Boc-piperazines

Boc piperazine conducted in the presence of Cs2C03 as base and added 18-crown-6 occurred in higher yields and shorter reaction times than those conducted without added crown ether 50... 

Recently, Torisawa reported that the addition of 18-crown-6 promotes the reactions of aryl triflates when Cs2C03 is used as the base [121]. This study focused on the reactions of N-Boc piperazine. In the absence of the crown ether, bis-N-Boc piperazine was produced as a byproduct, and reaction times were long. Yields for the reaction of 3,4-dichlorophenyl triflate with N-Boc piperazine were 35 % and 65 %, respectively, in the absence and presence of the crown ether. A similar effect was also observed for the reaction of the analogous dichloro bromoarene. 

A similar acid/base washing strategy has been employed for the synthesis of an aryl piperazine hbrary [9]. The synthesis was based on a nucleophilic aromatic substitution of nitro-fluoro aromatic compounds with Boc-piperazine and subsequent Schotten-Baumann acylation with acid chlorides. The products were purified by extractive work-up after each step. 

In all four examples, a large number of catalyst ligands were screened. In the cases of (d)-(+)-biotin, (an internal project) and 4-Boc-piperazine-2(S)-N- butylcarboxamide (the custom manufacture of a starting material for a cGMP production) the substrate structure could be modified to optimize the stereoselectivity. In the cases of dextro-metorphan (an internal project), and a benzodiazepine carboxylic ester (an intermediate in a custom manufacture cGMP project) moderate enantioselectivities (89% and 88% ee) could be tolerated, as favorable crystallization conditions could be chosen. 

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