Synthesis of 1,2,3-trisubstituted pyrrolidines and 2,3-disubstituted tetrahydrofurans via diastereoselective reductive cyclization of γ-chloroimines and γ-chloroketones

A new diastereoselective synthetic approach towards 1,2,3-trisubstituted pyrrolidines and 2,3-disubstituted tetrahydrofurans is described. The synthesis of the pyrrolidines involves reductive cyclization of gamma-chloroketimines, which were generated in situ from the reaction of 3-substituted 5-chloro-2-pentanones and a primary amine. Various reduction conditions were explored to induce a diastereoselective reductive cyclization. 2,3-Disubstituted tetrahydrofurans were obtained by the direct reduction of 3-substituted 5-chloro-2-pentanones with sodium borohydride