Benzofuran 2- acetyl-, ring synthesis

The synthesis of the (i) 4-hydroxy-6-methoxytetrahydrofuro[2,3-6]-benzofuran ring (116), a degradation product of natural substances of the sterigmatocystin series, is similar,318 as is the synthesis of the dihydro derivative (117) from the o-acetylated acetaldehyde (118), a nonisolated intermediate which is ring-closed to 119 and then heated in toluene to give 117. The last is the starting point for the synthesis of aflatoxin M4 (49).153... 

The Pechmann condensation also played a key role in the Biichi group s efforts toward the total synthesis of aflatoxin Bi (44). In this work, the central coumarinic ring system of aflatoxin was prepared by condensing the racemic tricyclic phenol 40 with ethyl methyl-3-oxoadipate (41) in methanolic HCl at 5 °C to provide tricycle 42 in 57% yield. The use of methanol as a solvent was crucial to the success of this reaction, as attempts to perform this reaction in sulfuric acid led to the rapid isomerization of 40 to the corresponding benzofuran-3-acetic acid, which could be converted to the analogous coumarin product only in very poor yield. Subsequent cyclization of the pendant ester moieties of 42 afforded pentacyclic lactone 43. Treatment of 43 with disiamylborane resulted in selective reduction of the dihydrofuranone to the corresponding hemiaminal, which was then acetylated and pyrolyzed (240 °C) to provide ( )-aflatoxin Bi (44). 

Several substituted benzofuransulfonyl derivatives are useful medicinal agents. 2-Acetyl-7-methoxybenzofuran 90 reacts with excess chlorosulfonic acid to yield the corresponding 4-sulfonyl chloride 91 (Equation 26). In this substrate, the 2-position of the benzofuran nucleus is blocked and hence sulfonation would be expected to occur in the 4-position of the phenyl ring as it is para to the electron-donating methoxy group. The sulfonyl chloride 91 is an intermediate in the synthesis of compounds which were useful in the treatment of diabetes. ... 

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