有机硼试剂的制备
在现代化学合成中，有机硼类化合物发挥着极其重要的作用，而在这些硼类化合物中，硼酸类又占据主导地位。随着大量新的化学反应被发现，特别是Suzuki-Miyaura 交叉偶联反应的出现，使得硼酸及其盐类化合物由于其自身的高获取性和易处理性，成为有着巨大价值的多功能中间体 。
一．硼酸的制备
通过有机金属试剂制备单取代芳基硼酸：
Grinard试剂制备单取代芳基硼酸
有机锂试剂制备单取代芳基硼酸
二、 硼酸酯的制备
1. 通过二硼烷频哪酯制备芳基硼酸酯
对于分子中带有酯基、氰基、硝基、羰基等官能团的芳香卤代物来说, 无法通过有机金属试剂来制备相应的芳基硼酸。
1995年由Ishiyama通过二硼烷频哪酯和芳基卤发生偶联反应制备相应的芳基硼酸酯。
Mechanism
1.极性溶剂里此偶联反应的产率可以得到很大的提高：DMSO≥ DMF > dioxane > toluene。
2.KOAc是应用于这个反应最合适的碱，其他的如K3PO4或K2CO3这些碱性略强的碱会进一步使原料芳基卤发生自偶联反应
3.制备溴代物和碘代物相应的芳基硼酸酯，Pd(dppf)Cl2一般可以得到很好的结果，又由于其具有易于反应的后处理的优点
4.2001年Ishiyama经过研究发现氯代物，在 Pd(dba)2/PCy3的催化下效果较好
2. 通过芳基硼酸转化为芳基硼酸酯
3. 烯基硼酸酯的制备
4. 烷基硼酸酯的制备
三、氟硼酸盐的制备
常用于特定醛酮的烷基化反应
四、实例
A solution of compound 1 (2g, 0.01mol) in THF was cooled at -78℃ followed by adding 2.5M n-BuLi (6mL, 0.015mol). The mixture was stirred for 4h at -78℃ and the compound 1A (1.65mL, 0.015mol) was added. The reaction mixture was warmed up to room temperature and stirred overnight. The reaction was quenched with 1M HCl and stirred for 0.5h. The mixture was extracted with EtOAc (50mL*3). The organic phase was washed with 1M NaOH. The aqueous was acetfied with con.HCl and extracted with EtOAc. The combined organic phase was dried over Na2SO4, filtered, concentracted and then washed with PE (30mL). Then the light yellow solid is compound 2 (1.5g, 90% yield).
A mixture of compound 1 (500 mg, 1.95 mmol), compound 1A (830 mg, 2.92 mmol), KOAc (572 mg, 5.84 mmol), and Pd(dppf)Cl2 (142 mg, 0.195 mmol) in Dioxane (10 mL) was heated at 80℃ for 5 hours under N2 atmosphere. The mixture was extracted with EtOAc (50 mL), washed with water. The solvent was removed under reduced pressure, and the residue was purified by pre-TLC to afford compound 2 (450 mg, yield: 76%).
“一锅法”
A mixture of compound 1 (80 mg, 0.16 mmol), bis(pinacolato)diboron (40 mg, 0.16 mmol), KOAc (48 mg, 0.48 mmol), X-phos (40 mg, 0.08 mmol), and Pd(dppf)Cl2 (40 mg, 0.04 mmol) in dioxane (10 mL) was stirred at 90℃ for 2 hours. TLC showed compound 1 was consumed completely. 2-Bromo-4,6-dimethylpyridine (88 mg, 0.48 mmol), Cs2CO3 (160 mg, 0.48 mmol) and Pd2(dba)3 (40 mg, 0.04 mmol) were added to the reaction mixture. The mixture was stirred at 90℃ for another 4 hours. The mixture was diluted with H2O and extracted with EtOAc. The EtOAc layer was dried over Na2SO4 and concentrated. The product was purified by pre-TLC to give the compound 2 (20 mg, yield: 22%).
To a mixture of 1 (188 mg, 1 mmol) in MeOH/H2O (1 mL/2 mL) was added KHF2 (156 mg, 2 mmol) at 0℃. The mixture was stirred at room temperature for 2 hours and stirred at 5℃ for 2 hours. The mixture was repeated crystal to give 2(197 mg, yield: 94%).
