Synthesis of N-Arylcytisine Derivatives Using the Copper-Catalyzed Chan-Lam Coupling

J Nat Prod. 2021 Jul 23;84(7):1985-1992. doi: 10.1021/acs.jnatprod.1c00275. Epub 2021 Jul 2.

Abstract

N-Arylcytisine derivatives are quite rare. We report here a practical methodology to obtain these compounds. Using the copper-catalyzed Chan-Lam coupling, we synthesized new N-arylcytisine derivatives at room temperature, in air and using inexpensive phenylboronic acids. Cytisine and 3,5-dihalocytisines can act as substrates, and among the products, the p-Br-derivative 2r was used as a substrate to obtain biaryl derivatives under Pd-coupling conditions; ester 2j was converted into its acid and amide derivatives using classical carbodiimide conditions. This shows that the Chan-Lam cross-coupling reaction can be included as a versatile synthetic tool in the derivatization of natural products.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemical synthesis*
  • Amides / chemical synthesis*
  • Azocines / chemical synthesis
  • Catalysis
  • Copper / chemistry*
  • Molecular Structure
  • Quinolizines / chemical synthesis

Substances

  • Alkaloids
  • Amides
  • Azocines
  • Quinolizines
  • cytisine
  • Copper