posted on 2023-02-17, 03:03authored byLuis Tarifa, M. Pilar del Río, Laura Asensio, José A. López, Miguel A. Ciriano, Ana M. Geer, Cristina Tejel
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.