piperidines and ammonium-acetate

A novel five-component diastereoselective synthesis of polysubstituted 2-piperidinones is reported. The Knoevenagel condensation-Michael addition-Mannich cascade of two equivalents of aromatic aldehydes, nitriles, dialkyl malonates and ammonium acetate or aqueous ammonia in alcohols provides convenient access to alkyl (3SR,4RS,6SR)-5,5-dicyano-2-oxo-4,6-diarylpiperidine-3-carboxylates with three stereocenters in 52-90% or dialkyl (2SR,3RS,4RS,5SR)-2,4-diaryl-3-cyano-6-oxopiperidine-3,5-dicarboxylates with four stereocenters in 38-88%. The formation of products was highly stereoselective, with only one diastereomer formed. Ammonium acetate or aqueous ammonia plays a role both as a catalyst and as a nitrogen source. 2,4,6-triaryl-3,3,5,5-tetracyanopiperidines were obtained as a side products in the reactions with nitro-substituted aldehydes or with ethyl and n-propyl cyanoacetates. A series of 14 2-piperidinones and piperidines was assessed for antimicrobial activity against a panel of five bacteria and two fungi; no significant activity was observed. Two side piperidines with nitro substituents in aromatic ring possess bacteriostatic action against S. aureus ATCC 43300 and A. baumannii ATCC 19606 at 32 ug/mL.

Topics: Acetates; Acinetobacter baumannii; Aldehydes; Catalysis; Malonates; Nitriles; Piperidines; Piperidones; Staphylococcus aureus; Stereoisomerism

An efficient and straightforward synthetic protocol has been developed for the diversity-oriented synthesis of highly functionalized piperidines containing a Meldrum's acid moiety via pseudo five-component reaction between aromatic aldehydes, ammonium acetate, substituted β-nitrostyrenes and Meldrum's acid for the generation of a wide range of structurally interesting and pharmacologically significant compounds.

Topics: Acetates; Aldehydes; Combinatorial Chemistry Techniques; Dioxanes; Molecular Structure; Piperidines; Styrenes