This work examines the reduction mechanisms of various substituted isoxazoles (ISXs) in the presence of FeII–tiron complex. The trend in the reactivity follows: 5-NH2-ISX &gt;&gt; 3-NH2-ISX &gt;&gt; 5-O-substituted ISX &gt;&gt; ISX. Electron withdrawing groups at the 3-position significantly enhanced the reactivity. Reduction products of ISXs were identified by HPLC/QToF-MS to be the ring opening analogs. The experimental solvent and iron kinetic isotope effects suggest protonation is not rate-limiting, while Fe(II) is directly involved in the rate-limiting step, which is likely electron transfer. The N–O bond in the ISX ring dissociates after accepting the first electron, and a 6-membered ring formed among the FeII in FeII–tiron complex, the N or O atom within the ring, and the 3-N or 5-N substituent. Electron transfer is significantly facilitated within the 6-membered ring, as confirmed by electrochemical cell experiments that separated complexation from electron transfer. Our ongoing work examines molecular descriptors that can be correlated to the reduction reactivity of all ISXs.

Structure-dependent reduction mechanisms of isoxazoles by aqueous FeII–tiron complex

252nd National Meeting (2016)

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