Photocatalysis Applied to the Synthesis of N-heterocycles: New Strategies for Intercepting Radical Intermediates Generated in Processes Promoted by Visible-light-Tris (trimethylsilyl)silane Combination.

• Grant number: 17/10015-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2017
• End date: January 31, 2022
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Márcio Weber Paixão
• Grantee: José Tiago Menezes Correia
• Host Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Associated scholarship(s): 19/01560-6 - Nickel-catalyzed intermolecular dicarbofunctionalization of unactivated alkenes, employing CO2 and radical precursors, BE.EP.PD

Abstract

The development of sustainable synthetic strategies that rapidly achieve the synthesis of (new) molecules with pharmacological or technological interest is one of the biggest challenges in the contemporaneous organic synthesis. The use of light to promote chemical transformations consist in great appeal in this regard, since light is the cleanest source of energy, and the sunlight stands out as an endless source. In this context, photocatalysis and photoredox catalysis have been gaining more attention in organic synthesis labs over the years. Our proposal consists in the development of photochemical strategies based on a protocol recently reported by our group. In these strategies, we will apply tris(trimethylsilyl)silane (TTMSS) and visible light irradiation to initiate the radical cascade process for the synthesis of a range of heterocyclic scaffolds. To this goals, two photochemical cyclization strategies promoted by TTMSS/visible light will be developed. In the first one, enamides derived from 2-iodo-aniline are going to be converted to functionalized amino-indolines and amino-oxindols through a radicalar cyclization reaction followed by oxidation of the radical intermediate and finally the attack of a nucleophile. In the second one, enamines generated in-situ from aldehydes also derived from 2-iodo-aniline and a chiral amine organocatalyst will be subject to the same radical cyclization process and oxidation, in order to access chiral 3-carbonyl-indolines and 3-carbonyl-oxindols. Furthermore, the concept will be extended an addition-cyclization strategy with maleimides (process that may be considered as a formal [4+2] cycloaddition). From this cascade reaction, densely functionalized tetrahydroquinolines will be achieved in a one-pot way. Finally, our attention will be turned toward the development of a cascade protocol that involves a photoredox cyclization followed by a cross-coupling protocol catalyzed by Iridium and Nickel respectively. In this strategy, alkenes and alkynes derived from 2-iodo-aniline will be convert to benzylic oxindoles and indoles, correspondingly.All designed N-heterocyclic frameworks are of great interest, once they are in close relation to systems founded in alkaloids and drug structures. It's also worth to emphasizing that, photochemistry, photoredox catalysis, organocatalysis and nickel catalyzed reactions are hot-topics and of great interest of both academia and industries. However, they are still less explored by the Brazilian community.

Scientific publications

(15)

(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)

MATSUO, BIANCA T.; OLIVEIRA, PEDRO H. R.; CORREIA, JOSE TIAGO M.; PAIXAO, MARCIO W.. Carbamoylation of Azomethine Imines via Visible-Light Photoredox Catalysis. ORGANIC LETTERS, v. 23, n. 17, p. 6775-6779, SEP 3 2021. (17/10015-6, 14/50249-8)

MATSUO, BIANCA T.; CORREIA, JOSE TIAGO M.; PAIXAO, MARCIO W.. Visible-Light-Mediated alpha-Amino Alkylation of Azomethine Imines: An Approach to N-(beta-Aminoalkyl)pyrazolidinones. ORGANIC LETTERS, v. 22, n. 20, p. 7891-7896, OCT 16 2020. (14/50249-8, 15/17141-1, 18/12986-1, 17/10015-6)

DELGADO, JOSE A. C.; CORREIA, JOSE T. M.; PISSINATI, EMANUELE F.; PAIXAO, MARCIO W.. Biocompatible Photoinduced Alkylation of Dehydroalanine for the Synthesis of Unnatural alpha-Amino Acids. ORGANIC LETTERS, v. 23, n. 13, p. 5251-5255, JUL 2 2021. (19/01973-9, 14/50249-8, 17/10015-6)

CORREIA, JOSE TIAGO M.; DA SILVA, GUSTAVO PIVA; KISUKURI, CAMILA M.; ANDRE, ELIAS; PIRES, BRUNO; CARNEIRO, PABLO S.; PAIXAO, MARCIO W.. Metal-Free Photoinduced Hydroalkylation Cascade Enabled by an Electron-Donor-Acceptor Complex. Journal of Organic Chemistry, v. 85, n. 15, p. 9820-9834, AUG 7 2020. (14/50249-8, 15/17141-1, 18/12986-1, 17/10015-6)

VEGA, KIMBERLY BENEDETTI; DELGADO, JOSE ANTONIO CAMPOS; PUGNAL, LUCAS V. B. L.; KOENIG, BURKHARD; CORREIA, JOSE TIAGO MENEZES; PAIXAO, MARCIO WEBER. Divergent Functionalization of Styrenes via Radical/Polar Crossover with CO₂ and Sodium Sulfinates. CHEMISTRY-A EUROPEAN JOURNAL, v. 29, n. 19, p. 9-pg., 2023-02-28. (21/06099-5, 21/01354-7, 19/01560-6, 17/10015-6)

PUGNAL, LUCAS V. B. L.; VEGA, KIMBERLY B.; PISSINATI, EMANUELE F.; CORREIA, JOSE TIAGO M.; ZUKERMAN-SCHPECTOR, JULIO; MARTIN, RUBEN; PAIXAO, MARCIO W.. 1,2-Arylsulfonylation of Vinyl Ethers and Esters Enabled by Dual Ni Catalysis. CHEMCATCHEM, v. N/A, p. 6-pg., 2023-06-19. (21/06099-5, 19/01560-6, 20/09353-7, 22/04597-0, 17/10015-6, 21/01354-7)

SOUZA, WANDERSON C.; CORREIA, JOSE TIAGO M.; MATOS, PRISCILLA M.; KISUKURI, CAMILA M.; CARNEIRO, PABLO S.; PAIXAO, MARCIO W.. Organophotocatalytic Intramolecular Formal Enyne-Metathesis - An Alternative to Transition-Metal Catalysis. EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, v. 2022, n. 16, p. 5-pg., 2022-02-05. (21/06099-5, 17/10015-6, 14/50249-8, 20/00556-2)

MENEZES CORREIA, JOSE TIAGO; DA SILVA, GUSTAVO PIVA; ANDRE, ELIAS; PAIXAO, MARCIO WEBER. Photoredox Decarboxylative Alkylation/(2+2+1) Cycloaddition of 1,7-Enynes: A Cascade Approach Towards Polycyclic Heterocycles Using N-(Acyloxy)phthalimides as Radical Source. ADVANCED SYNTHESIS & CATALYSIS, v. 361, n. 24, p. 7-pg., 2019-08-26. (15/17141-1, 17/10015-6, 14/50249-8)

MENEZES CORREIA, JOSE TIAGO; DA SILVA, GUSTAVO PIVA; ANDRE, ELIAS; PAIXAO, MARCIO WEBER. Photoredox Decarboxylative Alkylation/(2+2+1) Cycloaddition of 1,7-Enynes: A Cascade Approach Towards Polycyclic Heterocycles Using N-(Acyloxy)phthalimides as Radical Source. ADVANCED SYNTHESIS & CATALYSIS, AUG 2019. (15/17141-1, 14/50249-8, 17/10015-6)

CORREIA, JOSE TIAGO M.; SANTOS, MARILIA S.; PISSINATI, EMANUELE F.; DA SILVA, GUSTAVO P.; PAIXAO, MARCIO W.. Recent Advances on Photoinduced Cascade Strategies for the Synthesis of N-Heterocycles. CHEMICAL RECORD, v. 21, n. 10, SI, JUL 2021. (17/10015-6, 14/50249-8, 17/03120-8)

CORREIA, JOSE TIAGO M.; FERNANDES, VITOR A.; MATSUO, BIANCA T.; DELGADO, JOSE A. C.; DE SOUZA, WANDERSON C.; PAIXAO, MARCIO WEBER. Photoinduced deaminative strategies: Katritzky salts as alkyl radical precursors. CHEMICAL COMMUNICATIONS, v. 56, n. 4, p. 503-514, JAN 14 2020. (14/50249-8, 19/01973-9, 15/17141-1, 17/10015-6)

DANTAS, JULIANA A.; CORREIA, JOSE TIAGO M.; PAIXAO, MARCIO W.; CORREA, ARLENE G.. Photochemistry of Carbonyl Compounds: Application in Metal-Free Reactions. CHEMPHOTOCHEM, v. 3, n. 7, p. 506-520, JUL 2019. (14/50249-8, 17/10015-6)

DE SOUZA, WANDERSON C.; MATSUO, BIANCA T.; MATOS, PRISCILLA M.; CORREIA, JOSE TIAGO M.; SANTOS, MARILIA S.; KOENIG, BURKHARD; PAIXAO, MARCIO W.. Photocatalyzed Intramolecular [2+2] Cycloaddition of N-Alkyl-N-(2-(1-arylvinyl)aryl)cinnamamides. CHEMISTRY-A EUROPEAN JOURNAL, v. 27, n. 11, JAN 2021. (14/50249-8, 15/17141-1, 20/00556-2, 17/10015-6)

MATSUO, BIANCA T.; OLIVEIRA, PEDRO H. R.; PISSINATI, EMANUELE F.; VEGA, KIMBERLY B.; DE JESUS, IVA S.; CORREIA, JOSE TIAGO M.; PAIXAO, MARCIO. Photoinduced carbamoylation reactions: unlocking new reactivities towards amide synthesis. CHEMICAL COMMUNICATIONS, v. 58, n. 60, p. 18-pg., 2022-07-07. (21/06099-5, 17/10015-6)

PISSINATI, EMANUELE F.; DELGADO, JOSE A. C.; MORO, PEDRO A. M.; CORREIA, JOSE T. M.; BERLINCK, ROBERTO G. S.; PAIXAO, MARCIO W.. Expanding the Chemical Space of Non-Proteinogenic N-4-Substituted Asparagine: Racemic, Enantioenriched, and Deuterated Derivatives. EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, v. 26, n. 21, p. 7-pg., 2023-05-17. (17/10015-6, 15/01017-0, 21/06099-5, 19/17721-9)