Copper-Catalyzed Enantioselective Radical 1,4-Difunctionalization of 1,3-Enynes

Chiral allenes are important structural
motifs frequently found
in natural products, pharmaceuticals, and other organic compounds.
Asymmetric 1,4-difunctionalization of 1,3-enynes is a promising strategy
to construct axial chirality and produce substituted chiral allenes
from achiral substrates. However, the previous state of the art in
1,4-difunctionalization of 1,3-enynes focused on the allenyl anion
pathway. Because of this, only electrophiles can be introduced into
the allene backbones in the second functionalization step, consequently
limiting the reaction and allene product types. The development of
asymmetric 1,4-difunctionalization of 1,3-enynes via a radical pathway would complement previous methods and support expansion
of the toolbox for the synthesis of asymmetric allenes. Herein, we
report the first radical enantioselective allene formation via a group
transfer pathway in the context of copper-catalyzed radical 1,4-difunctionalization
of 1,3-enynes. This method addresses a longstanding unsolved problem
in asymmetric radical chemistry, provides an important strategy for
stereocontrol with free allenyl radicals, and offers a novel approach
to the valuable, but previously inaccessible, chiral allenes. This
work should shed light on asymmetric radical reactions and may lead
to other enantioselective group transfer reactions.