Enantioselective synthesis of 2-amino-3-nitrile-chromenes catalyzed by cinchona alkaloids: A remarkable additive effect

2-Amino-3-nitrile-chromenes with potential antitumor activity were constructed by a novel catalytic system. In combination with α-naphthol, quinine could effectively promote the Michael-cyclization process of malononitrile with functionalized chalcones in high yields and moderate to good enantioselectivity (up to 84% ee). It is notable that the enantioselectivity could be greatly improved when α-naphthol was employed as additive.

Graphical abstractThe natural cinchona alkaloid quinine could efficiently promote a tandem conversion of chalcones and 2-amino-3-nitrile-chromenes were furnished in high yields (75%–99%) and moderate to good enantioselectivity (49%–84% ee). In particularly, achiral α-naphthol exerted a positive impact on the stereoselectivity and a significant enantioselectivity improvement was observed.Figure optionsDownload full-size imageDownload as PowerPoint slide