Two homoallyl/cyclopropylalkyl rearrangements accompanying a Wolff-Kishner type reduction

Article abstract of DOI:10.1016/S0040-4039(01)01127-3

Conceived as a model study for the enantioselective synthesis of the natural product (S)-bakuchiol, the deoxygenation of a recently described trishomoallyl alcohol was attempted using the Kabalka modification of the Wolff-Kishner method after prior oxidation of the alcohol to the ketone. However, an unprecedented succession of homoallyl/cyclopropyl ring closure and ring opening altered the carbon skeleton profoundly. The crucial intermediates are assumed to be radicals although carbanions cannot yet be definitely ruled out.

Full text of DOI:10.1016/S0040-4039(01)01127-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 5863–5865
Two homoallyl/cyclopropylalkyl rearrangements accompanying a
Wolff–Kishner type reduction
Manfred Schlosser* and Armin Zellner
Section de Chimie de l’Universite´ (BCh), CH-1015 Lausanne, Switzerland
Received 25 April 2001; accepted 21 June 2001
Abstract—Conceived as a model study for the enantioselective synthesis of the natural product (S)-bakuchiol, the deoxygenation
of a recently described trishomoallyl alcohol was attempted using the Kabalka modification of the Wolff–Kishner method after
prior oxidation of the alcohol to the ketone. However, an unprecedented succession of homoallyl/cyclopropyl ring closure and
ring opening altered the carbon skeleton profoundly. The crucial intermediates are assumed to be radicals although carbanions
cannot yet be definitely ruled out. © 2001 Elsevier Science Ltd. All rights reserved.
(E)-1-(4-Anisyl)-3,7-dimethyl-3-vinyl-1,7-octadien-4-ol
(1)1 can be enantio- and diastereoselectively prepared in
a very simple way. It suffices to treat 5-(4-anisyl)-3-
H3CO
methyl-1,3-pentadiene consecutively with the butyl-
lithium/potassium tert-butoxide superbase2, the
Duthaler–Hafner complex3 and 4-methyl-3-pentenal
(Scheme 1)4,5
.
OH
CpTi(OR)2
In an attempt to convert it into the natural phenol
(S)-bakuchiol,6–11 biocondensation product12 of
a
tyrosine and geranyl pyrophosphate, we oxidized the
alcohol to the corresponding ketone13 which was then
submitted to the Kabalka modification15,16 of Caglioti’s
variation17–19 of the Wolff–Kishner method20,21. Upon
treatment of the tosylhydrazone 222 (Ts=p-toluenesul-
fonyl) with catechylborane, 1-(4-anisyl)-6-methyl-3-(1-
methyl-1-propenyl)-1,5-heptadiene (3)23 was isolated as
the sole volatile product in 30% yield (Scheme 2).
H3CO
H3CO
(OR)2 = TADDOLdiolate
1
Scheme 1. The regioselective and enantioselective a-hydroxy-
alkylation of a chiral 2,4-pentadienyltitanium intermediate.
1
According to H NMR and gas chromatography it was
The reorganization of the backbone structure
doubtlessly involves a homoallyl/cyclopropylalkyl re-
arrangement. The transient intermediate 5 generated by
a 1:5 (Z/E)-1% mixture, the side chain (E)-configuration
of the major component being clearly established by
1H,1H HOESY.
OH
N−NH−Ts
+
O
O
O
O
Z-3 (5%)
(1 : 5)
E-3 (25%)
1
2 (81%)
Scheme 2. The reductive rearrangement of the N-(p-toluenesulfonyl)hydrazone 2.
* Corresponding author. Fax: ++41/21/692 39 65; e-mail: manfred.schlosser@ico.unil.ch
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01127-3

5864
M. Schlosser, A. Zellner / Tetrahedron Letters 42 (2001) 5863–5865
O
O
B
N
H
NHTs
*
*
*
O
O
O
O
4
5
6
7
Scheme 3. Dediazotation triggering a ring closure/ring opening process.
the dediazotation of the catechylborane-tosylhydrazone
adduct 4 immediately undergoes a sequence of rapid
ring-closure and ring-opening to give rise to the ben-
zylic and allylic species 6 and 7, respectively (Scheme 3).
The latter one eventually forms the final product, a 1:5
(Z/E) mixture of the hydrocarbon 3.
amount of unvolatile material, may be taken as evi-
dence for the radical hypothesis.
Acknowledgements
The asterisk in formulas 5–7 stands either for an
unpaired electron or a doublet which confers a negative
charge to the atom where it is located. The symbol calls
attention to a mechanistic dilemma: it is presently not
possible to devise a clear-cut test for the radical or
anionic nature of the observed rearrangement. The
energetic differences between these mechanistic options
should be too small to be conclusive, since the reson-
ance stabilization of both a p-methoxybenzyl radical or
anion and of both a prenyl-type radical or anion should
approximate 20 kcal/mol. Thus, in either case, the
cyclization of the first intermediate (5) and the ring-
opening of the second (6) are exothermic, the anionic
This work was financially supported by the Swiss
National Science Foundation, Bern (grant 20-49’307-
96).
References
1. Zellner, A.; Schlosser, M. Synlett 2001, 1016–1018.
2. Schlosser, M. Pure Appl. Chem. 1988, 60, 1627–1634.
3. Hafner, A.; Duthaler, R. O.; Marti, R.; Rihs, G.; Rothe-
Streit, P.; Schwarzenbach, F. J. Am. Chem. Soc. 1992,
114, 2321–2336.
4. Julia, M.; Le Thuillier, G. Bull. Soc. Chim. Fr. 1966,
717–728.
5. Schulte-Elte, K. H.; Gadola, M.; Ohloff, G. Helv. Chim.
Acta 1971, 54, 1813–1822.
6. Mehta, G.; Nayak, U. R.; Dev, S. Tetrahedron Lett.
1966, 7, 4561–4567.
7. Damodaran, N. P.; Dev, S. Tetrahedron Lett. 1967, 8,
2897–2898.
8. (a) Carnduff, J.; Miller, J. A. J. Chem. Soc., Chem.
Commun. 1967, 606–607; (b) Carnduff, J.; Miller, J. A. J.
Chem. Soc. (C) 1968, 2671–2673.
9. Fujiwara, J.; Sato, T. J. Organomet. Chem. 1994, 473,
63–70.
cyclization strongly (DH°:−20 kcal/mol) and the three
r
other potential steps moderately (DH°:−5 kcal/mol).
r
The carbanion route of the ordinary Wolff–Kisher
reduction is well established.24–26 To set free the same
anion under Kabalka conditions, would require an
unprecedented,
though
Hofmann–Curtius–Lossen
related migration mechanism (characterized by the
transition state 8, Scheme 4). However, if the alkyldi-
azene 9 exists as a transient species as supposed in
similar cases27, it would be a plausible precursor to the
radical 5. Even aryldiazenes tend to generate aryl radi-
cals rather than arenide ions.28–30
10. Araki, S.; Bustugan, Y. J. Chem. Soc., Perkin Trans. 1
1991, 2395–2397.
11. Takano, S.; Shimazaki, Y.; Ogasawara, K. Tetrahedron
Lett. 1990, 31, 3325–3326.
The fact, that the hydrocarbon 3 is obtained only in
poor yield and is accompanied by a considerable
12. Risinger, G. E.; Karimian, K.; Jungk, S.; Simpson, J. B.
Experientia 1978, 34, 1121–1122.
O
O
13. 1-(4-Methoxyphenyl)-3,7-dimethyl-3-vinyl-1,6-octadien-
4-one: The alcohol 1 (8.6 g, 30 mmol) was added to a
solution of 1,1,1-triacetyloxy-1,1-dihydro-1,2-benzoiodo-
xol-3(1H)-one14 (14 g, 33 mmol) in dichloromethane
(0.10 L). After 45 min at 25°C, the mixture was absorbed
on silica gel and the product eluted with a 1:4 (v/v)
mixture of diethyl ether and hexanes; 7.8 g (91%); mp
B
N
Ts
H3CCOO
N=N−H
N
O
O
9
8
1
−35 to −31°C; bp 134–135°C/0.1 mmHg; n2D0 1.5993. H
Scheme 4. The two key intermediates, 8 and 9, preceding
carbanion or radical formation, respectively.
NMR (CDCl3, 400 MHz): l 7.33 (2H, dt, J=8.7, 2.5),

M. Schlosser, A. Zellner / Tetrahedron Letters 42 (2001) 5863–5865
5865
6.87 (2H, dt, J=8.7, 2.5), 6.41 (1H, d, J=16.2), 6.27 (1H,
d, J=16.2), 6.17 (1H, dd, J=17.5, 10.6), 5.28 (1H, t,
J=6.8), 5.27 (1H, d, J=10.6), 5.21 (1H, d, J 17.5), 3.82
(3H, s), 3.26 (2H, d, J=6.8), 1.73 (3H, s), 1.58 (3H, s),
1.43 (3H, s). C19H24O2 (284.40): calcd C 80.24, H 8.50;
found C 79.98, H 8.13%.
(452.62): calcd C 69.00, H 7.12; found C 68.89, H 7.17%.
23. (1E,5E)-1-(4-Methoxyphenyl)-6-methyl-3-(1-methyl-1-pro-
penyl)-1,5-heptadiene (3): 1,3,2-Benzodioxaborole (‘cate-
cholborane’; 1.1 mL, 1.2 g, 10 mmol) was added dropwise
to a solution of hydrazone 2 (4.5 g, 10 mmol) in
dichloromethane (50 mL) cooled to 0°C. Monitoring the
reaction by NMR revealed the instantaneous formation
of the adduct in a 1:1 diastereomeric ratio. The mixture
was treated with methanol (5.0 mL) and tetra-
butylammonium acetate (9.0 g, 30 mmol). After 4 h at
+25°C, chromatography on silica gel (eluent: diethyl ether
and hexanes in a 1:4 ratio) followed by distillation
afforded a colorless liquid; bp 128–130°C/0.2 mmHg; nD20
1.5390; 0.81 g (30%). 1H NMR (CDCl3, 400 MHz): l
7.29 (2H, dt, J=8.8, 2.5), 6.84 (2H, dt, J=8.8, 2.5), 6.29
(1H, d, J=15.9), 6.03 (1H, dd, J=15.9, 7.6), 5.34 (1H, q,
J=6.6), 5.10 (1H, t, J=6.9), 3.81 (3H, s), 2.77 (1H, q,
J=7.5), 2.2 (2H, m), 1.69 (3H, s), 1.63 (3H, s), 1.61 (3H,
d, J=6.6), 1.60 (3H, s). C19H26O (270.41): calcd C 84.39,
H 9.69; found C 84.49, C 9.62%.
24. (a) Szmant, H. H. Angew. Chem. 1968, 80, 141–149; (b)
Szmant, H. H. Angew. Chem., Int. Ed. Engl. 1968, 7,
120–128.
25. Wharton, P. S.; Bohlen, D. H. J. Org. Chem. 1961, 26,
3615–3616.
26. Wharton, P. S. J. Org. Chem. 1961, 26, 4781–4782.
27. Kabalka, G. W.; Yang, D. C. T.; Baker, J. D. J. Org.
Chem. 1976, 41, 574–575.
28. Rieker, A.; Niederer, P.; Leibfritz, D. Tetrahedron Lett.
1969, 11, 4287–4290.
14. Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48,
4155–4156.
15. Kabalka, G. W.; Baker, J. D. J. Org. Chem. 1975, 40,
1834–1835.
16. Kabalka, G. W.; Summers, S. T. J. Org. Chem. 1981, 46,
1217–1218.
17. Caglioti, L.; Magi, M. Tetrahedron 1963, 19, 1127–1131.
18. Caglioti, L. Tetrahedron 1966, 22, 487–493.
19. Cacchi, S.; Caglioti, L.; Paolucci, G. Bull. Chem. Soc.
Jpn. 1974, 47, 2323–2324.
20. Todd, D. Org. React. 1948, 4, 378–422.
21. Fu¨rst, A.; Berlo, R. C.; Hooton, A. S. Chem. Rev. 1965,
65, 63.
22. 1-(4-Methoxyphenyl)-3,7-dimethyl-3-vinyl-1,6-octadien-4-
one p-toluenesulfonylhydrazone (2): 4-Methoxybenzenesul-
fonic acid hydrazide (p-toluenesulfohydrazide; 4.7 g, 25
mmol) was added to a solution of the ketone (7.1 g, 25
mmol) described in the preceding paragraph in ethanol
(10 mL) and the suspension was stirred for 15 h at +25°C.
The product was isolated by chromatography on silica gel
using a 2:3 (v/v) mixture of diethyl ether and hexanes as
the eluent; mp −16 to −14°C; 10.1 g (89%). 1H NMR
(CDCl3, 400 MHz): l 7.80 (2H, dt, J=8.3, 1.9), 7.67 (1H,
s), 7.27 (2H, dt, J=8.3, 1.9), 7.26 (2H, dt, J=8.7, 2.4),
6.86 (2H, dt, J=8.7, 2.4), 6.18 (1H, d, J=16.2), 6.09 (1H,
d, J=16.2), 5.94 (1H, dd, J=17.6, 10.6), 5.15 (1H, dd,
J=10.6, 1.0), 5.02 (1H, dd, J=17.6, 1.0), 4.59 (1H, t,
J=6.6), 3.82 (3H, s), 2.86 (2H, d, J=6.6), 2.42 (3H, s),
1.73 (3H, s), 1.70 (3H, s), 1.33 (3H, s). C24H32N2O3S
29. Kosower, E. M.; Huang, P. K. C.; Tsuji, T. J. Am. Chem.
Soc. 1969, 91, 2325–2329.
30. Broxton, T. J.; McLeish, M. J. Aust. J. Chem. 1983, 36,
1031–1035.
.