Iridium-Catalyzed Regio- and Diastereoselective Synthesis of C‑Substituted Piperazines

Piperazine rings
are essential motifs frequently found in commercial
drugs. However, synthetic methodologies are mainly limited to N-substituted piperazines, preventing structural diversity.
Disclosed herein is a straightforward catalytic method for the synthesis
of complex C-substituted piperazines based on an uncommon head-to-head
coupling of easily prepared imines. This 100% atom-economic process
allows the selective formation of a sole diastereoisomer, a broad
substrate scope, and a good functional group tolerance employing a
bench-stable iridium catalyst under mild reaction conditions. Key
to the success is the addition of N-oxides to the
reaction mixture, as they notably enhance the catalytic activity and
selectivity.