Construction of Axially Chiral Styrene-Type Allylamines via Chiral Phosphoric Acid-Catalyzed Asymmetric Reductive Amination

The first enantioselective synthesis of axially chiral styrene-type allylamines was achieved through chiral phosphoric acid mediated atroposelective reductive amination of 1-enal substituted 2-naphthols. This protocol features a broad substrate scope,...

Enantioselective “Clip-Cycle” Synthesis of Di-, Tri- and Spiro- Substituted Tetrahydropyrans

ω-Unsaturated alcohols were “clipped” via alkene metathesis to a thioester activating group, which was followed by a chiral phosphoric acid catalyzed intramolecular oxa-Michael cyclization to yield tetrahydropyrans and spiro-tetrahydropyrans with...

Metal-free, visible-light induced enantioselective three-component dicarbofunctionalization and oxytrifluoromethylation of enamines via chiral phosphoric acid catalysis

Using diverse carbon-centered radical precursors and electron-rich (hetero)aromatics and alcohols as nucleophiles, a visible-light driven chiral phosphoric acid (CPA) catalyzed asymmetric intermolecular, three-component radical-initiated dicarbofunctionalization and oxytrifluoromethylation of enamines was...

Enantioselective construction of a congested quaternary stereogenic center in isoindolinones bearing three aryl groups via an organocatalytic formal Betti reaction

An efficient enantioselective formal Betti reaction between phenols and diaryl ketimines generated in situ from isoindolinone alcohols is described. In a reaction catalyzed by a chiral phosphoric acid, a broad...

Molecular Insights on Chirality Transfer from Double Axially Chiral Phosphoric Acid in a Synergistic Enantioselective Intramolecular Amination

In the most general practice of asymmetric catalysis, a chiral catalyst, typically bearing a center or an axis of chirality, is employed as the chiral source for imparting enantiocontrol over...

Chiral Phosphoric Acid Catalyzed Regio- and Enantioselective Reactions of Functionalized Propargylic Alcohols

Propargylic alcohols have been known as useful substrates in a wide range of asymmetric reactions. Particularly, the chiral phosphoric acids (CPAs) catalyzed reactions of functionalized propargylic alcohols opened a robust...

Organocatalytic Discrimination of Non-Directing Aryl and Heteroaryl Groups: Enantioselective Synthesis of Bioactive Indole-Containing Triarylmethanes

Despite the enormous developments of asymmetric catalysis, the basis for asymmetric induction is largely limited to spatial interaction between substrate and catalyst. Consequently, asymmetric discrimination between two sterically similar groups remains a challenge. This is particularly formidable for enantiodifferentiation between aryl and heteroaryl groups without a directing group or electronic manipulation. Here we address this challenge by a robust organocatalytic system leading to excellent enantioselection between aryl and heteroaryl groups. With the versatile 2-indole imine methide as platform, an excellent combination of a superb chiral phosphoric acid and the optimal hydride source provided efficient access to a range of highly enantioenriched indole-containing triarylmethanes. Control experiments and kinetic studies provided important insights into the mechanism. DFT calculations also indicated that, while hydrogen bonding is important for activation, the key interaction for discrimination of the two aryl groups is mainly π-π stacking. Preliminary biological studies also demonstrated the great potential of these triarylmethanes for anticancer and antiviral drug development.