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

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).

SUBMITTER: Panigrahi K 

PROVIDER: S-EPMC12084027 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature