金属有机试剂制备单取代芳基硼酸

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经典合成单取代芳基硼酸(酯)的方法是用格氏试剂或锂试剂和硼酸酯反应来制备。

用这种经典方法的缺点是单取代芳基硼酸酯有进一步生成二取代硼酸,甚至三烷基硼的可能,因此反应须在低温下进行。解决这个问题的一个有效的办法是使用硼酸三异丙酯和有机锂试剂反应, 可以避免二烷(芳)基硼烷和三烷(芳)基硼烷的产生。反应完后通常加入稀盐酸酸化直接高收率地得到芳基硼酸酯。【Brown, H. C.; Cole, T. E. Organometallics, 1983, 2, 1316. Brown, H. C.; Bhat, N. G.; Srebnik, M. TetrahedronLett. 1988,29,2631. Brown, H. C.; Rangaishenvi, M. V. Tetrahedron Lett. 1990,49, 7113, 7115.


反应实例

A 500-mL, three-necked, round-bottomed flaskcontaining magnesium turnings (1.94 g, 80 mmol) is equipped with a rubber septum, a 20-mLpressure-equalizing dropping funnel fitted with a rubber septum, aTeflon-coated magnetic stirring bar, and a reflux condenser fitted with anargon inlet adapter. The system is flame-dried and flushed with argon.Anhydrous ether (200 mL) is introduced to cover the magnesium,a crystal of iodine is added, and the mixture is heated to reflux in an oilbath.  The dropping funnel is filled with1-bromo-3,4,5-trifluorobenzene(8.36 mL, 14.8 g, 70.0 mmol) andca. 1 mL is added to the boiling reaction mixture. After reaction hascommenced, the oil bath is removed, and the remainder of the aryl bromide isadded slowly at a rate sufficient to maintain reflux (addition time ca. 1 hr).The resulting mixture is stirred for an additional 2 hr. During this period, aflame-dried, 500-mL, single-necked, round-bottomed flask equipped with aTeflon-coated magnetic stirring bar, a rubber septum, and an argon inlet ischarged with dry tetrahydrofuran(THF, 50 mL) and trimethylborate (15.7 mL, 14.5 g, 140 mmol).  Themixture is cooled to 0°C,and the ether solution of (3,4,5-trifluorophenyl)magnesiumbromide prepared above is introduced in one portion via adouble-ended needle. The reaction mixture is allowed to warm to roomtemperature, stirred for 1 hr, and then treated with 200 mL of saturated ammoniumchloride solution. The organic layer is separated and the aqueouslayer is extracted with three 100-mL portions of ethyl acetate.  The combined organic layers are washed withbrine (100 mL), dried over anhydrous magnesiumsulfate, filtered, and concentrated under reduced pressure.  The resulting white solid is dissolved in aminimal amount of hot (65°C) ethyl acetate,allowed to cool to room temperature, and then 600 mL of hexane is added.  The resulting solution is allowed to standovernight and then filtered to afford pure (3,4,5-trifluorophenyl)boronicacid as white crystals. Further recrystallization of the motherliquor 3-4 times provides a total of 6.3 g(51%) of (3,4,5-trifluorophenyl)boronic acid.



nBuLi (1.6_ in hexane, 1 mL, 1.6 mmol) at -78℃ under nitrogen was addedto a solution of 4-(trimethylsilylethynyl) iodobenzene (0.3 g, 1.13 mmol) in THF (5 mL).  After stirring for 15 min at - 78℃, trimethylborate (0.2 mL, 1.6 mmol)was added in one portion.  The mixture waswarmed to 25 ℃, stirred for 30 min, andquenched with dilute HCl solution.  Themixture was extracted with EtOAc (20 mL), washed with water, dried (MgSO4) andevaporated to obtain the crude 4-(trimethylsilylethynyl) phenylboronic acidthat was used without further purification.

Chem.Eur. J. 2003, 9, 4430-4441】



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