Metal-free, one-pot conversion of proline derivatives into 2-aryl-3-iodo pyrrolidines by a sequential scission–iodination–arylation process

Abstract

The metal-free, direct conversion of readily available proline derivatives into 2-aryl-3-iodopyrrolidines is carried out under mild conditions and in good yields, using a sequential radical decarboxylation-oxidation-iodination-arylation reaction. These iodinated pyrrolidines are valuable precursors of other compounds. For instance, they can be cyclized to tricyclic compounds or undergo dehalogenation to 2-aryl-2,5-dihydro-1H-pyrroles, which are iminosugar and 2-arylpyrrole precursors. This process provides a short pathway to a variety of alkaloid and drug analogues of potential pharmaceutical interest.

“Cut and Paste” Processes in the Search of Bioactive Products: One-Pot, Metal-free O-Radical Scission-Oxidation-Addition of C, N or P-Nucleophiles

“…Our group and others have described different applications of the β-scission of O -radicals, generated from alcohols, acetals or acids under Suárez conditions, to the preparation of bioactive products or their analogs ( Saavedra et al, 2020 ; Cuevas et al, 2021 and references cited therein). However, in these protocols a further development was introduced: coupling these oxidative scission processes to the addition of carbon, nitrogen, phosphorous, oxygen, hydrogen, sulfur and other nucleophiles ( Boto, Gallardo et al, 2006 ; 2007a ; Boto, Hernández et al, 2008a,b ; 2009 ; Batchu et al, 2014 ; Carro et al, 2017 ; Saavedra et al, 2018 ; Santana and González, 2020 ). In effect, the scission generates a C -radical that can be readily oxidized to a cationic intermediate when the latter is stabilized by adjacent groups.…”