EFFICIENT CONDITIONS FOR CONVERSION OF 2-SUBSTITUTED FURANS INTO 4-OXYGENATED 2-ENOIC ACIDS AND ITS APPLICATION TO SYNTHESIS OF (-ASPICILIN, (+)-PATULOLIDE-A, AND (-)-PYRENOPHORIN())

2-Substituted furans 1a,b,c were found to be conveniently transformed into trans 4-oxo-2-enals 2a,b,c in 62-87% yields by using NBS/pyridine in THF-acetone-H2O (<-15 degrees C then rt) or NBS/ NaHCO3 in acetone -H2O (<-15 degrees C then rt after addition of pyridine). Further oxid ation of the enals 2a-c using NaClO2 led to the trans 4-oxo-2-enoic ac ids 3a-c in good yields. With this transformation in mind, we designed syntheses of(+)-aspicilin, (+)-patulolide, and (-)-pyrenophorin. In t he synthesis of (+)-aspicilin as shown in Schemes 1 and 2, the pivotal intermediate 6 was prepared from olefin 7 in which 2-furyl group is a ttached. The AD reaction of 7 secured the C(5) and C(6) stereochemistr y of aspicilin, and the subsequent transformation using the protocol d escribed above afforded the ester 6. Stereocontrolled reduction of 6 f ollowed by deprotection and the Yamaguchi macrocyclization furnished ( +)-aspicilin. For the synthesis of(+)-patulolide (Scheme 3) and (-)-py renophorin (Scheme 4), the intermediates are the furans 38 and 44, whi ch were prepared easily by the classical methods using furyllithium 33 . The furan ring oxidations proceeded as well, furnishing acids 40 and 46 in good yields, acetalization of which afforded the known intermed iates 41 and 47, respectively.