Study of the Reactivity of N-Trifluoromethyl Carbamoyl Fluorides as Electrophiles and Radical Precursors in the Synthesis of N-Trifluoromethylamides via Dual Ni/Photoredox Catalysis

• Grant number: 23/12577-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: January 01, 2024
• End date: November 30, 2026
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Márcio Weber Paixão
• Grantee: Lucas Valentin Bosi Loss Pugnal
• Host Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

Organic compounds containing amide moieties in their structures are widely distributed in the pharmaceutical, agrochemical, and materials industries. Given their significance, various research groups are seeking to develop new methodologies for the synthesis and modification of this class of compounds. Among the modification methodologies, those capable of producing fluorinated analogs stand out, especially in the context of pharmaceutical chemistry. This is due to the significant impact of the presence of fluorine atoms in organic compounds, which can drastically alter their physicochemical properties. These alterations can result, for example, in increased metabolic stability, membrane permeability, and bioavailability, all of which are fundamental characteristics for the development of new drugs. In this context, significant advances have been made in the synthesis of N-trifluoromethyl amides. Methodologies involving the electrophilic trifluoromethylation of amides, carboxyamination of nucleophilic equivalents, and the formation of amide bonds between N-CF3 amines and carbonyl compounds have already been described in the literature. However, the development of methodologies focused on late-stage modifications, as well as the development of radical approaches, has not yet been reported. In this context, our research group proposes in this project the development of dual Ni/photoredox methodologies for the synthesis of N-trifluoromethyl amides using N-trifluoromethyl carbamoyl fluorides as organic electrophiles, as well as radical precursors.