* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Stage #1: 4-trifluoromethylbenzoic acid; methoxybenzene With trifluoroacetic anhydride at 80℃;
Stage #2: With boron trifluoride diethyl etherate at 80℃; Title compound not separated from byproducts;
With tri-tert-butyl phosphine; potassium carbonate; acetone In 1,4-dioxane; toluene at 20 - 80℃;
64%
With 3,3-dimethyl-butan-2-one; dichlorotricarbonylruthenium(II) dimer; potassium phosphate tribasic trihydrate; tri tert-butylphosphoniumtetrafluoroborate In water; toluene at 100℃; for 24h; Inert atmosphere;
Multi-step reaction with 2 steps
1: hexane / 3.5 h / 20 °C / Molecular sieve; Inert atmosphere; UV-irradiation
2: hydrogenchloride; water / tetrahydrofuran / 1 h / 20 °C
Multi-step reaction with 2 steps
1: hexane / 12 h / 20 °C / Molecular sieve; Inert atmosphere; UV-irradiation
2: hydrogenchloride; water / tetrahydrofuran / 1 h / 20 °C
Stage #1: p-trifluoromethylphenyl bromide With magnesium In tetrahydrofuran at 20℃; for 1h;
Stage #2: 4-methoxy-benzaldehyde In tetrahydrofuran at 0 - 20℃; for 2h;
Stage #3: With 1,3-Diiodo-5,5-dimethyl-2,4-imidazolidinedione; potassium carbonate In tetrahydrofuran; <i>tert</i>-butyl alcohol for 23h; Reflux; Darkness;
4.1.1. Typical experimental procedure for one-pot conversion of bromides into ketones (1)
General procedure: [Using Mg turnings]: A solution of p-bromotoluene (1112 mg, 6.5 mmol) in dry THF (4 mL) was added dropwise to Mg turnings (182 mg 7.5 mmol) in THF (6 mL) at room temperature and then, the mixture was stirred at room temperature for 1 h. A solution of p-chlorobenzaldehyde (703 mg, 5.0 mmol) in THF (5 mL) was added to the mixture at 0 °C and the obtained mixture was stirred at room temperature for 2 h. Then, DIH (1520 mg, 4.0 mmol), K2CO3 (1451 mg, 10.5 mmol), and t-BuOH (15 mL) were added and the obtained mixture was stirred for 20 h at refluxing conditions. The reaction mixture was quenched with satd aq Na2SO3 (10 mL) and was extracted with CHCl3 (3×25 mL). The organic layer was washed with brine and dried over Na2SO4. Purification by short column chromatography (silica gel; hexane/CHCl3=1:1) yielded p-chlorophenyl p-tolyl ketone (934 mg, 81%).
79%
Stage #1: p-trifluoromethylphenyl bromide With magnesium In tetrahydrofuran at 20℃; for 3h; Inert atmosphere;
Stage #2: 4-methoxy-benzaldehyde In tetrahydrofuran at -72 - 20℃; for 4h; Inert atmosphere;
Stage #3: With silica gel; pyridinium chlorochromate In dichloromethane at 20℃; for 14h;
45%
With tetrakis(tetrabutylammonium)decatungstate(VI); palladium diacetate; sodium carbonate; bis[2-(diphenylphosphino)phenyl] ether In acetone at 20℃; for 48h; Irradiation;
Stage #1: 1-bromo-4-methoxy-benzene With magnesium; ethylene dibromide In tetrahydrofuran at 0 - 20℃; for 1.5h;
Stage #2: 4-CF3C6H4CN In tetrahydrofuran at 0 - 70℃; for 3h;
Stage #3: With hydrogenchloride; water In tetrahydrofuran at 90℃; for 3h;
With bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; lithium carbonate; acetic acid; silver(I) triflimide In 1,2-dichloro-ethane at 20℃; for 12h; Inert atmosphere;
1-(4-(trifluoromethyl)benzoyl)piperidine-2,6-dione[ No CAS ]
[ 93296-09-4 ]
[ 6185-76-8 ]
Yield
Reaction Conditions
Operation in experiment
85%
Stage #1: 1-(4-(trifluoromethyl)benzoyl)piperidine-2,6-dione With bis(triphenylphosphine)nickel(II) chloride In diethyl ether at 23℃; for 0.0833333h; Inert atmosphere; Schlenk technique;
Stage #2: 4-methoxyphenylzinc chloride In tetrahydrofuran; diethyl ether at 23℃; for 12h; Inert atmosphere; Schlenk technique; chemoselective reaction;
With [(η3-1-tBu-indenyl)Pd(1,3-bis(2,6-diisopropylphenyl)-1,3-dihydro-2H-imidazol-2-ylidene)(Cl)]; potassium carbonate In tetrahydrofuran at 23℃; for 15h;
30%
With potassium phosphate; (3-phenylallyl)(chloro)-[1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene]palladium(II); water In tetrahydrofuran at 90℃; for 2h; Inert atmosphere; Sealed tube; Schlenk technique;
With [(η3-1-tBu-indenyl)Pd(1,3-bis(2,6-diisopropylphenyl)-1,3-dihydro-2H-imidazol-2-ylidene)(Cl)]; potassium carbonate In tetrahydrofuran at 23℃; for 15h;
97%
With potassium phosphate; (3-phenylallyl)(chloro)-[1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene]palladium(II); water In tetrahydrofuran at 90℃; for 2h; Inert atmosphere; Sealed tube; Schlenk technique;
64%
With C40H52ClN2Pd; potassium hydroxide In tetrahydrofuran; water at 20℃; for 6h; Glovebox;
sodium (4-trifluoromethylphenyltrihydroxyborate)[ No CAS ]
[ 100-07-2 ]
[ 6185-76-8 ]
Yield
Reaction Conditions
Operation in experiment
82%
With tetrakis(triphenylphosphine) palladium(0) In water; toluene at 60℃; for 24h; Inert atmosphere;
4.1.2 General procedure for the Suzuki-Miyaura acylation reactions
General procedure: The corresponding borate salt (1mmol), Pd(PPh3)4 (0.01mmol, 11.56mg), degassed toluene (2.0mL), degassed water (0.50mL) were place in a 50mL round-bottomed flask with a magnetic stirrer bar and a rubber septum. The content of the flask was kept under argon while acyl chloride (1.10mmol), dissolved in degassed toluene (1.0mL), was added dropwise via a syringe and the flask was heated to 60°C on the oil bath. After 24h, the reaction mixture was filtered and solvent removed under vacue. The resulting residue was dissolved in DCM and was purified using flash-column chromatography or centrifugal preparative thin-layer chromatography (chromatotron) using Hexane: Ethyl acetate (9:1) as an eluent.
1-(4-(trifluoromethyl)benzoyl)pyrrolidine-2,5-dione[ No CAS ]
[ 93296-09-4 ]
[ 6185-76-8 ]
Yield
Reaction Conditions
Operation in experiment
82%
With bis(triphenylphosphine)nickel(II) chloride In tetrahydrofuran; diethyl ether; hexane at 23℃; for 12h; Inert atmosphere; Schlenk technique; chemoselective reaction;
General Procedure for Negishi Cross-Coupling of Amides.
General procedure: An oven-dried vial equipped with a stir bar was charged with an amide substrate (neat, 1.0 equiv) and Ni(PPh3)2Cl2 (0.05 equiv), placed under a positive pressure of argon, and subjected to three evacuation/backfilling cycles under vacuum. Diethyl ether (0.20 M) was added with vigorous stirring at room temperature and the reaction was stirred at room temperature for 5 min. A solution of arylzinc reagent (THF solution, 1.5 equiv) was added with vigorous stirring and the reaction mixture was stirred for the indicated time at 23 °C. After the indicated time, the reaction mixture was diluted with HCl (0.1 N, 10 mL), the aqueous layer was extracted with EtOAc (3 x 20 mL), organic layers were combined, dried, filtered and concentrated. The sample was analyzed by 1H NMR (CDCl3, 500 MHz) and GC-MS to obtain conversion, yield and selectivity using internal standard and comparison with authentic samples. Purification by chromatography on silica gel (hexanes/EtOAc) afforded the title product.
tert-butyl (4-methoxybenzoyl)(phenyl)carbamate[ No CAS ]
[ 128796-39-4 ]
[ 6185-76-8 ]
Yield
Reaction Conditions
Operation in experiment
98%
With (3-phenylallyl)(chloro)-[1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene]palladium(II); water; potassium carbonate In 2-methyltetrahydrofuran at 23℃; for 15h; Inert atmosphere; Schlenk technique; Green chemistry; chemoselective reaction;
95%
With [(η3-1-tBu-indenyl)Pd(1,3-bis(2,6-diisopropylphenyl)-1,3-dihydro-2H-imidazol-2-ylidene)(Cl)]; potassium carbonate In tetrahydrofuran at 23℃; for 15h;
tert-butyl phenyl(4-(trifluoromethyl)benzoyl)carbamate[ No CAS ]
[ 6185-76-8 ]
Yield
Reaction Conditions
Operation in experiment
95%
With (3-phenylallyl)(chloro)-[1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene]palladium(II); water; potassium carbonate In 2-methyltetrahydrofuran at 23℃; for 15h; Inert atmosphere; Schlenk technique; Green chemistry; chemoselective reaction;
94%
With [(η3-1-tBu-indenyl)Pd(1,3-bis(2,6-diisopropylphenyl)-1,3-dihydro-2H-imidazol-2-ylidene)(Cl)]; potassium carbonate In tetrahydrofuran at 23℃; for 15h;
1-(4-(trifluoromethyl)benzoyl)pyrrolidine-2,5-dione[ No CAS ]
[ 6185-76-8 ]
Yield
Reaction Conditions
Operation in experiment
98%
With potassium phosphate; palladium diacetate; tricyclohexylphosphine In toluene at 110℃; for 4h; Inert atmosphere; Sealed tube;
General Procedures for the synthesis of products 3aa-3an, 3ba-3la
General procedure: In an oven-dried Teflon septum screw-capped tube (15 mL), add N-Acylsuccinimides (0.2 mmol), Aryl boronic acid (0.24 mmol, 1.2 equiv), K3PO4 (0.4 mmol, 2 eqiuv), Pd(OAc)2 (2.24 mg, 0.01 mmol), PCy3 (11.22 mg, 0.04 mmol), toluene (2.0 ml) The tube was then charged with nitrogen. The reaction was monitored by TLC. The reaction was then heated to 110 and stirred for 4 h. After cooling to room temperature, the solvents were removed, the crude product was purified by silica gel column chromatography using (petroleum ether/ethyl acetate = 20:1) as eluent.
(1H-pyrrol-1-yl)(4-(trifluoromethyl)phenyl)methanone[ No CAS ]
[ 6185-76-8 ]
Yield
Reaction Conditions
Operation in experiment
89%
With bis(1,5-cyclooctadiene)nickel (0); potassium phosphate; 1,1'-((2,4,6-trimethyl-1,3-phenylene)bis(methylene))bis(3-(2,6-diisopropylphenyl)-1H-imidazol-3-ium) chloride In water; toluene at 60℃; for 20h; Inert atmosphere; Darkness; Sealed tube;
4-methoxy-N-phenyl-N-((trifluoromethyl)sulfonyl)benzamide[ No CAS ]
[ 128796-39-4 ]
[ 6185-76-8 ]
Yield
Reaction Conditions
Operation in experiment
85%
With [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(ll) dichloride; potassium carbonate In tetrahydrofuran; water at 40℃; for 15h; Inert atmosphere; Schlenk technique; chemoselective reaction;
With sodium t-butanolate; In N,N-dimethyl acetamide; at 80℃; for 0.25h;
General procedure: Aryl halide (1.0 mmol), arylboronic acid (1.1 mmol),t-BuONa (2.0 mmol), SBA-16/DFMP-Pd (0.0026 g,0.2 mol%), and Cr(CO)6 (0.5 mmol, 0.11 g) in DMA(3.0mL) was stirred in a flask at 80C. The reaction progress was monitored by thin layer chromatography (TLC).Upon the reaction’s completion, the mixture was allowed to cool down to room temperature and then filtered and washed with H2Oand ethyl acetate. The organic fraction was separated,dried over anhydrous Na2SO4 and then the solvent was removed using a rotary evaporator. Further purification was performed on silica gel column chromatography to afford the pure products.
Stage #1: 4-trifluoromethylbenzoic acid With tert-butylmagnesium chloride In tetrahydrofuran; toluene at 0℃; for 0.25h; Inert atmosphere;
Stage #2: 4-methoxyphenyl magnesium bromide With diisopropylaminomagnesium chloride lithium chloride In tetrahydrofuran; toluene at 0 - 20℃; for 3.25h; Inert atmosphere; Sonication;
Stage #1: (4-methoxyphenyl)(4-(trifluoromethyl)phenyl)methanone With 4-pyridinecarboxylic acid, methyl ester; bis(pinacol)diborane at 20℃; for 1h; Inert atmosphere; Reflux;
Stage #2: With potassium hydrogen difluoride at 20℃; for 3h; Inert atmosphere;