Acid‐Catalyzed Intramolecular Imination / Nucleophilic Trapping of 4‐Aminobutanal Derivatives: One‐Pot Access to 2‐(Pyrazolyl)pyrrolidines

Abstract

A first successful synthesis of 2‐(pyrazolyl)pyrrolidines is reported starting from readily available reagents. A wide variety of N‐substituted 2‐(pyrazolyl)pyrrolidines are obtained with up to 96 % yield. The influence of the obtained compounds on biofilm formation by V. aquamarinus DSM 26054 and A. calcoaceticus VKPM B–10353 have been studied. Some of the tested compounds were found to suppress the growth of bacterial biofilms at nanomolar concentrations and thus are promising candidates for further studies.

Nucleophilic Cyclization/Electrophilic Substitution of (2,2-Dialkoxyethyl)ureas: Highly Regioselective Access to Novel 4-(Het)arylimidazolidinones and Benzo[d][1,3]diazepinones

“…Previously, we have utilized 1-pyrrolinium cations, either pre-formed 41 or generated in situ from N- (4,4diethoxybutyl)sulfonylamides or N- (4,4-diethoxybutyl)ureas, 42,43 for the synthesis of various 2-(het)arylpyrrolidine derivatives using electron-rich aromatics and heterocycles as C-nucleophiles. In general, this chemistry is similar to cyclic iminium ion chemistry developed by Speckamp and coworkers except that silyl enol ethers, 44 allylsilanes, 45 or alkenes 46,47 were used as C-nucleophiles in this case.…”

“…This probably is due to lowering of electron density at the 4-position of the pyrazole ring by electron-withdrawing substituents and is in accordance with our previous observations. 43…”

2‐(Het)aryl‐N‐phosphorylpyrrolidines via Cyclization of Phosphorus Acid Amides: A Regioselective Approach

“…Based on this data and our previous efforts on 2‐substituted pyrrolidines synthesis, we anticipated that a similar reaction of N ‐(4,4‐diethoxybutyl)amides of P(V) acids with electron‐rich (het)aryl nucleophiles would afford N ‐phosphorylated 2‐(het)aryl‐substituted pyrrolidine derivatives via intermediate 2‐ethoxypyrrolidine formation. Notably, the presence of phosphorylation‐sensitive groups in a nucleophile should not interfere with the reaction, thus allowing regioselective synthesis of hitherto unknown N ‐phosphorylpyrrolidines possessing hydroxyl(het)aryl moiety (Scheme , B).…”

The Highly Regioselective Synthesis of Novel Imidazolidin-2-Ones via the Intramolecular Cyclization/Electrophilic Substitution of Urea Derivatives and the Evaluation of Their Anticancer Activity

“…Nitrogen-containing aldehydes and acetals are widely used in the heterocycles synthesis [ 14 , 15 ]. Earlier, we have described the approach to 2-substituted pyrrolidine derivatives based on the in situ generation of a cyclic iminium ion from 4-aminobutanal acetals (4,4-diethoxybutan-1-amines) and its trapping by various nucleophiles [ 16 , 17 , 18 ]. Our preliminary studies indicate that N -(2,2-dialkoxyethyl) ureas are also capable of the formation of cyclic imidazolinium cations and the reaction results in cyclic urea derivatives—imidazolidinones or benzo [ d ] [1,3] diazepinones [ 19 ].…”