Development of a Tunable Chiral Pyridine Ligand Unit for Enantioselective Iridium-Catalyzed C–H Borylation

Although pyridine derivatives are versatile supporting ligands in catalysis, the development of their chiral versions has been relatively limited. Herein, we report the design, synthesis, and proof-of-concept application of a structurally tunable chiral pyridine framework featuring an annulated compact ring system. Using an N,B-bidentate ligand skeleton containing the chiral pyridine moiety, we have developed an enantioselective iridium-catalyzed desymmetrizing C–H borylation reaction of diaryl­(2-pyridyl)­methane compounds with up to 96% ee and 93% yield. The resulting borylation products could be readily transformed into various chiral tri­(hetero)­arylmethane compounds. Density functional theory investigations revealed that the two chair conformations of the flexible ketal motif both favored the enantiomer that was consistent with experimental results. This work has thus introduced an effective and tunable chiral pyridine ligand framework that may be used in many catalytic asymmetric transformations.

尽管吡啶衍生物在催化领域是用途广泛的辅助配体，但其手性衍生物的开发相对受限。在此，我们报道一种带有稠合紧凑环系的结构可调手性吡啶骨架的设计、合成与概念验证应用。我们以包含手性吡啶官能团的N,B双齿配体骨架为基础，开发了二芳基(2-吡啶基)甲烷类化合物的对映选择性铱催化去对称化C-H硼化反应，该反应的对映体过量百分数(ee)最高可达96%，产率达93%。所得硼化产物可便捷转化为各类手性三(杂)芳基甲烷类化合物。密度泛函理论研究表明，柔性缩酮结构基元的两种椅式构象均倾向于生成与实验结果一致的对映异构体。本工作因此构建了一种高效且可调的手性吡啶配体骨架，可应用于众多催化不对称转化反应中。