221876-80-8

Upstream product

• 591-18-4 1-Bromo-3-iodobenzene 
• 82845-20-3 [(diethoxyphosphoryl)difluoromethyl]zinc bromide 
• 80077-72-1 diethyl difluoro(trimethylsilyl)methylphosphonate 
• 1203709-76-5 3'-bromo-2,4,6-trimethyl(diphenyliodonium) trifluoromethanesulfonate 
• 65094-22-6 diethyl (bromodifluoromethyl)phosphonate 

Downstream Products

• 221876-90-0 [(3-ethynyl-phenyl)-difluoro-methyl]-phosphonic acid diethyl ester 
• 221876-89-7 [difluoro-(3-phenylethynyl-phenyl)-methyl]-phosphonic acid diethyl ester 
• 221876-88-6 {Difluoro-[3-((E)-styryl)-phenyl]-methyl}-phosphonic acid diethyl ester 

Relevant academic research and scientific papers

Copper-Mediated Introduction of the CF2PO(OEt)2 Motif: Scope and Limitations

Herein, a general procedure to access CF2PO(OEt)2-containing molecules is reported. The reagent CuCF2PO(OEt)2 is accessible by a simple protocol and a broad range of substrates can be functionalised. The procedure allows the conversion of aryl diazonium salts, as well as aryl, heteroaryl, vinyl and alkynyl iodonium salts, into the corresponding fluorinated molecules at room temperature. Mechanistic studies were performed to gain a better understanding of the reaction pathway. Under similar conditions, vinyl and aryl iodides, allyl halides, and benzyl bromides were also functionalised, and the scope and limitations of the reaction were studied. Finally, the procedure was extended to disulfides to offer new access to SCF2PO(OEt)2-containing molecules.

Copper-mediated synthesis of aryldifluoromethylphosphonates: A sandmeyer approach

Difluoromethylated arenes are scaffolds of great interest. We report herein a mild and general method for the introduction of the CF2PO(OEt)2 moiety into arenes. The CuCF2PO(OEt)2 species, which is generated in

Copper-Mediated Formation of Aryl, Heteroaryl, Vinyl and Alkynyl Difluoromethylphosphonates: A General Approach to Fluorinated Phosphate Mimics

A general and efficient access to aryl, heteroaryl, vinyl and alkynyl difluoromethylphosphonates is described. The developed methodology using TMSCF2PO(OEt)2, iodonium salts and a copper salt provided a straightforward manifold to re

Utilization of nitrophenylphosphates and oxime-based ligation for the development of nanomolar affinity inhibitors of the Yersinia pestis outer protein H (YopH) phosphatase

Our current study reports the first KM optimization of a library of nitrophenylphosphate-containing substrates for generating an inhibitor lead against the Yersinia pestis outer protein phosphatase (YopH). A high activity substrate identified by this method (KM = 80 μM) was converted from a substrate into an inhibitor by replacement of its phosphate group with difluoromethylphosphonic acid and by attachment of an aminooxy handle for further structural optimization by oxime ligation. A cocrystal structure of this aminooxy-containing platform in complex with YopH allowed the identification of a conserved water molecule proximal to the aminooxy group that was subsequently employed for the design of furanyl-based oxime derivatives. By this process, a potent (IC50 = 190 nM) and nonpromiscuous inhibitor was developed with good YopH selectivity relative to a panel of phosphatases. The inhibitor showed significant inhibition of intracellular Y. pestis replication at a noncytotoxic concentration. The current work presents general approaches to PTP inhibitor development that may be useful beyond YopH. This article not subject to U.S. Copyright. Published 2011 by the American Chemical Society.

Synthesis and biological evaluation of α,α-difluorobenzylphosphonic acid derivatives as small molecular inhibitors of protein-tyrosine phosphatase 1B

A series of α,α-difluorobenzylphosphonic acids having a hydrophobic functional group were prepared via the Stille coupling reaction from halogenated α,α-difluorobenzylphosphonates. Evaluation of inhibitory activity toward protein tyrosine phosphatase (PTP 1B) revealed that the ethynyl, phenylethynyl and (E)-styryl groups on the benzene nuclei increased the inhibitory activity of α,α-difluorobenzylphosphonic acid. Inhibitory activities significantly increased upon introducing both (E)-styryl and bis- methylsulfonamide functional groups onto the benzene nuclei of α,α- difluorobenzylphosphonic acid.