A novel synthesis of 2-functionalized benzofurans by palladium-catalyzed cycloisomerization of 2-(1-hydroxyprop-2-ynyl)phenols followed by acid-catalyzed allylic isomerization or allylic nucleophilic substitution

作者：Gabriele Bartolo^*; Mancuso Raffaella; Salerno Giuseppe

来源：Journal of Organic Chemistry, 2008, 73(18): 7336-7341.

DOI：10.1021/jo801444n

A novel two-step synthesis of 2-hydroxymethylbenzofurans 3 and 2-alkoxymethylbenzofurans 4-6, based on palladium-catalyzed cycloisomerization of 2-(1-hydroxyprop-2-ynyl)phenols 1 under basic conditions to give 2-methylene-2,3-dihydrobenzofuran-3-ols 2, followed by acid-catalyzed isomerization or allylic nucleophilic substitution with alcohols as nucleophiles, is reported. Cycloisomerization reactions leading to 2 (80-98% yields) were carried out at 40 degrees C in MeOH as the solvent, in the presence of a base and catalytic amounts of PdX(2) + 2KX (X = Cl, I). Isomerization reactions of 2 readily occurred at 25-60 degrees C in DME as the solvent, with H(2)SO(4) as the proton source, to give 2-hydroxymethylbenzofurans 3 in 65-90% yields. In a similar manner, allylic nucleophilic substitution reactions of 2 with ROH as nucleophiles [carried out at 25-40 degrees C in ROH (R = Me) or ROH-DME mixtures (R = Bu, Bn) in the presence of H(2)SO(4)] afforded 2-alkoxymethylbenzofurans 4, 5, and 6 (R = Me, Bu, and Bn, respectively), in 65-98% yields.

• 出版日期2008-9-19