Development of a photocatalyzed Pd-Heck reaction for the synthesis of C3-alkylated coumarins

• Grant number: 23/05757-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2023
• End date: February 28, 2025
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Marco Antonio Barbosa Ferreira
• Grantee: Camila Pelizzer de Oliveira
• Host Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

Methodologies involving the use of Pd complexes combined with the use of visible light have reached a unique range of applicability compared to other metals, leading to the formation of radical species in pairs of the type [Pd(I) + *R]. The great appeal of this methodology has been the possibility in the use of alkyl partners of low reactivity, when compared to conventional oxidative addition. Protocols involving alkyl halides have been the most used, generating alkyl radicals in coupling processes that can go through cross couplings reaction paths. In this context, although alkylative Heck reactions have advanced from the use of these methodologies for styrene derivatives and electron-rich double bonds, the application in activated doubles with electron-withdrawing substituents, and 1,2-disubstituted double bonds has not been fully developed. The general objectives of this work are to explore the chemistry of Pd-photocatalyzed reactions aiming at obtaining C3-alkylated coumarin derivatives from alkyl chlorides or bromides. This methodology will expand the synthetic potential of Pd/visible light catalyzed C3-alkyl functionalization in coumarins using alkyl halides, offering a powerful synthetic photochemical alternative that are currently focused on use of carboxylic acids. As a tool for simultaneous reaction development and study of the reaction mechanism, we intend to apply multivariate linear regression (MLR) models using physicochemical molecular descriptors obtained computationally and/or experimentally.