Enatioselective Synthesis of Tetrahydrocarbazoles via Chiral Phosphoric Acid Promoted Domino Friedel–Crafts‐type Reaction of Indole‐3‐butanal with Indoles

Abstract

By employing a chiral phosphoric acid as a catalyst, enantioselective domino Friedel–Crafts‐type reaction of indole‐3‐butanal with indoles was realized. This transformation allowed for the synthesis of a wide variety of enantioenriched 1‐indolyl‐tetrahydrocarbazoles with good yields (up to 99%) in moderate enantioselectivities (up to 81% ee).

An overview of the applications of chiral phosphoric acid organocatalysts in enantioselective additions to CO and CN bonds

“…A few years later, Xiaomei Zhang extended the scope of the reaction, this time performed in dichloroethane at −30 °C (instead of using dichloromethane at −50 °C), using also chiral phosphoric acid ( R )- BPA2 catalyst, obtaining products 402 in good yields and enantioselectivities (33–99%, 40–81% ee). 316…”

“…A few years later, Xiaomei Zhang extended the scope of the reaction, this time performed in dichloroethane at −30 °C (instead of using dichloromethane at −50 °C), using also chiral phosphoric acid (R)-BPA2 catalyst, obtaining products 402 in good yields and enantioselectivities (33-99%, 40-81% ee). 316 The scope limitations for Friedel-Crafts reactions with carbonyl compounds are clear since they are most likely to give subsequent eliminations of the formed alcohol, losing the stereochemical induction obtained during the process. However, some aldehydes and ketones that minimize the elimination step have been explored by several authors.…”

Metal-Free C–H Functionalization and Aromatization Sequence for the Synthesis of 1-(Indol-3-yl)carbazoles and Total Synthesis of 7-Bromo-1-(6-bromo-1H-indol-3-yl)-9H-carbazole

“…We envision that the C–H functionalization of tetrahydrocarbazoles at the 1-position using mild oxidizing reagents followed by aromatization will afford the required 1-substituted carbazoles. Moreover, this approach will provide 1-substituted tetrahydrocarbazoles and 1-substituted carbazoles where both of the scaffolds are biologically potent . Tetrahydrocarbazoles can be activated via thionium or peroxo- or chloroindolenine intermediates .…”