Synthesis of α,α-Difluoro-β-amino Ketones from N-Boc-α-Amidosulfones and Pentafluoro- gem-diols

Baharul Islam; Suresh P Sulochana; David A Colby

doi:10.1021/acs.joc.3c02181

Synthesis of α,α-Difluoro-β-amino Ketones from N-Boc-α-Amidosulfones and Pentafluoro- gem-diols

J Org Chem. 2024 May 3;89(9):6506-6512. doi: 10.1021/acs.joc.3c02181. Epub 2024 Apr 12.

Authors

Baharul Islam¹, Suresh P Sulochana², David A Colby¹

Affiliations

¹ Department of BioMolecular Sciences, University of Mississippi, University, Mississippi 38677, United States.
² Department of Pharmaceutics and Drug Delivery, University of Mississippi, University, Mississippi 38677, United States.

PMID: 38606727
DOI: 10.1021/acs.joc.3c02181

Abstract

To circumvent the synthesis and isolation of imines, a method was devised to construct α,α-difluoro-β-amino ketones from N-Boc-α-amidosulfones. The reactive nucleophiles, difluoroenolates, are generated in situ from the pentafluoro-gem-diols using cesium fluoride in pyridine. NMR studies confirm the role of the α-amidosulfones in this process. Incubation of the α,α-difluoro-β-amino ketones in rat serum demonstrates the relative stability of this structure as well as its value as a chemical probe or lead.