Copper-Catalyzed Yne-Allylic Substitutions Using Stabilized Nucleophiles

Using stabilized “soft” nucleophiles in copper-catalyzed allylic substitutions is highly desirable but remains an unsolved challenge for the last 40 years. In this work, a general protocol of copper-catalyzed allylic substitutions using “soft” nucleophiles such as indoles, pyrroles, amines, and 1,3-dicarbonyls has been developed, delivering a large variety of functionalized 1,3- and 1,4-enynes with high levels of regio- and stereoselectivities (67 examples). A range of further transformations of the products can be easily achieved to release various functionalized molecules. A mechanistic rationale with a copper acetylide-bonded allylic cation as the key intermediate that features an outer-sphere nucleophilic attack has been proposed. Additionally, a series of diversified reactivities have been demonstrated, which will inspire further studies.