# Regioselective Synthesis of 1,2,3-Trisubstituted Pyrroles via Addition–Cyclization of Crotonate-Derived Sulfonium Salts with a Carboxylic Acid and an Amine

## TL;DR

A new method for making 1,2,3-trisubstituted pyrroles is developed using a one-pot reaction that is efficient and uses common materials.

## Contribution

The paper introduces a general and efficient one-pot method for synthesizing 1,2,3-trisubstituted pyrroles via addition-cyclization.

## Key findings

- The method constructs the first C–C bond through regioselective addition of crotonate sulfonium salts to activated carboxylic acids.
- The reaction forms two C–N bonds in a single step with a primary amine.
- The transformation is versatile, scalable, and proceeds rapidly at room temperature.

## Abstract

A sequential addition-cyclization
reaction between carboxylic
acids, crotonate sulfonium salts, and amines has been developed for
the construction of 1,2,3-trisubstituted pyrroles. The reaction involves
regioselective addition of crotonate sulfonium salts directly to in situ-activated carboxylic acids to construct the first
C–C bond, followed by cyclization with a primary amine to create
the two C–N bonds in one pot. The new transformation appears
to have a general substrate scope, uses readily accessible starting
materials, and proceeds rapidly at room temperature. The reaction
is versatile and scalable, making it suitable for applications in
process and medicinal chemistry.