武汉大学吕辉课题组Nat. Commun.:铱催化实现2,3-二氨基-1,4-二酮的依次动态动力学拆分高效合成含连续四手性中心的手性邻二胺化合物
The stereoselective construction of chiral vicinal diamines bearing multiple contiguous stereocenters remains a formidable challenge in modern organic synthesis. Herein, we report an Ir-catalyzed sequential dynamic kinetic resolution of 2,3-diamino-1,4-diketones that furnishes acyclic vicinal diamines containing four contiguous stereocenters in high yields with excellent diastereo- and enantioselectivity. The protocol exhibits broad substrate generality and high catalytic efficiency, enabling streamlined access to structurally diverse, functionally enriched chiral vicinal diamines. A gram-scale reaction proceeds smoothly with only 0.1 mol% catalyst loading, and versatile downstream derivatizations further highlights the synthetic utility of the method. Mechanistic investigations support a stepwise dynamic kinetic resolution pathway operative in this transformation.图1. 研究背景及本策略 (图片来源于Nat. Commun.)图2. 条件优化 (图片来源于Nat. Commun.)图4. 2,3-二氨基-1,4-二酮底物范围 (图片来源于Nat. Commun.)图5. 克级反应及应用 (图片来源于Nat. Commun.)图6. 产物随反应时间的分布以及化合物1a随反应时间的对映选择性变化 (图片来源于Nat. Commun.)In conclusion, we have developed Ir/f-PNNO complex enabled asymmetric hydrogenation of the mixture of racemic 2,3-diamino-1,4-diketones, affording chiral 2,3-diamino-1,4-diols in high yields and excellent stereoselectivities. The mechanism studies revealed that a stepwise dynamic kinetic resolution was involved in this transformation. We anticipate that this facile, effective, and practical synthetic method will not only significantly facilitate the synthesis of functionalized vicinal diamines, but also provides a general strategy for the construction of challenging acyclic chiral molecules with four adjacent stereocenters. The application of the double DKR strategy in synthesis of complicated molecules with multiple stereocenters is undergoing in our lab.Jinming Ma, Jiaxin Yuan* & Hui Lv*, Efficient synthesis of chiral vicinal diamines with four contiguous stereocenters via sequential dynamic kinetic resolution of 2,3-diamino-1,4 diketones, Nat. Commun., 2026, 10.1038/s41467-025-67526-6.
