Potassium‐Persulfate‐Promoted Regioselective Azidation/Cyclization of 1,6‐Enynes

Abstract

An efficient, environmentally benign and sustainable method for the synthesis of 2-pyrrolidinones from 1,6enynes via an unusual regioselective azidation/cyclization is described. The products have been obtained in good yields without the assistance of any transition-metal catalysts or ligands. To demonstrate the utility of this protocol, the azidation products are converted to a synthetically valuable amine or triazole. This azidation cyclization involves a radical process, allows a regioselective way toward the formation of one CÀ N bond and one CÀ C bond.

New Strategies for the Synthesis of Aliphatic Azides

“…The cyclization of 1,n-enynes has attracted significant attention in synthetic chemistry because of their utility for the atom-and step-economic construction of a variety of complicated carbo- reaction was not compatible with N-benzyl or phenethyl or tert-butyl substituted 1,6-enynes (Scheme 53b). 228 The research group of Song and Li disclosed a coppercatalyzed azide radical-initiated [2 + 2 + 1] annulation/ azidation of benzene-linked 1,n-enynes 203 with azidobenziodoxolone to access diverse fused pyrrolines 204, including 3Hpyrrolo[3,4-c]quinolin-4(3aH)-ones, chromeno [3,4-c]pyrrol-4-(9bH)-one, and indeno[1,2-c]-pyrroline. A plausible mechanism might involve the initial azide radical addition to alkenes, annulation of the resulting vinyl radical intermediate, and azidation cascade (Scheme 54a).…”

“…Several N -substituted 1,6-enynes underwent the reaction in good yields. However, the reaction was not compatible with N -benzyl or phenethyl or tert -butyl substituted 1,6-enynes (Scheme b) …”

Radical Cyclization of 1,n‐Enynes and 1,n‐Dienes for the Synthesis of 2‐Pyrrolidone

“…In an attempt to develop a more cost‐effective and sustainable alternative method to access 2‐pyrrolidones, we developed a tandem azidation‐cyclization reaction of 1,6‐enynes in 2019 (Scheme 14). [26] Different from the chloroazidation strategy discussed prior, [24] the N 3 . radical was formed by the reaction of K 2 S 2 O 8 with TMSN 3 directly.…”

N-Radical enabled cyclization of 1,n-enynes

“…In 2019, Wei et al [124] reported a unique azidation/cyclization of 1,6-enynes with N3 sources for the synthesis of 2-pyrrolidinones using K2S2O8 as oxidant (Scheme 18). The reaction was conducted under metal-and ligand-free conditions by employing an inexpensive and stable inorganic oxidant, and the azidation process was terminated by the hydrogen atom abstraction from the solvent or H2O.…”