Rapid and practical access to diverse quindolines by catalyst-free and regioselectivity-reversed Povarov reaction

Abstract

Summary: The Povarov reaction, a formal [4 + 2] cycloaddition between N-aryl imines and electron-rich dienophiles, has been defined as an efficient method to approach tetrahydroquinolines and has been well established in the past decades. In general, electron-rich heterosubstituted alkenes have served as the most popular dienophiles to achieve the exclusive regioselectivity. However, the use of Lewis acids and Brønsted acids as catalysts is required in these transformations, and, to our knowledge, the Povarov reaction of electron-rich heterosubstituted alkynes has not been reported. Here, we disclose a catalyst-free Povarov reaction of formyl-ynamides with anilines for the rapid and practical synthesis of a diverse range of valuable quindolines, which not only represents the first Povarov reaction of ynamides to the best of our knowledge but also constitutes a very rare example of a catalyst-free ynamide cyclization reaction. This formal [1 + 2 + 3] annulation shows a reversed regioselectivity compared with the previous protocols.

Keywords

• Povarov reaction
• annulation
• regioselectivity
• ynamides
• N-heterocycles