Rh(I)-Catalyzed Asymmetric Synthesis of 3-Substituted Isoindolinones through CO Gas-Free Aminocarbonylation

A highly efficient and accessible synthesis of chiral
3-substituted
isoindolinone frameworks is described. The synthesis involved the
Rh­(I)-catalyzed asymmetric arylation of boronic acids to 2-halobenzaldimines
and the subsequent Rh­(I)-catalyzed intramolecular aminocarbonylation
of the resulting 2-halobenzylamines using an aldehyde as the carbonyl
source. The method tolerates a variety of functional groups, yielding
isoindolinone derivatives in moderate to high yields with high ee-values.
In addition, two Rh­(I)-catalyzed transformations could be efficiently
accomplished in a one-pot sequence to give chiral isoindolinones by
the simple addition of a ligand and an aldehyde after the Rh­(I)-catalyzed
asymmetric arylation.

本研究报道了一种高效且易于实施的手性3-取代异吲哚啉酮（isoindolinone）骨架的合成方法。该合成路线包含两步核心反应：首先通过铑(I)催化硼酸与2-卤代苯甲醛亚胺的不对称芳基化反应，得到中间体2-卤代苄胺；随后以醛作为羰基源，对该中间体进行铑(I)催化的分子内氨基羰基化反应。该方法官能团兼容性优异，可获得中等至较高收率的异吲哚啉酮衍生物，且产物具有较高的对映体过量值（ee值）。此外，在完成铑(I)催化的不对称芳基化反应后，仅需向反应体系中简单加入配体与醛，即可通过一锅法高效完成两步铑(I)催化转化，直接得到手性异吲哚啉酮产物。