Scheme 3
the same flask, and the reaction was continued for a further
3 h. Standard workup followed by chromatography on silica
gel gave a 67% yield of 12.
tion, the major product was de-MOM product not a desired
orthoester when 17 was treated with LTA in benzene.18 We
found that the oxidation was sensitive to the O-protecting
group at the C-6 position of 17. For example, the use of
ether-type protecting groups such as MOM, Bn, and TBDMS
resulted in a complex mixture or no reaction while introduc-
tion of electron-withdrawing groups like acetate into 6-OH
of 18 gave good results. Consequently, the MOM group in
17 was exchanged to a benzyloxycarbonyl group. LTA
oxidation of 19 thus obtained proceeded nicely, giving the
corresponding monoacetate 20 in good yield. Exposure of
this to mild acidic conditions led to removal of the acetal
group, providing an unstable catechol 2 (R ) OZ), which
was immediately submitted to phenylacetylation. Deproto-
nation from two hydroxyl groups in 2 was accomplished by
the action of lithium bis(trimethylsilylamide) (LHMDS) in
THF at -78 °C,19 and the resulting lithium salt reacted with
phenylacetyl chloride to provide 21 in good yield. Finally,
all benzyl groups in 21 were removed by hydrogenolysis
with Pd(OH)2 to give vialinin B (1). The spectral data of 1
were identical with those of the natural product.20
In constructing the p-terphenyl skeleton, we next turned
our attention to the benzofuran formation. Prior to the
reaction, the MOM group in 11 was hydrolyzed, giving 14
as an unstable solid (Scheme 3). The intramolecular O-
arylation of 14 was investigated under several conditions
including Pd(OAc)2 or Pd2(dba)3 in the presence of 13 or
2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl or 2-(di-
tert-butylphosphino)biphenyl,10,11 or Cu catalyst such as
Nano-CuO12 and Cu2O.13 All attempts, however, were
unsuccessful, and a desired benzofuran could not be isolated.
On the other hand, Bayer-Villiger oxidation14,15 of 12
provided the corresponding formate 15, which, upon treat-
ment with base, afforded an unstable phenol 16. The
cyclization from 16 to 17 was a troublesome step again. Pd-
catalyzed etherification of 16 did not proceed while the Cu-
mediated cyclization reaction gave 17 (∼54%) along with
an o-quinone without the MOM group (∼25%). These results
reflected the instability of 16 toward the reaction conditions
employed. After extensive experimentation, it was found that
treatment of the formate 15 with a Cu catalyst directly
produced 17. The use of Cu2O-pyridine was quite effective;
an 88% yield of 17 was attained. Removal of the methyl-
eneacetal moiety was performed by lead tetraacetate (LTA)
oxidation,16 which was previously employed in the total
synthesis of natural p-terphenyls.17 Contrary to our expecta-
We have developed a short and efficient method for the
synthesis of vialinin B (1) in 13 steps from a commercially
available sesamol (7). The key features of this synthesis are
as follows: (1) synthesis of a highly functionalized p-
terphenyl skeleton based on a Suzuki-Miyaura coupling;
(2) construction of a benzofuran skeleton by a Cu-mediated
(16) Ikeya, Y.; Taguchi, H.; Yoshioka, I. Chem. Pharm. Bull. 1981, 29,
2893–2898.
(11) Burgos, C. H.; Barder, T. E.; Huang, X.; Buchwald, S. L. Angew.
Chem., Int. Ed. 2006, 45, 4321–4326
.
(17) (a) Ye, Y.-Q.; Koshino, H.; Onose, J.; Yoshikawa, K.; Abe, N.;
Takahashi, S. Org. Lett. 2007, 9, 4131–4134. (b) Ye, Y.-Q.; Koshino, H.;
Onose, J.; Negishi, C.; Yoshikawa, K.; Abe, N.; Takahashi, S. J. Org. Chem.
2009, 74, 4642–4645.
(12) (a) Kidwai, M.; Mishra, N. K.; Bansal, V.; Kumar, A.; Mozumdar,
S. Tetrahedron Lett. 2007, 48, 8883–8887. (b) Zhang, J.; Zhang, Z.; Wang,
Y.; Zheng, X.; Wang, Z. Eur. J. Org. Chem. 2008, 511, 5112–5116. (c)
Schareina, T.; Zapf, A.; Cotte´, A.; Mu¨ller, N.; Beller, M. Tetrahedron Lett.
2008, 49, 1851–1855, and references cited therein.
(18) LTA oxidation of 5,6-bis(methoxymethoxy)benzo[d][1,3]dioxole
as a model compound gave the corresponding orthoester in high yield.
(19) Esterification of 2 in the presence of DMAP in pyridine or
triethylamine gave a mixture of 21 and its mono-phenylacetate.
(20) The original 13C NMR data (δ 119.83 for C-9b) of 1 denoted in
ref 1 was a typographical errror and should be revised to 119.38 ppm.
(13) Wipf, P.; Jung, J.-K. J. Org. Chem. 2000, 65, 6319–6337.
(14) Camps, F.; Coll, J.; Messeguer, A.; Perica´s, M. A. Tetrahedron
Lett. 1981, 22, 3895–3896
.
(15) No presence of potassium fluoride decreased the yield of 15.
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