Studies aiming the preparation of pro-chiral ²-ceto sulfoxônios -ketosulfoxonium ylides and their applications in the synthesis of isoquinoline derivatives

• Grant number: 20/07143-5
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: October 01, 2020
• End date: February 28, 2025
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Antonio Carlos Bender Burtoloso
• Grantee: Matheus Pereira de Jesus
• Host Institution: Instituto de Química de São Carlos (IQSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil

Abstract

Sulfur ylides represent an important synthetic tool for organic chemists since they are used as building blocks in total synthesis, in the materials chemistry, and in the production of drugs, for example. However, there is a great difficulty associated with the alkylation of these compounds, mainly of the stabilized ones, as is the case of the ²-ketosulfoxonium ylides. For this reason, obtaining pro-chiral sulfur ylides without the use of diazo compounds is still a synthetic challenge, considering that in the literature are not yet reported methodologies for the insertion of groups besides aryl in the ±-sulfoxonium position.In this context, in order to obtain pro-chiral molecules, the present research project proposes to develop a methodology for C-alkylation of ²-ketosulfoxonium ylides. For this, a series of alkylating agents will be investigated, especially those that have unreactive counterions, such as oxonium salts. Other strategies will be studied, such as the use of hypervalent iodine reagents and the possibility of obtaining pro-chiral ylides via Michael addition reaction.In addition, the synthetic potential associated with sulfur ylides will be explored in intramolecular cyclization reactions of amino-acetinyl-²-keto sulfoxonium ylides. The initial proposal is to obtain isoquinoline derivatives, a class of natural products that have important biological activities. For that, different gold(I/III) catalysts will be evaluated in the activation of the triple bond of the precursor molecule. (AU)

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)

DE JESUS, MATHEUS P.; ECHEMENDIA, RADELL; BURTOLOSO, ANTONIO C. B.. The alpha-alkylation of carbonyl sulfoxonium ylides: studies and applications in the synthesis of new sulfur heterocycles. ORGANIC CHEMISTRY FRONTIERS, v. 10, n. 14, p. 8-pg., 2023-06-09. (19/12300-5, 20/07147-0, 20/07143-5)

ECHEMENDIA, RADELL; DE JESUS, MATHEUS P.; FURNIEL, LUCAS G.; DAY, DAVID PHILIP; BURTOLOSO, ANTONIO C. B.. Molecular Iodine Mediated Oxidation of Arylated alpha-Carbonyl Sulfoxonium Ylides to 1,2-Dicarbonyl-Containing Compounds. EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, v. 2022, n. 26, p. 7-pg., 2022-07-14. (18/17800-3, 19/12300-5, 20/07143-5, 20/07147-0, 19/05002-8)

DE JESUS, MATHEUS P.; BURTOLOSO, ANTONIO C. B.. Revisiting the Reaction of Sulfur Ylides with Acetylenic Esters: Synthesis of Trisubstituted 1,3-Dienes, α-Carbonyl Vinyl Sulfoxides and α-Carbonyl Vinyl Sulfoxonium Ylides. CHEMISTRY-AN ASIAN JOURNAL, v. 19, n. 23, p. 7-pg., 2024-10-28. (20/07143-5, 20/15230-5, 23/02675-7)