Study on Deoxygenative Geminal Aminofluorination of 1,2-Diketones via the Kukhtin–Ramirez reaction

Abstract

Geminal aminofluorination is a versatile method that constructs C–N and C–F bonds on the same carbon. Recently, several synthetic methods for geminal aminofluoride have been reported. However, in most cases, an excess amount of a diazo compound was required, or a substrate already containing an amine was employed. Thus, we utilized the carbene-like reactivity of dioxaphospholene to overcome the drawbacks. On the basis of the Kukhtin–Ramirez reaction, geminal aminofluorination was investigated with various 1,2-diketones and the previously designed phosphoramidite in our group. The optimized reaction conditions were applied to a variety of 1,2-diketones with NFSI to afford geminal aminofluorides in moderate to good yields. In addition, scope expansion was pursued using various amine nucleophiles. When anilines were employed, imine was obtained instead of the desired product. With N-tosylbenzylamine, the product formation was observed albeit low yield. Interestingly, pyrazole afforded geminal dipyrazole in a synthetically useful yield. To gain insight into the unexpected geminal diamination, a series of control experiments will be conducted. Furthermore, other geminal difunctionalizations were also examined including geminal oxyfluorination, aminochlorination, and hydrogenation.