Solid-phase organic synthesis of difluoroalkyl entities using a novel fluorinating cleavage strategy: part 1. Linker development: scope and limitations.
An efficient method to synthesize gem-difluorinated compounds on solid supports is described. The strategy is based on the design of a novel sulfur linker system that enables, to the best of our knowledge for the first time, the release of target structures from the resin under simultaneous fluorination. Starting from an immobilized dithiol, coupling with an excess of aldehyde or ketone furnished dithianes. These can be further functionalized prior to release from the resin using our newly developed fluorinating cleavage conditions. Amide forming reactions, palladium-catalyzed reactions (Heck, Suzuki, and Sonogashira couplings), reductions, alkylations, and olefinations were successfully explored on the linker. The difluorinated target substances were obtained in modest to excellent yields and in high purities.
Wiehn
Matthias S
MS
Institut fur Organische Chemie, Karlsruhe Institute of Technology, Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany.
Lindell
Stephen D
SD
Bräse
Stefan
S
D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism
D006845:Hydrocarbons, Fluorinated