Geminal Chlorofluorination and Geminal Halofunctionalizations of 1,2-Dicarbonyl Compounds via the Kukhtin–Ramirez Reaction

Abstract

Halogenation of organic compounds is one of the most important transformations in synthetic chemistry. Also, organohalides can be utilized as synthetic intermediates for accessing other useful compounds. In particular, organohalides containing halogen and other functional groups on the same carbon center are useful synthetic precursors to tertiary halides, and therefore numerous methods for geminal halofunctionalization have been developed. However, synthetic methods for most of geminal halofunctionalization have been limited to sequential electrophilic halogenation and functionalization of carbonyl compounds, and only a few examples of using α-diazo compound, one of the carbene synthon, for geminal halogenation have been reported. Here, we describe another method for geminal halofunctionalization using dioxaphospholene which is one of carbene synthon. The reaction of 1,2-diketone and trivalent phosphorus reagent provides dioxaphospholene, and the electron-rich alkene of dioxaphospholene reacts with electrophile to produce oxaphosphonium. The formation of phosphoramidate drives the SN2 reaction of oxaphosphonium and nucleophile, and the reaction of dioxaphospholene, electrophile, and nucleophile has been well known chemistry which is named as the Kukhtin–Ramirez reaction. In our work, the reactions of 1,2-diketones, N-fluorobenzenesulfonimide (NFSI), and tetra-n-butyl ammonium chloride in the presence of phosphoramidite which prevents Arbuzov dealkylation resulted in a one-step construction of geminal interhalides via the Kukhtin–Ramirez reaction. The reaction provided up to 88% yield of geminal chlorofluorides from aryl-aryl 1,2-diketones and up to 71% yield from aryl-alkyl 1,2-diketones. Also, about 3:1 regioselectivities were observed when unsymmetrical 1,2-diketones were used. In addition, other geminal halofunctionalizations were studied to introduce amino, seleno, and trifluoromethyl groups. Among them, geminal fluoroamination was successful giving up to 54% yield of fluoroamide. In halogenative semi-pinacol rearrangement of 1,2-diketone, an unexpected 1,2-hydride shift was observed when hydrogen fluoride was applied to dioxaphospholene of 1-siloxy-2,3-diketone.