V. Gonnot et al. / Tetrahedron Letters 48 (2007) 7117–7119
7119
Scheme 4. Completion of the synthesis.
Interestingly at this stage of the synthesis, due to the
high convergence of our approach, the intermediate 5
contains the entire carbon unit necessary to reach the
targets. The resulting phthalide 5 was therefore reacted
with hydrogen in the presence of palladium catalyst on
carbon in acetic acid to afford O-benzyl benzoic acid 4
in quantitative yield (Scheme 4). Subsequent treatment
with trifluoroacetic anhydride in a 1/1 mixture of
DCM and TFA effected smooth Friedel–Craft acylation
to give anthracenone 16 in 96% of yield. Quantitative
and clean benzylic oxidation was then optimized using
mild experimental conditions (air, t-BuOK in DMSO
at room temperature) leading to the anthraquinone
17.21 Global deprotection and amide cleavage were then
effected by treating 17 with concentrated HCl for four
days at 120 °C, resulting in the formation of rhein 1 in
70% of yield. Acetylation of 1 under usual conditions
(Ac2O, pyr, cat. DMAP) gave substrate 2 quantitatively.
article can be found, in the online version, at
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We acknowledge the contribution of Alain Valleix for
MS analysis, Michel Mosser for his contribution and
the Laboratoire Pierre Fabre (Plantes et Industrie),
and the CNRS for financial support of V.G. and S.T.
Supplementary data
Supplementary data for the synthesis of compounds 4–
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