Atroposelective Synthesis of 2‐Arylindoles via Chiral Phosphoric Acid‐Catalyzed Direct Amination of Indoles^†

Abstract

Comprehensive SummaryIndole‐based atropisomers are a very important class of axially chiral compounds. However, the atroposelective synthesis of axially chiral 2‐arylindole remains largely unexplored. In this study, we report the successful synthesis of atropisomeric 2‐arylindoles using direct amination of indoles with p‐quinonediimines in the presence of chiral phosphoric acid as a catalyst. Quinonediimine acts as an aminating reagent through formal polarity inversion of imine. The malonate group on the 2‐aryl of 2‐indoles was found to be essential for high enantioselectivity of the products. This could be due to the additional interaction between the ester group and the catalyst, as well as the intramolecular hydrogen bonding. Our findings provide a new strategy for the asymmetric construction of 2‐arylindole atropisomers.This article is protected by copyright. All rights reserved.

Catalytic Asymmetric Diastereodivergent Synthesis of 2-Alkenylindoles Bearing both Axial and Central Chirality

“…Axially chiral indole-based scaffolds, a class of unique axially chiral skeletons, − are widely found in natural products, − pharmaceutically relevant molecules, − and chiral catalysts. − Therefore, catalytic asymmetric construction of axially chiral indole-based scaffolds has become an emerging field. , As shown in Scheme a, various elegant strategies have been developed for the enantioselective construction of axially chiral (hetero)­arylindoles, such as five-six-membered axially chiral arylindoles ,− and five-five-membered axially chiral (hetero)­arylindoles. ,,− However, in sharp contrast, axially chiral alkenylindoles, more challenging axially chiral...…”

Recent Advances in the Domino Annulation Reaction of Quinone Imines

“…Quinones and their derivatives have attracted increasing attention in organic synthesis because of their wide applications in medicine, pesticides, dyes, energy storage, and various fine chemical products [ 27 , 28 , 29 , 30 , 31 ]. Quinone imines, as highly reactive electrophiles containing multiple active sites, can be used in aromatic functionalization, amination, and cyclization reactions, providing efficient tools and methods for synthetic chemistry [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. In particular, annulation reactions involving quinone imines have been widely used to efficiently construct heterocycles, especially nitrogen- and oxygen-containing fused aromatic rings, providing an efficient method for the synthesis of complex molecules.…”