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可以在鈀催化下由芳基鹵代物制備芳基硼酸酯。 但是很多情況下，偶聯(lián)反應(yīng)無法得到相應(yīng)的硼酸酯，或者產(chǎn)率很低，如底物中含有巰基（可能是硫可以使催化劑中毒）。 這種情況下，通常我們會(huì)通過【 】，此方法通常是利用 格氏試劑或鋰試劑和硼酸三甲酯在低溫下反應(yīng)，接著酸性條件下水解得到芳基硼酸。

除了硼酸三甲酯和硼酸三異丙酯，還有一種比較常用的制備芳基硼酸酯的試劑，異丙醇頻哪醇硼酸酯。

利用此試劑可以直接得到芳基硼酸頻哪醇酯，操作也比硼酸三甲酯更方便。實(shí)際操作中可以在低溫下先用丁基鋰脫氫或拔鹵形成芳基鋰，然后加入 異丙醇頻哪醇硼酸酯。

對(duì)于一些不穩(wěn)定底物 如果 先拔鹵制備芳基鋰，再加硼酸酯反應(yīng)效果不好，可以考慮先將兩個(gè)底物溶于無水THF，降溫至-78℃，然后緩慢滴加正丁基鋰，加畢，升至室溫，攪拌1小時(shí)，即可得到產(chǎn)物（對(duì)一些吡啶4-位做硼酸酯的底物，不建議兩個(gè)試劑混合后滴加丁基鋰，吡啶氮原子可能會(huì)和硼形成絡(luò)合物，而不是得到芳基硼酸酯）。 飽和氯化銨淬滅反應(yīng)，萃取，干燥，濃縮得到粗產(chǎn)物。 如果反應(yīng)干凈的話，可以直接用于下一步反應(yīng)，剩余的 異丙醇頻哪醇硼酸酯 不影響下一步 。 有時(shí)會(huì)直接生成硼酸和硼酸酯的混合物，這種情況下，可以加入乙醇或甲醇淬滅反應(yīng)，濃縮直接用于下一步反應(yīng)。

操作要點(diǎn) ：反應(yīng)要求嚴(yán)格無水，具體操作參考“有機(jī)合成”公眾號(hào)往期文章【】，溶劑可以直接購(gòu)買超干溶劑，或者自己制備無水溶劑。

反應(yīng)實(shí)例

Synthesis of 2-(2,6-difluoro-4-methylphenyl)-4,4,5,5-tetramethyl-l ,3,2-dioxaboroane To a solution of 1 ,3-difluoro-5-methylbenzene (1.Oeq) in dry THF(0.2M) under an atmosphere of N2 at -78°C was added n-butyllithium (leq, 1.6M in hexanes) slowly keeping the internal temperature below -65°C. The reaction was stirred for 2 hrs at -78°C, followed by the addition of 2-isopropoxy-4,4,5,5-tetramethyl-l,3,2- dioxaborolane (1.15eq). The reaction was allowed to warm to room temperature. Upon completion, the reaction was quenched with NaHC03 (sat.) and extracted with EtOAc. The organics were washed with brine, dried over Na2S04, filtered and concentrated to yield 2-(2,6-difluoro-4-methylphenyl)-4,4,5,5-tetramethyl-l,3,2-dioxaboroane as a white solid in 92%. 1H NMR (400 MHz, ) δ ppm 6.67 (dd, J=9.39, 0.78 Hz, 2 H), 2.34 (s, 3 H), 1.38 (s, 12 H).

【W(wǎng)O2012/4217, 2012 , A1】

2-(4-Methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (5) : n-BuLi (2M in hexane, 21.4 mL, 3.39 g, 53.0 mmol) was added within 25 min at ?78 °C to a solution of 4-bromoanisole (4, 3.30 mL, 4.95 g, 26.5 mmol) in anhydrous THF (120 mL). The mixture was stirred at ?78 °C for 1.5 h, 2-isopropoxy-4,4,5,5-tetramethyl1,3,2-dioxaborolane (11.0 mL, 10.0 g, 53.8 mmol) was added and the temperature was raised to rt overnight. The mixture was brought to pH ~7 by addition of 1N HCl. EtOAc (100 mL) and brine were added and the layers were separated. The aqueous layer was extracted with EtOAc (2×100 mL). The combined organic layers were washed with brine, dried (Na2SO4) and concentrated at reduced pressure to yield the product as a colorless oil (5.96 g, 25.5 mmol, 95%). The NMR-spectroscopic data were in agreement with published data: 3 1 H NMR (300 MHz, CDCl3): δ=1.33 (s, 12H, 4×CCH3), 3.82 (s, 3H, OMe), 6.90 (m, 2H, 3?-H, 5?-H), 7.76 ppm (m, 2H, 2?-H, 4?-H).

【 European Journal of Organic Chemistry , 2019 , 6697 - 6701】