α、β-不饱和醛酮的选择性还原，溶剂说了算！

一项统计结果表明，约四分之一的化学转化中至少涉及一个氢化步骤，而

α、β

通常来讲，钯碳等贵金属催化的催化氢化先还原双键；加热才可以进一步还原；

而若想只还原酮，通常需要需要温和的“硬还原剂”。氢化铝锂虽然硬，但并不是优解；因为其还原强度太高，往往会导致竞争性还原，最终产物多为 1,2 - 与 1,4 - 还原的混合物，分离难度大、目标产物产率低。

目前只还原酮的方法最为人所知的就是luche还原，该种模式的还原反应中，NaBH₄原本是倾向于1,4 - 共轭还原的软还原剂，但经Ce³⁺在醇溶剂中改性后生成 “Ce³⁺- 烷氧基硼氢化物” 复合物；

这种复合物是硬还原剂，更易进攻电子云密度低的羰基碳，从而实现只还原羰基不还原双键；

相比较贵金属催化剂而言，Raney镍催化氢化是工业上使用最多的还原手段，因为雷尼镍便宜且有足够的活性，故而实现雷尼镍参与的选择性还原更具有实际的应用价值。

基于此，最近来自武汉理工大学的研究人员报道了一种由溶剂控制的α,β-不饱和酮/醛的化学选择性还原方法，在二氯甲烷中只还原双键，而在水中，则可以实现双键和羰基的全还原。

选择性还原双键的底物适配上

几种生物活性相关的

α,β

普通的

部分卤代到的底物在DCM中收率不好（毒化催化剂），可以使用甲醇做溶剂，加压/增加反应时间来实现选择性还原；

水相体系中底物还原成饱和醇的适配同样良好；

只有部分底物需要提高催化剂用量，但好的地方在于这种体系中雷尼镍催化剂可循环使用。

放大到克级规模，产物收率也没有明显减少；工业应用前景显著。

最后研究人员提出：溶剂通过影响雷尼镍活性来实现选择性！

DCM易积累于雷尼镍孔结构，降低催化活性，仅选择性还原 C=C 双键；而水分子足够小不积累于孔结构，且通过氢键稳定镍金属，提升催化活性，进而还原 C=O 羰基。

实验方法部分：

1. General procedures for synthesis of the compounds 2

Ketones (1.6 mmol), Raney Ni (10 wt. %), H2 (1.0 MPa), and DCM (8 mL) were added to a high pressure reactor equipped with a magnetic stirrer, which total volume of 100 mL. Hydrogen was charged into the reactor at the inlet, and the gas was replaced three times. Reaction kettle filled with hydrogen 1.0 MPa, and the mixture was stirred strongly at 30 °C for 3 h. The reactor was heated by the heating mantle. Then hydrogen in the reactor was released in the fume hood upon completion. After that, the reaction filtered to remove Raney Ni, washed by ethyl acetate (3×10 mL) and the combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated to dryness to obtain product 2. Raney Ni was recycled.

2. General procedures for synthesis of the compounds 5

Ketones (1.6 mmol), Raney Ni (10 wt. %), H2 (1.0 MPa), and MeOH (8 mL) were added to a high pressure reactor equipped with a magnetic stirrer, which total volume of 100 mL. Hydrogen was charged into the reactor at the inlet, and the gas was replaced three times. Reaction kettle filled with hydrogen 1.0 MPa, and the mixture was stirred strongly at 30 °C for 3 h. The reactor was heated by the heating mantle. Then hydrogen in the reactor was released in the fume hood upon completion. After that, the reaction filtered to remove Raney Ni, washed by ethyl acetate (3×10 mL) and the combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated to dryness to obtain product 5. Raney Ni was recycled.

3. General procedures for synthesis of the compounds 3

Ketones (1.6 mmol), Raney Ni (20 wt. %), H2 (3.0 MPa), and H2O (8 mL) were added to a high pressure reactor equipped with a magnetic stirrer, which total volume of 100 mL. Hydrogen was charged into the reactor at the inlet, and the gas was replaced three times. Reaction kettle filled with hydrogen 3.0 MPa, and the mixture was stirred strongly at 35 °C for 12 h. The reactor was heated by the heating mantle. Then hydrogen in the reactor was released in the fume hood upon completion. After that, the reaction filtered to remove Raney Ni, washed by ethyl acetate (3×10 mL) and the combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated to dryness to obtain product 3. Raney Ni was recycled.

4.General procedures for synthesis of the compounds 7

Aldehydes (1.6 mmol), Raney Ni (10 wt. %), H2 (1.0 MPa), and DCM (8 mL) were added to a high pressure reactor equipped with a magnetic stirrer, which total volume of 100 mL. Hydrogen was charged into the reactor at the inlet, and the gas was replaced three times. Reaction kettle filled with hydrogen 1.0 MPa, and the mixture was stirred strongly at 35 °C for 6 h. The reactor was heated by the heating mantle. Then hydrogen in the reactor was released in the fume hood upon completion. After that, the reaction filtered to remove Raney Ni, washed by ethyl acetate (3×10 mL) and the combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated to dryness to obtain product 7. Raney Ni was recycled.

参考文献：Zhang, Y. K.; Fayad, E.; Katouah, H. A.; Qin, H. L., Solvent-Controlled and Highly Chemoselective Reduction of alpha,beta-Unsaturated Ketones and Aldehydes. J Org Chem 2025, 90 (16), 5704-5709.