Inverse α‑Effect as the Ariadne’s Thread on the Way to Tricyclic Aminoperoxides: Avoiding Thermodynamic Traps in the Labyrinth of Possibilities

Stable
tricyclic aminoperoxides can be selectively assembled via
a catalyst-free three-component condensation of β,δ′-triketones,
H2O2, and an NH-group source such as aqueous
ammonia or ammonium salts. This procedure is scalable and can produce
gram quantities of tricyclic heterocycles, containing peroxide, nitrogen,
and oxygen cycles in one molecule. Amazingly, such complex tricyclic
molecules are selectively formed despite the multitude of alternative
reaction routes, via equilibration of peroxide, hemiaminal, monoperoxyacetal,
and peroxyhemiaminal functionalities! The reaction is initiated by
the “stereoelectronic frustration” of H2O2 and combines elements of thermodynamic and kinetic control
with a variety of mono-, bi-, and tricyclic structures evolving under
the conditions of thermodynamic control until they reach a kinetic
wall created by the inverse α-effect, that is, the stereoelectronic
penalty for the formation of peroxycarbenium ions and related transition
states. Under these conditions, the reaction stops before reaching
the most thermodynamically stable products at a stage where three
different heterocycles are assembled and fused at the acyclic precursor
frame.