N-alkyl-2-halo- and 2,2-dihaloaldimines in the Pudovik reaction

Acid‐Catalyzed Cascade Reaction of 4‐Aminobutanal Derivatives with (Hetero)aromatic Nucleophiles: A Versatile One‐Pot Access to 2‐(Hetero)arylpyrrolidines.

“…Carbamoyl, carboxyl and sulfonyl groups are used to a lesser extent. [6,21] Groups other than these are exceptionally rare, which may be attributed either to the complicated synthesis of the appropriate derivatives, or to the lack of research in this field, or to both of these reasons.…”

“…Inspired by this work, we developed a method of synthesis of 2-arylsubstituted N-carbamoylpyrrolidines 4 based on trifluoroacetic acid-catalyzed reaction of N-(4,4-diethoxybutyl) (thio)ureas 3 with aromatic nucleophiles (Scheme 3). [25][26][27][28][29] The reaction proceeds in mild conditions, and both aliphatic and aromatic substituents in ureas 3 are tolerated.…”

“…Probably it is the different solubility of diastereomers in chloroform and solvents used for compounds purification, which affects a diastereomeric ratio. Similarly, a reaction of compounds 8 having two N- (4,4-diethoxybutyl)urea moieties connected via polymethylene or 1,4-phenylene spacer give diastereomeric bis(2-aryl)pyrrolidines 9 (Scheme 3).. [25][26][27] The synthetic outcome of a reaction of bis(ureas) 8 with resorcinol derivatives depends on a structure of starting compound and reaction conditions (Scheme 5). [38,39] The reaction of urea 8 possessing hexamethylene spacer with two equivalents of resorcinol, 2-methylresorcinol, or pyrogallol in chloroform, benzene, or acetone in the presence of trifluoroacetic acid failed to produce the desired compounds.…”

“…[4,19,20] The methods based on the intramolecular cyclization of acyclic precursors are also widely used, especially in the case of polycyclic systems. [6,21,22] The essential drawback of these approaches is the need in preliminary synthesis of starting compounds with appropriate functional groups and desired (hetero)aryl fragment.…”

“…Most often this transformation is achieved by intramolecular Pictet-Spengler reaction of 4-aminocarbonyl compounds or their acetals possessing aryl moiety (Scheme 1, A). [6,21,23] How-ever, only polycyclic pyrrolidine derivatives are available via this approach. Intermolecular variants of such reactions allowing one-pot synthesis of 2-(hetero)arylpyrrolidines have received much less attention.…”