Enantioselective synthesis of 2-indolyl methanamine derivatives through disulfonimide-catalyzed Friedel–Crafts C2-alkylation of 3-substituted indoles with imines

Abstract

An asymmetric Friedel-Crafts C2-alkylation between 3-substituted indoles and imines catalyzed by chiral BINOL-derived disulfonimides (DSIs) has been developed. This reaction tolerated a wide range of 3-substituted indoles and imines, affording...

Enantioselective Synthesis of Diarylmethylamines through the Aza-Friedel–Crafts Reaction of 1,3,5-Trialkoxy Benzenes and N-Sulfonyl Aldimines Catalyzed by BINOL-Derived Disulfonimides

“…As a strong Brønsted acid, DSI is assumed to interact with the nitrogen of aldimine 3 by single hydrogen bonding, leading to an efficient attack from the Si face of the imine and thus giving S -configuration products. It is different from the transition state models in the BINOL-phosphoric acids , and our previous work, in which dual hydrogen bonding must be formed in the mechanism.…”

“…Developing practical and highly enantioselective synthesis of structurally diverse diarylmethylamines, under mild conditions, still remains desirable. Recently, in our previous work, Friedel–Crafts C2-alkylation of 3-substituted indoles with imines has been realized with excellent enantioselectivities by 1,1′-bi-2,2′-naphthol (BINOL)-derived chiral disulfonimides (DSIs) . Considering that DSIs are more acidic than CPAs, we envisioned that DSIs might also be suitable for aza-Friedel–Crafts reactions with less active substrates.…”

Recent Advancements in Typical Friedel–Crafts Alkylation Reactions Focused on Targeting Arene Nucleophiles

“…68 Since around 2000, the design and synthesis of chiral catalysts that can control the enantiodiscrimination of the asymmetric FC reactions using arenes or heteroarenes in aromatic electrophilic substitution reactions has attracted great interest. [69][70][71][72][73][74][75] The FC alkylation reaction of 2-indolylmethanes with arene nucleophiles has been mainly studied in the development of new methodologies to access unsymmetrical bisindolylmethanes 76 and especially triarylmeth-ane molecules containing the indole moiety. 77 In 2014, Han and co-workers reported the first asymmetric version for the synthesis of 2,3′-bisindolylmethanes by treating indoles with 2-indolylmethanols by using chiral phosphoramide 4.…”

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

“…A broad substrate scope was investigated by varying substituents on both substrates. A transition state involving dual noncovalent interactions between the catalyst and substrates directed the face-selective addition of the π-nucleophile to the electrophilic carbon of the imine (see transition state 130 , Scheme 33 ) [ 63 ].…”