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Synthesis of Piperazinones, Piperazines, Tetrahydropyrazines, and Dihydropyrazinones from Polymer‐Supported Acyclic Intermediates via N ‐Alkyl‐ and N ‐Acyliminiums
Author(s) -
Vaňková Barbora,
Brulíková Lucie,
Wu Boyuan,
Krchňák Viktor
Publication year - 2012
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201200591
Subject(s) - chemistry , triethylsilane , aldehyde , iminium , ketone , amide , substituent , alkyl , aryl , organic chemistry , stereochemistry , medicinal chemistry , catalysis
Trisubstituted piperazinones, piperazines, tetrahydropyrazines, and dihydropyrazinones were prepared in a one‐step procedure from easily accessible polymer‐supported acyclic precursors containing either a masked aldehyde or ketone group. Acid‐mediated unmasking of the aldehyde triggered cyclic iminium formation followed by reduction with triethylsilane present in the cleavage cocktail. The effect of the substituent at the iminium‐forming nitrogen was evaluated: whereas complete conversion to the target compounds was observed with N ‐alkyl, aryl, and phenylsulfonamido derivatives, the N ‐acyl compound suffered from a partial reduction of the aldehyde to an alcohol. Similarly, ketones readily provided cyclic iminiums with N ‐alkyl compounds, whereas their cyclization with N ‐acyl precursors proceeded unwillingly. Interestingly, cleavage of the resin‐bound acyclic precursor at 60 °C in the presence of triethylsilane resulted in the decomposition of the amide bond and formation of a lactone. An analogous synthetic route was also successfully used for the preparation of piperazines and tested as an alternative route for the synthesis of diazepanones.