Brønsted acid-catalyzed asymmetric dearomatization for synthesis of chiral fused polycyclic enone and indoline scaffolds.

In the past two decades, substantial advances have been made on the asymmetric alkyne functionalization by the activation of inert alkynes. However, these asymmetric transformations have so far been mostly limited to transition metal catalysis, and chiral Brønsted acid-catalyzed examples are rarely explored. Here, we report a chiral Brønsted acid-catalyzed dearomatization reaction of phenol- and indole-tethered homopropargyl amines, allowing the practical and atom-economical synthesis of a diverse array of valuable fused polycyclic enones and indolines bearing a chiral quaternary carbon stereocenter and two contiguous stereogenic centers in moderate to good yields with excellent diastereoselectivities and generally excellent enantioselectivities (up to >99% enantiomeric excess). This protocol demonstrates Brønsted acid-catalyzed asymmetric dearomatizations via vinylidene-quinone methides.

Synthesis of Axially Chiral N-Arylindoles via Atroposelective Cyclization of Ynamides Catalyzed by Chiral Brønsted Acids.

In recent years, asymmetric catalysis of ynamides has attracted much attention, but these reactions mostly constructed central chirality, except for a few examples on the synthesis of axially chiral compounds which exclusively relied on noble-metal catalysis. Herein, a facile access to axially chiral N-heterocycles enabled by chiral Brønsted acid-catalyzed 5-endo-dig cyclization of ynamides is disclosed, which represents the first metal-free protocol for the construction of axially chiral compounds from ynamides. This method allows the practical and atom-economical synthesis of valuable N-arylindoles in excellent yields with generally excellent enantioselectivities. Moreover, organocatalysts and ligands based on such axially chiral N-arylindole skeletons are demonstrated to be applicable to asymmetric catalysis.

C-H Acidity and Arene Nucleophilicity as Orthogonal Control of Chemoselectivity in Dual C-H Bond Activation.

We discovered a cooperative gold/silver catalysis mechanism in the oxidative cross-coupling reaction between 1,2,4,5-tetrafluorobenzene and N-TIPS-indole, using DFT calculations. A silver(I)-catalyzed CMD mechanism is responsible for the C-H activation of 1,2,4,5-tetrafluorobenzene, and C-H acidity determines the chemoselectivity. A gold(III)-catalyzed SE2Ar mechanism is responsible for the C3-H activation of N-TIPS-indole, and arene nucleophilicity determines the chemo- and regioselectivity. The orthogonal chemoselectivity control provides a mechanistic guide for dual C-H activation reactions.