AlCl₃-Catalyzed Annulation Reactions Of O-Quinone Methides And Ynamides

The unique molecular structure of ynamide ensures its perfect balance between reactivity and stability, and realizes a very good regioselectivity in chemical reactions,which affords ynamides great advantages in organic synthetic methodology and total synthesis of natural products, especially in the synthesis of compounds containing nitrogen. The cycloaddition reaction of ynamides is a kind of efficient method to synthesize monocyclic or polycyclic compounds. However, most previous works on the cycloaddition reaction of ynamides are about constructs of carbon rings,heterocyclic compounds synthesized by this method are rarely reported. Therefore,further study on their use in synthesis of heterocyclic compounds is very important for the research of these compounds.Amino-substituted chromene(benzopyran) structures commonly exist in many natural products and drugs, and its synthesis methods have been widely concerned.However, since previous traditional methods to synthesize these compounds are rare,few compounds have been reported. In this article, we introduced the cycloaddition of ynamides with o-quinone methides catalyzed by Al Cl3 and obtained different types of amino-substituted chromene compounds. We describe herein two catalytic processes for the preparation of amino-substituted 2H- and 4H-chromenes. A sequence comprising a cycloaddition of o-quinone methides with terminally substituted ynamides furnished 4-amino-2H-chromenes in generally excellent yields with high regioselectivities. While the reaction of o-quinone methides with terminally unsubstituted ynamides provided cycloadducts 2-amino-4H-chromenes with good to high yields. This methodology provides general and straightforward ways to construct amino-substituted chromenes under mild conditions and tolerated a wide range of functional groups.