High-Pressure Accelerated Enantioselective Addition of Indoles to Trifluoromethyl Ketones with a Low Loading of Chiral BINOL-Derived Phosphoric Acid

The effect of pressure (up to 10 kbar) on the Brønsted acid catalyzed enantioselective hydroxyalkylation of indoles with trifluoromethyl ketones was explored. The reaction was effectively accelerated at 9 kbar with a very low loading of a 1,1′-bi-2-naphthol (BINOL) -derived phosphoric acid (0.05–0.2 mol % of TRIP) and provided the products with high enantioselectivity (84–98 % ee).