treatment with sodium dimethyl malonate and methane-
sulfonic acid. The reported procedure (magnesium dimethyl
malonate, phosphoric acid-phosphorus pentoxide) proceeded
in only 36% yield.12 This naphthalene was found to be highly
susceptible to oxidation, and therefore it was best used
directly. Selective tert-butyldimethylsilylation of the more
accessible hydroxyl in 10, followed by methylation of the
one remaining, delivered the fully protected naphthalene 11
in 63% yield. After silyl f benzyl protecting group exchange
to afford 12,13 saponification led to the desired acid 5. The
overall yield of 5 from ester 7 was 21% for the nine steps
(84%/step).
resultant acid 15 with potassium acetate in acetic anhydride,
according to the procedure outlined by Rizzacasa and
collaborators,16 than through the Giles approach that involved
Stobbe condensation with dimethyl succinate and cyclization
with sodium acetate in acetic anhydride (51% versus 30%
overall yield). Compound 16 so obtained was next converted,
as described by Lown and co-workers,17 with methanol and
potassium carbonate in acetone into naphthol 17, which was
methylated (rather than isopropylated14) and then reduced
to provide alcohol 18 in excellent yield.
The acetate of 18, obtained conventionally, was dibromi-
nated to provide the highly substituted naphthalene 19.
Mono-debromination of 19 was effected by exposure to
trifluoroacetic acid and 1,2,4-trimethoxybenzene (TMB) in
refluxing dichloromethane14 to give a difficult to separate
mixture of the desired product18 together with TMB and
5-bromo-TMB. Fortunately, purification of the mono bro-
mide could be easily accomplished after saponification to
naphthol 6. This esterification partner of acid 5 was thus
obtained in nine steps from aldehyde 13 with an overall yield
of 29% (87%/step).
The second unit, naphthalene 6, was synthesized by
substantially modifying the procedure described by Giles and
collaborators14 (Scheme 3). It was found that ester 16 could
Scheme 3a
The anionic homo-Fries substrate, ester 4, could readily
be formed by Mitsunobu coupling of the naphthalene units
5 and 6 (Scheme 4). The key acyl transfer proceeded
Scheme 4a
a (a) Benzene, 20 °C, 12 d. (b) Ac2O, AcOK, reflux, 15 min. (c)
MeOH-acetone, K2CO3, 35 °C, 3 h. (d) DMS, K2CO3, acetone,
reflux, 16 h. (e) LiAlH4, THF, 20 °C, 1 h. (f) Ac2O, pyr., 50 °C,
1.5 h. (g) Br2, AcOH, 20 °C, 20 min. (h) CF3CO2H, 1,2,4-TMB,
CH2Cl2, reflux, 12 h. (i) 1% KOH, MeOH, 20 °C, 30 min.
be better obtained from 3,5-dimethoxybenzaldehyde (13) by
reaction with ylide 1415 followed by cyclization of the
(9) Miller, J. A. J. Org. Chem. 1987, 52, 322-323. Horne, S.; Rodrigo,
R. Ibid. 1990, 55, 4520-4522. Horne, S.; Rodrigo, R. J. Chem. Soc., Chem.
Commun. 1991, 1046-1048.
(10) See, for example: Yamaguchi, M.; Okuma, S.; Nakamura, S.;
Minami, T. J. Chem. Soc., Perkin Trans. 1 1990, 183-190. Harris, T. M.;
Wittek, J. J. Am. Chem. Soc. 1975, 11, 3270-3277. Dodd, J. H.; Weinreb,
S. M. Tetrahedron Lett. 1979, 38, 3593-3596. Carpenter, T. A.; Evans, G.
E.; Leeper, F. J.; Stauton, J.; Wilkinson, M. R. J. Chem. Soc., Perkin Trans.
1 1984, 1043-1050. Cameron, D. W.; Feutrill, G. I.; Pannan, L. J. H. Aust.
J. Chem. 1987, 40, 1737-1745.
(11) Viviani, F.; Gaudry, M.; Marquet, A. J. Chem. Soc., Perkin Trans.
1 1990, 1255-1261.
(12) Birch, A. J.; Donovan, F. W. Aust. J. Chem. 1955, 8, 529-534.
(13) The benzyl group could not be directly introduced in 10 because of
the unavoidable occurrence of C-4 benzylation.
a (a) DEAD, PPh3, THF, 20 °C, 4 h. (b) n-BuLi, THF, -55 f
-45 °C, 1.5 h. (c) Ag2O, MeI, CH2Cl2, 20 °C, 7 d. (d) H2, Pd(OH)2/
C, EtOH-CH2Cl2, 16 h. (e) KOH, MeOH, reflux, 12 h.
smoothly, following optimization, to afford naphthonaph-
thone 20 in a reproducible 50-60% yield. In view of the
steric encumbrance at the carbonyl site in 4, the efficiency
(14) Giles, R. G. F.; Green, I. V.; Knight, L. S.; Lee Son, V. R.; Mitchell,
P. R. K.; Yorke, S. C. J. Chem. Soc., Perkin Trans. 1 1994, 853-866.
Org. Lett., Vol. 4, No. 18, 2002
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