Acid-catalyzed intramolecular cyclization ofN-(4,4-diethoxybutyl)sulfonamides as a novel approach to the 1-sulfonyl-2-arylpyrrolidines

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

“…Phenols possessing two reactive positions give bis(pyrrolidines) 16 as diastereomeric mixtures . Remarkably, carrying out the same reactions in benzene instead of chloroform allowed to obtain some of target pyrrolidine derivatives as a single diastereomers …”

“…This may be attributed to the higher electron density on the nitrogen atom in sulfonylamides compared to ureas, which stabilizes the iminium cation B and decreases its deprotonation rate (see Scheme ). Interestingly, 1‐sulfonyl‐2‐ethoxypyrrolidines 14 also react with phenols under the same conditions to give pyrrolidines 15 and 16 . This fact, together with isolation of these compounds from the reaction mixtures, supports our proposal for the reaction mechanism.…”

“…Again, the less a nucleophilicity of aromatic compounds, the less readily it undergoes the reaction and an absence of electron‐donating substituent prevents the reaction completely. Phenols possessing two reactive positions give bis(pyrrolidines) 16 as diastereomeric mixtures . Remarkably, carrying out the same reactions in benzene instead of chloroform allowed to obtain some of target pyrrolidine derivatives as a single diastereomers …”

“…Additionally, during our studies we have also discovered that N ‐(4,4‐diethoxybutyl)sulfonylamides 13 are prone to intramolecular cyclization in the presence of acids (Scheme ). Based on these data, we have developed a one‐pot approach to 1‐sulfonyl‐2‐ethoxypyrrolidines 14 via a reaction of 4,4‐diethoxybutan‐1‐amine with various sulfonyl chlorides (Scheme ) . Notably, these compounds are valuable intermediates in the synthesis of various pyrrolidine derivatives …”

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

“…Earlier, we have developed the metal‐free approach to the 2‐arylsubstitued pyrrolidine derivatives based on the acid‐catalyzed intramolecular imination of 4,4‐diethoxybutyl‐1‐amine derivatives leading to the formation of pyrrolinium cation. Further Mannich‐type reaction of this cyclic iminium ion with various electron‐rich aromatic nucleophiles allowed us to obtain a range of 2‐arylpyrrolidine derivatives …”