Palladium-Catalyzed Four-Component Carbonylation Reactions of Acetylene: Synthesis of β-Perfluoroalkyl Acrylamides

The simplest alkyne, acetylene, is a suitable C2 linker synthon that enables the connection of organic molecules with different functional groups. However, reactions of acetylene with advanced organic building blocks are much less explored compared to substituted alkynes. In this article, we present a straightforward palladium-catalyzed four-component carbonylation reaction with acetylene, CO, amines, and perfluoroalkyl halides that enables the preparation of various β-perfluoroalkyl acrylamides in one step. This protocol also provides a new strategy for the late-stage modification of bioactive molecules, as demonstrated by the construction of β-perfluoroalkyl ibrutinib derivatives.