Rapid Entry into Biologically Relevant α,α-Difluoroalkylphosphonates Bearing Allyl Protection-Deblocking under Ru(II)/(IV)-Catalysis

Kaushik Panigrahi, Xiang Fei, Masato Kitamura, David B. Berkowitz

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

A convenient synthetic route to α,α-difluoroalkylphosphonates is described. Structurally diverse aldehydes are condensed with LiF2CP(O)(OCH2CH═CH2)2. The resultant alcohols are captured as the pentafluorophenyl thionocarbonates and efficiently deoxygenated with HSnBu3, BEt3, and O2, and then smoothly deblocked with CpRu(IV)(π-allyl)quinoline-2-carboxylate (1-2 mol %) in methanol as an allyl cation scavenger. These mild deprotection conditions provide access to free α,α-difluoroalkylphosphonates in nearly quantitative yield. This methodology is used to rapidly construct new bis-α,α-difluoroalkyl phosphonate inhibitors of PTPIB (protein phosphotyrosine phosphatase-1B).

Original languageEnglish (US)
Pages (from-to)9846-9851
Number of pages6
JournalOrganic Letters
Volume21
Issue number24
DOIs
StatePublished - Dec 20 2019

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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