# Employment of Two-Acid Promoter System in Pictet–Spengler Reaction: A Robust Two-Step Synthesis of Aza-Heterocycles

## TL;DR

This paper introduces a sustainable two-step method for making aza-heterocycles using a two-acid promoter system, which is efficient and produces high yields with minimal waste.

## Contribution

A novel two-acid promoter system using graphene oxide and Amberlyst 15 for the Pictet–Spengler reaction is introduced.

## Key findings

- The method achieves up to 92% yield without further purification.
- Promoters can be reused over multiple cycles while maintaining efficiency.
- The approach is tolerant to various functional groups and avoids interference between acids.

## Abstract

The growing demand for increasingly sustainable chemical
processes
continues to stimulate organic chemistry to develop highly efficient,
low-energy-consuming new reactions that require minimal effort to
isolate intermediates and produce reduced waste. In this context,
two-step reactions play an important role, and a good approach is
the two-step synthesis, in which reagents and catalysts or promoters
are introduced sequentially. Among these, the Pictet–Spengler-type
cyclization (PS) is a powerful stepwise strategy for the synthesis
of heterocyclic compounds. This article presents a novel and environmentally
friendly two-step strategy for the Pictet–Spengler reaction,
employing graphene oxide and Amberlyst 15 as acid promoters that yields
a diverse product library (up to 92% yield) without the need for further
purification. Both promoters can be reused over multiple reaction
cycles, maintaining high efficiency. The methodology demonstrates
broad functional group tolerance and provides a sustainable route
to various tetrahydro-β-carbolines (THβCs), including
biologically relevant compounds, and, above all, avoids negative interference
between the two acidic promoters.