Asymmetric [3 + 3] Annulation to Construct Trifluoromethylated Pyrazolo[3,4- b ]pyridin-6-ones via Chiral Phosphoric Acid and MgSO 4 Synergistic Catalysis.

We developed a novel asymmetric Friedel-Crafts alkylation/transamidation tandem reaction for the enantio- and diastereoselective synthesis of pyrazolo[3,4- b ]pyridin-6-ones bearing a -CF 3 unit via synergistic chiral phosphoric acid and MgSO 4 catalysis. This [3 + 3] annulation protocol allows the formation of trifluoromethylated pyrazolo[3,4- b ]pyridin-6-ones with two adjacent tertiary stereocenters in moderate to high yields (up to 90%), enantioselectivities (up to 97% ee), and diastereoselectivities (up to >20:1 dr).