Product Selectivity Control in the Brønsted Acid-Mediated Reactions with 2-Alkynylanilines

Area of Science:

• Organic Chemistry
• Catalysis
• Heterocyclic Chemistry

Background:

• Metal-catalyzed reactions of 2-alkynylanilines are established for synthesizing heterocyclic derivatives.
• There is a need for alternative, metal-free synthetic methodologies.

Purpose of the Study:

• To demonstrate the advantages of Brønsted acid-catalyzed/mediated reactions of 2-alkynylanilines under metal-free conditions.
• To investigate factors influencing product selectivity and explore diverse synthetic pathways.

Main Methods:

• Exploration of Brønsted acid-catalyzed/mediated reactions using 2-alkynylanilines.
• Systematic variation of reaction conditions to control chemo- and regioselectivity.
• Density Functional Theory (DFT) calculations to understand selectivity origins.

Main Results:

• Successful demonstration of metal-free synthesis of valuable heterocyclic derivatives from 2-alkynylanilines.
• Identification of reaction conditions that direct pathways towards diverse product formation.
• Explanation of chemo- and regioselectivity switching through DFT analysis.

Conclusions:

• Brønsted acid catalysis offers a practical and metal-free alternative for 2-alkynylaniline transformations.
• Tunable reaction conditions enable precise control over product selectivity and diversity.
• DFT calculations provide mechanistic insights into the observed selectivity.