Exploring the reactivity of diazocarbonyl compounds and sulfur ylides for the formation of carbon-carbon and carbon-heteroatom bonds

Author(s)

Clarice Alves Dale Caiuby

• Document type: Doctoral Thesis
• Press: São Carlos.
• Institution: Universidade de São Paulo (USP). Instituto de Química de São Carlos (IQSC/BT)
• Defense date: 2023-02-10

Examining board members

Antonio Carlos Bender Burtoloso; Emilio Carlos de Lucca Júnior; Igor Dias Jurberg; Camilla Djenne Buarque Muller; Ricardo Samuel Schwab

• Advisor: Antonio Carlos Bender Burtoloso

Abstract

Diazo compounds and sulfur ylides are promising substrates in organic synthesis. Their very unique structural features allow reactions with several electrophiles and nucleophiles, as well as the ability to form carbene-type intermediates. In this context, in the first chapter of this PhD thesis, the nucleophilicity of diazocarbonyl compounds and α-carbonyl sulfoxonium ylides was evaluated in epoxide ring opening methodologies to achieve functionalized alcohols and oxetanes. No success was obtained in the synthesis of the products of interest, since products resulting from the Meinwald rearrangement in epoxides catalyzed by Lewis acid (that leads to the formation of aldehydes) were identified. These aldehydes formed in situ reacted with the diazocompound by carbonyl addition reactions to provide dicarbonyl compounds (by Roskamp Reaction), epoxides (by Darzens Reaction) and 2-diazo-4-hydroxycarbonyl compounds. In the second chapter, imidoyl sulfoxonium ylides were presented as potential precursors of α-imino metal-carbenes species. Our hypothesis was supported by performing an intramolecular C-H functionalization reaction in the presence of an iridium catalyst, leading to the obtention of substituted indoles in a single step. In this case, 24 new examples of N-aryl-imidoyl sulfoxonium ylides were synthesized with 45 89% yield. This series of substrates was then subjected to the presence of [Ir(cod)Cl]2 catalyst (4 mol%) to afford 24 functionalized indoles in 15 70% yields. In the third chapter, in collaboration with Prof. Christophe Aïssa- University of Liverpool, we studied the synthesis of new bis-substituted sulfur ylides through cross-coupling methodologies catalyzed by palladium. Thirteen new cyclic α-carbonyl-α-aryl sulfoxonium ylides were successfully synthesized in good yields (up to 99%) using an intramolecular arylation strategy. These compounds were applied in X-H insertion and C-H functionalization reactions. Cyclic ketosulfoxonium ylides showed excellent reactivity for iridium-catalyzed C-H functionalization of indoles, providing 15 examples of functionalized indoles with (1,3-dihydro-2H-inden-2-one) in up to 98% yield. In contrast, for the ester series of substrates, a protonation approach was effective using a phosphoric acid. Under organocatalyzed reaction conditions, 10 examples of 4-(1H-indol-3-yl) isochroman-3-ones were synthesized in up to 82% yield and when (S)-TRIP was applied as organocatalyst, up to 94% yield and up to 90% enantiomeric excess was obtained. Finally, inspired by these Brønsted acid-catalyzed transformations, the synthesis of β-aminothioethers (26 examples, up to 99%) was carried out from transition metal-free S-H insertion into imidoyl sulfoxonium ylides. (AU)

• FAPESP's process: 17/23837-4 - Exploring the application of diazocarbonyl compounds and sulfur ylides in the asymmetric ring opening reactions with epoxides for the synthesis of oxetanes and functionalized alcohols
• Grantee: Clarice Alves Dale Caiuby
• Support Opportunities: Scholarships in Brazil - Doctorate