Enantioselective Synthesis of N-Alkylindoles Enabled by Nickel-Catalyzed Modular, Unified C-C Coupling

12 April 2022, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


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, unified, 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.


Chiral N-alkylindole
modular synthesis
C-C coupling
Nickel catalysis
Enantioselective hydrocarbonation

Supplementary materials

Supplementary Information
SI for Enantioselective Synthesis of N-Alkylindoles Enabled by Nickel-Catalyzed Modular, Unified C-C Coupling, including experiment details, NMR spectra, HPLC spectra.


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