Synthesis of 3-Aminobenzofurans via Cu-Catalyzed Annulative Amination

Significance

Reported is an effective copper-catalyzed annulative amination of ortho-alkynyl­phenols 1 with O-acylated hydroxylamine 2 yielding 3-aminobenzofurans 3. The transformation ­involved an annulative cupration of ortho-alkynyl-phenols (R. Alvarez et al. Chem. Eur. J. 2010, 16, 12746) followed by electrophilic C-N bond formation. The reaction was effected in the presence of Cu(OTf)₂ and LiOt-Bu as base in aprotic solvent (NMP) under optimized conditions. The scope was explored primarily with R^³ variation (EWGs and EDGs). ortho-Alkynyl hydroxythiophenes also participated in the reaction. Allylamine, benzyl­amine, and cyclic amines (morpholine, piperidine or tetrahydroisoquinoline) were also shown to be tolerated in the reaction.