One-Pot Synthesis of γ-Azidobutyronitriles and Their Intramolecular Cycloadditions

Efficient gram-scale, one-pot approaches to azidocyanobutyrates and their amidated or decarboxylated derivatives have been developed, starting from commercially available aldehydes and cyanoacetates. These techniques combine (1) Knoevenagel condensation, (2) Corey-Chaykovsky cyclopropanation and (3) nucleophilic ring opening of donor-acceptor cyclopropanes with the azide ion, as well as (4) Krapcho decarboxylation or (4 ') amidation. The synthetic utility of the resulting gamma-azidonitriles was demonstrated by their transformation into tetrazoles via intramolecular (3+2)-cycloaddition. A condition-dependent activation effect of the alpha-substituent was revealed in that case. Thermally activated azide-nitrile interaction did not differentiate the presence of an alpha-electron-withdrawing substituent in gamma-azidonitriles, whereas the Lewis acid mediated (SnCl(4)or TiCl4) reaction proceeded much easier for azidocyanobutyrates. This allowed us to develop an efficient procedure for converting azidocyanobutyrates into the corresponding tetrazoles.