An interesting reaction for the synthesis of aromatic carbo- and heterocycles is the transition-metal catalyzed [2 + 2 + 2] cycloaddition reaction. In this elegant and atom-efficient process three C-C or C-X (X = N, O, S.) bonds are formed in a single synthetic process. The [2 + 2 + 2] cycloaddition is catalyzed by a variety of organometallic complexes, including more than 15 different metals. In this work, we carry out computational studies of the reaction mechanism between two acetylenes and a nitrile to form substituted pyridines catalyzed by the Wilkinson complex. Our results show that initial oxidative addition between the two acetylene molecules is the rate-determining step. Oxidative addition between two acetylenes is more favorable than between acetylene and nitrile moieties. Our results are in agreement with the experimental finding that the formation of pyridines in some cases requires the use of an excess of nitrile. Nitriles with electron withdrawing substituents favor the incorporation of nitrile in the insertion process and improve the ratio of pyridine vs. benzene ; The following organizations are thanked for financial support: the Ministerio de Ciencia e Innovacion (MICINN, project numbers CTQ2011-23156/BQU and CTQ2011-23121 BQU), the Generalitat de Catalunya (projects number 2009SGR637, Xarxa de Referencia en Quimica Teorica i Computacional, and Fl PhD fellowship to O.T.), and the FEDER fund (European Fund for Regional Development) for the grant UNGI08-4E-003. Support for the research of M. S. was received through the ICREA Academia 2009 prize for excellence in research funded by the DIUE of the Generalitat de Catalunya