New methodologies using sulfur ylides for the enantioselective α-heterofunctionalization of carbonyl compounds

Author(s)

Lucas Giani Furniel

• Document type: Doctoral Thesis
• Press: São Carlos.
• Institution: Universidade de São Paulo (USP). Instituto de Química de São Carlos (IQSC/BT)
• Defense date: 2023-07-14

Examining board members

Antonio Carlos Bender Burtoloso; Marco Antonio Barbosa Ferreira; Fernanda Gadini Finelli; Paulo Cesar Muniz de Lacerda Miranda; Caio Costa Oliveira

• Advisor: Antonio Carlos Bender Burtoloso

Abstract

α-Heterofunctionalized carbonyl compounds show wide versatility as building blocks due to the wide variety of transformations in which they can participate. However, there is a limited number of methodologies for the preparation of these compounds in an enantioselective and efficient way, which makes the development of new methodologies for this type of transformation of great importance. Thus, this thesis addresses the development of methodologies for asymmetric α-heterofunctionalization of α-carbonyl sulfur ylides. The first part of this thesis consists in the development of an asymmetric N-H insertion methodology with sulfur ylides, using a chiral Cu(hfacac)2-squaramide cooperative catalytic system. This was the first work involving an asymmetric and catalytic transformation using sulfur ylides as precursors of metal-carbene intermediates and allowed the preparation of 39 α-aryl glycines in enantiomeric ratios up to 92:8 (99:1 after one recrystallization) and yields in the range of 31- 96%. In the second part of this work, the first methodology for enantioselective α-chlorofluorination of a carbonyl compound in one step was developed. Using achiral sulfoxonium ylides as starting materials, 21 α-chlorofluoro carbonyl compounds were prepared, with yields and enantioselectivity between 19-80% and 8-80% ee. Although the transformation is not catalytic, the chiral QD2PHAL promoter can be recovered in 82% yield and reused without loss of enantioselectivity in the next reaction. Alternatively, enantioenriched aminosulfoxonium ylides were also suitable substrates for the reaction, providing 4 examples with 19-75% yield and even higher enantioselectivities (70-90% ee). In addition, several different skeletons were evaluated, providing the most diversified study of α,α-chlorofluorination of carbonyl compounds. These results highlight the versatility and synthetic application of sulfoxonium ylides as important intermediates in organic synthesis. (AU)

• FAPESP's process: 18/17800-3 - New methodologies using sulfur ylides for the enantioselective alpha-Heterofunctionalization of carbonyl compounds
• Grantee: Lucas Giani Furniel
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)