Herein, the design and development of a new one-pot and metal-free oxidative C-H activation/aza-Prins type cyclization of alkynylamines is reported. The scope of this method was demonstrated by the preparation of ten new pyrido[2,1-a]isoquinolines in moderate to high yields (38-92%). Furthermore, a mechanistic proposal for the alkyne aza-Prins cyclization is described based on DFT calculations.