Xin-Yue Fan, Yuan Yu, Ru-De Lin, Yao Yao, Ming-Liang Shi, Kun Li, Xiao-Qi Yu, Yan-Hong Liu and Na Wang
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引用次数: 0
Abstract
Chiral malononitrile compounds, as universal modules, are extensively distributed in bioactive molecules (such as insecticides and herbicides). Developing efficient and highly enantioselective methods for synthesizing β-chiral malononitrile derivatives under mild conditions continues to pose a challenge. Here, we report a one-pot two-stage photoenzymatic strategy combining photocatalytic Knoevenagel condensation with enzymatic CC asymmetric reduction. In the first step, quantitative Knoevenagel reactions are achieved between substituted acetophenones and malononitrile, with methyl orange (MO) as the photocatalyst under white light irradiation. The next step is asymmetric hydrogenation mediated by ene reductase, which only takes 50 minutes to obtain a series of β-chiral malononitrile derivatives with good yields (43–99%) and excellent enantiomeric excess (ee > 99%). The differences in stereoselectivity and reaction activity of several ene reductases are reasonably explained through enzymatic kinetics, molecular docking and molecular dynamic simulation. Furthermore, a scale-up reaction gives 4e in good yield (80%) and excellent ee (>99%). This study provides a sustainable and highly enantioselective approach for accessing a series of valuable β-chiral malononitrile derivatives.
期刊介绍:
Organic Chemistry Frontiers is an esteemed journal that publishes high-quality research across the field of organic chemistry. It places a significant emphasis on studies that contribute substantially to the field by introducing new or significantly improved protocols and methodologies. The journal covers a wide array of topics which include, but are not limited to, organic synthesis, the development of synthetic methodologies, catalysis, natural products, functional organic materials, supramolecular and macromolecular chemistry, as well as physical and computational organic chemistry.