One-pot five-component high diastereoselective synthesis of polysubstituted 2-piperidinones from aromatic aldehydes, nitriles, dialkyl malonates and ammonium acetate

One-pot five-component high diastereoselective synthesis of polysubstituted 2-piperidinones from aromatic aldehydes, nitriles, dialkyl malonates and ammonium acetate Full article

Journal

Molecular Diversity
ISSN: 1573-501X , E-ISSN: 1381-1991

Output data

Year: 2020, Volume: 24, Number: 4, Pages: 1327-1342 Pages count : 16 DOI: 10.1007/s11030-019-09997-6

Authors

Vereshchagin Anatoly N. ¹ , Karpenko Kirill A. ¹ , Elinson Michail N. ¹ , Minaeva Alexandra P. ^2,1 , Goloveshkin Alexander S. ³ , Hansford Karl A. ⁴ , Egorov Mikhail P. ¹

Affiliations

1	N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia 119991
2	D. I Mendeleev University of Chemical Technology of Russia, Miusskaya Square 9, Moscow, Russia 125047
3	A. N. Nesmeyanov Institute of Organoelement Compounds, Vaviliva str., 28, Moscow, Russia 119991
4	Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia

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.

Vereshchagin A.N. , Karpenko K.A. , Elinson M.N. , Minaeva A.P. , Goloveshkin A.S. , Hansford K.A. , Egorov M.P.
One-pot five-component high diastereoselective synthesis of polysubstituted 2-piperidinones from aromatic aldehydes, nitriles, dialkyl malonates and ammonium acetate
Molecular Diversity. 2020. V.24. N4. P.1327-1342. DOI: 10.1007/s11030-019-09997-6 WOS Scopus OpenAlex

Web of science:	WOS:000495896500001
Scopus:	2-s2.0-85074585320
OpenAlex:	W2982125303

DB	Citing
OpenAlex	13
Scopus	10