Study on Phosphorus(III)-Mediated Deoxygenative Geminal Interhalogenation and Geminal Halocyclization of 1,2-Diketones via the Kukhtin-Ramirez Reaction

Abstract

Trivalent organophosphorus compounds are known to form dioxaphospholenes through the [1,4]-annulation with 1,2-dicarbonyl compounds. Dioxaphospholene, also known as Kukhtin-kylation was observed as a significant side reaction. To prevent the SN2 dealkylation, a new P(III) reagent was devised using pyrrolidine and neopentyl glycol. With the newly designed phosphoramidite, geminal chlorofluorination of benzil was accomplished in 76% yield by employing NFSI (N-fluorobenzenesulfonimide) and TBACl (tetra-n-butylammonium chloride). Furthermore, the optimized chlorofluorination conditions were successfully applied to a variety of benzil derivatives to afford geminal chlorofluorides in 58-82% yields. In addition, geminal halocyclization was investigated via the Kukhtin-Ramirez reaction by rendering the nucleophilic substitution intramolecular. If geminal halocyclizations proceed, cyclic structures containing a tetrasubstituted carbon will be constructed from dioxaphospholene. To that end, three 1,2-diketones with a pendant nucleophile were prepared, and the reactions with various trivalent phosphorous reagents were examined. Subsequently, the geminal halocyclizations were attempted with suitable P(III) reagents and electrophilic halogenating reagents. Unfortunately, the desired products were not obtained. To increase the reactivity of the pendant nucleophile, nitrogen-based functional groups will be introduced onto the substrates.