Catalyst‐free Chloroamination Cyclization Cascade with Sodium Hypochlorite: from N‐(Pentenyl)sulfonylamides to 2‐(1‐Chloromethyl)pyrrolidines

• Published in: European journal of organic chemistry Vol. 27; no. 21
• Main Authors: Scarfiello, Jacopo, Rusconi, Marco, Lanfranco, Alberto, Azzi, Emanuele, Caracciolo, Stefano, Ghigo, Giovanni, Renzi, Polyssena, Deagostino, Annamaria
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 03-06-2024
• Subjects: catalyst free; Catalysts; Chlorine; chloroamination; domino reaction; hypochlorite; Light sources; Oxidation; Oxidizing agents; pyrrolidines; sodium; Sodium hypochlorite
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.202400108

A mild and catalyst‐free protocol to obtain several 2‐chloromethylpyrrolidines by the use of a commercial solution of sodium hypochlorite is here reported, without the need for a light source. The choice of the solvent revealed to be crucial in the success of the reaction. Mechanistic studies, both experimental and computational, confirmed a radical mechanism, where the deprotonation step, followed by the oxidation of a N‐centered anion to the corresponding radical, allowed 2‐chloromethylpyrrolidines, by a very fast cyclization, to be obtained. Sodium hypochlorite plays the role of both the oxidant and the chlorine source.
No catalyst is needed to cyclize a sulfonylated aminoalkene in the presence of commercial sodium hypochlorite, a catalytic amount of a base in tetrahydrofuran (THF), thus obtaining valuable 2‐chloromethylpyrrolidines via a domino process and a key nitrogen‐centered radical