Cu‐Catalyzed Selective Synthesis of Propargylamines via A3‐Coupling/Aza‐Michael Addition Sequence: Amine Loading Controls the Selectivity

Abstract

AbstractPropargylamines are valuable molecules in medicinal chemistry and organic synthesis. A3 reaction is straightforward access to construct propargylamine and its derivatives. Here we report operationally simple catalytic domino A3‐coupling/aza‐Michael addition of a primary amine, formaldehyde solution, an alkyne, and an olefin using copper as a catalyst to produce a series of functionalized propargylamines in moderate to excellent yields. This protocol involves a competition between aza‐Michael addition and Mannich reaction. By changing the amount loading of amines to control the process of Mannich reaction is the key procedure of increasing the selectivity.