Cross-coupling of Indolizines with (Pseudo)halides and Grignard Reagents by Earth-abundant Transition Metal Catalysis

• Grant number: 24/19435-1
• Support Opportunities: Scholarships in Brazil - Master
• Start date: April 01, 2025
• End date: July 31, 2026
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Giuliano Cesar Clososki
• Grantee: Rafael Carvalhal do Nascimento
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 22/05327-7 - Exploring the medicinal chemical space of aromatics with highly selective synthetic tools, AP.R

Abstract

Indolizines are aromatic heterocyclic molecules composed of a five-membered pyrrolic ring fused to a six-membered pyridinic ring, with a nitrogen atom being shared by the two. These heterocycles have electron-deficient characteristics in their six-membered ring and electron-rich characteristics in their five-membered ring, so they can react both as nucleophiles and electrophiles. This class of compounds has interesting photophysical and electrochemical characteristics and has therefore been explored as photoresponsive materials and dyes. Cross-coupling reactions are widely used as a method of molecular functionalization because they are capable of forming carbon-carbon bonds and thus generating larger, more complex molecules with great pharmacological potential. There are many methodologies for cross-coupling reactions, such as the Sonogashira, Heck and Suzuki reactions. These reactions use rare transition metals as catalysts, especially palladium. Despite the effectiveness of palladium-catalyzed reactions, the high cost and toxicity of this metal reveal the demand for abundant transition metal catalysts such as nickel, copper, cobalt and iron. This project aims to develop new methodologies for using transition metals as catalysts in cross-coupling reactions between aromatic indolizines and (pseudo)halides and Grignard reagents.