The 1H NMR spectrum of 18 in CDCl3 revealed the existence of
rotational isomerism at the C4a–C5 axis. The ratio of the major and
minor rotamers was 5.1 : 1. When the two phenolic hydroxyl groups
in 18 were methylated, the ratio of the rotamers was changed to 2.1
: 1.12 Moreover, thin layer chromatographic analysis (silica gel,
hexane–ether) of 19 gave two spots, indicating that the rotational
isomerism was relatively slow at room temperature.
Oxidation of terminal alkene in 19 with OsO4–NMO along with
cleavage of the resultant diol with NaIO4 afforded the desired
aldehyde 2 (79% yield in 2 steps).
In summary, we have completed the asymmetric synthesis of the
C-glycosidic core of kendomycin. Highlights of the synthesis are
the Ag2O-mediated oxidative cyclization of the pyran ring and also
the Claisen rearrangement to construct fully substituted aromatic
nuclei. Further efforts toward the total synthesis of kendomycin
will be reported elsewhere.
The authors would like to thank Mr Hisashi Nishitani for his
contribution to the preliminary experiments. T. S. acknowledges
JSPS for the Research Fellowships for Young Scientists. This
research was partly supported by a Grant-in-Aid for Scientific
Research, and the 21st century COE program (Establishment of
COE on Materials Science) from the Ministry of Education,
Science, Sports, and Culture (MEXT), Japan.
Notes and references
† Electronic supplementary information (ESI) available: selected spectral
data for compounds 7, 8, 10, 11, 12, 15, 16, 17, 18, and 2. See http://
1 D. H. Williams and B. Bardsley, Angew. Chem., Int. Ed., 1999, 38,
1172; K. C. Nicolaou, C. N. C. Boddy, S. Brase and N. Winssinger,
Angew. Chem., Int. Ed., 1999, 38, 2096; H. Arimoto, J. Synth. Org.
Chem. Jpn., 2003, 61, 752.
2 H. Arimoto, K. Nishimura, T. Kinumi, I. Hayakawa and D. Uemura,
Chem. Commun., 1999, 1361; H. Arimoto, T. Oishi, M. Nishijima and
T. Kinumi, Tetrahedron Lett., 2001, 42, 3347.
3 Y. Funahashi, N. Kawamura and T. Ishimaru, Jap. Pat., 08 231 551 [A2
960 910] (1996) (Chem. Abstr., 1997, 126, 6553); Y. Funahashi, T.
Ishimaru and N. Kawamura Jap. Pat., 08 231 552 [A2 960 910] (1996)
(Chem. Abstr., 1996, 125, 326518); M. H. Su, M. I. Hosken, B. J.
Hotovec and T. L. Johnston, US Pat., 5 728 727 [A9803 17] (1998)
(Chem. Abstr., 1998, 128, 239489).
Scheme 2 a) Pyridinium bromide perbromide, K2CO3, CH2Cl2, 0 °C to
room temp.; b) ethyl vinyl ether, PPTS, room temp., 98% in 2 steps; c) n-
BuLi (2.5 equiv.), then B(OCH3)3, THF, 278 °C; d) H2O2, sat. Na2CO3 aq.,
82% in 2 steps; e) PPTS, n-propanol, room temp., 94%; f) Ag2O, CH2Cl2,
room temp., 94%; g) CH3I, K2CO3, acetone, reflux, 100%; h) pyridinium
bromide perbromide, CH2Cl2, room temp., 40%; i) (CF3COO)2IPh, K2CO3,
CH3CN, H2O, room temp.; j) Na2S2O4, THF, H2O, 0 °C, 83% in 2 steps; k)
allyl bromide, K2CO3, acetone, reflux, 100%; l) N,N-dimethylaniline,
reflux, 1.5 h, 66%; m) CH3I, K2CO3, acetone, reflux, 100%; n) OsO4, NMO,
aq. acetone, room temp., 82%; o) NaIO4, ethanol, room temp., 96%.
4 H. B. Bode and A. Zeeck, J. Chem. Soc., Perkin Trans. 1, 2000, 323; H.
B. Bode and A. Zeeck, J. Chem. Soc., Perkin Trans. 1, 2000, 2665.
5 Other synthetic studies: H. J. Martin, M. Drescher, H. Kahilg, S.
Schneider and J. Mulzer, Angew. Chem., Int. Ed., 2001, 40, 3186; M. M.
B. Marques, S. Pichlmair, H. J. Martin and J. Mulzer, Synthesis, 2002,
2766; S. Pichlmair, M. M. B. Marques, M. P. Green, H. J. Martin and J.
Mulzer, Org. Lett., 2003, 5, 4657.
6 R. T. Borchardt and A. K. Sinhababu, J. Org. Chem., 1981, 46, 5021; F.
A. Carey and R. M. Giuliano, J. Org. Chem., 1981, 46, 1366.
7 D. A. Evans, J. Bartroli and T. L. Shih, J. Am. Chem. Soc., 1981, 103,
2127; D. A. Evans, M. D. Ennis and D. J. Mathre, J. Am. Chem. Soc.,
1982, 104, 1737.
8 D. B. Dess and J. C. Martin, J. Org. Chem., 1983, 48, 4155.
9 W. R. Roush, K. Ando, D. B. Powers, A. D. Palkowitz and R. L.
Halterman, J. Am. Chem. Soc., 1990, 112, 6339; W. R. Roush, A. D.
Palkowitz and K. Ando, J. Am. Chem. Soc., 1990, 112, 6348.
10 S. R. Angle and K. D. Turnbull, J. Am. Chem. Soc., 1989, 111, 1136.
11 Y. Tamura, T. Yakuta, H. Tohma, K. Kikuchi and Y. Kita, Synthesis,
1989, 126.
12 1H NMR data of 19 (400 MHz, CDCl3) for the major rotamer: d 5.97
(1H, ddd, J = 17.1, 10.5, 5.4 Hz), 5.03 (1H, dd, J = 10.7, 1.5 Hz), 4.99
(1H, dd, J = 17.1, 1.5 Hz), 4.06 (1H, d, J = 10.3 Hz), 3.85 (3H, s), 3.81
(3H, s), 3.81–3.79 (1H, m), 3.64 (3H, s), 3.63–3.25 (4H, m), 2.64 (1H,
m), 2.19 (3H, s), 2.02–1.96 (1H, m), 1.84–1.68 (2H, m), 1.59–1.39 (4H,
m), 1.04 (3H, d, J = 6.8 Hz), 0.92 (3H, d, J = 6.1 Hz), 0.91 (9H, s), 0.85
(9H, s), 0.62 (3H, d, J = 6.6 Hz), 0.07 (6H, s), 0.00 (6H, s); HRMS (ESI)
calcd for C37H68O6Si2Na (M + Na)+ 687.4447 found 687.4463.
The ethoxyethyl group in 14 was removed by mild acidic
hydrolysis. The Ag2O oxidation10 of phenol proceeded at room
temperature to form the pyran 15. The mechanism for the formation
of 15 is presumed to involve initial o-quinone methide formation.
Intramolecular attack of the secondary alcohol on the quinone
methide occurs so that the bulky aromatic substituent is oriented as
equatorial. Actually, the coupling constant between C5-methine
and adjacent C6-methine protons was 10.4 Hz in the 1H NMR
spectrum, clearly indicating the relationship of these protons as
1,2-diaxial.
Severe difficulties were also encountered in installing the sixth
substituent on the aromatic nuclei. The pyran 15 could be converted
to bromide 16 in 2 steps, however, attempts at Stille coupling with
tributyl(vinyl)tin using Pd(PPh3)4 as a catalyst failed, presumably
due to the steric hindrance.
Selective removal of a methyl ether in 15,11 followed by
allylation, gave bis allyl ether 17. The heating of 17 in dimethylani-
line (degassed) at reflux, to our delight, formed 18 via a Claisen
rearrangement in 66% yield. We anticipated that the allyl ether
adjacent both to methoxy and pyranyl substituents would remain
after the rearrangement; we could not, however, find any
rearranged products with allyl ether. Efforts to provide more insight
into this mechanism are underway.
C h e m . C o m m u n . , 2 0 0 4 , 1 2 2 0 – 1 2 2 1
1221