for a different stabilized phenyl phosphonate ester system,7c
was found to lead to reduced Z-selectivity in the case of
reagent 6.
Scheme 1. Synthesis of the Naphthoic Acid Component of
NCS Chromophore by Oxidative Cyclization of an
Electron-Rich δ-Aryl â-Keto Ester4c
In the next step of the sequence, the 1,3-dioxolenone group
of the coupling products was transformed into the corre-
sponding â-keto trifluoroethyl ester, without detectable
isomerization of the adjacent (Z)-olefin, by subjecting the
coupling products to sodium trifluoroethoxide in trifluoro-
ethanol. The trifluoroethyl group was chosen because it is
more easily saponified than the more common methyl or
ethyl esters. The â-keto trifluoroethyl ester products, which
existed as a nearly equal mixture of keto and enol tautomeric
forms (CDCl3, ∼0.10 M), underwent smooth cyclization to
the corresponding trifluoroethyl 2-hydroxy-1-naphthoic acid
esters in the presence of manganese triacetate in acetic acid
(23 or 40 °C, depending upon the substrate; see Table 1).8
transformation. This transformation did not prove to be
general, however, for only electron-rich aromatic substrates
were found to undergo efficient oxidative cyclization by this
method.4c In our own published route to compound 1 (seven
steps, 33% yield), we employed the photochemical cycliza-
tion of eq 1 as a key step.4e In subsequent studies, we have
found that this sequence, too, is not general, for when we
attempted a closely analogous cyclization in an effort to
synthesize naphthoic acid 2 (eq 2), the desired product 3
was formed in no more than 30% yield; the dechlorination
product 4 was identified as one of several byproducts.
Finally, saponification of the trifluoroethyl ester group of
the cyclized products was readily achieved, in essentially
quantitative yield, using lithium hydroxide in aqueous
tetrahydrofuran at 40 °C.
In a new strategy for 2-hydroxy-1-naphthoic acid synthesis,
we have developed a four-step sequence that appears to offer
both greater generality and efficiency than any prior route.
The new protocol is illustrated first with the synthesis of 1,
shown in Scheme 2, and later (Table 1) for the preparation
of a number of different 2-hydroxy-1-naphthoic acid esters
of different substitution patterns. In the first step of the
sequence, an aromatic aldehyde is subjected to Z-selective
olefination using the novel phenyl phosphonate ester 6
(Scheme 2).6 Phenyl phosphonate esters have been widely
used as reagents for Z-selective olefin synthesis.7 In the case
of reagent 6, optimal Z-selectivity (∼4:1) in coupling with
aromatic aldehydes was achieved using 1,8-diazabicyclo-
[5.4.0]undec-7-ene (DBU) as a base in the absence of any
other additive. The inclusion of sodium iodide, recommended
Scheme 2. Synthesis of Complex 2-Hydroxy-1-naphthoic
Acids from Benzaldehyde Derivativesa
(4) (a) Shibuya, M.; Toyooka, K.; Kubota, S. Tetrahedron Lett. 1984,
25, 1171-1174. (b) Shishido, K.; Yamashita, A.; Hiroya, K.; Fukumoto,
K.; Kametani, T. Tetrahedron Lett. 1989, 30, 111-112. (c) Citterio, A.;
Pesce, L.; Sebastiano, R.; Santi, R. Synthesis 1990, 142-144. (d) Takahashi,
K.; Suzuki, T.; Hirama, M. Tetrahedron Lett. 1992, 33, 4603-4604. (e)
Myers, A. G.; Subramanian, V.; Hammond, M. Tetrahedron Lett. 1996,
37, 587-590. (f) Go¨rth, F. C.; Rucker, M.; Eckhardt, M.; Bru¨ckner, R.
Eur. J. Org. Chem. 2000, 14, 2605-2611.
a Reagents and conditions: (a) 6, DBU, THF, 0-23 °C, 82%;
(b) CF3CH2OH, NaH, THF, 23 °C; (c) Mn(OAc)3, HOAc, 23 °C,
93% (two steps); (d) LiOH, THF, H2O, 40 °C, 100%.
(5) Takahashi, K.; Hagiwara, M.; Ashizawa, S.; Hirama, M. Synlett 1999,
1, 71-72.
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Org. Lett., Vol. 6, No. 24, 2004
Ji, Nan
