Regioselective fluorination of N-heterocycles using electrosynthesis and continuous flow conditions

• Grant number: 22/00074-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2022
• End date: April 30, 2024
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Kleber Thiago de Oliveira
• Grantee: Guilherme Ariel Machado Martins
• Host Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

In this post-doctoral project, we aim to advance in the syntheses and studies on electrosynthetic fluorination reactions, applying these methodological approaches in the preparation of API's and compounds with potential biological activities, such as derivatives of oxazepines, indoles, pyrazines, pyrroles, imidazoles, among others, using electrosynthesis reactors coupled to a continuous flow regime (ElectroFlow Chemistry). This project is divided into 2 subprojects. In the first (subproject 1) we will apply the continuous flow electrosynthesis system for the selective fluorination of C(sp2) in nitrogen heterocycles using electric current as a redox reagent. As a fluoride source we propose the catalytic use of Cobalt salts or Silver salts (in their maximum oxidized states), which will be regenerated in the electrochemical reaction medium. We also emphasize the interest in using this methodology for the synthesis of the antiviral favipiravir, in order to solve the biggest synthetic problem of this important API, which is the fluorination step. In the second (subproject 2) we will invest efforts in the synthesis of fluoro-oxazepine derivatives using hypervalent iodine reagents, obtained by anodic oxidation. In this case, we propose the use of continuous flow chemistry coupled to an electrochemical reactor (ElectroFlow Chemistry) for the formation of a fluorinating species of hypervalent iodine (difluoroiodine-arene) in situ, which is a metal-free methodology.In general, this project aims to use the knowledge in continuous flow chemistry already consolidated in the team of Prof. Kleber and also incorporate the knowledge of Organic Electrosynthesis of this candidate for the scholarship obtained during his sandwich doctorate (2017), together with the group of Prof. Dr. Thomas Wirth, at Cardiff University - Cardiff - Wales - UK. We emphasize that this project is in line with the scientific research under development in the group of Prof. Dr. Timothy Noël, from the University of Amsterdam (UvA - Amsterdam - The Netherlands), connecting our team's interests and sealing the real perspective of developing part of this research at the University of Amsterdam (BEPE internship application perspective). (AU)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PEREIRA, VINICIUS R. D.; BEZERRA, MARCO A. M.; GOMEZ, MAURO R. B. P.; MARTINS, GUILHERME M.; DA SILVA, ADILSON D.; DE OLIVEIRA, KLEBER T.; DE SOUZA, RODRIGO O. M. A.; AMARANTE, GIOVANNI W.. Concise two-step chemical synthesis of molnupiravir. RSC ADVANCES, v. 12, n. 46, p. 5-pg., 2022-10-17. (22/00074-3, 19/27176-8, 20/06874-6)

SANTOS, WILLIAM A. B.; DE CASTRO, PEDRO P.; XAVIER, FERNANDO R.; BRAGA, ANTONIO L.; MARTINS, GUILHERME M.; MENDES, SAMUEL R.. Electrosynthesis of Flavanones via oxa-Michael Addition Using Sacrificial Electrodes. SYNTHESIS-STUTTGART, v. N/A, p. 8-pg., 2023-03-22. (22/00074-3, 21/13924-2)

DE CASTRO, PEDRO P.; MARTINS, GUILHERME M.; GOMES, RONEWALBER B.; SIMOSO, GUILHERME B.; AMARANTE, GIOVANNI W.; BROCKSOM, TIMOTHY J.; DE OLIVEIRA, KLEBER T.. Electrochemical reduction of 5-benzylidene thiazolidine-2,4-diones: a greener approach to the preparation of glitazone APIs. CHEMICAL COMMUNICATIONS, v. 59, n. 61, p. 4-pg., 2023-07-05. (20/06874-6, 21/13924-2, 21/14446-7, 22/00074-3)

GUILHERME M. MARTINS; KLEBER T. DE OLIVEIRA. EMERGING TRENDS OF ORGANIC ELECTROSYNTHESIS IN BRAZIL. Química Nova, v. 48, n. 1, 2024-06-07. (23/04020-8, 22/00074-3)