Ammonium Zincates as Catalysts for the Microwave‐Enhanced Synthesis of Symmetric Piperazines by Regioselective Opening of Aziridines

Abstract

2,5‐disubstituted N,N’‐alkylpiperazines represent an interesting target in organic synthesis both for pharmaceutical or agrochemical applications and as a promising class of ligands in coordination chemistry. We report here a microwave‐enhanced synthesis of these compounds starting from non‐activated N‐alkyl aziridines in the presence of catalytic amounts of simple ammonium metallates. A remarkable TOF of 2787.9 h‐1 has been observed in the case of [TBA]2[ZnI4] as the catalyst (catalyst loading 0.1 mol%) and with an almost complete selectivity (up to 97%) in favor of both diastereoisomers (meso and chiral form) of the target 2,5‐disubstituted piperazines, obtained in 1:1 ratio. The two isomers are easily separated, because the meso form precipitates in pure from the reaction crude. A stereochemical investigation and the unprecedented isolation of 2,6‐disubstituted N,N’‐alkylpiperazines allowed us to shed light on the reaction mechanism.