Asymmetric [3+3] Annulation to Construct Trifluoromethylated Pyrazolo[3,4-b]pyridin-6-ones via Chiral Phosphoric Acid and MgSO4 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 -CF3 unit via synergistic chiral phosphoric acid and MgSO4 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).

Automated summary

In this study, we developed a novel tandem reaction for the synthesis of pyrazolo[3,4-b]pyridin-6-ones bearing a -CF3 unit using chiral phosphoric acid and MgSO4 as catalysts. The reaction showed moderate to high yields, enantioselectivities, and diastereoselectivities, resulting in trifluoromethylated pyrazolo[3,4-b]pyridin-6-ones with two adjacent tertiary stereocenters.