Thorpe–Ingold effect in copper(II)-catalyzed formal hydroalkoxylation–hydroarylation reaction of alkynols with indoles

The use of Cu(OTf)2 as a catalyst for tandem hydroalkoxylation–hydroarylation reaction of alkynes tethered with hydroxyl group is reported. The reaction proceeds at 60 °C or even at room temperature with 5 mol % catalyst loading and produces C-3-substituted indoles in good to high yields. The method was shown to be applicable to a broad range of indoles, containing electron-withdrawing and electron-donating substituents, and alkynol substrates bearing sterically demanding substituents in the tether. Interestingly, it was found that Thorpe–Ingold effect is operating for this cyclization reaction. Easy availability and low cost of Cu(OTf)2 make this method attractive and amenable for large-scale synthesis compared to known literature methods.