Mixed organofluorine-organosilicon chemistry. 8. One-pot synthesis of 2,2-difluoro-1,5 diketones from acylsilanes, trifluoromethyltrimethylsilane and enones, and their annulation reaction

Enolate-Based Strategies to Construct <i>gem</i>-Difluoromethylene Compounds

“…For instance, Lewis acid promoted C C bond forming reactions such as the Mukaiyama aldol reaction and Michael addition using di uoroenol silanes 1 provided the corresponding adducts 8 and 9, respectively. 10b, 16,17 Aryl groups were successfully installed at the gem di uoromethylene position to give 11 and 12 by Pd catalyzed cross coupling and Cu mediated oxidative cross coupling respectively. 18,19 Thermal [2+2] cycloaddition of enol silanes 1 gave tetra uorocyclobutane 1,2 diols 12.…”

Recent Progress in One-Pot Syntheses of Fluorinated Building Blocks

“…Difluoroegomaketone with potential bovine respiratory toxicity [25], which contains the moiety of difluoroaldol 6, could be also prepared by using this one-pot methodology [17]. It's also reported that the Michael addition and subsequent annulation of 8 led to the formation of multisubstituted difluorocyclohexenones and fluorophenols [19]. It's also reported that the Michael addition and subsequent annulation of 8 led to the formation of multisubstituted difluorocyclohexenones and fluorophenols [19].…”

Developing the Saegusa–Ito Cyclisation for the Synthesis of Difluorinated Cyclohexenones

“…The crude product was eluted by washing with 10 %d iethyl ether in n-hexane (200 mL), and the eluent was evaporated under reduced pressure to give crude silyl enol ether 16 a (1.3 g) as am obile clear yellow oil. The crude silyl enol ether was purified by flash-column chromatography (90 g silica, 10 %d iethyl ether in n-hexane) to give 16 a as ac olourless oil (1.31 g, 67 %); R f = 0.25 ( The relative stereochemistry and identity of hydrate 19 a were confirmed by XRD analysis;C rystal data:C 13 Preparation of 18 a( general procedure for palladium-catalysed cyclisation) Palladium(II) acetate (10 mol %, 22.4 mg) and copper(I) chloride (100 mol %, 99 mg) were suspended in dry acetonitrile (4 mL) that had been sparged with air for 30 min through adrawn out pipette. The suspension was warmed to 70 8C, then as olution of silyl enol ether 16 a (1.00 mmol, 0.391 g) in dry acetonitrile (1.6 mL) added by syringe in ac onstant stream.…”

“…[11] However,a nnulation chemistry based on difluorinated building blocks is less well established. [11,12] The published chemistry of difluorinateds ilyl enol ethers is developing, with Mukaiyama-type aldol reactions, [13] including recent "on-water" examples, [14] additions to iminium electrophiles [15] andarecent Pd-catalysed arylation. [16] The latter example is relevant, because one mechanism involves nucleophilic attack by the difluorinated silyl enol ether on aP d II electrophile.…”

“…Crude product was eluted from the silica with 0-25 % ethyl acetate in n-hexane then concentrated under reduced pressure to afford ap ale yellow oil. J H-F = 7.1 Hz, 6H);13 CNMR (125 MHz, CDCl 3 ): d = 156.5, 139.3 (t, 2 J CÀF = 19.8 Hz), 117.4 (t, 1 J CÀF = 251.4 Hz), 113.9 (t, 3 J CÀF = 7.9 Hz), 94.2 (t, 3 J CÀF = 24.0 Hz) 42.3, 42.2, 36.1, 26.6, 19.2, 13.9, 13.3 ppm; 19 FNMR (376 MHz, CDCl 3 ): d = (À115.1)-(À116.8; broad, 1F), (À118.1)-(À120.7 ppm;b road, 1F);* ũ (film) = 3331, 1694, 1657, 1079 cm À1 ;L RMS (ES): m/z 316.2 (100) [M+ +Na] + ,2 94.1 (25) [M+ +H] + ;H RMS (ES-TOF): calcd for C 13 H 22 F 2 NO 4 294.1511 [M+ +H] + ,f ound 294.1507;e lemental analysis calcd (%) for C 13 H 21 F 2 NO 4 :C53.23, H7 .22, N4 .78;f ound:C53.28, H7 .46, N4 .74. *The NMR data were extracted from the spectrum of am ixture of 18 a and 19 a (see the Supporting Information);c rystals of 19 a equilibrate to the mixture when taken up in CDCl 3 .S ee below for the NMR dataset for pure 18 a,w hich hydrates slowly in dry CDCl 3 .…”