C-H Functionalization of Aliphatic and Aromatic Heterocycles by Visible Light Photoredox Catalysis

• Grant number: 18/20956-5
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: December 20, 2018
• End date: December 12, 2019
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Arlene Gonçalves Corrêa
• Grantee: Marília Simão dos Santos
• Supervisor: Burkhard Konig
• 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: 17/03120-8 - Photochemical reactions applied to the synthesis of substituted indoles via radical insertion reactions to isonitriles, BP.PD

Abstract

Visible light represents a safe, efficient and sustainable source of energy. Over the last decade, a major focus in visible light-mediated catalysis was on the access of highly reactive open shell species that are otherwise difficult or impossible to obtain by traditional chemical catalysis. Progress in the understanding of mechanisms and the properties of the photogenerated reactive intermediates has enabled photocatalytic variants for a wide number of traditional reactions, for instance, heterocyclic synthesis and functionalization. The direct transformation of C-H bonds render synthetic routes more straightforward and atom-economical and allow the site-selective modification of C-H bonds in such compounds bearing multiple functional groups. Additionally, regarding the prevalence of C-H bonds in many organic molecules, the ability to transform in a controlled manner a specific C-H bond gives us the opportunity to explore this strategy in many directions for the late-stage modification of complex molecules. This proposal aims towards the C-H functionalization of aliphatic and aromatic heterocycles via catalysis photoredox. We intend to study reaction conditions of the radical generation through the best combination of catalysts and substrates, as well to study the selectivity of the functionalization. Inspired by literature reports, the catalytic generation of chlorine radicals from mononuclear Ni (III) complexes under visible light radiation were employed for C(sp3)H arylation of cyclic and acyclic ethers, we envisioned to apply this principle to a metallaphotoredox-catalyzed C(sp3) C(sp3) bond formation. For that, selected alkyl chlorides could be the source of a chlorine radical able to perform the hydrogen atom transfer of aliphatic heterocycles. The heterocycle radical generated could finally couple with the alkyl partner mediated by nickel complex.In a second approach, the reactivity of electron poor heteroarenes will be tuned may by adding one electron resulting in a radical anion, which will be highly reactive for an electrophilic substitution reaction. Some different kind of eletrophiles will be tested such as fluorine, deuterium and electrophilic chlorine. The results of this research may enable the direct functionalization of complex structures, such as drugs and other biologically active compounds applying a late-stage functionalization concept in an unprecedented easy way.

Scientific publications

(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)

SANTOS, MARILIA S.; CYBULARCZYK-CECOTKA, MARTYNA; KOENIG, BURKHARD; GIEDYK, MACIEJ. Minisci C-H Alkylation of Heteroarenes Enabled by Dual Photoredox/Bromide Catalysis in Micellar Solutions. CHEMISTRY-A EUROPEAN JOURNAL, v. 26, n. 66, p. 15323-15329, NOV 26 2020. (18/20956-5)

SANTOS, MARILIA S.; CORREA, ARLENE G.; PAIXAO, MARCIO W.; KOENIG, BURKHARD. C(sp(3))-C(sp(3)) Cross-Coupling of Alkyl Bromides and Ethers Mediated by Metal and Visible Light Photoredox Catalysis. ADVANCED SYNTHESIS & CATALYSIS, v. 362, n. 12, APR 2020. (14/50249-8, 18/20956-5, 17/03120-8)