Enantioselective synthesis of N-alkylindoles enabled by nickel-catalyzed C-C coupling

Abstract

Enantioenriched N-alkylindole compounds, in which nitrogen is bound to a stereogenic sp3 carbon, are an important entity of target molecules in the fields of biological, medicinal, and organic chemistry. Despite considerable efforts aimed at inventing methods for stereoselective indole functionalization, straightforward access to a diverse range of chiral N-alkylindoles in an intermolecular catalytic fashion from readily available indole substrates remains an ongoing challenge. In sharp contrast to existing C–N bond-forming strategies, here, we describe a modular nickel-catalyzed C–C coupling protocol that couples a broad array of N-indolyl-substituted alkenes with aryl/alkenyl/alkynyl bromides to produce chiral N-alkylindole adducts in single regioisomeric form, in up to 91% yield and 97% ee. The process is amenable to proceed under mild conditions and exhibit broad scope and high functional group compatibility. Utility is highlighted through late-stage functionalization of natural products and drug molecules, preparation of chiral building blocks.

Helicoselective Synthesis of Indolohelicenoids through Organocatalytic Central‐to‐Helical Chirality Conversion

“…Yan and co‐workers developed chiral bifunctional amide catalyzed intramolecular cyclization of 1‐alkynylnaphthalen‐2‐ol derivatives for the enantioselective synthesis of helicenes via vinylidene ortho ‐quinone methide intermediates [17] . Recently, Li and Yang independently reported a stepwise method for preparing enantiomerically pure quinohelicenes by construction of the terminal pyridine ring [18a,b] . Additionally, Wang reported a peptide‐mimic phosphonium salt catalyzed dynamic kinetic resolution and oxidative aromatization method for synthesizing phosphorus‐containing chiral helicenes [18c] …”

Helicoselective Synthesis of Indolohelicenoids through Organocatalytic Central‐to‐Helical Chirality Conversion

“…Yan and co‐workers developed chiral bifunctional amide catalyzed intramolecular cyclization of 1‐alkynylnaphthalen‐2‐ol derivatives for the enantioselective synthesis of helicenes via vinylidene ortho ‐quinone methide intermediates [17] . Recently, Li and Yang independently reported a stepwise method for preparing enantiomerically pure quinohelicenes by construction of the terminal pyridine ring [18a,b] . Additionally, Wang reported a peptide‐mimic phosphonium salt catalyzed dynamic kinetic resolution and oxidative aromatization method for synthesizing phosphorus‐containing chiral helicenes [18c] …”

Boosting Photocatalytic Hydrogen Evolution Through Local Charge Polarization in Chemically Bonded Single‐Molecule Junctions Between Ketone Molecules and Covalent Organic Frameworks

“…[ 3 ] Various approaches, including donor‐acceptor (D–A) effects and edge‐capping, have been demonstrated to effectively enhance π‐system polarization, thereby improving the photocatalytic performance of the materials. [ 4 ] However, limited strategies are available to precisely control the polarization structure within organic semiconductors and further enhance their photocatalytic activity.…”

“…In addition, edge‐capping modifications and mechanical/chemical preparation of COF nanosheets have been developed. [ 4a,8 ] Though these modification strategies have achieved some success, they still face challenges, such as unclear modification sites and potential damage to the crystallinity of COFs. Therefore, it is crucial and urgent to establish new strategies that can precisely enhance the polarization of COFs for various photocatalytic applications.…”