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

The Journal of Organic Chemistry
Bartolo GabrieleGiuseppe Salerno

Abstract

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 PdX2 + 2KX (X = Cl, I). Isomerization reactions of 2 readily occurred at 25-60 degrees C in DME as the solvent, with H2SO4 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 H2SO4] afforded 2-alkoxymethylbenzofurans 4, 5, and 6 (R = Me, Bu, and Bn, respectively), in 65-98% yields.

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Citations

Sep 7, 2013·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Raffaella Mancuso, Bartolo Gabriele
Mar 3, 2017·The Journal of Organic Chemistry·Mohammad RehanPrasanta Ghorai
Apr 12, 2016·Organic & Biomolecular Chemistry·Gadi Ranjith KumarMaddi Sridhar Reddy
Apr 24, 2015·Journal of Natural Products·Kouji Kuramochi, Kazunori Tsubaki
Sep 18, 2012·The Journal of Organic Chemistry·Niranjan Panda, Raghavender Mothkuri
Dec 7, 2011·The Journal of Organic Chemistry·Amandine CarrërEmmanuel Bertounesque
Jul 11, 2012·The Journal of Organic Chemistry·Stefano ProttiAngelo Albini

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