# Synthesis and meta-Amination of Pyridines via Multicomponent Cascade Reaction

## TL;DR

This paper introduces a new green method to synthesize 3-aminopyridines using a cascade reaction, which can be adapted to make various substituted pyridines.

## Contribution

A novel multicomponent cascade synthesis of 3-aminopyridines via Zincke aminolysis with ammonia is presented.

## Key findings

- The method shows broad scope with over 20 examples and good functional group tolerance.
- It allows scalable synthesis in both batch and flow procedures.
- The approach enables the production of 3-halo, 3-hydroxy, and 3-thiopyridines through peripheral editing.

## Abstract

We report a green, multicomponent cascade synthesis of
3-aminopyridines via [1,3′-bipyridin]-1-ium
intermediates undergoing
Zincke aminolysis with ammonia supported by experimental evidence
and DFT calculations. The method offers broad scope (>20 examples),
good functional group tolerance, and scalability in batch and flow
procedures. Synthetic utility is demonstrated through conversion into
3-halo, 3-hydroxy, and 3-thiopyridines, expanding the access to meta-substituted pyridines through peripheral editing of
the unprotected amino group.