Exploration of the Asymmetric Induction in Ugi Variations Aiming the Stereoselective Synthesis and Functionalizationof N-Heterocycles

• Grant number: 19/01973-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): April 01, 2019
• Effective date (End): April 07, 2023
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Márcio Weber Paixão
• Grantee: Vitor Alcantara Fernandes da Silva
• Host Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Associated scholarship(s): 21/10246-3 - Hemiacetals as versatile substrates for organocatalytic asymmetric transformations, BE.EP.DR

Abstract

Since its inception, multicomponent reactions (MCRs) have positioned themselves as an important and powerful tool for the synthesis of compounds with potential biological activity. The great diversity and complexity, generated in a single reactional step, arouse great interest of the pharmaceutical industries. Among the multicomponent reactions, those that exploit the reactivity of isonitriles (isocyanides) are in a prominent position.In this context, the Ugi 4-Component Reaction and its variations appear as unique strategies, which enable the introduction of an amide function in molecular architecture. However, in spite of the advantages offered by these reactions, the lack of control of the stereochemical course during the addition of isonitrile to the pro-chiral carbonyl derivative (kinetic control) - this characteristic hampers the implementation of stereoselective syntheses and is the major limitation of this methodology.Therefore, this project aims to develop new stereoselective methodologies for variations of Ugi reactions, which will have different approaches. Initially the induction of asymmetry by control of the enantioenriched substrate will be evaluated. In this sense, heterocyclic compounds, with a high degree of diversity and structural complexity, will be synthesized through the combination of an organocatalytic step and variations of the Ugi-3-components-4-centers reaction. In a second moment, the induction of asymmetry will be studied by the use of chiral organocatalysts in variations of the Ugi reaction. Through this catalytic approach, several chiral N-heterocycles, with a high degree of substitution, will be synthesized. Finally, in order to better understand the mechanisms of the reactions developed, kinetic and computational studies will be carried out. Further, it is intended, after the synthesis of a wide variety of compounds, to test the biological activity of these compounds.

Scientific publications

(6)

(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)

FERNANDES, VITOR A.; LIMA, RAFAELY N.; BROTERSON, YOISEL B.; KAWAMURA, MEIRE Y.; ECHEMENDIA, RADELL; DE LA TORRE, ALEXANDER F.; FERREIRA, MARCO A. B.; RIVERA, DANIEL G.; PAIXAO, MARCIO W.. Direct access to tetrasubstituted cyclopentenyl scaffolds through a diastereoselective isocyanide-based multicomponent reaction. CHEMICAL SCIENCE, v. 12, n. 48, SEP 2021. (15/17141-1, 17/01754-0, 14/50249-8, 20/01255-6, 20/10246-0, 19/01973-9)

KISUKURI, CAMILA M.; FERNANDES, VITOR A.; DELGADO, JOSE A. C.; HAERING, ANDREAS P.; PAIXAO, MARCIO W.; WALDVOGEL, SIEGFRIED R.. Electrochemical Installation of CFH2-, CF2H-, CF3-, and Perfluoroalkyl Groups into Small Organic Molecules. CHEMICAL RECORD, v. 21, n. 9, SI, p. 2502-2525, SEP 2021. (18/12986-1, 15/17141-1, 14/50249-8, 19/01973-9)

KISUKURI, CAMILA M.; FERNANDES, VITOR A.; DELGADO, JOSE A. C.; HAERING, ANDREAS P.; PAIXAO, MARCIO W.; WALDVOGEL, SIEGFRIED R.. Electrochemical Installation of CFH2-, CF2H-, CF3-, and Perfluoroalkyl Groups into Small Organic Molecules. CHEMICAL RECORD, JUN 2021. (19/01973-9, 18/12986-1, 15/17141-1, 14/50249-8)

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.; 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)

DELGADO, JOSE A. C.; VICENTE, FIDEL E. M.; DE LA TORRE, ALEXANDER F.; FERNANDES, VITOR A.; CORREA, ARLENE G.; PAIXAO, MARCIO W.. Synthesis of N-alkylated lipopeptides and their application as organocatalysts in asymmetric Michael addition in aqueous environments. NEW JOURNAL OF CHEMISTRY, v. 45, n. 31, JUL 2021. (14/50249-8, 19/01973-9)