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Rational design and first principles studies toward the discovery of a small and versatile proton sponge.

More than 30 years ago, Alder et al. challenged our classical view of acid–base properties with their discovery of a simple organic compound that showed a basicity ten million times higher than typical organic bases. This superbase, 1,8-bis(dimethylamino)naphthalene (DMAN), is known as “proton sponge” because of its high thermodynamic basicity combined with a kinetic inactivity to deprotonation that resembles the affinity of a sponge for water. Since then, many families of proton sponges have been created and they are finding a growing number of interesting applications. Quantum chemical studies have shed some light on the structural factors influencing the high basicity of proton sponges. Their abnormally high basicity is accepted to be produced by strong crowding of unshared electron pairs on nitrogen atoms, a strong intramolecular hydrogen bond in the protonated form, and relief of steric strain upon protonation. These characteristics are usually achieved by anchoring two nitrogen atoms sufficiently close in a rigid framework of condensed phenyl rings. Furthermore, hydrophobic substituents on the nitrogen atoms confer kinetic stability. Herein we report the design of a new molecular framework that differs significantly from the traditional topology of proton sponges.We began with the simplest structure in which two nitrogen atoms are about 250 pm apart and have their lone pairs of electrons facing each other, namely, the boat conformation of piperazine. To enforce the boat conformation, we integrated this unit into the minimal framework provided by the structure of 3,6,7,8-tetraazatricyclo[3.1.1.1]octane (1; Scheme 1). This molecule has two