A new approach to the synthesis of 1,2-diazines (pyridazines) is reported. Pyridazine substructures are found in many fragment-based screening libraries as well as the antidepressants minaprine and pipofezine and the anti-hypertensive hydralazine, but their synthesis has not been widely explored previously. Cobalt(I)-catalyzed intramolecular [2 + 2 + 2] cyclizations have been applied to alkynl-linked bisnitrile species to afford annulated pyridazines (Figure 1, where X = O, NR). The application of this chemistry to form annulated pyridazines represents the first time that nitrogen-nitrogen bond formation has been achieved in a [2 + 2 + 2] cyclization strategy. Diversification of the resulting pyridazines has been illustrated for the incorporation of these previously inaccessible molecules into small molecule libraries.

N,N-Bond formation through the intramolecular cobalt-catalyzed [2+2+2] cyclizations of alkynyl-linked bisnitriles in the preparation of annulated pyridazines

247th National Meeting (2014)

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