Regio- and Diastereoselective Synthesis of E-Allylic Amines through Hydroalkylation of Terminal Alkynes

Allylic amines make up an important class of organic compounds that have inspired the development of numerous methods for their synthesis. One of the most effective transformations involves the coupling of internal alkynes with appropriate nitrogen-containing electrophiles in the presence of a transition metal catalyst. We have developed a method that allows transformation of terminal alkynes into allylic amines through a copper-catalyzed reductive cross coupling with alpha-chloro phthalimides. The method has a broad substrate scope and results in the highly selective formation of the E-isomer of the anti-Markovnikov hydroamination product. A preliminary mechanistic study supports a mechanism that involves the hydrocupration of the alkyne and the formation of a solvent-caged radical pair.