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 γ-azidonitriles was demonstrated by their transformation
into tetrazoles via intramolecular (3+2)-cycloaddition. A condition-dependent activation
effect of the α-substituent was revealed in that case. Thermally activated azide–nitrile
interaction did not differentiate the presence of an α-electron-withdrawing substituent
in γ-azidonitriles, whereas the Lewis acid mediated (SnCl4 or TiCl4) reaction proceeded much easier for azidocyanobutyrates. This allowed us to develop
an efficient procedure for converting azidocyanobutyrates into the corresponding tetrazoles.
Key words
azides - nitriles - one-pot synthesis - 1,3-dipolar cycloaddition - tetrazoles - Knoevenagel
condensation - Corey–Chaykovsky reaction - nucleophilic ring opening
