Chemoselective intramolecular alkylation of the Blaise reaction intermediates: Tandem one-pot synthesis of exo -cyclic enaminoesters and their applications toward the synthesis of N -heterocyclic compounds

Abstract

The intramolecular alkylative reactivity and N/C selectivity of the various Blaise reaction intermediates, which are formed from the reaction of the Reformatsky reagents with ω-chloroalkyl nitriles, did not reach the synthetic potential as an entry to exo-cyclic enaminoesters. To circumvent this issue, various additives were investigated, among which the addition of NaHMDS dramatically enhanced the reactivity and N/C selectivity. This modification provided a highly efficient route for the synthesis of various N-fused heterocyclic compounds, as it requires only two steps from nitriles. © 2012 American Chemical Society.