Chemistry of 1,2-dialkynylimidazoles: rearrangements to cyclopentapyrazines and imidazo[1,2-a]pyridines

A series of 1,2-dialkynylimidazoles (1,2-DAIs) intended as azaenediynes wherein the nitrogen is part of a heterocyclic imidazole ring were synthesized and their chemistry studied. The key N-alkynyl group was introduced using iodonium salts followed by a palladium coupling to add the 2-alkynyl side chain. Upon thermolysis in neat 1,4- cyclohexadiene, all of the 1,2-DAIs underwent an unprecedented molecular rearrangement to cyclopentapyrazine carbenes. These carbenes participated in hydrogen atom abstraction, cyclopropanation and C-H insertion. In benzene, all of the cyclopentapyrazine carbenes react with benzene, by presumably first forming a ix norcaradiene intermediate that rearranges to the phenyl adduct without any detection of cycloheptatriene intermediates. The carbene was also found to perform intramolecular olefin addition and C-H insertion forming interesting three- and four-membered ring pyrazines, yields of which were were maximized upon thermolysis in hexafluorobenzene. The rearrangement mechanisms of 1,2-DAIs were transformed in halogenated solvents. When compound 2.12 with an N-phyenylethynyl group was thermolyzed in chlorobenzene, a chloroimidazopyridine product derived from the 2,3-didehydropyridine intermediate was isolated. N-Ethynylated 1,2-DAIs, however, underwent a rearrangement to chlorinated imidazo[1,2-a]pyridines via a electrocyclic rearrangement of an α- chloroenamine intermediate. This rearrangement also occurred when an amine was the nucleophile while compounds in which the 2-alkynyl side chain is sterically demanding do not cyclize. Inclusion of the ynamine into an imidazole ring reversed the electronics of the N-alkynyl group in a few cases, with nucleophilic attack occurring at the β carbon of the ynamine.