Synthesis of Chiral Diarylmethylamides via Catalytic Asymmetric Aza-Michael Addition of Amides to ortho-Quinomethanes

Chiral
diarylmethylamides are a privileged skeleton in many bioactive
molecules. However, the enantioselective synthesis of such molecules
remains a long-standing challenge in organic synthesis. Herein, we
report a chiral bifunctional squaramide catalyzed asymmetric aza-Michael
addition of amides to in situ generated ortho-quinomethanes, affording enantioenriched diarylmethylamides in good
yields with excellent enantioselectivities. This work not only provides
a new strategy for the construction of the diarylmethylamides but
also represents the practicability of amides as nitrogen-nucleophiles
in asymmetric organocatalysis.

手性 diarylmethylamides 作为众多生物活性分子中的重要骨架，然而，此类分子的对映选择性合成在有机合成领域一直是一个长期存在的难题。本研究报道了一种手性双官能团 squaramide 催化的不对称 aza-Michael 反应，该反应将酰胺加成到原位生成的邻位喹啉甲烷上，以优异的对映选择性和良好的产率，得到了富集的对映选择性 diarylmethylamides。此项研究不仅为 diarylmethylamides 的构建提供了一种新的策略，同时也展现了酰胺作为氮亲核体在不对称有机催化中的实用性。