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

铵锌酸盐作为催化剂,通过微波增强氮丙啶区域选择性开环合成对称哌嗪

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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.

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