American Chemical Society
cs2c05895_si_002.cif (5.39 MB)

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

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posted on 2023-02-17, 03:03 authored by Luis 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.