Exploring New Reactivities Through Titanium Photoredox Catalysis

• Grant number: 24/21114-9
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: August 01, 2025
• End date: July 31, 2030
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: José Tiago Menezes Correia
• Grantee: José Tiago Menezes Correia
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Until my appointment, the Institute of Chemistry at USP had three research groups active in the field of Organic Synthesis: the group of Prof. Bruno Paz, dedicated to the study of Asymmetric Catalysis; the group of Prof. Alcindo dos Santos, focused on the Synthesis of Sulfur, Selenium, and Tellurium Compounds; and the group of Prof. Leandro Helguera, oriented toward Sustainability in Molecular Construction. However, none of these groups is exclusively dedicated to the Development of Photocatalytic Strategies (visible light) for the Functionalization of Organic Molecules.Given this scenario, this request for support aims to obtain the necessary resources to consolidate my newly established research group, PHOTOSYN (Laboratory of Photocatalysis and Organic Synthesis), whose main objective is to explore the combination of titanium redox catalysis, N-heterocyclic carbene (NHC) redox organocatalysis, and photocatalysis, with the goal of developing innovative and sustainable synthetic methodologies. The proposal is divided into two subprojects:The first subproject will focus on the development of photocatalytic processes for the opening and functionalization of four classes of strained heterocycles: epoxides, oxetanes, aziridines, and azetidines. Initially, to validate the proof of concept and introduce sustainable innovations, the reported protocols for the photocatalytic opening of epoxides will be revisited. The main proposed modification is the replacement of the commonly used Hantzsch ester with a benzothiazoline. This change aims to ensure that the byproduct generated is more easily recycled or reused, while also eliminating the need for co-catalysts and other additives.To test the potential of the new protocol, the opening of other strained heterocycles, particularly those derived from terpenes, isatin, and pharmaceuticals, will be investigated, as well as cascade cyclization processes.Following the validation of the proof of concept, two tricatalytic strategies will be explored, adding greater complexity and innovation to the proposal:1) Fluoroalkylation of Strained Heterocycles: Using benzothiazolines as precursors for fluoroalkyl radicals, this strategy will require the incorporation of a copper salt as a co-catalyst, responsible for coupling the generated radical fragments. Once optimized, this protocol will enable the synthesis of alcohols and amines containing tertiary and quaternary fluoroalkylated centers, with a regiochemistry opposite to that traditionally reported in the literature.2) Opening and Coupling of Strained Heterocycles to Aldehydes: This methodology will combine titanium photo-redox catalysis with N-heterocyclic carbene (NHC) organocatalysis. The Breslow intermediate, formed from the reaction of the aldehyde with the NHC catalyst, will act simultaneously as a reducing agent (quencher) and a precursor for a ketyl radical, enabling access to tertiary and quaternary acylated centers. Both protocols will also be applied to the functionalization of terpenoid, isatin-based, and pharmaceutical derivatives.The second subproject will focus on the deoxygenation and deoxy-functionalization of alcohols using titanium photo-redox catalysis. Based on mechanistic principles similar to those described for the opening of strained heterocycles, the previously developed protocols will be adapted to this new system. The main advantage of these strategies is the promotion of deoxygenation, fluoroalkylation, and acylation of alcohols without the need for pre-activation of the hydroxyl group, a significant challenge in organic synthesis.Additionally, cascade reactions triggered by the deoxygenation of alcohols will be investigated, aiming to obtain molecules with greater structural complexity. These methodologies will provide valuable alternatives for retrosynthetic rationalization, contributing to the development of more efficient and sustainable processes. (AU)