Vinylogous Winstein Rearrangement: Unexpected Isomerization of an Azide-Substituted Cyclohexadiene–Fe(CO)3Complex

In the course of our research into enzyme-triggered CO-releasing molecules (ET-CORMs), we were interested in using 2-acetoxy-5-azido-1,3-cyclohexadiene–Fe(CO)3(rac-2) as a building block for further structural modification by means of Cu-catalyzed azide–alkyne cycloaddition (CuAAC click chemistry). Treatment of [2-acetoxy-cyclohexadienyl–Fe(CO)3]+[PF6]−with Zn(N3)2, TMS-N3, or NaN3surprisingly afforded 2-acetoxy-1-azido-2,4-cyclohexadiene–Fe(CO)3(rac-9) as the main product. We could show that rac-2is primarily formed under kinetic control but undergoes a rapid isomerization to rac-9(as the thermodynamic product) in a formal vinylogous Winstein rearrangement under concomitant migration of the Fe(CO)3moiety. This unprecedented reaction displays a 1st order kinetics and appears to proceed via an ionic (rather than a concerted intramolecular) mechanism as supported by crossover experiments using deuterated compounds. The CuAAC reaction of rac-9with propargylic alcohol afforded triazole rac-13, which was demonstrated (by headspace-gas chromatography (GC)) to act as an ET-CORM in the presence of porcine liver esterase.