Marriage
of Peroxides and Nitrogen Heterocycles: Selective
Three-Component Assembly, Peroxide-Preserving Rearrangement, and Stereoelectronic
Source of Unusual Stability of Bridged Azaozonides
posted on 2021-04-20, 20:30authored byIvan A. Yaremenko, Yulia Yu. Belyakova, Peter S. Radulov, Roman A. Novikov, Michael G. Medvedev, Nikolai V. Krivoshchapov, Alexander A. Korlyukov, Igor V. Alabugin, Alexander O. Terent’ev
Stable
bridged azaozonides can be selectively assembled via a catalyst-free
three-component condensation of 1,5-diketones, hydrogen peroxide,
and an NH-group source such as aqueous ammonia or ammonium salts.
This procedure is scalable and can produce gram quantities of bicyclic
stereochemically rich heterocycles. The new azaozonides are thermally
stable and can be stored at room temperature for several months without
decomposition and for at least 1 year at −10 °C. The chemical
stability of azaozonides was explored for their subsequent selective
transformations including the first example of an aminoperoxide rearrangement
that preserves the peroxide group. The amino group in aminoperoxides
has remarkably low nucleophilicity and does not participate in the
usual amine alkylation and acylation reactions. These observations
and the 15 pKa units decrease in basicity
in comparison with a typical dialkyl amine are attributed to the strong
hyperconjugative nN→σ*C–O interaction with the two antiperiplanar C–O bonds. Due to
the weakness of the complementary nO→σ*C–N donation from the peroxide oxygens (a consequence
of “inverse α-effect”), this interaction depletes
electron density from the NH moiety, protects it from oxidation, and
makes it similar in properties to an amide.