Radical Ring‐Opening Reaction of Non‐Activated Oximes Catalyzed by Aldoxime Dehydratases

Abstract The iminyl radical is a distinctive N ‐centered radical which serves as a versatile synthon in preparation of nitrogen‐containing compounds. In principle, iminyl radicals can be directly generated by single electron reduction of oximes through elimination of OH group. However, due to the low reactivity of the oxime N─OH bonds, direct conversion of the oximes does not proceed efficiently, thereby enforcing chemical activation of the oxime OH group which results in the formation of stoichiometric by‐products. To overcome this problem, we are developing a new biocatalytic system using aldoxime dehydratases. Through a series of enzyme screenings, we identified an aldoxime dehydratase from N. simplex (NsOxd) which is capable of catalyzing iminyl radical‐mediated ring‐opening reactions. Notably, NsOxd efficiently converts the “non‐activated” 2‐phenylcyclobutanone oxime within 10 min under ambient conditions and quantitatively produces the corresponding γ‐sulfinylated nitrile in >95% yield. This enzyme activity is even faster than that of previously‐reported chemo‐catalysts. Furthermore, evaluation of the scope of potential substrates indicates that NsOxd has a versatile N─O bond cleaving activity which efficiently generates iminyl radicals from various “non‐activated” oximes. These findings highlight the utility of aldoxime dehydratases for managing the reactivity of “non‐activated” oximes and for achieving challenging iminyl radical‐mediated catalytic reactions.