Synthesis of highly substituted quinolines via heterocyclization of fluorinated acetylenephosphonates with ortho-aminoaryl ketones

A synthetic route to a series of 4-alkyl- or arylquinolines, bearing in 2- and 3-position fluorinated and phosphonate functions at the same time, is reported for the first time. These compounds are synthesized via regioselective heterocyclization of XCF2-alkynylphosphonates (X=F, Cl, Br, H, CF3) with ortho-aminoaryl ketones (R=CH3, CF3, Ph) in the presence of K2CO3 or Li2CO3/TMEDA as mediators. 2-Fluoro- and 3-phosphorus-containing 4-Me, 4-CF3 or 4-Ph quinolines are obtained in good to excellent yields. The influence of substituents in the aromatic ketone, the XCF2-group in the alkyne as well as mediators and the reaction medium on the reactivity and specificity of the reaction is also investigated.

Figure optionsDownload as PowerPoint slide