Electrochemical Borylation of Alkyl Halides: Fast, Scalable Access to Alkyl Boronic Esters
Bingbing Wang, Pan Peng, Wan Ma, Zhao Liu, Cheng Huang, Yangmin Cao, Ping Hu, Xiaotian Qi* and Qingquan Lu*
*Wuhan University, Wuhan 430072, P. R. China,
Email: qi7xiaotian
whu.edu.cn, gci2011whu.edu.cn
B. Wang, P. Peng, W. Ma, Z. Liu, C. Huang, Y. Cao, P. Hu, X. Qi, Q. Lu, J. Am. Chem. Soc., 2021, 143, 12985-12991.
DOI: 10.1021/jacs.1c06473
see article for more reactions
Abstract
Electroreduction at a high current enables a fast, scalable, and transition-metal-free borylation of alkyl halides (X = I, Br, Cl) at room temperature. This process provides an efficient and practical access to primary, secondary, and tertiary boronic esters, including late-stage borylation of natural products and drug derivatives.
see article for more examples
proposed mechanism
General Procedure
B2cat2 (2.4 mmol, 4.0 equiv., 571.0 mg) and nBu4NBF4 (0.3 mmol, 99.0 mg) were added into an oven-dried undivided three-necked cell (20 mL) equipped with a Teflon-coated magnetic stir bar. The undivided cell was equipped with Mg plate (15 mm×15 mm×0.5 mm) as the anode and carbon cloth electrode (15 mm×15 mm) as the cathode and then charged with argon to replace air atmosphere. Alkyl bromide (0.6 mmol, solid bromide was added into electrolyzer cell in advance) and DMAc (6.0 mL) were added to the tube through a syringe. Pre-stirring the resulting mixture until it is completely dissolved, and then the reaction mixture was electrolyzed at a constant current of 150 mA until passing 3.0 F/mol of charge (around 19 min) at room temperature (around 25 °C). Afterwards, a solution of pinacol (4.8 mmol, 8.0 equiv., 567.2 mg) in triethylamine (1.5 mL) was added to the electrolyzer cell and the reaction mixture kept stirring at room temperature for 1 h. Then, saturated brine water was added into the reaction mixture and the aqueous layer was extracted with ethyl acetate (3 x 15 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated in vacuum. The concentrated reaction mixture was filtered through silica gel with copious washings to remove the partial impurity (ethyl acetate:petroleum ether = 1:10), concentrated, and purified by column chromatography (eluted with ethyl acetate/petroleum ether) to afford the pure desired product.
Key Words
borylation, electrochemistry
ID: J48-Y2021
