Work

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

Year: 2026

Type: article

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.

Source: ACS Omega

DOI: 10.1021/acsomega.5c11423