A serendipitous one-pot synthesis of the octahydro-2 H -pyrazino[1,2- a ]pyrazine core.

An unexpected nitro group displacement during a nitro-Mannich reaction led to the one-pot formation of the octahydro-2 H -pyrazino[1,2- a ]pyrazine core, representing the shortest access to date to this pharmacologically relevant heterobicyclic system. A mechanistic hypothesis is suggested and supported by specific experiments and HRMS analysis of reaction mixtures.