Synthesis of 1,3-bifunctional cyclobutane derivatives with α-CHF₂/CF₃ group – advanced building blocks for medicinal chemistry

Efficient synthesis of novel α-CF₃/CHF₂-substituted 1,3-bifunctional cyclobutane building blocks – conformationally restricted analogs of γ-amino- and γ-hydroxybutyric acids – important neurotransmitters, as well as fluorinated derivatives of 3-oxocyclobutanecarboxylic acid – a bulk reactant widely used in synthetic and medicinal chemistry, is described. The target products were obtained on a gram scale as single (1s_n,3s_n) diastereomers, which was enabled by good diastereoselectivity of the process for the CF₃-substituted derivatives and by diastereomer separation – for both series.