Asymmetric [3 + 3] Annulation to Construct Trifluoromethylated Pyrazolo[3,4-<i>b</i>]pyridin-6-ones via Chiral Phosphoric Acid and MgSO<sub>4</sub> Synergistic Catalysis
Alemayehu Gashaw Woldegiorgis, Zhao Han, Xufeng Lin
Abstract
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).
Topics & Concepts
ChemistryAnnulationStereocenterPhosphoric acidCatalysisTandemAlkylationEnantioselective synthesisCombinatorial chemistryOrganocatalysisStereochemistryOrganic chemistryMedicinal chemistryComposite materialMaterials scienceFluorine in Organic ChemistryAsymmetric Synthesis and CatalysisSynthetic Organic Chemistry Methods