The preparation of 2,3,5-tri- and 2,3-disubstituted furans by regioselective palladium(0)-catalyzed coupling reactions: Application to the syntheses of rosefuran and the F-5 furan fatty acid

The 5-acceptor-substituted 2,3-dibromofurans 1 and 2 underwent a regioselec tive Pdo-catalyzed coupling reaction dt the C-2 carbon atom. With alkynes t he corresponding 2-alkynylfurans 4 and 5 were accessible (49-97% yield). Al kyl-, aryl-, and alkenylzinc reagents gave the 2-substituted furans 8 start ing from compound 2 (66-84 % yield). The 2-allylfurans 8e and 8f were obtai ned by a regioselective Stille coupling in 79% and 73% yield. The latter re action was also applied to the parent 213-dibromofuran (27) and yielded the substitution product 28 (60% yield). Subsequent Pd-0-catalyzed reactions t o,introduce a methyl group in 3-position by a methyldebromination were succ essfully conducted for 2- alkynyl-3-bromofurans with MeZnCl and PdCl2(PPh3) (2) as the catalyst in THF (reflux) to yield compounds 13-16 and 24 (67-76% ) and with SnMe4 and PdCl2[P(o-Tol)(3)](2) as the catalyst in DMA (90 degre es C) for the 2-allyl-3-bromofuran 8e to yield 18 (70%). The more facile re action of the 2-alkynylfurans relative to those of furans bearing an sp(3)- carbon atom at C-2 appears to be due to steric reasons. Studies-on the 2-al kyl-3-bromofuran 20 supported this notion. With the regioselective coupling methodology the terpene rosefuran (22) was prepared in four steps starting from furan 2 (35% yield overall). The F-5 furan fatty acid (26) was synthe sized from furan 1 in five steps (29% yield overall).