Fully and differently arylated pyridines (pictured) are challenging targets in organic synthesis. There are only a few synthetic methods including successive Suzuki-Miyaura cross-coupling reactions or ring transformation of five-membered heterocyclic compounds. However, these methods require at least seven-step reactions and sometimes suffer from control of the regioselectivity.

Nagatoshi Nishiwaki, Kochi University of Technology, Japan, and colleagues have synthesized differently substituted pentaarylpyridines in only three steps:

1. Condensation of methylpyridine with benzonitrile forming β-pyridylenamine.
2. Aldol condensation of benzaldehyde with β-phenylacetophenone to form an enone.
3. Condensation of the enamine and the enone under microwave heating in the presence of FeCl₃ under air, in which FeCl₃ serves as both an acid catalyst and an oxidant for the intermediate.

This protocol facilitates the synthesis and molecular design of multiply arylated/alkylated pyridines by simple alteration of the starting materials with simple experimental manipulations. The team also synthesized polyarylated bipyridines and terpyridine using this method.

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• Three Step Synthesis of Fully and Differently Arylated Pyridines,
  Mao Arita, Soichi Yokoyama, Haruyasu Asahara, Nagatoshi Nishiwaki,
  Europ. J. Org. Chem. 2019.
  https://doi.org/10.1002/ejoc.201901663