炔类化合物是有机合成中的重要中间体，目前已经发展出了一些非常常用的人名反应，例如Corey-Fuchs reaction, Seyferth-Gilbert reaction和 Sonogashira Coupling reaction。合成炔类化合物的方法按照反应类型可以分为两大类：官能团转化构建碳碳三键；在分子中引入带有碳碳三键的部分。但是在反合成设计上，按照炔基在分子中所处的位置（处于末端；或中间位置）对合成方法进行分类，更加方便应用，因此，接下来介绍的是中间炔烃的合成。
n-BuLi (6.0 mL, 2.5 M in hexane, 15.0 mmol) was added dropwise via an addition funnel to a solution of 3,3-diethoxyprop-1-yne B (1.92 g, 15.0 mmol) in anhydrous THF(30 mL) at 0 °C under N2. The resulting mixture was stirred for 1 hat 0 °C, then a solution of A (1.85g, 5.0 mmol) in dry THF (20 mL) was slowly added to the mixture. The resulting solution was stirred for 5 h at room temperature, then was cooled to 0 °C and quenched with saturated NH4Cl solution. The aqueous layers were extracted with EtOAc (3 × 20 mL). The combined organic phases were dried over MgSO4,and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (PE/EtOAc 5:1 ) to afford P (2.37 g, 95%) as colorless oil.
Reference: Angew.Chem. Int. Ed. 2012, 4909-4912.
To a solution of methyl propargyl ether (4.9 g, 70 mmol) in THF was added n-butyllithium (1.7 M in pentane, 3.53 mL, 6.0 mmol) at −78 °C within 20 min. The solution was stirred for 1 h at this temperature before paraformaldehyde (3.46 g, 115 mmol) was added. The reaction was stirred over night while warming to room temperature. Then saturated ammonium chloride solution(50 mL) was added. It was extracted three times with MTBE (50 mL in each case),dried with magnesium sulfate, and filtered. The solvent was removed in vacuo.The crude product was purified through distillation (80−82 °C, 20 mbar), and the title compound was obtained as a colorless liquid (5.5 g, 55 mmol, 79%).
Reference: J. Org. Chem. 2012, 77, 2360−2367.
A rt solution of A(1.0 eq) and alkyne B (1.1 eq) in THF (0.3 M) was treated dropwise with sodium hexamethyldisilazane (NaHMDS, 1.0M in THF, 1.5 eq) then stirred for 1-5h at 60°C. On completion of the reaction, the mixture was diluted with Et2O, washed with water and brine, dried over MgSO4, filtered, concentrated and purified by flash chromatography using Et2O/hexanes (1/4) to afford the desired product P (71%).
Reference:Org. Lett., 2007, 9 (14), 2741–2743.