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Transition-Metal-Free Borylation of Aryl Bromide Using a Simple Diboron Source
Lim, Taeho ; Ryoo, Jeong Yup ; Han, Min Su ;
Abstract: In this study, we developed a simple transition-metal-free borylation reaction of aryl bromides. Bis-boronic acid (BBA), was used, and the borylation reaction was performed using a simple procedure at a mild temperature. Under mild conditions, aryl bromides were converted to arylboronic acids directly without any deprotection steps and purified by conversion to trifluoroborate salts. The functional group tolerance was considerably high. The mechanism study suggested that this borylation reaction proceeds via a radical pathway.
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Purchased from AmBeed: 20469-65-2 ; 13675-18-8 ; 2564-83-2 ; 872-31-1 ; 192863-35-7 ; 871231-46-8 ; 192863-36-8 ; 6793-92-6 ; 3972-65-4 ; 2398-37-0 ; 850623-47-1 ; 929626-22-2 ; 705254-31-5 ; 580-13-2 ; 2635-13-4 ; 623-12-1 ; 1015082-71-9 ; 52415-29-9 ; 23145-07-5 ; 619-42-1 ; 99-90-1 ; 192863-37-9 ; 578-57-4 ; 407-14-7 ; 216434-82-1 ; 668984-08-5 ; 423118-47-2 ; 108-85-0 ; 252726-24-2 ; 101-55-3 ; 850623-36-8 ; 4923-87-9 ; 1394827-04-3 ; 850623-42-6 ; 438553-44-7 ; 460-00-4 ; 1187951-62-7 ; 705254-34-8 ; 111-83-1 ; 111-83-1 ; 906007-40-7 ; 1443282-44-7 ; 1000160-76-8 ; 1111733-01-7 ; 99-90-1
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CAS No. : | 52415-29-9 |
Formula : | C8H6BrN |
M.W : | 196.04 |
SMILES Code : | C1=C[NH]C2=C1C=CC(=C2)Br |
MDL No. : | MFCD00238550 |
InChI Key : | MAWGHOPSCKCTPA-UHFFFAOYSA-N |
Pubchem ID : | 676493 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | To a solution of 6-bromo-lH-indole (202a) (5 g, 25.5 mmol) in toluene (80 mL) at 0 C under inert atmosphere was added acetyl chloride (2.72 mL, 38.3 mmol), stirred for 10 mins followed by dropwise addition of Tin(IV) chloride (4.49 mL, 38.3 mmol) in toluene (20 mL). The reaction mixture was stirred at 0 C for 3h in ice-water bath and the pink fine suspension was poured into a bi-phasic layer of aqueous saturated NaHCCb (600 mL) and EtOAc (400 mL). The mixture was stirred vigorously for 15 min and filtered over Celite pad to remove inorganic impurities. The organic layer was separated washed with brine, dried, filtered and concentrated in vacuum to afford l-(6-bromo-lH-indol-3-yl)ethanone (202b) (4.15 g, 17.43 mmol, 68% yield) as a white solid; 1H MR (300 MHz, OMSO-de) δ 12.04 (s, 1H), 8.34 (d, J = 1.6 Hz, 1H), 8.10 (dd, J = 8.5, 0.6 Hz, 1H), 7.65 (dd, J = 1.8, 0.6 Hz, 1H), 7.31 (dd, J = 8.5, 1.8 Hz, 1H), 2.44 (s, 3H); MS (ES+): 238.2, 240.2 (M+2); MS (ES-): 236.1, 238.1 (M-2). | |
62% | At room temperature, dissolve 6-bromoindole (7) (15.0g, 76.5mmol) in anhydrous toluene (150mL), cool to 0C, add acetyl chloride (10.9mL, 153.0mmol), Stir at 0 C for 15 min. Then add tin tetrachloride (17.9ml, 153.0 mmol) in toluene (75mL), stir the reaction at 0C for 2h. TLC monitoring, after the reaction is complete, add 8% sodium bicarbonate solution (75mL) dropwise, then add ethyl acetate (150 mL), stirring at room temperature for 10 min. The organic layer was separated, the aqueous layer was extracted with ethyl acetate (150 mL*2), the organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered with suction, concentrated under reduced pressure and evaporated to remove the solvent to obtain a brown solid. Recrystallized with acetone to obtain 11.3g of gray solid with a yield of 62%. | |
11% | To a solution of 46-S1 (5 g, 25.5 mmol) in dry DCM (50 mL) was added SnCl4 (5 mL) under an atmosphere of nitrogen at 0 C. The mixture was stirred at this temperature for 30 minutes and acetyl chloride (3.0 g, 38.3 mmol) was added dropwise to the reaction mixture, followed by nitromethane (30 mL). The reaction mixture was stirred at room temperature for 4 hours. The mixture was quenched with ice water and extracted with DCM twice. The combined organic layers were washed with water and brine, dried over anhydrous Na2SO4, filtered, and concentrated to dryness. The remaining residue was purified by column chromatography on silica gel (eluted with DCM/MeOH = 100:1) to afford 46-S2 (669 mg, 11% yield) as a yellow solid. LC/MS (ESI) m/z: 238/240 (M+H)+. |
With tin(IV) chloride; In toluene;Inert atmosphere; | [0505] 1-(6-Bromo-1H-indol-3-yl)ethanone 51 was prepared from 6-bromoindole 50 according to the procedure of MacKay et al. (MacKay, J. A.; Bishop, R.; Rawal, V. H. Org. Lett. 2005, 7, 3421-3424.) | |
General procedure: To a CH2Cl2 solution of indole A was added Et2AlCl (1.5 equiv, 2M in hexane) dropwise at 0 C. After stirred for 30 min, the substituted acid chlorides were added dropwise to this solution at 0 C. The resulting mixture was allowed to stir at same temperature for 2-4 hours. After completion of the reaction it was quenched with aqueous buffer (Ph = 7) and extracted by CH2Cl2. The organic layer was dried over anhydrous Na2SO4, concentrated under pressure and then purified by column chromatography on silica gel to provide the indole B. Indole B was suspended in N, N-dimethylformamaide (DMF) and NaH (1.5 equiv) was added under ice cooled conditions. Then DMF solution of TsCl (1.2 equiv) was added dropwise at 0 C. After stirred at room temperature overnight, the mixture was quenched with water and then extracted with CH2Cl2 three times. The organic layer was dried over anhydrous Na2SO4, concentrated under pressure and then purified by column chromatography on silica gel to provide the N-Ts indoles C. Under argon, a flask was charged with the N-Ts indoles C and anhydrous THF. Under the ice cooled conditions, Grignard reagents (1M in THF, 1.5 equiv) were added dropwise. Then, the reaction mixture was stirred at 50 C overnight. After completion of the reaction it was quenched with a saturated solution of NH4Cl and extracted with CH2Cl2. Combined organic layers were dried over Na2SO4, the solvent was evaporated and the residue was purified by a silica gel chromatography column to afford the 3-indolymethanols D (1a-1p). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | General procedure: To a stirred solution of 5-bromo-1H-indole 7c (0.5 g, 2.5 mmol) in CH2Cl2 (20 mL) under argon atmosphere at 0C, was added SnCl4 (0.2 mL, 3.0 mmol) drop-wise over 5 minutes. The reaction mixture was then slowly warmedto room temperature and stirred for 30 minutes. Acetic anhydride (0.24 mL, 2.5 mmol) was added into the reactionmixture, followed by nitromethane (5 mL). The reaction mixture was then stirred for 2 h at room temperature. Afterthe completion of the reaction, it was then quenched with ice and water (10 mL). The reaction mixture was thenfiltered to remove the inorganic precipitates, and the organic material was extracted with ethyl acetate (2 x 20 mL).The organic phase was then dried over anhy. Na2SO4 and concentrated under reduced pressure, to afford theproduct 13c (0.556 g, 92% yield) as a crystalline solid. 1-(6-Bromo-1H-indol-3-yl)ethanone (13b):Yield: 90%; pale yellow solid; mp: 240-242 C; IR (KBr, cm-1) 3858, 3735, 3615, 3564, 2918, 2364, 1717, 1622;1H NMR (DMSO-d6, 400 MHz): δ (ppm) 2.45 (s, 3H), 7.31 (d, J = 8.3 Hz, 1H), 7.65 (s, 1H), 8.11 (d, J = 8.3 Hz,1H), 8.33 (s, 1H), 12.10 (bs, 1H); 13C NMR (DMSO-d6, 100 MHz): δ (ppm) 27.2, 114.7, 115.3, 116.7, 122.9,124.3, 124.5, 135.2, 137.5, 192.7; LRMS (ESI): m/z = 238 and 240 [(M+H)+]. HRMS (ESI) calcd. for C10H8NOBr[(M+H)+]: 237.9868, found: 237.9863. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With oxygen; copper(II) bis(trifluoromethanesulfonate); cobalt(II) chloride; In ethanol; at 40℃; under 760.051 Torr; for 48h;Sealed tube; | Add 2-methyl carboxylate to phenol (0.2mmol, 1.0equiv.), 6-bromoindole (0.2mmol, 1.0equiv.), CoCl2 (1.3mg, 5mol%), Cu( OTf)2 (7.3mg, 10mol%) and magnet, sealed with a rubber stopper, vacuumed and then filled with O2, transferred 4ml of 95% ethanol with a syringe to the sealed sample bottle, and then the atmosphere in the bottle was changed to 1 atm After the reaction was stirred at 40C for 48h, the solvent was removed by blowing air pump for 1 hour at a constant temperature of 30C. The residue was purified by column chromatography on silica gel. The eluent was petroleum ether/ethyl acetate 20:1 to 5 :1 Gradient elution. The target product was collected and the isolated yield was 75%. |
Tags: 6-Bromoindole | Indoles | Bromides | Organic Building Blocks | Heterocyclic Building Blocks | 52415-29-9
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