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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2,6-difluorophenyltrifluoroborate potassium salt[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
66%
General procedure: an oven dried glass vessel capable of being sealed with a Teflon cap (for microwave vials) was added XPhos-Pd-G2 (5.89mg, 7.5mumol), XPhos (7.14mg, 15mumol), B2(OH)4 (203mg, 2.25mmol), KOAc (441mg, 4.5mmol), and halide (only if a solid). The vessel was sealed, evacuated, and filled with an inert gas (4×). EtOH (15mL, degassed) was added via syringe followed by the addition of ethylene glycol (280mg, 250muL, 4.5mmol) and the halide (1.5mmol) in a similar manner (if applicable). The reaction was heated to the specified temperature until the starting material was consumed (monitored by GC). The reaction was cooled to rt and filtered through a very thin pad of Celite and decolorizing carbon (eluting with 5×10mL of EtOAc) and concentrated. The crude reaction was dissolved in EtOAc (10mL), transferred to a separatory funnel, and then H2O (10mL) was added. The layers were separated, and the organic layer was washed with brine (5mL). The combined aqueous layers were extracted with EtOAc (3×5mL) dried (Na2SO4), filtered, and concentrated. MeOH (?15mL) was added to concentrated crude reaction mixture, which was cooled to 0C. To this reaction mixture, KHF2 (1mL of 4.5M soln, 4.5equiv) was added. The reaction was stirred at 0C for 10min before removing the bath and allowing the reaction mixture to stir for 20min (or until conversion to trifluoroborate is complete as observed by 11B). The resulting mixture was concentrated and then lyophilized overnight to remove any traces of H2O. The compound was purified with continuous Soxhlet extraction (8h or by complete disappearance of RBF3K in the thimble as determined by 11B NMR). The collected solvent was concentrated until a minimum amount of acetone (?3mL) remained. The addition of Et2O (?25mL) led to the precipitation of the desired product.
potassium (6-fluoropyridin-3-yl)trifluoroborate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
76%
General procedure: an oven dried glass vessel capable of being sealed with a Teflon cap (for microwave vials) was added XPhos?Pd-G2 (5.89mg, 7.5mumol), XPhos (7.14mg, 15mumol), B2(OH)4 (203mg, 2.25mmol), KOAc (441mg, 4.5mmol), and halide (only if a solid). The vessel was sealed, evacuated, and filled with an inert gas (4×). EtOH (15mL, degassed) was added via syringe followed by the addition of ethylene glycol (280mg, 250muL, 4.5mmol) and the halide (1.5mmol) in a similar manner (if applicable). The reaction was heated to the specified temperature until the starting material was consumed (monitored by GC). The reaction was cooled to rt and filtered through a very thin pad of Celite and decolorizing carbon (eluting with 5×10mL of EtOAc) and concentrated. The crude reaction was dissolved in EtOAc (10mL), transferred to a separatory funnel, and then H2O (10mL) was added. The layers were separated, and the organic layer was washed with brine (5mL). The combined aqueous layers were extracted with EtOAc (3×5mL) dried (Na2SO4), filtered, and concentrated. MeOH (?15mL) was added to concentrated crude reaction mixture, which was cooled to 0°C. To this reaction mixture, KHF2 (1mL of 4.5M soln, 4.5equiv) was added. The reaction was stirred at 0°C for 10min before removing the bath and allowing the reaction mixture to stir for 20min (or until conversion to trifluoroborate is complete as observed by 11B). The resulting mixture was concentrated and then lyophilized overnight to remove any traces of H2O. The compound was purified with continuous Soxhlet extraction (8h or by complete disappearance of RBF3K in the thimble as determined by 11B NMR). The collected solvent was concentrated until a minimum amount of acetone (?3mL) remained. The addition of Et2O (?25mL) led to the precipitation of the desired product.
With potassium acetate; palladium diacetate; tris-(o-tolyl)phosphine; In tetrahydrofuran; methanol; at 0 - 20℃;Inert atmosphere;
Example 3 Synthesis of 4-pentyloxy-4'-biphenylboronic acid under nitrogen protection, Add 5g of 4'-bromo-4-n-pentyloxybiphenyl to a 100mL three-necked flask. 88 mg of palladium acetate, 4.6 g of potassium acetate, 144 mg of tris(o-methylphenyl)phosphine and 15 mL of tetrahydrofuran, The ice water bath is cooled to 0-10 C. 1.84 g of tetrahydroxydiboron was dissolved in 10 mL of methanol and added dropwise to the reaction. Stir the reaction at room temperature, After the raw materials disappeared, add 30mL of ethanol to dilute. Filtering, The filter cake was washed with 10 mL of ethanol. The filtrate was spun dry, and then 80 ml of a dichloromethane/water mixed solvent (1:1) was added and hot-battered at 40 C for 1 h. After cooling to room temperature, suction filtration, The filter cake was washed sequentially with 5 mL of water and 5 mL of dichloromethane. Drying at 50 C under vacuum gave 2.84 g of a white solid. The yield was 64%.
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