# Reductive Transamination of Pyridinium Salts to N-Aryl Piperidines

## TL;DR

A new rhodium-catalyzed method converts pyridinium salts into N-aryl piperidines, useful in pharmaceuticals.

## Contribution

A novel reductive transamination method for synthesizing N-(hetero)aryl piperidines from pyridinium salts.

## Key findings

- The reaction involves a dihydropyridine intermediate formed via reduction with HCOOH.
- Hydrolysis and reductive amination with (hetero)aryl amines yield N-(hetero)aryl piperidines.
- This method expands the options for dearomatization and skeletal editing of heterocycles.

## Abstract

Saturated N-heterocycles are found in numerous bioactive
natural
products and are prevalent in pharmaceuticals and agrochemicals. While
there are many methods for their synthesis, each has its limitations,
such as scope and functional group tolerance. Herein, we describe
a rhodium-catalyzed transfer hydrogenation of pyridinium salts to
access N-(hetero)aryl piperidines. The reaction proceeds via a reductive
transamination process, involving the initial formation of a dihydropyridine
intermediate via reduction of the pyridinium ion with HCOOH, which
is intercepted by water and then hydrolyzed. Subsequent reductive
amination with an exogenous (hetero)aryl amine affords an N-(hetero)aryl
piperidine. This reductive transamination method thus allows for access
of N-(hetero)aryl piperidines from readily available pyridine derivatives,
expanding the toolbox of dearomatization and skeletal editing.