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 [ZnI 4 ] 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.