Chiral Bidentate Boryl Ligand Enabled Iridium-Catalyzed Asymmetric C(sp²)–H Borylation of Diarylmethylamines

Optically active organoboronic acids and their derivatives are an important family of target compounds in organic chemistry, catalysis, and medicinal chemistry. Yet there are rare asymmetric catalytic examples reported for the synthesis of these compounds via atom and step economic ways. Herein, we report a chelate-directed iridium-catalyzed asymmetric C­(sp2)–H borylation of aromatic C–H bonds directed by free amine groups. The success of these transformations relies on a novel family of chiral bidentate boryl ligands (L). They can be synthesized straightforwardly in three steps starting from readily available (S,S)-1,2-diphenyl-1,2-ethanediamie ((S,S)-DPEN). The Ir-catalyzed C­(sp2)–H borylation comprises two parts. The first part is desymmetrization of prochiral diarylmethylamines. In the presence of L3/Ir, a vast array of corresponding borylated products were obtained with high regioselectivity and good to excellent enantioselectivities (26 examples, up to 96% ee). The second part, kinetic resolution of racemic diarylmethylamines, was also conducted. Good selectivity values (up to 68%, 11 examples) were obtained when L8 was used. We also demonstrated the synthetic utility of the current method on gram-scale reaction for several transformations. The C–B bonds of borylated products could be converted to a variety of functionalities including C–O, C–C, C–C, C–Br, and C–P bonds. Finally, we performed DFT calculations of desymmetrization to understand its reaction pathways.光学活性有机硼酸（optically active organoboronic acids）及其衍生物是有机化学、催化领域及药物化学中一类重要的目标化合物。然而，通过原子经济性与步骤经济性的路径合成此类化合物的不对称催化案例仍较为罕见。本文中，我们报道了一种由游离氨基导向、经螯合辅助的铱催化芳香族C(sp²)–H键不对称硼化反应。该转化的成功实施依赖于一类新型手性双齿硼基配体（L）。此类配体可从市售易得的(S,S)-1,2-二苯基乙二胺((S,S)-DPEN)出发，通过三步反应简洁合成。铱催化的C(sp²)–H硼化反应包含两个反应模块：第一部分为前手性二芳基甲胺的去对称化反应。在L3/Ir催化体系作用下，可得到一系列相应的硼化产物，其区域选择性优异，对映选择性良好至优异（共26个反应实例，对映体过量值最高可达96% ee）。第二部分为外消旋二芳基甲胺的动力学拆分反应。当使用L8作为配体时，可获得良好的拆分选择性（共11个反应实例，选择性最高可达68%）。我们还通过多组克级规模转化实验，验证了该方法的合成实用性。硼化产物中的C–B键可转化为多种官能团，包括C–O、C–C、C–C、C–Br及C–P键。最后，我们针对去对称化反应开展了密度泛函理论（DFT）计算，以阐明其反应路径。