) at −78°C and transformed to the cyclopropyl-
carbinols 1a and 1a% (82%) as an inseparable 88/12
mixture.12
Compounds 1a and 1a% could also be obtained by
reduction of the tricyclo[5.3.1.0]undecanone 12. A mix-
ture of 1a and 1a% was obtained in a ratio of 21/79 when
NaBH4 was used for the reduction and a ratio of 43/57
by using DIBAL-H (Scheme 2). For the synthesis of
alcohols 1b–e, ketone 1213 was treated with various
Grignard reagents. The addition of vinylmagnesium
bromide produced 1b, as an inseparable 74/26 mixture,
in 88% yield, whereas isopropylmagnesium bromide led
to 1c as a single isomer in 68% yield and while allyl-
magnesium bromide afforded alcohol 1d as a single
isomer in 86% yield. Oxidative cleavage of the allyl
group present in 1d, by using O3 in 2.5 M methanolic
NaOH,14 afforded the methyl ester 1e (Scheme 2).
Tricyclo[5.3.1.0]undecanols 1a/1a% and 1b–e were pre-
pared from hydroazulenol 11 (Schemes 1 and 2) and the
tricyclo[5.3.1.0]undecanols 4a/4a% and 4b/4b% were pre-
pared from hydroazulenone 14 (Scheme 3). After treat-
ment of 1,2-cyclohexanedione 7 with vinylmagnesium
bromide (2 equiv., THF, 0°C), hydroxy ketone 8 was
obtained (98% yield) and transformed to diol 9 (98%
yield) as a mixture of two isomers in a ratio 46/54 by
* Corresponding author.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)02291-2

824
J. Cossy et al. / Tetrahedron Letters 43 (2002) 823–827
Scheme 1. Synthesis of 1a and 1a%.
Scheme 2. Synthesis of tricyclo[5.3.1.0]undecanols 1a/1a% and 1b–e.
The rearrangement of tricyclo[5.3.1.0]undecanols 1a/
1a%, 1b–e, 4a–b were carried out with PCC18 or 10%
aqueous HCl in THF (1/1).19 Cyclopropylcarbinols 1a/
1a% afforded two compounds with PCC (3 equiv.,
CH2Cl2, rt): the rearranged product 2a20,21 and ketone
3. These two products were easily separated by flash
chromatography. It is worth noting that the ratio of 2a
and 3 depends on the ratio of 1a and 1a%. Under acidic
conditions, 2a was the only isolated product (87% yield)
(Table 1). In the case of compounds 1b–e, regardless of
the conditions (PCC or HCl), the only products formed
Cyclopropylcarbinols 4a and 4a% were synthesized from
cycloheptanone 13 which was transformed to hydroazul-
enone 1415 and subsequently converted to 6 by treat-
ment with trimethysulfoxonium iodide.16 Reduction of
6 with NaBH4 in MeOH at room temperature led to the
separable alcohols 4a and 4a% as a 96/4 mixture in 93%
yield. Reaction of 6 with methylmagnesium bromide
afforded cyclopropylcarbinols 4b and 4b% (ratio: 98/2,
yield: 97%). Compound 4a was purified by chromato-
graphy and characterized by 1H NMR-NOE
experiments9b,17 (Scheme 3).
Scheme 3. Synthesis of 4a/4a% and 4b/4b%. (i) Trimethylsulfoxonium iodide, NaH, DMSO, 0°C; (ii) NaBH4, MeOH/THF, 0°C; (iii)
CH3MgBr, ether, 0°C.

J. Cossy et al. / Tetrahedron Letters 43 (2002) 823–827
825
Table 1. Rearrangement of 1a/1a%, 1b–e by using PCC or 10% HCl in THF
Starting material
PCC
10% HCl
T (°C), t (h)
2 (Yield (%))
3 (Yield (%))
T (°C), t (h)
2 (Yield (%))
3 (Yield (%))
1a/1a%=88/12
1a/1a%=55/45
1a/1a%=21/79
1b
1c
1d
1e
rt, 0.5
rt, 0.5
rt, 0.5
rt, 20
rt, 0.5
rt, 0.3
rt, 24
48
52
27
73
85
95
72
40
43
63
0
0
0
rt, 1
87
0
rt, 0.7
rt, 0.3
rt, 0.3
rt, 0.5
82
94
92
78
0
0
0
0
0
of the C1ꢀC7 bond of the cyclopropyl ring. As a
tertiary carbocation is formed more easily than a sec-
ondary carbocation, the weak acidity of PCC can
induce the formation of 5b via intermediate I (ionic
mechanism) (Scheme 4).
were the rearranged products 2 in yields up to 70%
(Table 1). The reactivity of alcohols 4a and 4b were
also examined. When 4a was treated with PCC (3
equiv., CH2Cl2, rt), ketone 6 was isolated in 80% yield.
On the contrary, the rearranged product 5a was
obtained in 92% yield when 4a was treated under acidic
conditions. In the case of 4b, PCC as well as acidic
conditions led to the corresponding rearranged com-
pound 5b in up to 90% yield (Table 2).
Contrary to the secondary cyclopropylcarbinol 4a (R=
H), which was transformed only to the oxidized
product 6, the treatment of 1a/1a% with PCC led to a
mixture of the rearranged compound 2a and ketone 3.
The ratio of these products depended on the ratio of
1a/1a%. A 55/45 mixture of 1a/1a% produced 2a and 3 in
a ratio of 52/43, whereas a 21/79 mixture of 1a/1a% led
to 2a/3 in a ratio of 27/63 and a 88/12 mixture of 1a/1a%
led to a mixture of 2a/3 in a ratio of 48/40. In alcohol
1a, where the trans periplanar arrangement of the
C1ꢀC7 and the C8ꢀOCr bonds is fullfilled (cf. interme-
diate III), oxidation can compete with rearrangement
and the rearranged product 2a can be formed as well as
ketone 3. The rearrangement of 1a by a stepwise mech-
anism (ionic) cannot be excluded. In the case of com-
pound 1a%, as the C1ꢀC7 and the C8ꢀOCr bonds are
not trans periplanar (cf. intermediate IV), this com-
The conversion of cyclopropylcarbinols to b,g-unsatu-
rated alcohols has been previously explained by the
formation of intermediate cyclopropylcarbinyl cations
under acidic conditions.22 In the case of the secondary
cyclopropylcarbinol 4a, it seems that the weak acidity
of PCC is not sufficient to induce the formation of a
cyclopropylcarbinyl cation and, the oxidation process
takes place to produce ketone 6. As in compound 4b,
the trans periplanar arrangement of the C1ꢀC7 and the
C8ꢀOCr bonds is not fulfilled, the rearranged product
5b could not be the result of a concerted fragmentation
process in which the initially formed chromic ester II
will be the leaving group that will promote the cleavage
Table 2. Rearrangement of alcohols 4a and 4b by using PCC or 10% HCl in THF
Starting material
PCC
10% HCl
T (°C), t (h)
5 (Yield (%))
6 (Yield (%))
T (°C), t (h)
5 (Yield (%))
6 (Yield (%))
4a
4b
rt, 0.8
rt, 0.8
0
83
80
0
60, 10
rt, 3
92
90
0
0

826
J. Cossy et al. / Tetrahedron Letters 43 (2002) 823–827
Scheme 4. Mechanism of the rearrangement induced by PCC and Newman projections according to the C7ꢀC8 bond of the
tricyclo[5.3.1.0]undecane system.
5. Friedrich, E. C.; Coooper, J. D. J. Org. Chem. 1979, 24,
4224.
6. Olah, G. A.; Prakash, G. K. S.; Rawdah, T. N. J. Org.
Chem. 1980, 45, 965.
pound can be oxidized or rearranged by a stepwise
ionic mechanism (Scheme 4).
We have demonstrated that tricyclo[5.3.1.0]undecanols
can be transformed to bicyclo[5.3.1.0]undecanols in
good yields under mild conditions by using PCC. The
use of other PCC-induced rearrangements in the syn-
thesis of natural products is under investigation.
7. Gassman, P. G.; Steppel, R. N.; Armour, E. A. Tetra-
hedron Lett. 1973, 14, 3287.
8. Kumar, P.; Rao, A. T.; Pandey, B. Tetrahedron Lett.
1995, 36, 3397.
9. (a) Thielemann, W. Master Thesis, Westfa¨lische Wil-
helms–Universita¨t Mu¨nster, 1994; (b) Thielemann, W.;
Scha¨fer, H. J.; Kotila, S. Tetrahedron 1995, 51, 12027.
10. Cossy, J.; Bouzbouz, S. Tetrahedron Lett. 1997, 38, 1931.
11. Leriverend, P.; Conia, J. M. Bull. Soc. Chim. Fr. 1970,
1040.
12. The ratio was determined by GC/MS at 70 eV by using a
Hewlett Packard 5971 instrument.
13. Ketone 12 was obtained by oxidation of 1a/1a% by using
PDC (3 equiv.) in CH2Cl2.
14. Marshall, J. A.; Garofalo, A. W. J. Org. Chem. 1993, 58,
3675.
15. (a) Kovats, E.; Fu¨rst, A.; Gu¨nthard, H. H. Helv. Chim.
Acta 1954, 34, 534; (b) Tobe, Y.; Fukuda, Y.; Kakiuchi,
K.; Odaira, Y. J. Org. Chem. 1984, 49, 2012.
References
1. (a) Gue´nard, D.; Gue´ritte-Voegelin, F.; Potier, P. Acc.
Chem. Res. 1993, 26, 160; (b) Nicolaou, K. C.; Dai,
W.-M.; Guy, R. K. Angew. Chem., Int. Ed. Engl. 1994,
33, 15.
2. Friedrich, E. C.; Saleh, M. A.; Winstein, S. J. Org. Chem.
1973, 38, 860.
3. Friedrich, E. C.; Saleh, M. A. J. Am. Chem. Soc. 1973,
94, 2617.
4. Friedrich, E. C.; Coooper, J. D. Tetrahedron Lett. 1976,
17, 4397.

J. Cossy et al. / Tetrahedron Letters 43 (2002) 823–827
827
16. Corey, E. J.; Chaykovsky, M. J. Am. Chem. Soc. 1965,
H2O) (2 mL) at 25°C. After completion of the reaction
(indicated by TLC and GC/MS), the reaction mixture
was extracted with ether. The organic phase was washed
with H2O and then with brine, dried over MgSO4, and
concentrated in vacuo. The residue was purified by silica
gel chromatography (hexanes/EtOAc: 9/1).
87, 1353.
1
17. Compound 4a;9b IR (film): 3580 cm−1; H NMR (CDCl3,
300 MHz): l 0.10 (d, 1H, J=4.8 Hz); 0.58 (d, 1H, J=4.8
Hz); 0.80–2.00 (m, 15H), 4.08 (t, 1H, J=8.1 Hz); 13C
NMR (CDCl3, 75 MHz): l 16.7 (t), 26.5 (t), 26.6 (t), 29.7
(t), 29.9 (t), 31.4 (t), 32.0 (t), 32.6 (t), 36.8 (s), 77.0 (d);
MS (EI, 70 eV) m/z: 166 (28), 151 (24), 148 (12), 137 (59),
123 (100), 109 (51), 91 (47), 81 (55), 55 (34).
1
20. Compound 2a; IR (film): 3340 cm−1; H NMR (CDCl3,
300 MHz): l 1.09–3.10 (m, 16H), 5.50 (d, 1H, J=7.7 Hz);
13C NMR (CDCl3, 75 MHz): l 23.9 (t), 26.2 (t), 27.5 (t),
32.2 (t), 34.9 (t), 37.0 (t), 40.1 (t), 40.3 (t), 77.8 (s), 122.4
(d), 139.9 (s); MS (EI, 70 eV) m/z: 166 (5), 151 (35), 148
(91), 133 (40), 123 (87), 106 (61), 97 (100).
18. To a solution of tricyclo[5.3.1.0]undecanols (0.2 g, 1.2
mmol), dissolved in CH2Cl2 (3 mL), was added PCC
(0.77 g, 3.6 mmol) at 25°C. After completion of the
reaction (indicated by TLC and GC/MS) the reaction
mixture was diluted with ether and filtered on Celite. The
organic phase was concentrated in vacuo and the residue
was purified by silica gel chromatography (hexanes/
EtOAc: 9/1).
21. The relative stereochemistry of the tertiary alcohol in 2a
was proved by hydrogenation to the saturated alcohol
described in the literature: Molander, G. A.; McKie, J. A.
J. Org. Chem. 1991, 56, 4112.
22. (a) Sarel, S.; Yovell, J.; Sarel-Imber, M. Angew. Chem.,
Int. Ed. Engl. 1968, 577; (b) Vogel, P. Carbocation Chem-
istry; Elsevier: Amsterdam, 1985.
19. To a solution of tricyclo[5.3.1.0]undecanols (0.2 g, 1.2
mmol), dissolved in THF (2 mL), was added HCl (10% in