Effect of Remote Trigonal Carbons on the Kinetics of Bergman Cyclization: Synthesis and Chemical Reactivity of Pyridazinedione-Based Enediynes

The synthesis and chemical reactivity of pyridazinedione-based enediynes (1, 2) are described. Both of
these enediynes, namely the dihydro compound 1 and its
corresponding tetrahydro analogue 2, were prepared by
double N,O-alkylation of the corresponding heterocyclic
system with the acyclic enediynyl dibromide 8 in good yields.
Their single-crystal X-ray structures revealed similar c, d
distances (distance between the acetylenic carbons undergoing covalent connection in Bergman cyclization). Interestingly, these molecules undergo Bergman cyclization at
different rates, and the reactivity is shown to be dependent
upon the state of hybridization of C-4 and C-5 atoms of the
parent heterocyclic ring.