Enantioselective Synthesis of Thioamides via dual Nickel/Photoredox Catalyzed Functionalization of Isothiocyanates

• Grant number: 25/15435-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: November 01, 2025
• End date: October 31, 2026
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Márcio Weber Paixão
• Grantee: Lucas Valentin Bosi Loss Pugnal
• Supervisor: Burkhard Koenig
• Host Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Institution abroad: University of Regensburg, Germany
• Associated to the scholarship: 23/12577-2 - 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, BP.DR

Abstract

Thioamides are ubiquitous motifs in natural products and bioactive compounds and are widely employed as amide bioisosteres. Although they show great similarity with oxoamides, the substitution of oxygen by sulfur results in significant changes in physicochemical properties and biological behavior. Due to their relevance, a wide range of methodologies has been developed over the years to enable efficient thioamide synthesis. Among the most established strategies is the use of commercially available thionating agents to promote amide deoxygenation; nucleophilic substitution with thiocarboxylic derivatives or multicomponent reactions, such as the classical Willgerodt-Kindler transformation. More recently, visible-light photoredox catalysis has emerged as a powerful and sustainable platform for the synthesis of thioamide-containing compounds under mild conditions. Despite recent advances, all reported methodologies continue to furnish racemic mixtures, revealing a critical unmet need for the development of asymmetric strategies. In view of the synthetic and biological significance of chiral thioamide motifs, this project aims to develop a novel enantioselective platform for thioamide synthesis, leveraging the synergistic merger of visible-light photoredox and nickel catalysis. By integrating the sustainability of visible-light activation with the stereochemical control afforded by chiral transition-metal complexes, this approach seeks to expand the current repertoire of catalytic methods for the asymmetric construction of structurally diverse sulfur-containing scaffolds. (AU)