Asymmetric [3 + 3] Annulation to Construct Trifluoromethylated Pyrazolo[3,4-b]pyridin-6-ones via Chiral Phosphoric Acid and MgSO₄ Synergistic Catalysis

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).

Chiral organophosphates as ligands in asymmetric metal catalysis

“…Once again, coordination of the nucleophile is also possible, in this case most likely via the indole (see figure 7). 28 In contrast to the other examples in this review, Lin used the catalyst as a combination of phosphoric acid (not phosphate) and magnesium sulfate, so this protocol might be termed as Lewis acid assisted phosphoric acid catalysis (not Lewis acid catalysis with a magnesium phosphate, as in Antilla´s work).…”

“…1,4-dioxane:CCl 4 (1:1), 40°C, 96 h 24 25 28 Mg-bisphosphates were also used for the synthesis of 1,3-oxazolidines and 1,3-oxazinanes 29 , for the Diels-Alder reaction of benzoquinones with vinylindoles 30 as well as for the synthesis of spirocyclic dihydroquinolones 31 (not shown in detail).…”

“…Figure 7: Enantioselective [3+3] annulation catalyzed by synergistic action of a phosphoric acid and Mg 2+ 28. …”

Recent Advancement in H8–BINOL Catalyzed Asymmetric Methodologies

“…67 Lin and his group (Scheme 61; Figure 25) applied a [3 + 3] addition protocol via a novel asymmetric Friedel−Crafts alkylation/trans-amidation tandem reaction using N-arylpyrazoline 281 and 2-oxaindole 282 for the enantio-and diasteroselective synthesis of pyrazolo[3,4-b]pyridin-6-ones 283 employing synergistic chiral phosphoric acid 284 and MgSO 4 catalysis. 68 Investigation of various additives such as MgSO 4 , Na 2 SO 4 , and molecular sieves (5 Å, 4 Å, and 3 Å molecular sieves), but only MgSO 4 is suitable for this conversion. Solvent screening also reports a mixed result about dichloroethane, 1,4dioxane, and carbon tetrachloride.…”

Organocatalytic diastereo- and enantioselective conjugate addition of pyrazol-3-ones to 3-trifluoroethylidene oxindoles with a newly developed squaramide catalyst

“…5 The chiral framework of the catalyst plays a crucial role in its performance, thus the development of new and efficient bifunctional squaramide catalysts with different backbones is still highly valuable and desirable for asymmetric transformations. Based on our interest in the discovery of chiral spirobiindane-derived organocatalysts for asymmetric synthesis, 6 a new chiral bifunctional squaramide catalyst based on spirobiindane was synthesized and applied in the asymmetric conjugate addition of pyrazol-3-ones with 3-trifluoroethylidene oxindoles.…”