Defluorophosphorylation of fluoroalkyl peroxides for the synthesis of highly substituted furans

Abstract

Transformation of multifunctional materials with control over site-selectivity and chemical diversity remains challenging. Herein, we present a metal-free, one-pot strategy for the defluorophosphorylation of polyfluoroalkyl peroxides that enables expedient construction...

Na2S·9H2O Enabled Defluorodisulfuration and Hydrodefluorination of Perfluorobutyl Tetralones: Synthesis of Trifluoromethyl 1,2-Dithioles

“…On the basis of the experimental results obtained as described above and a literature survey, − we propose plausible mechanisms for the formation of trifluoromethyl 1,2-dithioles 2 and byproduct 2a′ in Scheme . Initially, the reaction begins with an oxidative addition of Pd(0) to the C­(sp 2 )–F bond of defluorinated ketone A , which is generated in situ from perfluorobutyl tetralone 1 after removing an HF under basic conditions, to give an alkenyl–Pd­(II)–F species B .…”

“…Although a large number of methods for constructing carbon–sulfur bonds have been developed by taking advantage of defluorinative sulfuration, defluorinative disulfuration has remained virtually unexplored. As part of our interest in the conversion of polyfluorinated molecules to value-added heterocycles through successive selective defluorination events at different carbon sites, herein, we describe a palladium-catalyzed defluorodisulfuration and hydrodefluorination sequence of perfluorobutyl tetralones with readily available Na 2 S·9H 2 O for the synthesis of 5-trifluoromethyl 1,2-dithiole derivatives (Scheme D). The unprecedented heteroannulation enabled (1) the formation of four C–H/C–S/S–S bonds, an S-heterocycle assembly, and regiospecific installation of a biologically and pharmaceutically relevant fluorine-containing group, (2) the cleavage of six C­(sp 3 )–F bonds at three carbon sites, (3) the multi-bond-interconverting cascade with high levels of Z -configuration control and chemoselectivity, (4) the utility of cheap, weakly toxic, and odorless inorganic sulfide as a unique disulfurating precursor and a defluorinative reagent, and (5) the use of water as a hydrogen source for the hydrodefluorination.…”

“…14 Although a large number of methods for constructing carbon−sulfur bonds have been developed by taking advantage of defluorinative sulfuration, 15 defluorinative disulfuration has remained virtually unexplored. As part of our interest in the conversion of polyfluorinated molecules to value-added heterocycles through successive selective defluorination events at different carbon sites, 16 T h i s c o n t e n t i s Guided by the hypothesis, we initially began our study by using 2-(perfluorobutyl)-3,4-dihydronaphthalen-1(2H)-one (1a) and commercially available Na 2 S•9H 2 O as benchmark substrates to optimize the the conditions (Scheme 2; also see Tables S1−S3 for more details). When the model reaction was performed in the presence of Pd(PPh 3 ) 2 Cl 2 (5 mol %), 1,4bis(diphenylphosphino)butane (dppb, 10 mol %), and Cs 2 CO 3 (3 equiv) in EtOAc at 90 °C for 12 h under a nitrogen atmosphere, the desired 5-trifluoromethyl 1,2dithioles 2a together with an unexpected trifluoromethyl benzochromene-4-thione 2a′ could be obtained in 62% NMR yield with a ratio of >20:1 (isolated yield of 2a of 49%; S1).…”

Selective and Controllable Defluorophosphination and Defluorophosphorylation of Trifluoromethylated Enones: An Auxiliary Function of the Carbonyl Group

“…However, the vast majority of reported reactions relied on γ-selective defluorination because of the interference of the highly activated alkenyl part and generally produced one class of products. 15 Inspired by these elegant works and in continuation of our research efforts in defluorinative reactions, 16 we herein presented a defluorophosphination and defluorophosphorylation of trifluoromethylated enones with phosphine oxides (Figure 1B). The RC�O moiety was attached to trifluoromethyl alkenes, which acts as a switch to enable the replacement of one or two fluorine atoms by fine-tuning the reaction conditions.…”

“…Inspired by these elegant works and in continuation of our research efforts in defluorinative reactions, we herein presented a defluorophosphination and defluorophosphorylation of trifluoromethylated enones with phosphine oxides (Figure B). The RCO moiety was attached to trifluoromethyl alkenes, which acts as a switch to enable the replacement of one or two fluorine atoms by fine-tuning the reaction conditions.…”