Synthesis of gem‐Difluorinated Keto‐Sulfoxides from Sulfoxonium Ylides

Organic molecules containing fluorine and sulfur atoms represent a large percentage of approved pharmaceuticals. Those with combination of both S and F atoms in their structure such as Xtandi, approved in 2012 for prostate cancer, indicates the importance of synthetic methods that accommodates both...

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Bibliographic Details
Published in:Chemistry : a European journal 2024-04, Vol.30 (21), p.e202400108-n/a
Main Authors: Hayashi, Marcio, Burtoloso, Antonio C. B.
Format: Article
Language:English
Subjects:
Atomic structure
Fluorinated Compounds
Fluorine
gem-difluoroalkyl
NMR
Nuclear magnetic resonance
Organic chemistry
Prostate cancer
Selectfluor
Sulfoxide
Sulfoxides
Sulfoxonium Ylides
Sulfur
Sulphur
Synthesis
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Summary:Organic molecules containing fluorine and sulfur atoms represent a large percentage of approved pharmaceuticals. Those with combination of both S and F atoms in their structure such as Xtandi, approved in 2012 for prostate cancer, indicates the importance of synthetic methods that accommodates both atoms in an organic moiety. In this study, a novel aspect of sulfoxonium ylide reactivity was explored, unveiling a streamlined and mild synthesis method for gem‐difluorinated keto‐sulfoxides. Our protocol offers a direct and practical approach to prepare these compounds in 14–80 % chemical yields, that were represented by 21 examples. NMR studies and Hammett correlations gave strong evidence about the mechanism of this transformation. Gem‐difluorinated sulfoxides were obtained in a simple procedure from sulfoxonium ylides, in a different reaction mode from the classical behaviour (geminal addition of a nucleophile and electrophile, followed by sulfoxide extrusion. Experimental studies give insight to the mechanism of the reaction, with a change in the RDS according with ylide substitution. Sulfur‐ and fluorine‐containing organic compounds are quite attractive and important in medicinal chemistry.
ISSN:0947-6539
1521-3765
DOI:10.1002/chem.202400108