Pd-Catalyzed Highly Enantioselective Synthesis of Planar Chiral Ferrocenylpyridine Derivatives

A highly efficient synthesis of planar chiral ferrocenylpyridine derivatives via Pd-catalyzed intramolecular C–H arylation was developed, and quantitative yields and excellent enantioselectivity were obtained for a wide range of substrates. Notably, the catalyst loading could be lowered to 0.2 mol %, which represents the highest catalytic efficiency found for asymmetric C–H bond activation (TON up to 495). These compounds could be easily transformed to pyridine N-oxides, displaying promising catalytic reactivity in the asymmetric opening of meso-epoxide. Moreover, computational investigations were conducted to clarify the origin of the excellent enantioselectivity. The compatibility of large-scale synthesis and low catalyst loading should enhance the practicality of the synthetic application of the current method.本研究开发了一种通过钯（Pd）催化分子内C-H芳基化反应合成平面手性二茂铁吡啶衍生物的高效方法，针对宽泛范围的底物均可实现定量产率与优异的对映选择性。值得注意的是，该方法的催化剂负载量可低至0.2 mol%，这代表了不对称C-H键活化领域已报道的最高催化效率（转化数（TON）最高可达495）。所得目标化合物可便捷转化为吡啶氮氧化物，在催化内消旋环氧化物的不对称开环反应中展现出极具应用前景的催化反应活性。此外，本研究通过计算化学研究阐明了该反应优异对映选择性的起源机制。该方法兼具大规模合成兼容性与极低催化剂负载量的特点，将有效提升当前合成方法的实际应用价值。