Synthesis of Trifluoromethylbenzofurans by Extended Pummerer Reaction

Significance

Reported is the synthesis of 3-tri­fluoromethylbenzofurans 3 from phenols 1 via sequential Pummerer-[3,3]-sigmatropic rearrangement reactions mediated by Tf₂O. Weakly nucleo-philic phenols require elevated reaction temperatures, while phenols bearing strong EDGs (R^¹ = OMe) are not suitable substrates due to triflation of the phenol occurring in competition with the desired reaction. The meta-substituted phenols give products 9 with excellent regiocontrol (except for R^³ = Me). Further useful transformations of the 2-methylthio group by Negishi cross-coupling (72% to quantitative yield, 3 examples) and by conversion to a formyl group via the sulfoxide (73% yield over two steps) were reported.