Chemistry Letters Vol.32, No.5 (2003)
421
ditions to give ketone 9 in 88% yield. The diastereoselectivity
1
overall yield) which included regioselective oxidation of phenol
to o-quinone with IBX and the [4+2] cycloaddition of resultant
o-quinone and cinnamyl alcohol as key steps. We also devel-
oped a synthetic procedure for key intermediate 2, which was
useful for the synthesis of a variety of benzodioxane neolignans
and flavonolignans. Further refinement of the synthetic scheme
and preparation of an optically active form will be reported in
due course.
of the cycloaddition was determined as trans/cis = 2/1 by H
NMR analysis of ketone 9. This geometric mixture was treated
under basic conditions reported by Pan3 et al. to convert it to
trans isomer in 57% yield. The isomerization necessitated de-
protection of the acetal group of 8. The resultant acetophenone
9 was protected by MOM group and converted to methyl ester
10 by sequential iodoform reaction and esterification in 69%
yield.
The next step was construction of a stilbene skeleton by
Wittig olefination using phosphonium 3, which was prepared
from benzyl alcohol 119 in the 2 steps described below. Alcohol
11 was converted to benzyl chloride 12 with methanesulfonyl
chloride and triethylamine in 95% yield. Chloride 12 was trea-
ted with triphenylphosphine to afford 3 in 38% yield.
The authors thank Dr. D. Lee at the Research Triangle In-
stitute for his kindness in providing the NMR spectrum of 1 and
information on HPLCconditions. We express deep thanks to
Prof. T. Sato at Kurashiki University of Science and the Arts
for kind information on cesium fluoride mediated Wittig olefi-
nation.
References and Notes
OH
Cl
1
D. Lee, M. Cuendet, J. S. Vigo, J. G. Graham, F. Cabieses,
H. H. S. Fong, J. M. Pezzuto, and A. D. Kinghorn, Org.
Lett., 3, 2169 (2001).
MOMO
MOMO
a
b
3
2
3
4
5
D. Magdziak, A. A. Rodriguez, R. W. V. D. Water, and T.
R. R. Pettus, Org. Lett., 4, 285 (2002).
X. She, X. Jing, X. Pan, A. S. C. Chan, and T.-K. Yang, Tet-
rahedron Lett., 40, 4567 (1999).
OMOM
11
OMOM
12
Scheme 3. (a) MsCl, Et3N, CH2Cl2, rt, overnight (95%); (b)
Ph3P, toluene, reflux, overnight (38%).
When DMF or CHCl3 was used as solvent following the re-
ported procedure,2 the oxidation was decelerated markedly.
4-tert-Butylphenol, 4-isopropylphenol, 4-ethylphenol, and
4-methylphenol were subjected to the oxidation, respec-
tively. Although corresponding o-quinone could be detected
by TLCor 1H NMR in all cases, o-quinone could be only
isolated from 4-tert-butylphenol.
N. Daubresse, C. Francesch, F. Mhamdi, and C. Rolando,
Synthesis, 1994, 369.
L. Merlini, A. Zanarotti, A. Pelter, M. P. Rochefort, and R.
Ester 10 was converted to benzaldehyde 2 by sequential re-
duction with LiAlH4 and oxidation with Dess-Martin periodi-
nane. Aldehyde 2 was treated with 3 in the presence of cesium
fluoride in toluene under reflux conditions10 to give protected
Aiphanol 13 as E=Z diastereomeric mixture in 59% yield from
10. The whole MOM group of 13 was removed under acidic
conditions to afford Aiphanol 1 as a mixture of diastereomers
6
7
8
9
1
in 65% yield. The ratio was determined as E=Z ¼ 7=1 by H
NMR analysis. Finally, the remaining Z-isomer of 1 was sepa-
rated by HPLCto give pure ( ꢁ)-Aiphanol 1. The spectral data
(1H, 13CNMR) of the synthetic 111 were in good accordance
with those already reported.1
Hansel, J. Chem. Soc., Perkin Trans. 1, 1980, 775.
¨
X. She, W. Gu, T. Wu, and X. Pan, J. Chem. Res., Synop.,
1999, 100.
C. A. Townsend, S. G. Davis, S. B. Christensen, J. C. Link,
and C. P. Lewis, J. Am. Chem. Soc., 103, 6885 (1981).
In conclusion, the first total synthesis of (ꢁ)-Aiphanol was
achieved using a convergent strategy (14 steps from 6, 5.8%
10 M. Morimoto, K. Takeda, T. Yoshiyama, and T. Sato, Nip-
ponkagaku-kai Nishinihontaikai Kouen Yokousyu (2002),
p 398 (1PB17).
a,b
c
11 Data for Aiphanol 1: 1H NMR (500 MHz, acetone-d6) d
7.10 (1H, d, J ¼ 2:1 Hz), 7.05 (1H, dd, J ¼ 8:5, 2.1 Hz),
6.98 (1H, d, J ¼ 16:2 Hz), 6.91 (1H, d, J ¼ 16:2 Hz), 6.87
(1H, d, J ¼ 8:5 Hz), 6.80 (2H, s), 6.52 (1H, d,
J ¼ 2:1 Hz), 6.24 (1H, dd, J ¼ 2:1, 2.1 Hz), 4.93 (1H, d,
J ¼ 7:9 Hz), 4.10 (1H, ddd, J ¼ 7:9, 4.3, 2.4 Hz), 4.06
(1H, dd, J ¼ 6:7, 4.9 Hz), 3.81 (6H, s), 3.70 (1H, ddd,
J ¼ 12:2, 4.9, 2.4 Hz), 3.50 (1H, ddd, J ¼ 12:2, 6.7,
4.3 Hz); 13CNMR (100 MHz, acetone-d 6) d 160.1, 149.7,
146.0, 145.4, 141.6, 138.2, 132.8, 129.7, 129.1, 129.0,
121.9, 118.7, 116.4, 108.8, 106.7, 103.8, 80.6, 78.5, 62.8,
57.6.
10
2
O
O
OMOM
OMe
d
MOMO
1
OMOM
MOMO
13
OMe
Scheme 4. (a) LiAlH4, THF, rt, 1 h (94%); (b) Dess-Martin
periodinane, CH2Cl2, rt, 0.5 h; (c) 3, CsF, toluene, reflux, 4 h
(64% in 2 steps); (d) AcCl, MeOH, rt, overnight [65%
(E=Z ¼ 7=1)].
Published on the web (Advance View) April 2, 2003; DOI 10.1246/cl.2003.420