A novel one-step method for the preparation of 5H-pyrazino[2,3-b]indoles with different substitution patterns in all rings of the tricyclic system via the Rh₂(OAc)₄-catalyzed reaction of 2H-azirines with 3-diazoindolin-2-imines is reported. Alkyl 5H-pyrazino[2,3-b]indole-3-carboxylates were also prepared by a one-pot procedure from synthetic equivalents of alkyl 2H-azirine-2-carboxylates, 5-alkoxyisoxazoles. The reactions provide the first examples of the use of Rh(II) catalysis for intermolecular annulations with 2H-azirines and isoxazoles.