trans-Dihydrobenzofurans via Diazotization-Palladium-Catalyzed Oxyarylation

Significance

Reported is the stereoselective synthesis of trans-2-aryl-3-methyldihydrobenzofurans 3 from ortho-aminophenols 1 and arylal­kenes 2 via diazotization and palladium-catalyzed oxyarylation in a one-pot reaction. The sequence is based on the diastereoselective Heck oxyarylation reaction of anethole with 2-hydroxybenzenediazonium salts 4 in the presence of Pd₂(dba)₃ and CaCO₃ as base (K. Kikukawa, K. Nagira, F. Wada, T. Matsuda Tetrahedron 1981, 37, 31). However, due to the unavailability and difficult preparation of the diazonium salt, an in situ generation followed by palladium-catalyzed oxyarylation in one-pot was developed for the synthesis of 3. After screening of bases, catalysts, ligands (NHC), solvents, and diazotization reagents, the optimum conditions of NOPF₆ as diazotization ­reagent and Pd₂(dba)₃/ZnCO₃ as catalyst/base for the Heck oxyarylation were established. The scope of the ­diazotization-oxyarylation was examined with 2-aminophenols bearing EDGs and EWGs in reactions with a variety of alkenes. However, alkenes with ortho-substituents on the aromatic ring as well as heteroatoms on the propenyl moiety afforded decreased product yields.