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.